The nanocrystalline minerals contents predominantly and positively controlled the sizes of intermediate and stable SOC pools, and the mean residence time of intermediate SOC pool. Biotic and climatic factors (i.e., microbial biomass, available N for microbes, and excess precipitation) controlled the labile SOC pool. Compared with topsoil, stabilized organic matters were more in the intermediate rather than in the stable SOC pool, and the temperature had a more significant effect on the stable SOC pool in subsoil than in topsoil. Available N for microbes partially controlled the labile and intermediate SOC pools in subsoil (more limited available N for microbes), but not in topsoil. Thus, subsoil SOC would be more sensitive to climate change than topsoil SOC. This study helped to understand the SOC stabilization mechanism and emphasized the high climate- and mineral-dependence of SOC in subsoil of tropical volcanic regions.The aim of this study was to investigate reported cases of honeybee mortality incidents and the potential association to pesticide exposure and to their metabolites. The same honeybee samples were also assessed for Varroa mites, and Nosema microsporidia provoked infections to provide an integrated picture of all observable stressors that may impact bees' survival. Thus, honeybee samples from different areas of Greece (2014-2018) were analyzed for the presence of pesticide residues and metabolites. In this context, an existing LC-ESI-QqQ-MS multiresidue method of analytes of different chemical classes such as neonicotinoids, organophosphates, triazoles, carbamates, was enriched with additional active substances, developed and validated. A complementary GC-EI-QqQ-MS method was also exploited for the same scope covering pyrethroid compounds. Both methods monitored more than 150 active substances and metabolites and presented acceptable linearity over the ranges assayed. The calculated recoveries ranged from 65 to 120% for the three concentration levels, while the precision (RSD%) values ranged between 4 and 15%. Therefore, this approach proved sufficient to act as a monitoring tool for the determination of pesticide residues in cases of suspected honeybee poisoning incidents. From the analysis of 320 samples, the presence of 70 active substances and metabolites was confirmed with concentrations varying from 1.4 ng/g to 166 μg/g. Predominant detections were the acaricide coumaphos, several neonicotinoids exemplified by clothianidin, organophosporous compounds dimethoate and chlorpyrifos, and some pyrethroids. Metabolites of imidacloprid, chlorpyrifos, coumaphos, acetamiprid, fenthion and amitraz were also identified. Concerning Nosema and Varroa they were identified in 27 and 22% of samples examined, respectively, verifying their prevalence and coexistence with pesticides and their metabolites in honeybees.The development of carbon-based materials to catalyze two-electron (2e-) pathway of oxygen reduction reaction (ORR) offers great potential for hydrogen peroxide (H2O2) production. https://www.selleckchem.com/products/SB-203580.html As a class of novel two-dimensional (2D) carbon materials, graphene and its derivatives have raised increasing attention as excellent noble-metal-free catalysts in 2e ORR due to their unique structure, physical and chemical properties. This review focuses on the synthesis of main graphene family members and graphene based electrodes, as well as their applications for H2O2 generation in electrochemical systems. We describe the functions of the graphene family in electrochemical systems, such as accelerating electron transfer and increasing oxygen transfer for cathodes in electrochemical systems, aiming to reveal the enhancement mechanisms of graphene and its derivatives on H2O2 production. Furthermore, the challenges and prospects for graphene family used as catalyst for H2O2 production in the future are also proposed.Agricultural water demand, groundwater extraction, surface water delivery and climate have complex nonlinear relationships with groundwater storage in agricultural regions. As an alternative to elaborate computationally intensive physical models, machine learning methods are often adopted as surrogate to capture such complex relationships due to their high computational efficiency. Inevitably, using only one machine learning model is prone to underestimate prediction uncertainty and subjected to poor accuracy. This study presents a novel machine learning-based groundwater ensemble modeling framework in conjunction with a Bayesian model averaging approach to predict groundwater storage change and improve overall model predicting reliability. Three different machine learning models have been developed namely artificial neural network, support vector machine and response surface regression. To explicitly quantify uncertainty from machine learning model parameter and structure, Bayesian model averaging is employeg framework can serve as an alternative approach to simulating groundwater response, especially in those agricultural regions where lack of subsurface data hinders physically-based modeling.Marine shipping emissions exert important air quality and climate impacts. This study characterized the ambient pollutants predominant by emissions from a variety of marine vessel types near the mid-latitude East China Sea. Two discernible primary shipping emissions were identified by factorization analysis on detailed mass spectra of organic aerosol (OA), as emissions in maneuvering and cruise, highly linked with NOx (and less oxidized OA, black carbon, BC) or CO (and more oxidized OA), respectively. Using radio-recorded quantities and activities of 3566 vessels mixed with slow and high-speed diesel engines, we found emission of NOx or BC per vessel was positively correlated with vessel speed, while CO emission peaked at moderate speed. The approach here based on vessel operation mode directly linked the vessel activities to ambient concentrations of pollutants from marine shipping emission, and may synthesize the complex vessel types in shipping emission inventory.To reduce cadmium (Cd) pollution of food chains, screening and breeding of low-Cd-accumulating genotypes have received increasing attention. However, the mechanisms involving Cd tolerance and accumulation are not fully understood. Here, we investigated the physiological responses and metabolomics profiling on two wheat (Triticum aestivum L.) genotypes, a low-Cd-accumulating genotype in grains (Aikang58, AK58) and a high-Cd-accumulating genotype in grains (Zhenmai10, ZM10), in hydroponic culture treated without/with Cd for 7 days. The results showed that AK58 was a Cd tolerant genotype with higher capacity of antioxidant systems in root. In addition, the concentrations of Cd bound to root cell walls were higher in AK58 than ZM10, of which pectin and hemicellulose played important roles in Cd binding. Moreover, subcellular distribution manifested that Cd sequestrated in the vacuoles was another tolerance mechanism in AK58. Simultaneously, metabolomics profiling showed that, in AK58, phenylalanine metabolism, alanine, aspartate and glutamate metabolism, isoquinoline alkaloid biosynthesis, arginine and proline metabolism, arginine biosynthesis and glyoxylate and dicarboxylate metabolism are highly related to antioxidant defense system, cell wall biosynthesis and metabolisms of phytochelatins together with other organic ligands, playing crucial roles in Cd tolerance and Cd fixation mechanisms in roots.

