Accurate damage detection in engineering structures is a critical part of structural health monitoring. A variety of non-destructive inspection methods has been employed to detect the presence and severity of the damage. In this research, machine learning (ML) algorithms are used to assess the dynamic response of the system. It can predict the damage severity, damage location, and fundamental behaviour of the system. Fatigue damage data of aluminium and ABS under coupled mechanical loads at different temperatures are used to train the model. The model shows that natural frequency and temperature appear to be the most important predictive features for aluminium. It appears to be dominated by natural frequency and tip amplitude for ABS. The results also show that the position of the crack along the specimen appears to be of little importance for either material, allowing simultaneous prediction of location and damage severity.We aimed to investigate the role of positron emission computed tomography (PET/CT) with 18F-choline for predicting the outcome of metastatic castration-resistant prostate cancer (mCRPC) submitted to treatment with Radium-223 (223Ra-therapy). Clinical records of 20 mCRPC patients submitted to PET/CT with 18F-choline before 223Ra-therapy were retrospectively evaluated. The following PET-derived parameters were calculated number of lesions, maximum and mean standardized uptake values (SUVmax, SUVmean), lean body mass corrected SUV peak (SULpeak), metabolic tumor volume (MATV), and total lesion activity (TLA). After 223Ra-therapy, all patients underwent regular follow-up until death. The predictive power of clinical and PET-derived parameters on overall survival (OS) was assessed by Kaplan-Meier analysis and the Cox proportional hazard method. All the patients showed 18F-choline-avid lesions at baseline PET/CT. Among the enrolled subjects, eleven (55%) completed all the six scheduled cycles of 223Ra-therapy; seven (35%) were responders according to imaging and biochemical parameters. Mean OS was 12.7 ± 1.4 months by Kaplan-Meier analysis, number of lesions, PSA level and TLA were significantly correlated with OS. In multivariate Cox analysis, TLA remained the only significant predictor of survival (p = 0.003; hazard ratio = 7.6, 95% confidence interval = 1.9-29.5 months). 18F-choline PET may be useful for patients' stratification before 223Ra-therapy. In particular, high metabolically active tumor burden (i.e., TLA) was predictive of poor outcome.Background and objectives The aim of the study was to scrutinize the ability of epsilon-aminocaproic acid (EACA) to prevent radiation-induced damage to human cells. Materials and Methods Human peripheral blood mononuclear cells (PBMCs) were exposed to ionizing radiation at three low doses (22.62 mGy, 45.27 mGy, and 67.88 mGy) in the presence of EACA at the concentration of 50 ng/mL. Results EACA was able to prevent cell death induced by low-dose X-ray radiation and suppress the formation of reactive oxygen species (ROS). EACA also demonstrated a capacity to protect DNA from radiation-induced damage. The data indicated that EACA is capable of suppression of radiation-induced apoptosis. Comparative tests of antioxidative activity of EACA and a range of free radical scavengers showed an ability of EACA to effectively inhibit the generation of ROS. Conclusions This study showed that the pretreatment of PBMCs with EACA is able to protect the cells from radiation-elicited damage, including free radicals' formation, DNA damage, and apoptosis.The adsorbed magnetic molecules with tunable spin states have drawn wide attention for their immense potential in the emerging fields of molecular spintronics and quantum computing. One of the key issues toward their application is the efficient controlling of their spin state. This review briefly summarizes the recent progress in the field of molecular spin state manipulation on surfaces. We focus on the molecular spins originated from the unpaired electrons of which the Kondo effect and spin excitation can be detected by scanning tunneling microscopy and spectroscopy (STM and STS). Studies of the molecular spin-carriers in three categories are overviewed, i.e., the ones solely composed of main group elements, the ones comprising 3d-metals, and the ones comprising 4f-metals. Several frequently used strategies for tuning molecular spin state are exemplified, including chemical reactions, reversible atomic/molecular chemisorption, and STM-tip manipulations. The summary of the successful case studies of molecular spin state manipulation may not only facilitate the fundamental understanding of molecular magnetism and spintronics but also inspire the design of the molecule-based spintronic