eed for new clinical trials using vulnerable plaque imaging to select high-risk patients despite maximal medical therapy who may benefit from procedural intervention. We found heterogeneity in current practices of carotid stenosis imaging and management in this worldwide survey with many respondents including vulnerable plaque imaging into their decision analysis despite the lack of proven benefit from clinical trials. This study highlights the need for new clinical trials using vulnerable plaque imaging to select high-risk patients despite maximal medical therapy who may benefit from procedural intervention.Objective.Understanding and differentiating brain states is an important task in the field of cognitive neuroscience with applications in health diagnostics, such as detecting neurotypical development vs. autism spectrum or coma/vegetative state vs. locked-in state. Electroencephalography (EEG) analysis is a particularly useful tool for this task as EEG data can detect millisecond-level changes in brain activity across a range of frequencies in a non-invasive and relatively inexpensive fashion. The goal of this study is to apply machine learning methods to EEG data in order to classify visual language comprehension across multiple participants.Approach.26-channel EEG was recorded for 24 Deaf participants while they watched videos of sign language sentences played in time-direct and time-reverse formats to simulate interpretable vs. uninterpretable sign language, respectively. Sparse optimal scoring (SOS) was applied to EEG data in order to classify which type of video a participant was watching, time-direct or time-reversed. The use of SOS also served to reduce the dimensionality of the features to improve model interpretability.Main results.The analysis of frequency-domain EEG data resulted in an average out-of-sample classification accuracy of 98.89%, which was far superior to the time-domain analysis. This high classification accuracy suggests this model can accurately identify common neural responses to visual linguistic stimuli.Significance.The significance of this work is in determining necessary and sufficient neural features for classifying the high-level neural process of visual language comprehension across multiple participants.The repair and treatment of articular cartilage injury is a huge challenge of orthopedics. Currently, most of the clinical methods applied in treating cartilage injuries are mainly to relieve pains rather than to cure them, while the strategy of tissue engineering is highly expected to achieve the successful repair of osteochondral defects. Clear understandings of the physiological structures and mechanical properties of cartilage, bone and osteochondral tissues have been established, but the understanding of their physiological heterogeneity still needs further investigation. Apart from the gradients in the micromorphology and composition of cartilage-to-bone extracellular matrixes, an oxygen gradient also exists in natural osteochondral tissue. The response of hypoxia-inducible factor (HIF)-mediated cells to oxygen would affect the differentiation of stem cells and the maturation of osteochondral tissue. This article reviews the roles of oxygen level and HIF signaling pathway in the development of articular cartilage tissue, and their prospective applications in bone and cartilage tissue engineering. The strategies for regulating HIF signaling pathway and how these strategies finding their potential applications in the regeneration of integrated osteochondral tissue are also discussed.For tissue engineering (TE), decellularized matrices gained huge potential as they consist of natural biomolecules which help in cell attachment and proliferation. Among various animal tissues, goat tissue has gained least attention in spite of the fact that goat tissue is less susceptible to disease transmission as compared to cadaveric porcine and bovine tissue. In this study, goat small intestine submucosa (G-SIS) was isolated from goat small intestine (G-SI), a waste from goat-slaughterhouse, and decellularized to obtain decellularized G-SIS (DG-SIS) biomatrix in the form of powder, gel and sponge form, so that it can be used for healing various types of wounds. Further, nanoceria (NC), owing to its free radical scavenging, anti-inflammatory, antibacterial and angiogenic properties, was incorporated in the DG-SIS in to fabricate DG-SIS/NC nanobiocomposite scaffold, which may exhibit synergistic effects to accelerate tissue regeneration. The scaffolds were found to be hydrophilic, biodegradable, haemocompatible, biocompatible, antibacterial and showed free radical scavenging capability. https://www.selleckchem.com/products/arv-825.html The scaffold containing NC concentration (500 µg ml-1) depicted highest cell (fibroblast cells) adhesion, MTT activity and free radical scavenging as compared to the DG-SIS and other nanobiocomposite scaffolds. Thus, DG-SIS/NC3 (NC with concentration 500 µg ml-1) scaffold could be a potential scaffold biomaterial for skin TE application.Objective.We address the problem of hemodynamic response (HR) estimation when task-evoked extra-cerebral components are present in functional near-infrared spectroscopy (fNIRS) signals. These components might bias the HR estimation; therefore, careful and accurate denoising of data is needed.Approach.We propose a dictionary-based algorithm to process each single event-related segment of the acquired signal for both long separation (LS) and short separation (SS) channels. Stimulus-evoked components and physiological noise are modeled by means of two distinct waveform dictionaries. For each segment, after removal of the physiological noise component in each channel, a template is employed to estimate stimulus-evoked responses in both channels. Then, the estimate from the SS channel is employed to correct the evoked superficial response and refine the HR estimate from the LS channel.Main results.Analysis of simulated, semi-simulated and real data shows that, by averaging single-segment estimates over multiple trials in an experiment, reliable results and improved accuracy compared to other methods can be obtained. The average estimation error of the proposed method for the semi-simulated data set is 34% for oxy-hemoglobin (HbO) and 78% for deoxy-hemoglobin (HbR), considering 40 trials. The proposed method outperforms the results of the methods proposed in the literature. While still far from the possibility of single-trial HR estimation, a significant reduction in the number of averaged trials can also be obtained.Significance.This work proves that dedicated dictionaries can be successfully employed to model all different components of fNIRS signals. We demonstrate the effectiveness of a specifically designed algorithm structure in dealing with a complex denoising problem, enhancing the possibilities of fNIRS-based HR analysis.