g-C3N4 has been used as a photocatalyst to overcome the issues of environmental crises and energy shortages. Here, red g-C3N4 nanosheets (Eg ∼ 1.89 eV) were used as seeds for the edge-epitaxial growth of yellow g-C3N4 (Eg ∼ 2.59 eV) to form type II heterostructures. The heterostructures revealed superior photocatalytic activity for enhanced H2 (3996 μmol g-1 h-1), CO (3.8 μmol g-1 h-1), and CH4 (1.8 μmol g-1 h-1) evolution.Carboxylesterase 2 (CES 2) is a key enzyme in the activation of the prodrug irinotecan (CPT-11) in the treatment against colorectal cancer and also has some relationship with the side effect of CPT-11 in clinical applications. Herein, a near infrared (NIR) fluorescent probe (DSAB) has been designed for CES 2 which possesses the advantages of prominent selectivity and high sensitivity, and DSAB has been successfully applied for the imaging of endogenous CES 2 in living cells. Moreover, a high-throughput screening method for CES 2 inhibitors has been established using DSAB and discovered four novel CES 2 inhibitors from various herbal medicines. These results fully demonstrated that DSAB is a promising molecular tool for the investigation of the biological functions of CES 2 in living systems and the discovery of novel CES 2 inhibitors for the treatment of CES 2 related physiological diseases.Using solely highly hydrophilic particles to stabilize emulsions, especially high internal phase emulsions, has always been an important challenge. Here pH-responsive Pickering emulsions stabilized by a low concentration of bare highly hydrophilic Ludox CL nanoparticles without surface modification or addition of surfactants are developed at neutral pH. The dispersed nanoparticles can be transformed into an aggregate state with a network-like structure near the isoelectric point, which contributes to the stabilization of the emulsions. Moreover, the vdW attraction between particles and droplets also plays a key role in the formation of emulsions, which can make the aggregated nanoparticles adsorb tightly around the droplets rather than penetrate the oil-water interface. The formed protective armor and network-like aggregates separate droplets from each other to prevent coalescence. At a low nanoparticle concentration (0.5 wt%), a high internal phase emulsion can be formed and can last up to half a year. This system can emulsify not only the hydrocarbon oil but also the fluoroalkane oil phase. Finally, organic-inorganic composite particles are fabricated using the template action of the Pickering emulsions. The method of preparing composite particles is more convenient than the traditional Pickering emulsion polymerization which often requires the modification of the surface of the hydrophilic particles or the addition of auxiliary monomers. This study provides a simple green strategy for the preparation of a more stable Pickering emulsion stabilized by surface-inactive nanoparticles and will broaden the scope of applications.Controlling the reaction selectivity of organic transformations without losing high conversion is always a challenge in catalytic processes. In this work, a H3PO4·12WO3/OMS-2 nanocomposite catalyst ([PW]-OMS-2) was prepared through the oxidation of a Mn(ii) salt with sodium phosphotungstate by KMnO4. Comprehensive characterization indicates that different Mn2+ precursors significantly affected the crystalline phase and morphology of the as-synthesized catalysts and only MnSO4·H2O as the precursor could lead to a cryptomelane phase. Moreover, [PW]-OMS-2 demonstrated excellent catalytic activity toward aerobic oxidative dehydrogenation of tetrahydro-β-carbolines due to mixed crystalline phases, enhanced surface areas, rich surface oxygen vacancies and labile lattice oxygen species. In particular, β-carbolines and 3,4-dihydro-β-carbolines could be obtained from tetrahydro-β-carbolines with very high selectivity (up to 99%) over [PW]-OMS-2 via tuning the reaction solvent and temperature. https://www.selleckchem.com/products/CHR-2797(Tosedostat).html Under the present catalytic system, scalable synthesis of a β-carboline was achieved and the composite catalyst showed good stability and recyclability. This work not only clarified the structure-activity relationship of the catalyst, but also provided a practical pathway to achieve flexible, controllable synthesis of functional N-heterocycles.Exploiting new non-metal-based peroxidase-mimic nanoenzymes for chemodynamic therapy (CDT) in cancer treatment is an active and challenging field. Here, we found that activated carbon nanoparticles (denoted as ANs) fabricated from coconut shell have satisfactory peroxidase-mimic nanoenzyme activity. Based on this positive result, gadodiamide, a clinically used nuclear magnetic imaging contrast agent, was loaded inside the AN pores and encapsulated by polyvinylpyrrolidone (PVP) to obtain Gd@PANs. PANs (ANs modified using PVP) efficiently catalyze the massive decomposition of endogenous hydrogen peroxide (H2O2) inside cancer cells to produce toxic oxidized hydroxyl radicals (˙OH) for the CDT treatment of cancer, but they showed no toxicity toward normal cells. Additionally, under 808 nm laser irradiation, the photothermal conversion efficiency of the PANs reaches 45.20%, ensuring their effective photothermal therapy (PTT) treatment functionality. Simultaneously, during PTT treatment, the heating effect significantly enhances the peroxidase-mimic activity of the PANs to achieve an ideal PTT-CDT synergistic therapeutic outcome. Gd@PANs can also be used for the T1-magnetic resonance imaging (MRI) of tumors to integrate treatment and diagnosis.A 2-pyridone modified zinc phthalocyanine (denoted ZnPc-PYR) achieves a one stone for three birds outcome in the photodynamic therapy (PDT) treatment of cancer. ZnPc-PYR can be excited by both 665 and 808 nm light to treat superficial and deep tumors, store and slowly release singlet oxygen (1O2) to improve its utilization and downregulate the HIF-1 (hypoxia-inducible factor 1) expression level to enhance the tumor cell's sensitivity to PDT treatment under hypoxic conditions.To establish how the hydrophobic surfactant proteins, SP-B and SP-C, promote adsorption of lipids to an air/water interface, we used X-ray diffuse scattering (XDS) to determine an order parameter of the lipid chains (Sxray) and the bending modulus of the lipid bilayers (KC). Samples contained different amounts of the proteins with two sets of lipids. Dioleoylphosphatidylcholine (DOPC) provided a simple, well characterized model system. The nonpolar and phospholipids (N&PL) from extracted calf surfactant provided the biological mix of lipids. For both systems, the proteins produced changes in Sxray that correlated well with KC. The dose-response to the proteins, however, differed. Small amounts of protein generated large decreases in Sxray and KC for DOPC that progressed monotonically. The changes for the surfactant lipids were erratic. Our studies then tested whether the proteins produced correlated effects on adsorption. Experiments measured the initial fall in surface tension during adsorption to a constant surface area, and then expansion of the interface during adsorption at a constant surface tension of 40 mN m-1.