devices and materials.Heme oxygenase-1 (HO-1) catalyzes the degradation of heme molecules releasing equimolar amounts of biliverdin, iron and carbon monoxide. Its expression is induced in response to stress signals such as reactive oxygen species and inflammatory mediators with antioxidant, anti-inflammatory and immunosuppressive consequences for the host. Interestingly, several intracellular pathogens responsible for major human diseases have been shown to be powerful inducers of HO-1 expression in both host cells and in vivo. Studies have shown that this HO-1 response can be either host detrimental by impairing pathogen control or host beneficial by limiting infection induced inflammation and tissue pathology. These properties make HO-1 an attractive target for host-directed therapy (HDT) of the diseases in question, many of which have been difficult to control using conventional antibiotic approaches. Here we review the mechanisms by which HO-1 expression is induced and how the enzyme regulates inflammatory and immune responses during infection with a number of different intracellular bacterial and protozoan pathogens highlighting mechanistic commonalities and differences with the goal of identifying targets for disease intervention.The purpose of the study was to elucidate the anti-hepatoma effects and mechanisms of Pogostemon cablin essential oils (PPa extract) in vitro and in vivo. https://www.selleckchem.com/products/ceftaroline-fosamil.html PPa extract exhibited an inhibitory effect on hepatocellular carcinoma (HCC) cells and was less cytotoxic to normal cells, especially normal liver cells, than it was to HCC cells, exerting a good selective index. Additionally, PPa extract inhibited HCC cell growth by blocking the cell cycle at the G0/G1 phase via p53 dependent or independent pathway to down regulated cell cycle regulators. Moreover, PPa extract induced the FAS-FASL-caspase-8 system to activate the extrinsic apoptosis pathway, and it increased the bax/bcl-2 ratio and reduced ΔΨm to activate the intrinsic apoptosis pathway that might be due to lots of reactive oxygen species (ROS) production which was induced by PPa extract. In addition, PPa extract presented to the potential to act synergistically with sorafenib to effectively inhibit HCC cell proliferation through the Akt/mTOR pathway and reduce regrowth of HCC cells.

Late Cretaceous trends in Asian dinosaur diversity are poorly understood, but recent discoveries have documented a radiation of oviraptorosaur theropods in China and Mongolia. However, little work has addressed the factors that facilitated this diversification. A new oviraptorid from the Late Cretaceous of Mongolia sheds light on the evolution of the forelimb, which appears to have played a role in the radiation of oviraptorosaurs. Surprisingly, the reduced arm has only two functional digits, highlighting a previously unrecognized occurrence of digit loss in theropods. Phylogenetic analysis shows that the onset of this reduction coincides with the radiation of heyuannine oviraptorids, following dispersal from southern China into the Gobi region. This suggests expansion into a new niche in the Gobi region, which relied less on the elongate, grasping forelimbs inherited by oviraptorosaurs. Variation in forelimb length and manus morphology provides another example of niche partitioning in oviraptorosaurs, which may have made possible their incredible diversity in the latest Cretaceous of Asia.To evaluate DNA fragmentation and GMO quantification during soya bean protein concentrate and isolate preparation, genetically modified soya bean event GTS 40-3-2 (Roundup ReadyTM soya bean, RRS) was blended with conventional soya beans at mass percentages of 0.9%, 2%, 3%, 5% and 10%. Qualitative PCR and real-time PCR were used to monitor the taxon-specific lectin and exogenous cp4 epsps target levels in all of the main products and by-products, which has practical significance for RRS labelling threshold and traceability. Along the preparation chain, the majority of DNA was distributed in main products, and the DNA degradation was noticed. From a holistic perspective, the lectin target degraded more than cp4 epsps target during both of the two soya bean proteins preparations. Therefore, the transgenic contents in the final protein products were higher than the actual mass percentages of RRS in raw materials. Our results are beneficial to the improvement of GMO labelling legislation and the protection of consumer rights.In this study, an environmentally friendly extraction method for flavonoid compound from Ixora javanica, as a new raw material candidate for herbal medicine and cosmetics, was developed. The objectives of the present work were to provide recommendations