The traditional approach for measuring myelin-associated water with quantitative magnetic resonance imaging (MRI) uses multi-echo T2 relaxation data to calculate the myelin water fraction (MWF). A fundamentally different approach, abbreviated "mcDESPOT", uses a more efficient steady-state acquisition to generate an equivalent metric (fM). Although previous studies have demonstrated inherent instability and bias in the complex mcDESPOT analysis procedure, fM has often been used as a surrogate for MWF. We produced and compared multivariate atlases of MWF and fM in healthy human brain and cervical spinal cord (available online) and compared their ability to detect multiple sclerosis pathology. https://www.selleckchem.com/products/z-vad(oh)-fmk.html A significant bias was found in all regions (p   ~ 10%, the relationship broke down and fM no longer increased in tandem with MWF. For multiple sclerosis patients, MWF and fM Z score maps showed overlapping areas of low Z score and similar trends between patients and brain regions, although those of fM generally had greater spatial extent and magnitude of severity. These results will guide future choice of myelin-sensitive quantitative MRI and improve interpretation of studies using either myelin imaging approach.Acute ischemia/reperfusion (I/R) liver injury is a clinical condition challenging to treat. Meldonium is an anti-ischemic agent that shifts energy production from fatty acid oxidation to less oxygen-consuming glycolysis. Thus, we investigated the effects of a 4-week meldonium pre-treatment (300 mg/kg b.m./day) on the acute I/R liver injury in Wistar strain male rats. Our results showed that meldonium ameliorates I/R-induced liver inflammation and injury, as confirmed by liver histology, and by attenuation of serum alanine- and aspartate aminotransferase activity, serum and liver high mobility group box 1 protein expression, and liver expression of Bax/Bcl2, haptoglobin, and the phosphorylated nuclear factor kappa-light-chain-enhancer of activated B cells. Through the increased hepatic activation of the nuclear factor erythroid 2-related factor 2, meldonium improves the antioxidative defence in the liver of animals subjected to I/R, as proved by an increase in serum and liver ascorbic/dehydroascorbic acid ratio, hepatic haem oxygenase 1 expression, glutathione and free thiol groups content, and hepatic copper-zinc superoxide dismutase, manganese superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase activity. Based on our results, it can be concluded that meldonium represent a protective agent against I/R-induced liver injury, with a clinical significance in surgical procedures.Complementary optical and neutron-based vibrational spectroscopy techniques (Infrared, Raman and inelastic neutron scattering) were applied to the study of human bones (femur and humerus) burned simultaneously under either aerobic or anaerobic conditions, in a wide range of temperatures (400 to 1000 °C). This is the first INS study of human skeletal remains heated in an oxygen-deprived atmosphere. Clear differences were observed between both types of samples, namely the absence of hydroxyapatite's OH vibrational bands in bone burned anaerobically (in unsealed containers), coupled to the presence of cyanamide (NCNH2) and portlandite (Ca(OH)2) in these reductive conditions. These results are expected to allow a better understanding of the heat effect on bone´s constituents in distinct environmental settings, thus contributing for an accurate characterisation of both forensic and archaeological human skeletal remains found in distinct scenarios regarding oxygen availability.Fipronil (FIP) is a phenylpyrazole insecticide that is commonly used in agricultural and veterinary fields for controlling a wide range of insects, but it is a strong environmentally toxic substance. Exposure to FIP has been reported to increase the hepatic fat accumulation through altered lipid metabolism, which ultimately can contribute to nonalcoholic fatty liver disease (NAFLD) development. The present study aimed to examine the function of cerium oxide nanoparticles (CeNPs) in protecting against hepatotoxicity and lipogenesis induced by FIP. Twenty-eight male albino rats were classified into four groups FIP (5 mg/kg/day per os), CTR, CeNPs (35 mg/kg/day p.o.), and FIP + CeNPs (5 (FIP) + 35 (CeNPs) mg/kg/day p.o.) for 28 consecutive days. Serum lipid profiles, hepatic antioxidant parameters and pathology, and mRNA expression of adipocytokines were assessed. The results revealed that FIP increased cholesterol, height-density lipoprotein, triacylglyceride, low-density lipoprotein (LDL-c), and very-low-density lipoprotein (VLDL-c) concentrations. It also increased nitric oxide (NO) and malondialdehyde (MDA) hepatic levels and reduced glutathione peroxidase (GPx) and superoxide dismutase (SOD) enzyme activities. Additionally, FIP up-regulated the fatty acid-binding protein (FABP), acetyl Co-A carboxylase (ACC1), and peroxisome proliferator-activated receptor-alpha (PPAR-α). Immunohistochemically, a strong proliferation of cell nuclear antigen (PCNA), ionized calcium-binding adapter molecule 1 (Iba-1), cyclooxygenase-2 (COX-2) reactions in the endothelial cells of the hepatic sinusoids, and increased expression of caspase3 were observed following FIP intoxication. FIP also caused histological changes in hepatic tissue. The CeNPs counteracted the hepatotoxic effect of FIP exposure. So, this study recorded an ameliorative effect of CeNPs against FIP-induced hepatotoxicity.To compare the encapsulation of annatto extract by external gelation (EG) and internal gelation (IG) and to maximize process yield (% Y), two central composite designs were proposed. Calcium chloride (CaCl2) concentration (0.3-3.5%), alginate to gelling solution ratio (12-16); acetic acid (CH3COOH) concentration (0.2-5.0%) and alginate to gelling solution ratio (12-16) were taken as independent variables for EG and IG respectively. Release studies were conducted under different conditions; morphology, particle size, the encapsulation efficiency (EE), and release mechanism were evaluated under optimized conditions. The optimized EG conditions were 0.3% CaCl2 and 11.2 alginate to gelling solution ratio, whereas a 0.3% CH3COOH and 15 alginate to gelling solution ratio were optimized conditions for IG. When 20% extract was employed, the highest EE was achieved, and the largest release was obtained at a pH 6.5 buffer. The Peppas-Sahlin model presented the best fit to experimental data. Polyphenol release was driven by diffusion, whereas bixin showed anomalous release.