6%; p  less then  0.001). Additionally, FMI showed that the mean was significantly higher among males (8.65 ± 6.06) compared to females (7.26 ± 3.30; p  less then  0.019). Analysis of the predictors' indices for cardiometabolic risk score highlighted a significantly higher percentage of WC, WHR, and C index among male students (50, 38.5, 59) compared to females (16.9, 14.2, 34; p  less then  0.001). Significant positive correlations were observed between C index quartiles and BMI with the other cardiometabolic indices (p  less then  0.001). https://www.selleckchem.com/products/nfat-inhibitor-1.html This study highlighted a high prevalence of adiposity and CMD risk among university students. The prediction of CMD in early age is quite helpful in preventing adiposity related health issues. Decision makers need to spread awareness about healthy consumption as well as the relationship between physical inactivity and chronic diseases. Patellar instability is frequently encountered in the athletic population. Medial patellofemoral ligament (MPFL) reconstruction is a common strategy to treat recurrent patellar dislocation and demonstrates good clinical outcomes. The purpose was to examine return to sport after MPFL reconstruction for patellar instability. We hypothesized that patients would resume athletic activity at a high rate and that a large proportion would return to their preoperative level of performance. Systematic review and meta-analysis. A systematic review of the literature was conducted using PubMed and Cochrane Library databases to identify articles reporting return to sport after MPFL reconstruction for recurrent patellar dislocation. Athletes were defined as those reporting a preoperative sport. A random-effects model was used to evaluate return to sport rates, subsequent level, and rate of instability recurrence. Meta-regression was used to compare return to sport rates in patients undergoing MPFL reconstruction witof instability (1.9%; 95% CI, 0.4-4.0). The Kujala score was reported by 13 studies, with pre- and postoperative combined means of 60.3 and 90.0, respectively. MPFL reconstruction is an effective and reliable treatment in the setting of patellofemoral instability. Surgeons can counsel their patients that they can expect a high rate of return to sport after MPFL reconstruction surgery alone or with concomitant osteotomy. MPFL reconstruction is an effective and reliable treatment in the setting of patellofemoral instability. Surgeons can counsel their patients that they can expect a high rate of return to sport after MPFL reconstruction surgery alone or with concomitant osteotomy.Objective To determine how well comorbid depression is described, defined, and measured in the rehabilitation literature that pertains to TBI and depression.Method Scoping review of the rehabilitation sciences literature. Six databases were searched (to October 17, 2018) using the three core concepts of TBI, depression, and rehabilitation, as was for gray literature. Two independent reviewers reviewed documents for eligibility.Results 3737 records were reviewed and 137 documents were analyzed. Primary studies (n = 126) were most prevalent and of quantitative descriptive design (n = 102). The number of participants with TBI and comorbid depression could only be determined for 81/126 (64%) of primary studies, in which they are the minority (median of 30% of sample). Depression reporting was heterogeneous and individuals with TBI and depression were not analyzed as a subgroup in most studies (n = 68, 55%). Depression self-report instruments are commonly used (14 instruments used in 111 studies). Few studies (n = 14, 19%) have participant samples with discrete severity levels of TBI and depression.Conclusions Better participant representation and reporting of TBI and depression variables are needed to enhance comparability across studies and improve rehabilitation outcomes.Background Parents experience high distress following their child's diagnosis of cancer. We previously tested two delivery models (group and one-on-one) of the "Promoting Resilience in Stress Management for Parents" (PRISM-P) intervention in a randomized trial one-on-one delivery improved resilience and benefit finding at three months when compared to usual care (UC). Objective The objective of this analysis was to evaluate quantitative and qualitative outcomes at six months. Design In this single-center, phase 2, parallel, 111 randomized trial conducted December 2016 to December 2018, English-speaking parents with a 2-24 year-old child diagnosed with new cancer were randomly assigned to UC, one-on-one, or group PRISM-P, a brief, skill-based curriculum targeting stress management, goal setting, cognitive reframing, and meaning making. We collected parent-reported outcomes (resilience, benefit finding, and psychological distress) at baseline and three and six months. We applied linear mixed-effects regression models to examine six-month outcomes among all participants and conducted directed content analyses of exit interviews with the first 12 parents to complete each study arm. Results The 94 participating parents were median aged 35-38 years and predominantly white, college-educated mothers. At six months, there was no statistically significant difference in parent-reported outcomes. Exit interviews (n = 36) suggested that PRISM-P was highly valued 100% of interviewed recipients recommended it for other parents. Most suggested more coaching would help them retain skills, and almost all endorsed a combined one-on-one and group program. Conclusions Although the PRISM-P benefits observed at three months were not sustained for six months, all interviewed parents found it valuable. Additional opportunities to strengthen and sustain resilience resources include longer follow-up, flexible format, and skill reinforcement. Trial Registration NCT02998086. While some studies have failed to reveal any significant relationship between magnetic resonance imaging (MRI) grading and return to sports after bone stress injuries, others have reported either a linear or nonlinear relationship. To evaluate the prognostic value of MRI grading for time to return to sports and rate of return to sports after bone stress injuries. Systematic review and meta-analysis. A systematic search was performed in PubMed, Web of Science, SPORTDiscus, and Google Scholar. Studies reporting return to sports data after bone stress injuries using MRI grading systems were included in this review. The risk of bias was evaluated using the Quality in Prognosis Studies tool. Meta-analyses were performed to summarize the mean time to return to sports. The Pearson correlation was used to determine the relationship between time to return to sports and MRI grade. A meta-analysis of proportions was conducted to determine the percentage of athletes who successfully returned to sports. A total of 16 studies with 560 bone stress injuries met inclusion criteria.