for the optimal extraction conditions and to investigate the effects of any extraction parameters on flavonoid yields from the I. javanica flower. The extraction process was performed using deep eutectic solvent (DES) (choline chloride and propylene glycol at molar ratio of 1 1) and the ultrasound-assisted extraction method. Both single-factor and response surface analyses using three-level and three-factor Box Behnken designs were conducted to obtain the optimum flavonoid concentrations. The results showed that the optimum extraction conditions for total flavonoids featured an extraction time of 40 min, 25% water content in DES and a solid-to-liquid ratio of 1 25 g ml-1. An extract obtained under optimum extraction conditions showed higher total flavonoid yields than an ethanolic extract which was used for comparison. https://www.selleckchem.com/products/en460.html Scanning electron microscope images demonstrated that both of the solvents also showed different effects on the outer surface of the I. javanica flower during the extraction process. In summary, our work succeeded in determining the optimum conditions for total flavonoids in the I. javanica flower using a green extraction method.High pre-tension bolt is an effective strata control technique and is the key to ensure the stability of anchorage and roadway. Based on the performances of high energy storage tension rock bolts in different rock properties, this study proposed a constitutive model to describe the energy balance of anchor under uniaxial compression. UDEC was used to simulate the behaviour of anchor in coal under uniaxial compression and the results were analysed to study the rock mechanical properties, degree of damage and energy evolution. Simulation results showed that tension rock bolts can improve the mechanical properties and energy storage capacities of the anchor. The energy evolution was divided into three stages (i) the external work was stored in the form of elastic strain energy (Ue ) in the anchor prior to the yielding strength; (ii) the elastic strain energy reached its maximum near the peak strength; (iii) energy was dissipated from fracture friction (Wf) , plastic deformation (Wp ) and acoustic emission (Ur ) during post-peak stage. The installation of tension rock bolts was more suitable for medium hard rock (e.g. sandy mudstone), whereas it was not effective for hard rock (e.g. sandstone).The antibacterial activity of silver nanoparticles (AgNPs) stabilized with a four-armed star-shaped poly(ε-caprolactone)-block-poly(ethylene oxide) copolymer [St-P(CL-b-EO)] and its application as a drug delivery vehicle for cephalexin (Cp) was evaluated against pathogenic Staphylococcus aureus. The prepared AgNPs were characterized by ultraviolet-visible spectroscopy, Fourier transform infrared spectroscopy, zeta sizer and atomic force microscopy (AFM). The antibacterial efficiency of Cp is enhanced several-fold by its delivery through complexation with St-P(CL-b-EO)-AgNPs, monitored by microplate assay and biofilm destruction studies. Finally, the visual destruction of bacterial cells and its biofilms by employing Cp and its conjugates at their minimum inhibitory concentration (MIC50) and minimum biofilm inhibitory concentration (MBIC50), respectively, is observed by topographic imaging by AFM. Enhanced antibacterial activity of St-P(CL-b-EO)-AgNPs loaded Cp is attributed to penetrative nature of the drug cargo St-P(CL-b-EO)-AgNPs towards the bacterial cell wall.Theories of vocal signalling in humans typically only consider communication within the interactive group and ignore intergroup dynamics. Recent work has found that colaughter generated between pairs of people in conversation can afford accurate judgements of affiliation across widely disparate cultures, and the acoustic features that listeners use to make these judgements are linked to speaker arousal. But to what extent does colaughter inform third party listeners beyond other dynamic information between interlocutors such as overlapping talk? We presented listeners with short segments (1-3 s) of colaughter and simultaneous speech (i.e. cospeech) taken from natural conversations between established friends and newly acquainted strangers. Participants judged whether the pairs of interactants in the segments were friends or strangers. Colaughter afforded more accurate judgements of affiliation than did cospeech, despite cospeech being over twice in duration relative to colaughter on average. Sped-up versions of colaughter and cospeech (proxies of speaker arousal) did not improve accuracy for either identifying friends or strangers, but faster versions of both modes increased the likelihood of tokens being judged as being between friends.