A significant reduction was observed in SFA and TFA after 8 and 12 weeks in the active group; TFA was significantly lower than that in the placebo group at 8 and 12 weeks. No adverse events associated with the test supplements were observed in either group. Our study shows that administration of polymethoxyflavone purified from K. parviflora reduces visceral fat in Japanese overweight adults.Oxidative C-C bond cleavage of 2-aminophenols mediated by transition metals and dioxygen is a topic of great interest. While the oxygenolytic C-C bond cleavage reaction relies on the inherent redox non-innocent property of 2-aminophenols, the metal complexes of 2-aminophenolates often undergo 1e-/2e- oxidation events (metal or ligand oxidation), instead of the direct addition of O2 for subsequent C-C bond cleavage. In this work, we report the isolation, characterization and dioxygen reactivity of a series of ternary iron(ii)-2-aminophenolate complexes [(TpPh,Me)FeII(X)], where X = 2-amino-4-tert-butylphenolate (4-tBu-HAP) (1); X = 2-amino-4,6-di-tert-butylphenolate (4,6-di-tBu-HAP) (2); X = 2-amino-4-nitrophenolate (4-NO2-HAP)(3); and X = 2-anilino-4,6-di-tert-butylphenolate (NH-Ph-4,6-di-tBu-HAP) (4) supported by a facial tridentate nitrogen donor ligand (TpPh,Me = hydrotris(3-phenyl-5-methylpyrazol-1-yl)borate). Another facial N3 ligand (TpPh2 = hydrotris(3,5-diphenyl-pyrazol-1-yl)borate) has been used to ihe metal/ligand oxidation of the complexes. The study further reveals that proper modulation of the stereoelectronic factors enables us to design a well synchronised proton transfer (PT) and dioxygen binding events for complexes 1 and 2 that mimic the structure and function of the nonheme enzyme 2-aminophenol-1,6-dioxygenase (APD).Pyrene is one of the most widely investigated aromatic hydrocarbons given to its unique optical and electronic properties. Hence, pyrene-based ligands have been attractive for the synthesis of metal-organic frameworks (MOFs) in the last few years. In this review, we will focus on the most important characteristics of pyrene, in addition to the development and synthesis of pyrene-based molecules as bridging ligands to be used in MOF structures. We will summarize the synthesis attempts, as well as the post-synthetic modifications of pyrene-based MOFs by the incorporation of metals or ligands in the structure. The discussion of promising results of such MOFs in several applications; including luminescence, photocatalysis, adsorption and separation, heterogeneous catalysis, electrochemical applications and bio-medical applications will be highlighted. Finally, some insights and future prospects will be given based on the studies discussed in the review. This review will pave the way for the researchers in the field for the design and development of novel pyrene-based structures and their utilization for different applications.Proteins are fundamentally the most important macromolecules for biochemical, mechanical, and structural functions in living organisms. Therefore, they provide us with diverse structural building blocks for constructing various types of biomaterials, including an important class of such materials, hydrogels. Since natural peptides and proteins are biocompatible and biodegradable, they have features advantageous for their use as the building blocks of hydrogels for biomedical applications. They display constitutional and mechanical similarities with the native extracellular matrix (ECM), and can be easily bio-functionalized via genetic and chemical engineering with features such as bio-recognition, specific stimulus-reactivity, and controlled degradation. This review aims to give an overview of hydrogels made up of recombinant proteins or synthetic peptides as the structural elements building the polymer network. A wide variety of hydrogels composed of protein or peptide building blocks with different origins and compositions - including β-hairpin peptides, α-helical coiled coil peptides, elastin-like peptides, silk fibroin, and resilin - have been designed to date. https://www.selleckchem.com/products/dbr-1.html In this review, the structures and characteristics of these natural proteins and peptides, with each of their gelation mechanisms, and the physical, chemical, and mechanical properties as well as biocompatibility of the resulting hydrogels are described. In addition, this review discusses the potential of using protein- or peptide-based hydrogels in the field of biomedical sciences, especially tissue engineering.Radiotherapy occupies an essential position in curing and palliating a wide range of solid tumors based on DNA damage responses to eradicate cancer cells. However, the tumor microenvironment generally exhibits the characteristics of hypoxia and glutathione overexpression, which play a critical role in radioresistance, to prevent irreparable breaks to DNA and necrocytosis of cancer cells. Herein, polyethylene glycol (PEG) functionalized manganese ferrite nanoparticles (MnFe2O4-PEG) are designed to enable self-sufficiency of oxygen by continuously catalyzing the decomposition of endogenous hydrogen peroxide. Simultaneously, the nano-platform can consume GSH to reduce the loss of reactive oxygen species in radiotherapy and achieve better therapeutic effects at the cellular and animal levels. In addition, the MnFe2O4-PEG could act as an optimal T1- and T2-weighted contrast medium for tumor-specific magnetic resonance imaging. This work proposes a systematically administered radiosensitizer that can selectively reside in tumor sites via the enhanced permeability and retention effect to relieve hypoxia and reduce GSH concentration, combined with dual-mode magnetic resonance imaging, achieving precise and effective image-guided tumor therapy.PD1/PD-L1 antibody blockade-based immunotherapy has been widely recognized in the field of cancer treatment; however, only a small number of cancer patients have been shown to respond well due to the PD1/PD-L1 antibody hydrolysis induced substandard immunotherapeutic efficacy and the low immunogenicity and immunosuppressive tumor microenvironment of the patients. Here, we present a novel tumor microenvironment (TME) responsive particle delivery system with a metformin-loaded chitosan (CS) inverse opal core and a manganese dioxide (MnO2) shell (denoted as CS-metformin@MnO2 particles) for inhibiting the PD-1/PD-L1 signaling pathway and promoting tumor immunotherapy. Benefiting from the interconnected porous structure of the inverse opal, metformin can be easily extensively loaded into the CS particles. With the coating of the TME responsive MnO2 shells, the particle delivery system was imparted with an intelligent "trigger" to prevent premature leaking of the drug until it reaches the tumor tissue. We have demonstrated that CS-metformin@MnO2 particles were able to promote the apoptosis of tumor cells through immunotherapeutic means both in vivo and in vitro.

The first complete chloroplast genome (cpDNA) sequence of Cinnamomum kotoense was determined from Illumina HiSeq pair-end sequencing data in this study. The cpDNA is 154,010 bp in length, contains a large single copy region (LSC) of 93,676 bp and a small single copy region (SSC) of 18,830 bp, which were separated by a pair of inverted repeats (IR) regions of 20,752 bp. The genome contains 127 genes, including 82 protein-coding genes, 8 ribosomal RNA genes, and 36 transfer RNA genes. The overall GC content of the whole genome is 39.2%, and the corresponding values of the LSC, SSC, and IR regions are 37.9%, 33.9%, and 44.3%, respectively. Further phylogenomic analysis showed that C. kotoense and Cinnamomum bodinieri clustered in a clade in Cinnamomum genus.Vanda coerulea possess a high ornamental value and medical effect against glaucoma and cataract. The whole complete chloroplast (cp) genome of V. coerulea and the phylogenetic position based on the cp sequences remain unclear. Herein, we report the complete chloroplast genome of V. coerulea. The chloroplast genome was 149,376 bp in length, including a large single-copy (LSC) region of 86,100 bp, a small single-copy (SSC) region of 11,702 bp, and two inverted repeat (IRs) regions of 25,787 bp. A total of 129 genes were characterized, including 74 protein-coding genes, 36 tRNA genes, and 8 rRNA genes. The overall GC content was 36.6%, and GC percentages range from 27.9% to 43.2% throughout LSC, IRs, and SSC regions. Phylogenetic analysis based on 20 chloroplast genomes of Orchidaceae indicated that V. coerulea is closely related to