In this paper, two kinds of Al-Zn-Mg-Cu alloys with high Zn content (Al-8.1Zn-2.0Mg-2.3Cu-0.12Zr-0.12Sc and Al-10.5Zn-2.5Mg-1.5Cu-0.12Zr-0.12Sc) are fabricated by powder hot extrusion. Microstructure and mechanical properties are investigated by optical microscopy (OM), scanning electron microscopy (SEM), X-ray diffraction (XRD), transmission electron microscopy (TEM) and tensile tests. The results show that the formation of ultrafine grains and homogeneous second phases in as-extruded alloys is achieved by perfect metallurgical bonding during severe plastic deformation. After the optimal solution treatment and peak aging treatment, the strength of the two alloys reaches up to 734 MPa and 802 MPa, and the elongation is 9.8 % and 5.3 %, respectively. The excellent mechanical properties are attributed to the grain boundary strengthening, precipitation strengthening and homogenous microstructure. The element content has little effect on the grain size of the powder hot-extruded Al-Zn-Mg-Cu alloy, but high Zn and Mg contents can improve the density of strengthening phases while low Cu content can reduce the difficulty of solution treatment by inhibiting the precipitation of S(Al2CuMg) phase.Peroxidase activity of cytochrome c (cyt c)/cardiolipin (CL) complex is supposed to be involved in the initiation of apoptosis via peroxidative induction of mitochondrial membrane permeabilization. As cyt c binding to CL-containing membranes is at least partially associated with electrostatic protein/lipid interaction, we screened single-point mutants of horse heart cyt c with various substitutions of lysine at position 72, considered to play a significant role in both the binding and peroxidase activity of the protein. Contrary to expectations, K72A, K72R and K72L substitutions exerted slight effects on both the cyt c binding to CL-containing liposomal membranes and the cyt c/H2O2-induced calcein leakage from liposomes, used here as a membrane permeabilization assay. Both the binding and permeabilization were decreased to various extents, but not significantly, in the case of K72E and K72N mutants. A drastic difference was found between the sequence of the permeabilizing activities of the cyt c variants and the previously described order of their proapoptotic activities (Chertkova et al., 2008).Lipocalin family members, LCN8 and LCN9, are specifically expressed in the initial segment of mouse caput epididymis. However, the biological functions of the molecules in vivo are yet to be clarified. In this study, CRISPR/Cas9 technology was used to generate Lcn8 and Lcn9 knockout mice, respectively. https://www.selleckchem.com/products/torin-1.html Lcn8-/- and Lcn9-/- male mice showed normal spermatogenesis and fertility. In the cauda epididymis of Lcn8-/- male mice, morphologically abnormal sperm was increased significantly, the proportion of progressive motility sperm was decreased, the proportion of immobilized sperm was elevated, and the sperm spontaneous acrosome reaction (AR) frequency was increased. Conversely, the knockout of Lcn9 did not have any effect on the ratio of morphologically abnormal sperm, sperm motility, and sperm spontaneous AR frequencies. These results demonstrated the role of LCN8 in maintaining the sperm quality in the epididymis, and suggested that the deficiency of LCN8 leads to epididymal sperm maturation defects.The expression and roles of FLOT2, especially for its underlying mechanism, in gliomas have been rarely revealed. In this study, upregulations of both FLOT2 and EphA2 in gliomas tissues were validated by immunohistochemistry (IHC) staining and Western blot. FLOT2 silencing notably inhibited the growth and invasion of gliomas cells. Simultaneously, FLOT2 depletion suppressed Akt and NF-κB activities, induced apoptosis, cell cycle arrest, and epithelial-mesenchymal transition (EMT) inhibition, demonstrated by expression alterations of key proteins of the above processes. Mechanistically, FLOT2 could maintain EphA2 stability viainteraction, and restoration of EphA2 could remarkably release the suppressive effects on gliomas cells induced by FLOT2 knockdown. Lastly, FLOT2 and EphA2, whose protein and mRNA levels are both positively correlated in gliomas, shows significant association with clinical characteristics like Ki67 intensity, p53 expression, and tumor stage in patients with gliomas. In conclusion, our results reveal the upregulation, oncogenic roles of FLOT2, and the corresponding underlying mechanism in gliomas, highlighting that the FLOT2-EphA2 axis is served as a promising therapeutic target for gliomas.Repeated and long-term oxaliplatin therapy leads to drug resistance and severe adverse events, which limit its clinical use. These difficulties highlight the importance of identifying potent and specific drug combinations to enhance the antitumor effects of oxaliplatin. The farnesoid X receptor (FXR) deficiency in colorectal cancer (CRC) suggests that restoring FXR function might be a promising strategy for CRC treatment. A drug combination study showed that the GW4064 acted synergistically with oxaliplatin in colon cancer cells. The combination of oxaliplatin plus GW4064 inhibited cell growth and colony formation, induced apoptosis and pyroptosis in vitro, and slowed tumor growth in vivo. Mechanistically, GW4064 enhanced the chemosensitivity of cells to oxaliplatin by inducing BAX/caspase-3/GSDME-mediated pyroptosis. Furthermore, the combination of oxaliplatin and GW4064 synergistically inhibited STAT3 signaling by restoring SHP expression. Our study revealed that GW4064 could enhance the antitumor effects of oxaliplatin against CRC, which provides a novel therapeutic strategy based on a combinational approach for CRC treatment.Lung cancer is the leading cause of cancer-related deaths worldwide. Lung cancer stem cells (CSCs) are a small population of cancer cells with self-renewal, therapeutic resistance, and tumor relapse capability. Yet the molecular mechanisms underlying lung CSCs self-renewal remain largely unknown. Here, we report that SH3BGRL were down-regulated in lung cancer tissues comparing with normal lung tissues and SH3BGRL low expression was correlated with the poor clinical outcomes of patients with lung cancer. Moreover, SH3BGRL was also weakly expressed in lung CSCs compared with its corresponding lung cancer cells. We first characterize that EZH2 directly binds to SH3BGRL promoter and transcriptional represses SH3BGRL expression in epigenetic level. Functionally, overexpression of SH3BGRL potently suppresses Lung CSCs self-renewal in vitro. The gain of function study reveals that SH3BGRL acts as a novel tumor suppressor via inhibiting lung cancer cell proliferation and migration as well as Lung CSCs self-renewal in vitro.