Despite a range of interventions available to treat mental health symptoms experienced by youth with a history of child sexual abuse (CSA), limited empirical work has examined practitioner delivery of these interventions in real-world practice. This paper aimed to qualitatively explore the delivery of trauma-based interventions in community settings in Ontario, Canada. Using qualitative description, a purposeful sample of service providers (N = 51; 92 % female) were recruited from nine community-based organizations located in Southern Ontario, Canada providing psychotherapeutic trauma-based interventions to youth with a history of child sexual abuse. Semi-structured one-on-one (n = 17), joint (n = 3) and focus group (n = 5) interviews elicited provider descriptions of their strategies and approaches for addressing trauma-related symptoms in this population. Data were interpreted using conventional content analyses. Eclectic delivery of interventions and multifactorial decision-making processes were identified as core elements of treatment planning and intervention delivery among providers. Eclectic treatment was described to involve the consideration of four core elements (provider judgement; youth voice; youth characteristics; and clinical team discussion) of intervention and three key principles (meeting youth needs; providing client-centered care; addressing safety and stability). Research capable of characterizing the efficacy of client-centered, eclectic approaches to treat symptoms experienced by youth with a history of CSA is needed. Research capable of characterizing the efficacy of client-centered, eclectic approaches to treat symptoms experienced by youth with a history of CSA is needed.Sinomenine is an alkaloid derived from Chinese medicinal plant Sinomenium acutum. Our previous studies suggested that sinomenine can inhibit the metastasis of breast cancer. However, whether sinomenine can inhibit the metastasis characteristics of breast cancer side population (SP) cells is still unknown. In present study, we isolated the side population (SP) cells from MDA-MB-231 cells by fluorescence-activated cell sorting (FACS). MDA-MB-231 SP cells were treated with different concentrations of sinomenine at the absence or presence of hypoxia, and cell viability were measured by CCK-8 assay. The transwell invasive assay were conducted to assess of the effect of sinomenine on the invasion of hypoxic MDA-MB-231 SP cells. The protein expression was detected by Western blot assay. Sinomenine inhibited the cell viability and invasion of hypoxic MDA-MB-231 SP cells. Western blot assay results showed that the upregulation of MMP-2 and MMP-9 by hypoxia was inversed by sinomenine. Additionally, it was found that sinomenine suppressed the activation of PI3K/Akt/mTOR pathway under hypoxia in MDA-MB-231 SP cells. Moreover, the inhibiton of sinomenine on metastasis of hypoxic MDA-MB-231SP cells and PI3K/Akt/mTOR pathway could be rescued by PI3K activator IGF-1. Our study suggested that sinomenine inhibits invasion of breast cancer SP cells under hypoxia through PI3K/Akt/mTOR pathway.We examined the pathogenicity of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in cynomolgus macaques for 28 days to establish an animal model of COVID-19 for the development of vaccines and antiviral drugs. https://www.selleckchem.com/products/ap-3-a4-enoblock.html Cynomolgus macaques infected with SARS-CoV-2 showed body temperature rises and X-ray radiographic pneumonia without life-threatening clinical signs of disease. A neutralizing antibody against SARS-CoV-2 and T-lymphocytes producing interferon (IFN)-γ specifically for SARS-CoV-2 N-protein were detected on day 14 in one of three macaques with viral pneumonia. In the other two macaques, in which a neutralizing antibody was not detected, T-lymphocytes producing IFN-γ specifically for SARS-CoV-2 N protein increased on day 7 to day 14, suggesting that not only a neutralizing antibody but also cellular immunity has a role in the elimination of SARS-CoV-2. Thus, because of similar symptoms to approximately 80% of patients, cynomolgus macaques are appropriate to extrapolate the efficacy of vaccines and antiviral drugs for humans.Small-scale experiments performed at