V. brunnea. Our study provides a valuable resource for the identification and distinction of Vanda genus, and will lay a foundation for further research and conservation measures of V. coerulea.Stuckenia pectinata is widely distributed submerged macrophyte in the world. Herein, the complete chloroplast genome of this species was assembled and characterized using whole genome next-generation sequencing. The complete chloroplast genome showed a circular genome of 156,669 bp size with 36.5% GC content. The genome is of typical structure and contain a pair of inverted repeat (IR) regions with 26,074 bp, separated by one large single-copy (LSC) with 86,285 bp, and one small single-copy (SSC) regions with 18,236 bp. De novo assembly and annotation showed the presence of 131 unique genes with 85 protein-coding genes, 38 tRNA genes, and eight rRNA genes. A maximum-likelihood phylogenomic tree reconstructed based on 15 chloroplast genomes reveals that S. pectinata is most closely related to Zostera marina.Knema furfuracea is a member of Myristicaceae. The K. furfuracea chloroplast genome is found to be 154,527 bp in length and has a base composition of A (29.99%), G (19.31%), C (19.92%), and T (30.78%). The genome contained two short inverted repeat (IRa and IRb) regions (48,110 bp) which were separated by a large single copy (LSC) region (86,188 bp) and a small single copy (SSC) region (20,229 bp). The chloroplast genome has 87 protein-coding genes, 27 transfer RNA (tRNA) genes, and 8 ribosomal RNA (rRNA) genes. Further, complete chloroplast sequence of K. furfuracea was aligned together with two species of Myristicaceae and five basal angiosperms species which have reported the complete chloroplast sequence. This complete chloroplast genome will provide valuable information for the development of DNA markers for future species resource development and phylogenetic analysis of K. furfuracea.Cymbidium bicolor belongs to Orchid family (Orchidaceae), it has high ornamental and traditional medicinal value. The complete chloroplast genome of C. bicolor was sequenced using the Illumina Hiseq platform. The size of the C. bicolor chloroplast genome is 156,528 bp, with an average GC content of 36.8%. This chloroplast genome has containing a large single copy (LSC) region of 85,907 bp, a small single copy (SSC) region of 17,215 bp, and two inverted (IRa and IRb) repeat regions of two 26,703 bp. A total of 124 genes were annotated, including 78 protein-coding genes, 38 tRNA genes, and 8 rRNA genes. A maximum likelihood phylogenetic tree indicated that C. bicolor is closely related to C. mannii in the genus Cymbidium based on 16 whole chloroplast genome sequences.The lychee stinkbug Mattiphus splendidus is an important pest which mainly distributed in southern China. In this study, we sequenced and described the complete mitochondrial genome (mitogenome) of M. splendidus, which is the first record in the genus Mattiphus. This mitogenome is 15,973 bp long and comprises of 13 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA genes, and a control region. Gene order is identical to that of the putative ancestral arrangement of insects. All protein-coding genes initiate with ATN, expect ND1and COI use GTG or TTG as start codons and terminate with TAG or TAA, expect COI and COIII use TA or a single T residue as the stop codon. All tRNAs, ranging from 62 to 74 bp, can be folded into typical clover-leaf structure expect for tRNASer(GCU) and tRNAVal . The control region is 1,357 bp long with 73.5% A + T content. https://www.selleckchem.com/products/Aloxistatin.html The phylogenetic analysis supports the monophyly of Tessaratomidae and the sister relationship between M. splendidus and Eusthenes cupreus.Sophora japonica 'JinhuaiJ2' (Papilionaceae), known as Chinese Scholar Tree, is an important traditional herb with a long history of cultivation in China. It's well known for its valuable medicinal values due to its flower buds contains abundant rutin. Here, we reported and characterized its complete chloroplast genome based on Illumina paired-end sequencing data. The complete plastid genome was 158,690 bp, which contained inverted repeats (IR) of 25,339 bp separated by a large single-copy (LSC) and a small single copy (SSC) of 88,978 bp and 19,034 bp, respectively. The cpDNA contains 129 genes, comprising 83 protein-coding genes, 38 tRNA genes and 8 rRNA genes. The overall GC content of the plastome is 36.1%. The phylogenetic analysis of 18 selected chloroplast genomes demonstrated that S. japonica 'JinhuaiJ2' was close to the species Tapiscia sinensis.

Coronavirus disease-2019 (COVID-19), caused by SARS-CoV-2, has led to the ongoing global pandemic. Although most patients experience no or only mild symptoms, some patients can develop severe illness, such as progressive pneumonia, acute respiratory distress syndrome, secondary hemophagocytic lymphohistiocytosis and multiple organ failure caused by cytokine release syndrome. A majority of COVID-19 patients also develop gastrointestinal symptoms. These can present special challenges to the management of patients with inflammatory bowel disease (IBD) due to potential interactions between the immune response related to SARS-CoV-2 infection and dysregulated immunity associated with IBD. In this context, the pathogenesis of COVID-19 is reviewed in order to address these questions regarding immune interactions between COVID-19 and IBD.Nitrogen (N) pollution and the resulting eutrophication can have deleterious consequences on estuaries, such as hypoxia, fish kills, and loss of biotic diversity. An understanding of N sources and cycling in estuaries is fundamental to determining how to effectively manage these ecologically and commercially important areas. We applied a multiple-isotopic approach to examine the transformations and sources of the N pools in the Pearl River Estuary (PRE) during winter. The surface water in the West PRE was characterized by low salinity and high NO3-, while that in the east had high salinity and low NO3-. The NO3- in the West PRE was largely regulated by a conservative mixing process. In contrast, assimilation and nitrification dominated in the East PRE, which was attributed to the long water-residence time. For the first time, the source contributions of NO3- and NH4+ were estimated by isotope mixing models. Our results suggest that river discharge and nitrification contributed 81% and 12% to the NO3- pool, respectively. A major portion (68%) of the NH4+ was from river discharge, with the remainder likely from sewage and the aquitard-aquifer system. Our study demonstrates that internal nitrification can potentially be of pivotal importance in determining the NO3- level in an estuary and its export to coastal waters.Forest and agricultural land use affects the concentration and composition of dissolved organic carbon (DOC) in streams and rivers. To elucidate the impacts of forest and agricultural land use on stream DOC during storm events, we investigated DOC concentration ([DOC]), optical properties of dissolved organic matter (DOM), and Δ14C-DOC in both forest- and agriculture-dominated headwater streams in South Korea in the summer of 2012. One forested and five agricultural streams were investigated. During storms, the peak [DOC] of forest stream increased to 5.8 mg L-1, approximately two times larger than that of the most agricultural stream (3.2 mg L-1), demonstrating the weaker storm responses of the [DOC] of agricultural streams to hydrological change. Five PARAFAC components were identified, including three terrestrial humic-like substances (C1, C2, C3), one microbial humic substance (C4), and one microbial protein-like substances (C5). The mean (C4+C5)/(C1+C2+C3) of all storm events at the most agricultural stream was 1.5 times larger than that of the most forested stream, suggesting that more protein-like DOM is exported from agricultural watersheds. Whereas a forest stream was primarily composed of terrestrially derived and 14C-enriched modern DOC, the 14C-age of the most agricultural stream was up to ∼1000 years old. https://www.selleckchem.com/products/jq1.html The results suggest that agricultural practices could decrease the old organic carbon pools from soils. However, how quickly the aged DOC can be degraded to CO2 in streams is unknown, warranting future investigation on lability of the aged DOC and their effects on CO2 evasion from rivers and estuaries downstream.Cadmium (Cd) and excess molybdenum (Mo) are harmful to animals, but the combined nephrotoxic