All photoreceptor types were affected even though sws1 is only expressed in the single cones of wild fish. Our results reveal unprecedented developmental defects associated with diminished cone opsin expression and suggest that visual opsin genes are involved in regulatory processes that precede photoreceptor differentiation.Apoptotic effects of secoisolariciresinol diglucoside (SDG) in 2D and 3D cultures of SW480 cells were investigated. 40-200 μM SDG was used and IC50 values were determined for three different time intervals as 24, 48, or 72 hr for further experiments. BrdU, TUNEL, AIF, and caspase-3 stainings were used. SDG inhibited cell proliferation almost half and half for all time intervals in 2D and 3D cultures and also, induced apoptosis. Apoptotic cell percentages in the control group for 24, 48, and 72 hr were 27.00%, 29.00%, and 28.00%, respectively, while in the SDG treatment group were 59.00%, 61.00%, and 62.00%, respectively. In the spheroid cell culture, apoptotic cell percentages in the control group for 24, 48, and 72 hr were 6.90%, 7.20%, and 7.10%, respectively, while in the SDG treatment group were 19.50%, 19.50%, and 20.70%, respectively. Caspase-3 and AIF antibodies were used to indicate caspase-dependent and -independent apoptotic pathways. Significant increases were seen in both AIF and caspase-3 staininy, SDG was evaluated for its apoptotic effects in colon carcinoma cell line via monolayer and spheroid cultures using immunohistochemical and gene expression techniques. Findings of this study suggest that SDG may protect against cancers and in particularly against colon cancer and further investigations has to be carried out for detailed underlying mechanisms. Low bone mineral density (BMD) in anorexia nervosa (AN) leads to increased risk of fractures. Debate exists whether to medicinally treat young patients with AN based on abnormal dual-energy x-ray absorptiometry (DXA) scores or to weight restore and reassess when older. Trabecular bone score (TBS), a technology measuring bone quality, is used in conjunction with DXA. This report explores the potential additional value of TBS, in adults with severe AN, to augment the DXA diagnostic information. Seventy-one DXA scans were reanalyzed to obtain TBS results from patients (mean age 36.3 years). Differences in laboratory, anthropometric values and concomitant DXA measurements in relation to TBS results are reported. For the cohort, mean body mass index (BMI) was 13.6 kg/m (SD 2.1). The vast majority of patients had normal TBS with a mean of 1.395 (SD 0.08) but, most patients (69%) had abnormal average DXA BMD Z-scores of -2.2 (SD 1.2). The patients who also demonstrated degraded bone quality on TBS had significantly lower percent ideal body weight and elevated alkaline phosphatase compared to patients with normal TBS (p's < .05). Low BMD treatment decisions in AN may be optimized by considering both DXA and TBS results. Low BMD treatment decisions in AN may be optimized by considering both DXA and TBS results.Phosphorus (P) assimilation and polyphosphate (polyP) synthesis were investigated in Chlamydomonas reinhardtii by supplying phosphate (PO4 3- ; 10 mg P·L-1 ) to P-depleted cultures of wildtypes, mutants with defects in genes involved in the vacuolar transporter chaperone (VTC) complex, and VTC-complemented strains. https://www.selleckchem.com/products/gdc-0068.html Wildtype C. reinhardtii assimilated PO4 3- and stored polyP within minutes of adding PO4 3- to cultures that were P-deprived, demonstrating that these cells were metabolically primed to assimilate and store PO4 3- . In contrast, vtc1 and vtc4 mutant lines assayed under the same conditions never accumulated polyP, and PO4 3- assimilation was considerably decreased in comparison with the wildtypes. In addition, to confirm the bioinformatics inferences and previous experimental work that the VTC complex of C. reinhardtii has a polyP polymerase function, these results evidence the influence of polyP synthesis on PO4 3- assimilation in C. reinhardtii. RNA-sequencing was carried out on C. reinhardtii cells that were either P-depleted (control) or supplied with PO4 3- following P depletion (treatment) in order to identify changes in the levels of mRNAs correlated with the P status of the cells. This analysis showed that the levels of VTC1 and VTC4 transcripts were strongly reduced at 5 and 24 h after the addition of PO4 3- to the cells, although polyP granules were continuously synthesized during this 24 h period. These results suggest that the VTC complex remains active for at least 24 h after supplying the cells with PO4 3- . Further bioassays and sequence analyses suggest that inositol phosphates may control polyP synthesis via binding to the VTC SPX domain.The thymus regulates a specific microenvironment for the growth and maturation of naive T cells. Involution of immune function was an important factor during body aging. Preventing the senescence of immune organs has become a major medical issue. Resveratrol (RSV) has been proved to delay the aging of many organs including the thymus. However, the underlying mechanism remains indefinite and the dosages of RSV on thymus involution need to be further clarified. In the current study, the senescence-accelerated mice were produced using d-galactose for two months. RSV at different dosages (25, 50, 100 mg kg-1 day-1 ) was then administered. The alteration of the thymic morphological structure was observed. It showed that three dosages of RSV significantly decreased cellular senescence of the thymus and no dosage difference was detected. For cellular proliferation and apoptosis of the thymus, 50 and 25 mg/kg per day of RSV displayed the best effects on cellular proliferation and apoptosis in the thymus, respectively to explore the mechanism for the enhancement of thymus immunity. To assess changes in physicians' provision of care to duals (low-income individuals with Medicare and Medicaid) in response to a policy that required Medicaid to fully pay Medicare's cost sharing for office visits with these patients. This policy-a provision of the Affordable Care Act-effectively increased payments for office visits with duals by 0%-20%, depending on the state, in 2013 and 2014. Fee-for-service claims for a 5% random sample of Medicare beneficiaries in 2010-2016. We conducted a difference-in-differences analysis to compare changes in office visits among Qualified Medicare Beneficiaries (QMBs)-the largest subpopulation of duals for whom payment rates were affected by this policy-to changes among other low-income Medicare beneficiaries for whom payment rates were unaffected (pooled across all states). Next, we conducted a triple-differences analysis that compared changes between QMBs and other low-income beneficiaries in 33 states with payment rate increases of approximately 20% to analogous changes in 14 states without payment increases.

Applications of these reactions in a variety of chemical syntheses, materials chemistry, and biological contexts are surveyed, with particular attention paid to the respective strengths and limitations of each reaction and how that reaction benefits from its combination with light. Finally, challenges to broader employment of these reactions are discussed, along with strategies and opportunities to mitigate such obstacles.Regenerated silk nanofibers are interesting as protein-based material building blocks due to their unique structure and biological origin. Here, a new strategy based on control of supramolecular assembly was developed to regulate interactions among silk nanofibers by changing the solvent, achieving tough mechanical features for silk films. Formic acid was used to replace water related to charge repulsion of silk nanofibers in solution, inducing interactions among the nanofibers. The films formed under these conditions had an elastic modulus of 3.4 ± 0.3 GPa, an ultimate tensile strength of 76.9 ± 1.6 MPa, and an elongation at break of 3.5 ± 0.1%, while the materials formed from aqueous solutions remained fragile. The mechanical performance of the formic acid-derived nanofiber films was further improved through post-stretching or via the addition of graphene. In addition, the silk nanofiber films could be functionalized with various bioactive ingredients such as curcumin. These new silk nanofiber films with a unique combination of mechanical properties and functions provide new biomaterials achieved using traditional solvents and processes through insight and control of their assembly mechanisms in solution.Lithium metal secondary batteries (LMBs) have extremely high energy densities and are considered the most promising energy storage and conversion systems in the future. We start with the formation and growth process of the Li metal deposited layer to reveal and clarify the reasons for the