SINTEF, Norway in 2011-12 led to the development of a modified Weber scaling algorithm. The algorithm predicts initial oil droplet sizes (d50) from a subsea oil and gas blowout. It was quickly implemented in a high number of operational oil spill models used to predict fate and effect of subsea oil releases both in academia and in the oil industry. This paper presents experimental data from large-scale experiments generating oil droplet data in a more realistic multi-millimeter size range for a subsea blow-out. This new data shows a very high correlation with predictions from the modified Weber scaling algorithm both for untreated oil and oil treated by dispersant injection. This finding is opposed to earlier studies predicting significantly smaller droplets, using a similar approach for estimating droplet sizes, but with calibration coefficients that we mean are not representative of the turbulence present in such releases. Teratomas are germ cell neoplasms that can be malignant or benign. Their occurrence is more prevalent in gonads, but there are rare extragonal reports, and splenic teratomas are exceptionally uncommon. A 44-year-old woman with a report of abdominal pain on the left flank for 12 h, was evaluated with TC that visualized spleen showing an oval, intraparenchymal, hypodense image with dense areas, submitted to conventional splenectomy, what identified mature cystic teratoma. Dermoid cysts have nonspecific symptoms, usually related to extrinsic compression of other structures or rupture of the splenic capsule; the diagnosis is complex, since the alterations in imaging exams are not very specific. Thus, the confirmation is made through anatomopathological analysis. Mature splenic cystic teratomas are rare and treatment should be evaluated according to the presence or absence of symptoms and diagnostic certainty. Mature splenic cystic teratomas are rare and treatment should be evaluated according to the presence or absence of symptoms and diagnostic certainty.

The newest detection methods of the influenza virus responsible for acute respiratory syndrome were compared with conventional methods, highlighting the newest trends in diagnostics, applications, and challenges of SARS-CoV-2 (COVID-19 causative virus) nanobiosensors.During pregnancy, the mother's immune system has to tolerate the persistence of paternal alloantigens without affecting the anti-infectious immune response. Consequently, several mechanisms aimed at preventing allograft rejection, occur during a pregnancy. In fact, the early stages of pregnancy are characterized by the correct balance between inflammation and immune tolerance, in which proinflammatory cytokines contribute to both the remodeling of tissues and to neo-angiogenesis, thus, favoring the correct embryo implantation. In addition to the creation of a microenvironment able to support both immunological privilege and angiogenesis, the trophoblast invades normal tissues by sharing the same behavior of invasive tumors. Next, the activation of an immunosuppressive phase, characterized by an increase in the number of regulatory T (Treg) cells prevents excessive inflammation and avoids fetal immuno-mediated rejection. When these changes do not occur or occur incompletely, early pregnancy failure follows. All these events are characterized by an increase in different growth factors and cytokines, among which one of the most important is the angiogenic growth factor, namely placental growth factor (PlGF). PlGF is initially isolated from the human placenta. It is upregulated during both pregnancy and inflammation. In this review, we summarize current knowledge on the immunomodulatory effects of PlGF during pregnancy, warranting that both innate and adaptive immune cells properly support the early events of implantation and placental development. Furthermore, we highlight how an alteration of the immune response, associated with PlGF imbalance, can induce a hypertensive state and lead to the pre-eclampsia (PE).Alginates are one of the major polysaccharide constituents of marine brown algae in commercial manufacturing. However, the content and composition of alginates differ according to the distinct parts of these macroalgae and have a direct impact on the