mechanism of Cd and Mo in duck remains poorly elucidated. To assess joint effects of Cd and Mo on pyroptosis via ROS/PTEN/PI3K/AKT axis in duck renal tubular epithelial cells, cells were cultured with 3CdSO4·8H2O (4.0 μM), (NH4)6Mo7O24·4H2O (500.0 μM), MCC950 (10.0 μM), BHA (100.0 μM) and combination of Cd and Mo or Cd, Mo and MCC950 or Cd, Mo and BHA for 12 h, and the joint cytotoxicity was explored. The results manifested that toxicity of non-equitoxic binary mixtures of Mo and Cd exhibited synergic interaction. Mo or/and Cd elevated ROS level, PTEN mRNA and protein levels, and decreased PI3K, AKT and p-AKT expression levels. Simultaneously, Mo or/and Cd upregulated ASC, NLRP3, NEK7, Caspase-1, GSDMA, GSDME, IL-18 and IL-1β mRNA levels and Caspase-1 p20, NLRP3, ASC, GSDMD protein levels, increased the percentage of pyroptotic cells, LDH, NO, IL-18 and IL-1β releases as well as relative conductivity. Moreover, NLRP3 inhibitor MCC950 and ROS scavenger BHA could ameliorate the above changed factors induced by Mo and Cd co-exposure. Collectively, our results reveal that combination of Mo and Cd synergistically cause oxidative stress and trigger pyroptosis via ROS/PTEN/PI3K/AKT axis in duck tubular epithelial cells.Oxytetracycline (OTC) is a broad-spectrum antibiotic widely used in aquaculture, resulting in contamination of aquatic environments. In a previous study, we observed significant effects of OTC sublethal concentrations in zebrafish, its microbiome and the water bacterial community. Here we assessed the extent to which these effects are reversible after a recovery period. Zebrafish adults were exposed to OTC (10,000 μg/L) via water exposure. Effects were analyzed at 5 days (5 dE) and 2 months (2 mE) of exposure and recovery was assessed at 5 days (5dPE) and 1 month (1mPE) after exposure Impacts were observed in fish energetic reserves and in fish and water microbiomes structure, being significant even at 5 dE. At energetic reserves level, the effect in cellular energy allocation (CEA) was dependent on the exposure time initially CEA increased while after 2 mE CEA decreased. At microbiome level, diversity was not affected but the richness of the water microbiome significantly decreased at 2 mE. Regarding the post-exposure period, at CEA level, organisms seem to recover.

tory function of its ligand and ii) offering a novel opportunity to promote CNS regeneration and survival following injuries.Retinal ganglion cells (RGCs) expanding from the retina to the brain are primary victims of neurodegeneration in glaucoma, a leading cause of blindness; however, the neighboring astroglia survive the glaucoma-related stress and promote neuroinflammation. In light of diverse functions of caspase-8 in apoptosis, cell survival, and inflammation, this study investigated the importance of caspase-8 in different fates of glaucomatous RGCs and astroglia using two experimental approaches in parallel. In the first approach, cell type-specific responses of RGCs and astroglia to a caspase-8 cleavage-inhibiting pharmacological treatment were studied in rat eyes with or without experimentally induced glaucoma. The second approach utilized an experimental model of glaucoma in mice in which astroglial caspase-8 was conditionally deleted by cre/lox. Findings of these experiments revealed cell type-specific distinct processes that regulate caspase-8 functions in experimental glaucoma, which are involved in inducing the apoptosis of RGCs and promoting the survival and inflammatory responses of astroglia. Deletion of caspase-8 in astroglia protected RGCs against glia-driven inflammatory injury, while the inhibition of caspase-8 cleavage inhibited apoptosis in RGCs themselves. Various caspase-8 functions impacting both RGC apoptosis and astroglia-driven neuroinflammation may suggest the multi-target potential of caspase-8 regulation to provide neuroprotection and immunomodulation in glaucoma.TGFβ-activated kinase 1 (TAK1) is a master regulator that drives multiple cell death and proinflammatory signaling pathways, making it a promising therapeutic target to treat ischemic stroke. However, whether targeting TAK1 could improve stroke outcomes has never been tested in female subjects, hindering its potential translation into clinical use. Here we examined the therapeutic effect of 5Z-7-Oxozeaenol (OZ), a selective TAK1 inhibitor, in ovariectomized female mice after middle cerebral artery occlusion (MCAO). OZ significantly reduced neuronal cell death and axonal injury at the acute stage and mitigated neuroinflammation at the subacute stage after MCAO in ovariectomized female mice. Consistent with RNA sequencing analysis that TAK1 activation contributed to microglia/macrophage-mediated inflammatory responses in the post-stroke brain, inhibition of TAK1 with OZ caused phenotypic shift of microglia/macrophages toward an inflammation-resolving state. Furthermore, microglia/macrophage-specific TAK1 knockout (TAK1 mKO) reproduced OZ's effects, causally confirming the role of TAK1 in determining proinflammatory microglial/macrophage responses in post-stroke females. Post-stroke treatment with OZ for 5 days effectively promoted long-term neurological recovery and the integrity of both gray matter and white matter in female mice. Together, the TAK1 inhibitor OZ elicits long-lasting improvement of stroke outcomes in female mice, at least partially through enhancing beneficial microglial/macrophage responses and inflammation resolution. Given its therapeutic efficacy on both male and female rodents, TAK1 inhibitor is worth further investigation as a valid treatment to ischemic stroke.The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) altered the logistics of ongoing randomized controlled trials (RCTs). https://www.selleckchem.com/products/Nicotinamide(Niacinamide).html The need to reduce in-person research and clinical activities, however, presented an additional level of complexity in order to continue conducting RCTs that focused on the development of medications for Alcohol Use Disorder (AUD). The visits required a systematic objective evaluation from the physician and mental health professional and clinical staff, as many of the safety and efficacy assessments are self-reported. The following commentary addresses the successes and limitations our RCTs encountered during the coronavirus (COVID-19) pandemic.Curiosity and intent to use alcohol in pre-adolescence is a risk factor for later experimentation and use, yet we know little of how curiosity about use develops. Here, we examine factors that may influence curiosity about alcohol use, as it may be an important predictor of later drinking behavior. Cross-sectional data on youth ages 10-11 from the ongoing Adolescent Brain Cognitive Development℠ (ABCD) Study Year 1 follow-up were used (n = 2,334; NDA 2.0.1). All participants were substance-naïve at time of assessment. Group factor analysis identified latent factors across common indicators of risk for early substance use (i.e., psychopathology and trait characteristics; substance use attitudes/behaviors; neurocognition; family and environment). Logistic mixed-effect models tested associations between latent factors of risk for early substance use and curiosity about alcohol use, controlling for demographics and study site. Two multidimensional factors were significantly inversely and positively associated withne the extent to which these factors and curiosity predict alcohol use among youth.Sensory attenuation (i.e., the phenomenon whereby self-produced sensations are perceived as less intense compared to externally occurring ones) is among the neurocognitive processes that help distinguishing ourselves from others. It is thought to be rooted in the motor system (e.g., related to motor intention and prediction), while the role of body awareness, which necessarily accompanies any voluntary movement, in this phenomenon is largely unknown. To fill this gap, here we compared the perceived intensity, somatosensory evoked potentials, and alpha-band desynchronization for self-generated, other-generated, and embodied-fake-hand-generated somatosensory stimuli. We showed that sensory attenuation triggered by the own hand and by the embodied fake hand had the same behavioral and neurophysiological signatures (reduced subjective intensity, reduced of N140 and P200 SEP components and post-stimulus alpha-band desynchronization). Therefore, signals subserving body ownership influenced attenuation of somatosensory stimuli, possibly in a postdictive manner.