apparent comprehensive performance of the Li metal anode. Specifically, under the conditions of ether electrolyte and typical additives, the apparent Coulombic efficiency, micromorphology of the deposition layer, SEI information, and the kinetic mechanism of the Li plating/stripping process under a series of current density conditions are studied. The results show that in the electrolyte containing LiNO3, Li metal exhibits excellent cycling performance, the Li plating layer is denser, and the particles in the plating layer are smooth and uniform. In the electrolyte containing FEC, the performance of Li metal is also improved to some extent. Then, we use microelectrode technology to obtain the kinetic parameters of elementary steps in the deposition process of Li metal and find that the stability of the kinetic parameters of mass transfer, interface, and surface steps and their good matching degree are conducive to the good cycling stability of the Li metal anode. https://www.selleckchem.com/products/3-methyladenine.html This study reveals the kinetic relationship among the apparent comprehensive performances of Li metal, the electrolyte composition, and operating conditions, which provides a reliable dynamic reference for screening and optimizing electrolytes.Despite widespread interest in the amphiphilic polymeric micelles for drug delivery systems, it is highly desirable to achieve high loading capacity and high efficiency to reduce the side effects of therapeutic agents while maximizing their efficacy. Here, we present a novel hydrophobic epoxide monomer, cyclohexyloxy ethyl glycidyl ether (CHGE), containing an acetal group as a pH-responsive cleavable linkage. A series of its homopolymers, poly(cyclohexyloxy ethyl glycidyl ether)s (PCHGEs), and block copolymers, poly(ethylene glycol)-block-poly(cyclohexyloxy ethyl glycidyl ether)s (mPEG-b-PCHGE), were synthesized via anionic ring-opening polymerization in a controlled manner. Subsequently, the self-assembled polymeric micelles of mPEG-b-PCHGE demonstrated high loading capacity, excellent stability in biological media, tunable release efficiency, and high cell viability. Importantly, quantum mechanical calculations performed by considering prolonged hydrolysis of the acetal group in CHGE indicated that the CHGE monomer had higher hydrophobicity than three other functional epoxide monomer analogues developed. Furthermore, the preferential cellular uptake and in vivo therapeutic efficacy confirmed the enhanced stability and the pH-responsive degradation of the amphiphilic block copolymer micelles. This study provides a new platform for the development of versatile smart polymeric drug delivery systems with high loading efficiency and tailorable release profiles.Structure and dielectric properties of gillespite-type ceramics ACuSi4O10 (A = Ca, Sr, Ba) were investigated by crystal structure refinement, far-infrared reflectivity spectroscopy, and microwave dielectric measurements. A series of (CaxSr1-x)CuSi4O10 (0 less then x less then 1) ceramics with relative permittivities of 5.70-5.82, Q × f values of 20391-48794 GHz (@ ∼ 13.5 GHz), and τf of -46.3 to -38.9 ppm/°C were synthesized. By Ca2+ substitution for Sr2+ at the A-site, the rigid double-layered copper silicate framework remains stable, resulting in the nearly unchanged relative permittivity, while the [(Ca,Sr)O8] dodecahedron undergoes shrinkage and distortion, which is correlated to the changes in the Q × f and τf values. The normalized bond valence sums indicate that almost all ions are rattling, weakening the bond strengths and enlarging the molecular dielectric polarizability. The fitting of far-infrared reflectivity spectra reveals that the local structure changes suppress the intermediate and low-frequency vibrational modes significantly and improves the contribution from electronic polarization to permittivity. Symmetry breaking of the [(Ca,Sr)O8] dodecahedron conforms to the elevated restoring forces acting on the ions and improves the τf value. The large span in Q × f value may have intricate correlations to local structure changes and defects. Machine learning methods were introduced to explore the decisive structural factors for the Q × f value. A Q × f value prediction model correlated with the A-O2 bond length and the variance of A-O bond lengths was established. The Q × f values of isostructural (BaySr1-y)CuSi4O10 ceramics were predicted and verified by experiments.

The small LOV/F-box/Kelch family of E3 ubiquitin ligases plays an essential role in the regulation of plant circadian clocks and flowering time by sensing dusk. The family consists of three members, ZEITLUPE (ZTL), LOV KELCH PROTEIN 2 (LKP2), and FLAVIN-BINDING KELCH REPEAT F-BOX PROTEIN 1 (FKF1), which share a unique protein domain architecture allowing them to act as photoreceptors that transduce light signals via altering stability of target proteins. Despite intensive study of this protein family we still lack important knowledge about the biochemical and functional roles of the protein domains that comprise these unique photoreceptors. Here, we perform comparative analyses of transgenic lines constitutively expressing the photoreceptor LOV domain or the Kelch repeat protein-protein interaction domains of ZTL, FKF1, and LKP2. Expression of each domain alone is sufficient to disrupt circadian rhythms and flowering time, but each domain differs in the magnitude of effect. Immunoprecipitation followed by mass spectrometry with the ZTL Kelch repeat domain identified a suite of potential interacting partners. Furthermore, the ZTL Kelch repeat domain can interact with the ZTL homologs, LKP2 and FKF1, and the LOV domain of ZTL itself. This suggests a hypothesis that the Kelch repeat domain of ZTL may mediate inter- and intra-molecular interactions of the three LOV/F-box/Kelch proteins and provides added insight into the composition of the protein complexes and an additional role for the Kelch repeat domain.After being isolated from a sugarcane pile, the bacterium Chitinophaga sp. CB10 demonstrated to be a rich source of carbohydrases, with 350 predicted CAZyme domains. CB10 was able to grow on carbohydrates of different structural complexities glucose, carboxymethylcellulose, corn starch, galactomannan, Aloe vera gum and sugarcane bagasse. The sugarcane bagasse is a rich source of complex polymers, and the diversity of metabolites released by its enzymatic hydrolysis has an important role for green chemistry, including minority pathways such as the degradation of mannan conjugates. In this sense, CB10 demonstrated considerable levels of gene expression for mannanases, and was stable for a period of 96-144 hours in the presence of sugarcane bagasse as sole carbon source. The bacterium showed respectively 4.8x and 5.6x expression levels for two genes predicted for GH2 β-mannosidase one located within a gene cluster identified as "polysaccharide utilization loci" (PUL), and another a classic β-mannosidase. These enzymes shared less than 45% of identity with enzymes characterized from the genus Chitinophaga belonging to the phylum Bacteroidetes. https://www.selleckchem.com/products/torin-1.html The degree of novelty-as demonstrated by the low identity with previously characterized enzymes; the remarkable capability to grow in different substrates; mannanase activity, evidenced by the release of residual oligosaccharides in the cultivation with galactomannan (HPLC-RID, 12.3 mMol); associated to the ability of mannanases expression in a low concentration of inductor conditions (sugarcane bagasse, 0.2%) indicate the high potential for the application of CB10 as a source of enzymes in the production of oligosaccharides from biomass. This capacity might prove to be very valuable for the biorefinery process of pre-biotic precursors and other functional oligosaccharides focused on the food and pharmaceutical industries.Latinos in the US live significantly longer than non-Latino whites, but spend more years disabled. Differentials in socioeconomic status account for part, but not all, of the difference in older age disability between Latinos and whites. We hypothesize that a factor often ignored in the literature-the fact that Latinos, on average, have more physically strenuous jobs than non-Latino whites-contributes to the higher Latino risk of functional limitations at older ages. We use longitudinal data from the 1998-2014 Health and Retirement Study (HRS) comprising 17,297 respondents. Compared to US-born whites, Latinos, especially Latino immigrants, report substantially higher levels of physical effort at work. Latino-black differences are much smaller than Latino-white differences. As hypothesized, physical work effort is strongly related to functional limitations. However, differentials in physical work effort for Latinos and whites in