concentration of guluronate and subsequent commercial value of the final product. The Azotobacter vinelandii mannuronan C-5 epimerases AlgE1 and AlgE4 were used to determine their potential value in tailoring the production of high guluronate low-molecular-weight alginates from two sources of high mannuronic acid alginates, the naturally occurring harvested brown algae (Ascophyllum nodosum, Durvillea potatorum, Laminaria hyperborea and Lessonia nigrescens) and a pure mannuronic acid alginate derived from fermented production of the mutant strain of Pseudomonas fluorescens NCIMB 10,525. The mannuronan C-5 epimerases used in this study increased the content of guluronate from 32% up to 81% in both the harvested seaweed and bacterial fermented alginate sources. The guluronate-rich alginate oligomers subsequently derived from these two different sources showed structural identity as determined by proton nuclear magnetic resonance (1H NMR), high-performance anion-exchange chromatography with pulsed amperometric detection (HPAEC-PAD) and size-exclusion chromatography with online multi-angle static laser light scattering (SEC-MALS). https://www.selleckchem.com/products/Avasimibe(CI-1011).html Functional identity was determined by minimum inhibitory concentration (MIC) assays with selected bacteria and antibiotics using the previously documented low-molecular-weight guluronate enriched alginate OligoG CF-5/20 as a comparator. The alginates produced using either source showed similar antibiotic potentiation effects to the drug candidate OligoG CF-5/20 currently in development as a mucolytic and anti-biofilm agent. These findings clearly illustrate the value of using epimerases to provide an alternative production route for novel low-molecular-weight alginates.Mycobacterial infections are a major concern in veterinary medicine because of the difficulty achieving an etiological diagnosis, the challenges and concerns of treatment, and the potential zoonotic risk. Mycobacterium kansasii, a slow-growing non-tuberculous mycobacteria, causes disease in both humans and animals. While infections have been well described in humans, where it may be misdiagnosed as tuberculosis, there are fewer reports in animals. Only four cases have been reported in the domestic cat. This case report describes systemic M. kansasii infection in two sibling indoor-only cats that presented two and half years apart with cutaneous disease that was found to be associated with osteolytic and pulmonary pathology. Infection with M. kansasii was confirmed in both cats by polymerase chain reaction on fine-needle aspirate of a lumbosacral soft tissue mass in one cat and on a tissue punch biopsy of a skin lesion in the other; interferon-gamma release assay inferred M. avium-complex and M. tuberculosis-complex infection in the two cats, respectively. Both patients made a full recovery following antimicrobial therapy with rifampicin, azithromycin, and pradofloxacin (plus N-acetyl cysteine in cat 2). This report highlights successful treatment of systemic M. kansasii mycobacteriosis in the cat and the challenge of accurately diagnosing this infection.The early detection of fire is one of the possible applications of LiDAR techniques. The smoke generated by a fire is mainly compounded of CO2, H2O, particulate, and other combustion products, which involve the local variation of the scattering of the electromagnetic wave at specific wavelengths. The increases of the backscattering coefficient are transduced in peaks on the signal of the backscattering power recorded by the LiDAR system, located exactly where the smoke plume is, allowing not only the detection of a fire but also its localization. The signal processing of the LiDAR signals is critical in the determination of the performances of the fire detection. It is important that the sensitivity of the apparatus is high enough but also that the number of false alarms is small, in order to avoid the trigger of useless and expensive countermeasures. In this work, a new analysis method, based on an adaptive quasi-unsupervised approach was used to ensure that the algorithm is continuously updated to the boundary conditions of the system, such as the weather and experimental apparatus issues.