Previous studies have shown seasonal variation in asthma exacerbations, peaking over the winter months. Asingle-inhaler triple therapy containing extrafine formulations of the inhaled corticosteroid (ICS) beclomethasone dipropionate (BDP), long-acting β -agonist formoterol fumarate (FF), and long-acting muscarinic antagonist glycopyrronium (G) is in development for asthma. We sought to evaluate whether calendar season impacted the relative effect of BDP/FF/G versus BDP/FF on moderate and severe asthma exacerbations. TRIMARAN and TRIGGER were double-blind 52-week studies comparing BDP/FF/G with BDP/FF (TRIMARAN medium-dose ICS; TRIGGER high-dose) in adults with uncontrolled asthma (Asthma Control Questionnaire-7 score ≥1.5), prebronchodilator FEV less than 80% predicted, history of 1 or more asthma exacerbation, who had been receiving ICS/long-acting β -agonist for at least 4 weeks before entry. Moderate and severe asthma exacerbations were captured throughout each study. In these post hoc analyses, aks in moderate and severe exacerbations, and confirm the overall utility of adding long-acting muscarinic antagonist to ICS/long-acting β2-agonist in the management of asthma. Lung function impairment in early life often persists into adulthood. Therefore, identifying risk factors for low childhood lung function is crucial. We examined the effect of 25-hydroxyvitamin D (25[OH]D) level and childhood asthma phenotype on childhood lung function in the Vitamin D Antenatal Asthma Reduction Trial (VDAART). The 25(OH)D level was measured at set time points in mothers during pregnancy and in children during early life. On the basis of parental reports, children were categorized into 3 clinical phenotypes asymptomatic/infrequent wheeze, early transient wheeze, and asthma at age 6 years. Lung function was assessed with impulse oscillometry at ages 4, 5, and 6 years and with spirometry at ages 5 and 6 years. A total of 570 mother-child pairs were included in this post hoc analysis. Mean gestational 25(OH)D-level quartiles were negatively associated with child respiratory resistance at 5 Hz (R5) from age 4 to 6 years (β, -0.021 kPa/L/s; 95% CI, -0.035 to -0.007; P= .003) and positively associated with FEV (β, 0.018 L; 95% CI, 0.005-0.031; P= .008) and forced vital capacity (β, 0.022 L; 95% CI, 0.009-0.036; P= .002) from age 5 to 6 years. Children with asthma at age 6 years had lower lung function from age 4 to 6 years than the asymptomatic/infrequent wheeze group (β, 0.065 kPa/L/s; 95% CI, 0.028 to 0.102; P< .001 for R5 and β, -0.063 L; 95% CI, -0.099 to -0.028; P< .001 for FEV ). Low gestational 25(OH)D level and childhood asthma are important risk factors for decreased lung function in early childhood. Low gestational 25(OH)D level and childhood asthma are important risk factors for decreased lung function in early childhood. Coronavirus disease 2019 (COVID-19) is commonly associated with skin manifestations, and may also exacerbate existing skin diseases, yet the relationship between COVID-19 and skin diseases remains unclear. By investigating this relationship through a multiomics approach, we sought to ascertain whether patients with skin conditions are more susceptible to COVID-19. We conducted an epidemiological study and then compared gene expression across 9 different inflammatory skin conditions and severe acute respiratory syndrome coronavirus 2-infected bronchial epithelial cell lines, and then performed a genome-wide association study transdisease meta-analysis between COVID-19 susceptibility and 2 skin diseases (psoriasis and atopic dermatitis). Skin conditions, including psoriasis and atopic dermatitis, increase the risk of COVID-19 (odds ratio, 1.55; P= 1.4×10 ) but decrease the risk of mechanical ventilation (odds ratio, 0.22; P= 8.5×10 ). We observed significant overlap in gene expression between the infeand higher risk of COVID-19, but with less severe course, and highlight shared components involved in anti-COVID-19 immune response.Astrocytes play pivotal roles in the brain and they become reactive under stress conditions. Here, we carried out, for the first time, an integrative meta-analysis of genome-wide expression profiling of astrocytes from human and mouse exposed to different stressful stimuli (hypoxia, infections by virus and bacteria, cytokines, ethanol, among others). We identified common differentially expressed genes and pathways in human and murine astrocytes. Our results showed that astrocytes induce expression of genes associated with stress response and immune system regulation when they are exposed to stressful stimuli, whereas genes related to neurogenesis are found as downregulated. https://www.selleckchem.com/products/GSK872-GSK2399872A.html Several of the identified genes showed to be important hubs in the protein-protein interaction analysis (TRAF2, CDC37 and PAX6). This work demonstrates that despite astrocytes are highly heterogeneous and complex, there are common gene expression signatures that can be triggered under distinct detrimental stimuli, which opens an opportunity for exploring other possible markers of reactivity.Single-cell transcriptomics (SCT) is a tour de force in the era of big omics data that has led to the accumulation of massive cellular transcription data at an astounding resolution of single cells. It provides valuable insights into cells previously unachieved by bulk cell analysis and is proving crucial in uncovering cellular heterogeneity, identifying rare cell populations, distinct cell-lineage trajectories, and mechanisms involved in complex cellular processes. SCT data is highly complex and necessitates advanced statistical and computational methods for analysis. This review provides a comprehensive overview of the steps in a typical SCT workflow, starting from experimental protocol to data analysis, deliberating various pipelines used. We discuss recent trends, challenges, machine learning methods for data analysis, and future prospects. We conclude by listing the multitude of scRNA-seq data applications and how it shall revolutionize our understanding of cellular biology and diseases.Kelp species (Laminariales, Phaeophyceae) are globally widespread along temperate to Polar rocky coastal lines. Here we analyse the mitochondrial and chloroplast genomes of Laminaria rodriguezii, in comparison to the organellar genomes of other kelp species. We also provide the complete mitochondrial genome sequence of another endemic kelp species from a Polar habitat, the Arctic Laminaria solidungula. We compare phylogenetic trees derived from twenty complete mitochondrial and seven complete chloroplast kelp genomes. Interestingly, we found a stretch of more than 700 bp in the mitochondrial genome of L.rodriguezii, which is not present in any other yet sequenced member of the Phaeophyceae. This stretch matches a protein coding region in the mitochondrial genome from Desmarestia viridis, another brown seaweed. Their high similarity suggests that these sequences originated through independent introduction into the two species. Their origin could have been by infection by yet unknown similar mitoviruses, currently only known from fungi and plants.