their fifties and early sixties are weakly related to Latino-white differentials in FL at later ages.The focus of this research was to develop and validate a suitable HPLC method, which allows simultaneous determination of three proposed skin model penetrants to investigate the percutaneous diffusion behavior of their combination caffeine, methyl paraben and butyl paraben. These penetrants were selected because they represent a wide range of lipophilicities. This model highlights the effect of combining penetrants of different molecular properties on their diffusion behavior through skin. The proposed method employed a gradient system that was systematically optimized for separation and quantification of the penetrants. The effect of the stationary phase (C18, C4 and cyano (CN)) was assessed with CN proven to be superior in terms of peak shape, retentivity and dynamic linear range. Significant differences in retention time, peak broadening, and quantifiability between different stationary phases could be demonstrated. The method was validated as per ICH guidelines Q2 (R1) with a satisfactory outcome. The method was successfully applied for real diffusion experiments, and revealed notable differences between the individual penetrants and their ternary mixture on transdermal permeation. The method could potentially be extended to determine these analytes in other related skin permeation investigations.Demographic models of human cultural evolution have high explanatory potential but weak empirical support. Here we use a global dataset of rock art sites and climate and genetics-based estimates of ancient population densities to test a new model based on epidemiological principles. The model focuses on the process whereby a cultural innovation becomes endemic in a population, predicting that this cannot occur unless population density exceeds a critical threshold. Analysis of the data, using a Bayesian statistical framework, shows that the model has stronger empirical support than a proportional model, where detection is directly proportional to population density, or a null model, where rock art detection ratios and population density are independent. Results for different geographical areas and periods are compatible with the predictions of the model and confirm its superiority with respect to the null model. Re-analysis of the rock art data, using a second set of independent population estimates, again supports the superiority of the model.

Spermatogenesis is a cell differentiation process that ensures the production of fertilizing sperm, which ultimately fuse with an egg to form a zygote. Normal spermatogenesis relies on Sertoli cells, which preserve cell junctions while providing nutrients for mitosis and meiosis of male germ cells. Several genes regulate normal spermatogenesis, some of which are not exclusively expressed in the testis and control multiple physiological processes in an organism. Loss-of-function mutations in some of these genes result in spermatogenesis and sperm functionality defects, potentially leading to the insurgence of rare genetic disorders. To identify genetic intersections between spermatogenesis and rare diseases, we screened public archives of human genetic conditions available on the Genetic and Rare Diseases Information Center (GARD), the Online Mendelian Inheritance in Man (OMIM), and the Clinical Variant (ClinVar), and after an extensive literature search, we identified 22 distinct genes associated with 21 rare genetic conditions and defective spermatogenesis or sperm function. These protein-coding genes regulate Sertoli cell development and function during spermatogenesis, checkpoint signaling pathways at meiosis, cellular organization and shape definition during spermiogenesis, sperm motility, and capacitation at fertilization. A number of these genes regulate folliculogenesis and oogenesis as well. For each gene, we review the genotype-phenotype association together with associative or causative polymorphisms in humans, and provide a description of the shared molecular mechanisms that regulate gametogenesis and fertilization obtained in transgenic animal models.Following their discovery over 50 years ago, mesenchymal stromal cells (MSCs) have become one of the most studied cellular therapeutic products by both academia and industry due to their regenerative potential and immunomodulatory properties. The promise of MSCs as a therapeutic modality has been demonstrated by preclinical data yet has not translated to consistent, successful clinical trial results in humans. Despite the disparities across the field, MSC shareholders are unified under one common goal-to use MSCs as a therapeutic modality to improve the quality of life for those suffering from a malady in which the standard of care is suboptimal or no longer effective. Currently, there is no Food and Drug Administration (FDA)-approved MSC therapy on the market in the United States although several MSC products have been granted regulatory approval in other countries. In this review, we intend to identify hurdles that are impeding therapeutic progress and discuss strategies that may aid in accomplishing this universal goal of widespread therapeutic use.Little is known about the molecular relationships among follicle stimulating hormone (FSH), lipid droplet (LD) degradation, and autophagy. In this study, we aimed to investigate the pathway by which FSH regulates autophagy and the potential role of autophagy in progesterone production. Our results revealed that FSH stimulated progesterone production in mammalian follicular granulosa cells (GCs) through a non-canonical pathway. In porcine secondary follicles cultured in vitro, FSH treatment increased the level of the autophagic marker, LC3-II, as well as increased the number of autophagic vacuoles in GCs. The underlying molecular mechanism and biological functions were then investigated in porcine GCs. Our results demonstrated that FSH could upregulate Beclin1 levels in porcine GCs; however, this effect was blocked by LY294002 (a PI3K/AKT inhibitor) and SP600125 (SAPK/JNK inhibitor). Further research confirmed that the transcriptional factor, c-Jun, was phosphorylated by FSH, then translocated into the nucleus from the cytoplasm and bound to the BECLIN1 promoter region, and that LY294002, SP600125, or c-Jun knockdown prevented the increase in Beclin1 levels induced by FSH. Interestingly, inhibition of autophagy using chloroquine or SP600125 decreased progesterone production in porcine GCs treated with FSH, although the expression of StAR and P450scc was not disturbed. Moreover, FSH treatment reduced the average number and size of LDs in porcine GCs, but these effects were eliminated by knocking down the key autophagy genes, ATG5 and BECLIN1; in addition, the effect of FSH on promoting progesterone secretion by the cells was also reduced significantly. Based on the above results, we concluded that FSH promoted progesterone production by enhancing autophagy through upregulation of Beclin1 via the PI3K/JNK/c-Jun pathway to accelerate LD degradation in porcine GCs, independent of the classical steroidogenic pathway.Mutations/deficiency of TDRD7, encoding a tudor domain protein involved in post-transcriptional gene expression control, causes early onset cataract in humans. While Tdrd7 is implicated in the control of key lens mRNAs, the impact of Tdrd7 deficiency on microRNAs (miRNAs) and how this contributes to transcriptome misexpression and to cataracts, is undefined. We address this critical knowledge-gap by investigating Tdrd7-targeted knockout (Tdrd7-/-) mice that exhibit fully penetrant juvenile cataracts. https://www.selleckchem.com/products/pf-06700841.html We performed Affymetrix miRNA 3.0 microarray analysis on Tdrd7-/- mouse lenses at postnatal day (P) 4, a stage preceding cataract formation. This analysis identifies 22 miRNAs [14 over-expressed (miR-15a, miR-19a, miR-138, miR-328, miR-339, miR-345, miR-378b, miR-384, miR-467a, miR-1224, miR-1935, miR-1946a, miR-3102, miR-3107), 8 reduced (let-7b, miR-34c, miR-298, miR-382, miR-409, miR-1198, miR-1947, miR-3092)] to be significantly misexpressed (fold-change ≥ ± 1.2, p-value less then 0.05) in Tdrd7-/- lenses. o lens biology. Gene ontology (GO) provided further insight into their relevance to lens pathology. For example, the Tdrd7-deficient lens capsule defect may be explained by reduced mRNA targets (e.g., Col4a3, Loxl1, Timp2, Timp3) associated with "basement membrane". GO analysis also identified new genes (e.g., Casz1, Rasgrp1) recently linked to lens biology/pathology. Together, these analyses define a new Tdrd7-downstream miRNA-mRNA network, in turn, uncovering several new mRNA targets and their associated pathways relevant to lens biology and offering molecular insights into the pathology of congenital cataract.