Microencapsulation of cells in hydrogel-based porous matrices is an approach that has demonstrated great success in regenerative cell therapy. These microcapsules work by concealing the exogenous cells and materials in a robust biomaterial that prevents their recognition by the immune system. A vast number of formulations and additives are continuously being tested to optimize cell viability and mechanical properties of the hydrogel. Determining the effects of new microcapsule additives is a lengthy process that usually requires extensive in vitro and in vivo testing. In this paper, we developed a workflow using nanoindentation (i.e., indentation with a nanoprobe in an atomic force microscope) and a custom-built microfluidic constriction device to characterize the effect of graphene oxide (GO) on three microcapsule formulations. With our workflow, we determined that GO modifies the microcapsule stiffness and surface properties in a formulation-dependent manner. Our results also suggest, for the first time, that GO alters the conformation of the microcapsule hydrogel and its interaction with subsequent coatings. Overall, our workflow can infer the effects of new additives on microcapsule surfaces. Thus, our workflow can contribute to diminishing the time required for the validation of new microcapsule formulations and accelerate their clinical translation.Inefficient charge injection and transport across the electrode/semiconductor contact edge severely limits the device performance of coplanar organic thin-film transistors (OTFTs). To date, various approaches have been implemented to address the adverse contact problems of coplanar OTFTs. However, these approaches mainly focused on reducing the injection resistance and failed to effectively lower the access resistance. Here, we demonstrate a facile strategy by utilizing the blurring effect during the deposition of metal electrodes, to significantly reduce the access resistance. We find that the transition region formed by the blurring behavior can continuously tune the molecular packing and thin-film growth of organic semiconductors across the contact edge, as well as provide continuously distributed gap states for carrier tunnelling. Based on this versatile strategy, the fabricated dinaphtho[2,3-b2',3'-f]thieno[3,2-b]thiophene (DNTT) coplanar OTFT shows a high field-effect mobility of 6.08 cm2 V-1 s-1 and a low contact resistance of 2.32 kΩ cm, comparable to the staggered OTFTs fabricated simultaneously. https://www.selleckchem.com/products/geldanamycin.html Our work addresses the crucial impediments for further reducing the contact resistance in coplanar OTFTs, which represents a significant step of contact injection engineering in organic devices.l-Threonine transaldolases (lTTAs) are a poorly characterized class of pyridoxal-5'-phosphate (PLP) dependent enzymes responsible for the biosynthesis of diverse β-hydroxy amino acids. Here, we study the catalytic mechanism of ObiH, an lTTA essential for biosynthesis of the β-lactone natural product obafluorin. Heterologously expressed ObiH purifies as a mixture of chemical states including a catalytically inactive form of the PLP cofactor. Photoexcitation of ObiH promotes the conversion of the inactive state of the enzyme to the active form. UV-vis spectroscopic analysis reveals that ObiH catalyzes the retro-aldol cleavage of l-threonine to form a remarkably persistent glycyl quinonoid intermediate, with a half-life of ∼3 h. Protonation of this intermediate is kinetically disfavored, enabling on-cycle reactivity with aldehydes to form β-hydroxy amino acids. We demonstrate the synthetic potential of ObiH via the single step synthesis of (2S,3R)-β-hydroxyleucine. To further understand the structural features underpinning this desirable reactivity, we determined the crystal structure of ObiH bound to PLP as the Schiff's base at 1.66 Å resolution. This high-resolution model revealed a unique active site configuration wherein the evolutionarily conserved Asp that traditionally H-bonds to the cofactor is swapped for a neighboring Glu. Molecular dynamics simulations combined with mutagenesis studies indicate that a structural rearrangement is associated with l-threonine entry into the catalytic cycle. Together, these data explain the basis for the unique reactivity of lTTA enzymes and provide a foundation for future engineering and mechanistic analysis.Pericarditis is an inflammatory disease of the pericardium. Progress has been done in recent years in the understanding of its pathophysiology. In particular, pre-clinical and clinical studies have contributed to increasing our knowledge on the role of interleukin (IL)-1 and NLRP3 (NACHT, leucine- rich repeat, and pyrin domain- containing protein 3) inflammasome. Based on current evidence, pericarditis should be considered as an inflammatory reaction to various stimuli, including chemical/physical, infectious, or ischemic ones, with a viral infection being a common etiology. Interaction of pathogens or irritants with toll-like receptor (TLRs) and stimulation of IL-1 receptor by IL-1α and IL-1β lead to an increased transcription of pro-inflammatory genes, including those needed for NLRP3 inflammasome assembly. This pathway is confirmed indirectly by the beneficial effect of colchicine (an indirect NLRP3 inflammasome inhibitor) and IL-1 blockers in patients with recurrent pericarditis. More recently, a direct evidence of the NLRP3 inflammasome within the inflamed pericardium has been provided as well. It may, however, occur that selfantigens on the surface of mesothelial cells or microbial peptides may stimulate autoreactive T cells along with B cells producing anti-heart antibodies, although less evidence is available on this. Some uncertainties still remain about the role of neutrophils, neutrophil extracellular traps (NETs), and pericardial interstitial cells in recurrent and constrictive pericarditis. Unraveling these aspects might have a direct impact on the development of novel targeted therapies, especially considering the increasing number of drugs targeting NETs.Chronic musculoskeletal pain is a highly prevalent condition that is commonly encountered in both general and specialist practice. Nonetheless, it still represents a significant challenge to the practitioners because of the lack of substantial evidence-based guidance. This review aimed to summarize the main pathophysiological mechanisms of chronic pain offering a mechanism-oriented approach to diagnosis and management. We believe that a basic knowledge of the physical signs and symptoms of these mechanisms could empower the clinician to choose appropriate medication and identify high-risk pain patients. Central sensitization and neuropathic features may arise in previously nociceptive and inflammatory pain syndromes. Central sensitization is a functional remodeling of the spinal cord, where light touch afferents are recruited by nociceptive second-order neurons. Neuropathic features include both negative signs, such as reduced perception of vibration and touch, and positive symptoms, such as paroxysmal electric shock pain, due to ectopic discharge.