Aiming to develop ALK/ROS1 dual inhibitors overcoming ceritinib-resistant G1202R mutant, a dedicated structure-guided modification campaign was conducted based on ALK co-crystal structures. Twenty eight diarylaminopyrimidine (DAAP) analogues possessing furan or tetrahydrofuran group were designed and synthesized, among which compound 16 bearing (dimethylamino)methyl)furan-2-yl)methyl)thio fragment was identified. Compound 16 exhibited significant cytotoxicity on ALK-positive Karpas299 and H2228 cells with IC50 values of 20 nM and 110 nM. Meanwhile, compound 16 turned out as the most potent entity superior to ceritinib with IC50 values of 2.8, 2.6, 3.8 and 2.3 nM against ALKWT, ALKL1196M, ALKG1202R and ROS1WT, respectively. Subsequently, western blot assay showed that compound 16 significantly suppressed ALK and its downstream protein expression in a dose-dependent manner. Alternatively, the Hoechst 33258 and AO/EB staining assays illustrated that compound 16 could induce H2228 cell apoptosis. Ultimately, the binding models of compound 16 with ALKWT, ALKG1202R as well as ROS1 clearly presented the essential interactions within the active site. Together, compound 16 was validated as a promising ALK/ROS1 dual inhibitor for ALKG1202R mutation correlated tumors.To continue our ongoing studies on discovery of new potent antifungal leads, 43 novel pyrazole-aromatic containing carboxamides were rationally designed and synthesized. Bioassays indicated that most target compounds displayed good in vitro antifungal activities against Botrytis cinerea, Rhizoctonia cerealis and Sclerotinia sclerotiorum and in vivo antifungal activity against R. solani. Compound 11ea exhibited the most significant in vitro activity against R. cerealis (EC50 = 0.93 μg/mL) with about 2-fold more potent than a previously reported lead compound A1 (EC50 = 2.01 μg/mL), and about 11-fold more potent than the positive control/commercial succinate dehydrogenase inhibitor thifluzamide (EC50 = 23.09 μg/mL). Structure-activity relationship analysis and molecular docking simulations indicated that the presence of difluoromethyl pyrazole-(m-benzene) carboxamide scaffold obviously increased the antifungal activity. The further enzymatic bioassay showed that both thifluzamide and compound 11ea displayed excellent SDH inhibitory effects, and fluorescence quenching analysis suggested that they may share the same target SDH.A series of d-proline peptidomimetics were evaluated as dual inhibitors of both human carbonic anhydrases (hCAs) and human gelatinases (MMP2 and MMP9), as these enzymes are both involved in the carcinogenesis and tumor invasion processes. The synthesis and enzyme inhibition kinetics of d-proline derivatives containing a biphenyl sulfonamido moiety revealed an interesting inhibition profile of compound XIV towards MMP9 and CAII. The SAR analysis and docking studies revealed a stringent requirement of a trans geometry for the two arylsulfonyl moieties, which are both necessary for inhibition of MMP9 and CAII. As MMP9 and CAII enzymes are both overexpressed in gastrointestinal stromal tumor cells, this molecule may represent an interesting chemical probe for a multitargeting approach on gastric and colorectal cancer.Cyclin-dependent kinases (CDKs) are a family of Ser/Thr kinases involved in cell cycle and transcriptional regulation. CDK9 regulates transcriptional elongation and this unique property has made it a potential target for several diseases. Due to the conserved ATP binding site, designing selective CDK9 inhibitors has been challenging. Here we report our continued efforts in the optimization of 2,4,5-tri-substituted pyrimidine compounds as potent and selective CDK9 inhibitors. https://www.selleckchem.com/products/sis3.html The most selective compound 30m was >100-fold selective for CDK9 over CDK1 and CDK2. These compounds showed broad anti-proliferative activities in various solid tumour cell lines and patient-derived chronic lymphocytic leukaemia (CLL) cells. Decreased phosphorylation of the carboxyl terminal domain (CTD) of RNAPII at Ser-2 and down-regulation of anti-apoptotic protein Mcl-1 were confirmed in both the ovarian cancer model A2780 and patient-derived CLL cells.SMARCA4 and SMARCB1 loss of function has been implicated in many different tumors. The objective of this study was to investigate the loss of BRG1 and INI1 expression in TTF-1 negative neuroendocrine carcinomas to see if they are analogous to small-cell carcinoma of the ovary, hypercalcemic type. The potential role of these tumor suppressor genes in high-grade neuroendocrine carcinoma largely remains unknown. Cases of previously diagnosed Small cell carcinoma (SmCC), Large cell neuroendocrine carcinoma (LCNEC) and Merkel cell carcinoma (MCC) were selected. Immunohistochemical expression patterns for BRG1 and INI1 were interpreted as intact, hybrid and complete loss of nuclear staining. SmCC and LCNEC cases were divided as TTF-1 positive and TTF-1 negative subsets. One case of TTF-1 negative SmCC (lung) showed loss of SMARCA4(BRG1) expression. Amongst TTF-1 negative LCNEC, one case (lung) showed complete loss of SMARCA4(BRG1) and partial loss of SMARCB1(INI1) and one case (lymph node) had hybrid expression of SMARCA4(BRG1) with intact SMARCB1(INI1) expression. All TTF-1 positive cases and all MCC cases showed intact expression of SMARCA4(BRG1) and SMARCB1(INI1). Our study highlights that SMARCA4(BRG1) is deficient in a subset of NEC. Inactivation of SMARCA4 in a subset of TTF-1 negative neuroendocrine carcinomas especially of pulmonary site can be further studied for their therapeutic response to targeted therapy e.g. EZH2 inhibitors. In addition, our study is the first to show that BRG1 and INI1 expression are intact in MCC and hence the biology of MCC might be completely exclusive of these two tumor suppressor genes. Rothia sp. are Gram-positive bacteria in the class of Actinobacteria that are part of the physiological oral flora. In rare cases, Rothia aeria and Rothia dentocariosa can cause infective endocarditis (IE). The biofilm potential of Rothia in endocarditis is unknown. Specimen from two cases of Rothia endocarditis were obtained during cardiac surgery. One of the patients suffered mitral valve IE from Rothia aeria. In the other case, IE of a prosthetic pulmonary valve was caused by Rothia dentocariosa. Fluorescence in situ hybridization (FISH) was used for visualization of microorganisms within heart valve tissues in combination with PCR and sequencing (FISHseq). The two heart valve specimens featured mature biofilms of bacteria that were identified by FISHseq as Rothia aeria and Rothia dentocariosa, respectively. FISH showed in situ biofilms of both microorganisms that feature distinct phenotypes for the first time ex vivo. Both of our reported cases were treated successfully by heart valve surgery and antibiotic therapy using beta-lactam antibiotics.