rters of patients developed permanent impairment of orbital function and/or visual loss. Sinonasal malignancies that present with orbital invasion are probably at the more aggressive end of the cancer spectrum, might be expected to carry a worse prognosis, and usually arise from the ethmoid or maxillary sinuses. Carcinomas and sarcomas were the commonest malignancies, with similar 5-year overall survivals (of just over 50%), and over three-quarters of patients developed permanent impairment of orbital function and/or visual loss. To compare the clinical features, treatment outcomes, and prognoses of immunoglobulin G4-related ophthalmic disease (IgG4-ROD) and idiopathic sclerosing orbital inflammation (ISOI). This retrospective case series included 40 and 22 biopsy-proven cases of IgG4-ROD and ISOI, respectively. The authors reviewed medical charts and images to determine the clinical presentation, involvement pattern, and treatment outcomes. The main outcome measures were differences in disease manifestation, treatment modalities and efficacy, medication-free remission rate, and predictive factors for remission. The median ages were 51 (range 31-72) and 39 (range 9-73) years in the IgG4-ROD and ISOI groups, respectively. The most frequently involved sites were the lacrimal gland (39 cases, 98%) in IgG4-ROD patients and the extraconal region (15 cases, 68%) in ISOI patients. https://www.selleckchem.com/products/jhu395.html No significant difference was observed in the initial treatment response between the groups. Medication-free remission was achieved in 22 (55%) IgG4-ROD paticourse, resulting in ocular dysfunction even after remission. Different pathogeneses may account for the different disease characteristics. To describe a technique for retrieving an inferomedially migrated Jones lacrimal tube. The distal end of the migrated Jones tube is visualized directly via the nose. The tip of an endoilluminator (23 Gauge Constellation Vision Systems) is bent to form a 45° to 60° angle using a mosquito forceps and inserted into the distal opening of the tube. The endoilluminator is used to push the tube upward toward the original medial canthal opening and limit downward displacement as the caruncular area is surgically explored. The light transilluminating the tube facilitates its visualization and retrieval in the caruncular area. A new tube may be threaded through the same passage, or if the ostium is traumatized, through a new passage. This technique is time-efficient and has proven to be safe and successful in subsequent patients. The described technique aids in retrieving an inferomedially migrated Jones tube with minimal trauma to the surrounding structures. The described technique aids in retrieving an inferomedially migrated Jones tube with minimal trauma to the surrounding structures. To identify the frequency of intraepithelial (Pagetoid) spread beyond the ocular surface-namely beyond conjunctiva and cornea-in patients undergoing orbital exenteration for advanced periocular Sebaceous carcinoma (SC). A retrospective, noncomparative observational case series. Patients undergoing orbital exenteration for biopsy-proven SC, at Moorfields Eye Hospital between 1997 and 2013. Review of clinical records and histological specimens, with particularly reference to involvement of conjunctiva and the extent of Pagetoid infiltration beyond the examinable ocular surface-here termed "hidden" disease. Histological evidence of intraepithelial SC within the lacrimal sac or lacrimal gland. Twenty-nine patients had clinical data and histological specimens adequate for review. Seventeen (59%) did not have a discrete mass (clinically or histologically) and, on clinical examination, were thought to only have extensive intraepithelial carcinoma; foci of microscopic invasion were, however, detected histising both the lacrimal gland and sac in all orbital exenterations for this particular tumor. Although-due to their being operated in the era prior to the accepted usage of topical therapy for this condition-some of these exenterations might have had particularly advanced in situ SC, over a quarter of patients with periocular SC warranting orbital exenteration show "hidden" intraepithelial tumor within the lacrimal gland and sac. This important finding might significantly reduce the efficacy (particularly in the lacrimal gland) of the various topical therapies used for in situ SC of the ocular surface, and it also emphasizes the importance of excising both the lacrimal gland and sac in all orbital exenterations for this particular tumor. The tension balance of the upper eyelid following ptosis repair is crucial to a successful postoperative outcome. To improve on existing surgical techniques, the authors developed a new refined frontalis muscle flap suspension (FMFS) for severe ptosis repair and explored the balancing effect between the orbicularis muscle and frontalis muscle following surgery. Forty-three patients (47 eyes) with a mean age of 6.07 ± 2.55 years old were diagnosed with severe congenital ptosis and underwent refined FMFS with complete orbicularis preservation between January 1, 2010 and December 31, 2017 in the Wenzhou Eye Hospital, Wenzhou, China. The outcomes measured include upper eyelid margin reflex distance (MRD1), degree of lagophthalmos, and cosmetic outcome (lash angle, eyelid contour, and crease). Surgical complications were also recorded. The preoperative mean MRD1 was -1.29 ± 0.88 mm and preoperative levator function was 1.87 ± 0.82 mm (ranged from 0 to 3.0 mm). Following surgery, lagophthalmos was observed in all cases in the first week with a mean palpebral fissure height of 1.68 ± 0.40 mm and diminished over 3 months. The MRD1 improved to +3.04 ± 0.68 mm at 6 months following surgery. All cases showed excellent cosmetic outcomes. There were no significant complications. The refined FMFS is a safe and reliable surgery in treating severe ptosis. The eye-closing power of the intact orbicularis muscle is sufficient at countering the lifting power of the frontalis muscle suspension, achieving a balanced blink mechanism and eyelid closure. The refined FMFS is a safe and reliable surgery in treating severe ptosis. The eye-closing power of the intact orbicularis muscle is sufficient at countering the lifting power of the frontalis muscle suspension, achieving a balanced blink mechanism and eyelid closure.