Investigations of the pubic ligaments might help to determine symphysis instability or severity of injury and should be included as a further criterion for surgical management. The APL is the ligamentous anchor for the originating and inserting muscles. https://www.selleckchem.com/products/Aloxistatin.html Investigations of the pubic ligaments might help to determine symphysis instability or severity of injury and should be included as a further criterion for surgical management.Validation of CRISPR-Cas9 editing typically explores the immediate vicinity of the gene editing site and distal off-target sequences, which has led to the conclusion that CRISPR-Cas9 editing is very specific. However, an increasing number of studies suggest that on-target unintended editing events like deletions and insertions are relatively frequent but unfortunately often missed in the validation of CRISPR-Cas9 editing. The deletions may be several kilobases-long and only affect one allele. The gold standard in molecular validation of gene editing is direct sequencing of relatively short PCR amplicons. This approach allows the detection of small editing events but fails in detecting large rearrangements, in particular when only one allele is affected. Detection of large rearrangements requires that an extended region is analyzed and the characterization of events may benefit from long-read sequencing. Here we implemented Xdrop™, a new microfluidic technology that allows targeted enrichment of long regions (~100 kb) using just a single standard PCR primer set. Sequencing of the enriched CRISPR-Cas9 gene-edited region in four cell lines on long- and short-read sequencing platforms unravelled unknown and unintended genome editing events. The analysis revealed accidental kilobases-large insertions in three of the cell lines, which remained undetected using standard procedures. We also applied the targeted enrichment approach to identify the integration site of a transgene in a mouse line. The results demonstrate the potential of this technology in gene editing validation as well as in more classic transgenics.Circular RNAs (circRNAs) have recently gained substantial attention as potential biomarkers in several human diseases, most prominently in cancer. However, the detection and quantification of circRNA biomarkers pose specific challenges owing to their circular nature. In particular, the use of enzymes, such as reverse transcriptases, may lead to impaired quantification, poor interlaboratory reproducibility and even false-positive results. Therefore, the development of methods for accurate quantification of circRNA biomarkers is a high priority. An enzyme-free and digital quantification method, named NanoString nCounter, was recently adapted for circRNA detection. In this review, I describe the advantages of using this technology for circRNA quantification as well as methodological considerations, potential pitfalls and disadvantages.For annotation in cancer genomic medicine, oncologists have to refer to various knowledge bases worldwide and retrieve all information (e.g., drugs, clinical trials, and academic papers) related to a gene variant. However, oncologists find it difficult to search these knowledge bases comprehensively because there are multiple paraphrases containing abbreviations and foreign languages in their terminologies including diseases, drugs, and genes. In this paper, we propose a novel search method considering deep paraphrases, which helps oncologists retrieve essential annotation resources swiftly and effortlessly. Our method recursively finds paraphrases based on paraphrase corpora, expands a source document, and finally generates a paraphrase lattice. The proposed method also feedbacks beneficial information regarding the paraphrases applied for a search, which is useful for selecting search results and considering a query for the succeeding search. The results of an experiment demonstrated that our method could retrieve important annotation information that could not be retrieved using a conventional search system and simple paraphrasing. Additionally, annotation experts evaluated our method and found it to be practical.About a third of college students struggle with anxiety, depression, or an eating disorder, and only 20-40% of college students with mental disorders receive treatment. Inadequacies in mental health care delivery result in prolonged illness, disease progression, poorer prognosis, and greater likelihood of relapse, highlighting the need for a new approach to detect mental health problems and engage college students in services. We have developed a transdiagnostic, low-cost mobile mental health targeted prevention and intervention platform that uses population-level screening to engage college students in tailored services that address common mental health problems. We will test the impact of this mobile mental health platform for service delivery in a large-scale trial across 20+ colleges. Students who screen positive or at high-risk for clinical anxiety, depression, or an eating disorder and who are not currently engaged in mental health services (N = 7884) will be randomly assigned to 1) intervention via the mobile mental health platform; or 2) referral to usual care (i.e., campus health or counseling center). We will test whether the mobile mental health platform, compared to referral, is associated with improved uptake, reduced clinical cases, disorder-specific symptoms, and improved quality of life and functioning. We will also test mediators, predictors, and moderators of improved mental health outcomes, as well as stakeholder-relevant outcomes, including cost-effectiveness and academic performance. This population-level approach to service engagement has the potential to improve mental health outcomes for the millions of students enrolled in U.S. colleges and universities. The Journal of Oral Biosciences is devoted to the advancement and dissemination of fundamental knowledge concerning every aspect of oral biosciences. This review featured the review articles in the fields of "Microbiology," "Palate," "Stem Cells," "Mucosal Diseases," "Bone Cell Biology," "MicroRNAs," "TRPV1 Cation Channels," and "Interleukins" in addition to the review article by prize-winners of the "Rising Members Award" ("DKK3 expression and function in head and neck squamous cell carcinoma and other cancers"), presented by the Japanese Association for Oral Biology. These reviews in the Journal of Oral Biosciences have inspired the readers of the journal to broaden their knowledge regarding the various aspects of oral biosciences. The current editorial review introduces these exciting review articles. These reviews in the Journal of Oral Biosciences have inspired the readers of the journal to broaden their knowledge regarding the various aspects of oral biosciences. The current editorial review introduces these exciting review articles.