Thus, we first suggest considering the number of surviving plants up to adulthood as a proxy for population performance to address this question. Using this proxy, we show that the increase in seed output due to the parasitoid is beneficial to the plant population until its carrying capacity is achieved. Next, using a population dynamics model, we show under which particular conditions the negative effect of intraspecific competition outweighs the positive effect of seed density increase (due to parasitoid's defense). When these conditions do not hold, the role of plant intraspecific competition is basically limited to the prevention of unbounded population growth, while the parasitoid increases the plant's equilibrium density above its carrying capacity as measured when interacting only with the pollinating seed predator, thus making the system more stable.Studies on extrapair paternity (EPP) are key to understanding the ecological and evolutionary drivers of variation in avian mating strategies, but information is currently lacking for most tropical and subtropical taxa. We describe the occurrence of EPP in two populations of a South American socially monogamous bird, the Thorn-tailed Rayadito, based on data from 266 broods and 895 offspring that were sampled during six breeding seasons in north-central and southern Chile. In the northern population, 21% of the broods contained at least one extrapair young and 14% of all offspring were sired by an extrapair male, while in the southern population, we detected extrapair offspring (EPO) in 14% of the broods, and 6% of all offspring were EPO. Variation in the frequency of EPP could stem from population differences in the duration of the breeding season or the density of breeding individuals. Other factors such as differences in breeding synchrony and variation in food availability need to be evaluated. More reports on EPP rates are necessary to determine the patterns of taxonomic and geographic variation in mating strategies in Neotropical birds, and to better understand the differences in ecological dynamics between northern and southern hemisphere populations.Both sexes of Indian weta Gryllacropsis sp. communicate acoustically. Females lack an external ovipositor making it difficult to differentiate between the sexes in the field. There is limited ecological information on the species as it is found high up on the trunks of evergreen trees, well camouflaged, and active only at night. The present study was conducted to gain ecological information on this little known yet intriguing species. We tested the hypotheses that (a) calling activity of Indian weta is uniformly distributed throughout the year and (b) there is no difference in morphometric measurements between the sexes. The study was conducted in Bhagwan Mahavir Wildlife Sanctuary and Mollem National Park, Goa, India. Visual scanning of tree trunks followed by vegetation sampling, psychoacoustic sampling, and morphometric analyses was carried out. Resource selection function values, obtained for a total of 52 tree species from 1984 individuals, were less than 0.1 for all plant species indicating no preference by the wetas. Peak calling activity was observed in the month of November (Rayleigh's test, Z = 7.90, p less then .01). Discriminant function analysis on morphometric characters of males and females (Wilk's λ = 0.32 approx. F (4, 21) = 11.24 p less then .0001, classification accuracy = 96.15%) provided clear distinction between males and females. Contribution of body weight was significant (standardized canonical discriminant function coefficients = +1) and could be used for identification of sexes in the field. These polyphagous insects provide insights on understanding ecological specialization due to host plant association, signal evolution, and mating behavior.Ticks are unique hematophagous arthropods and possess an astounding array of salivary molecules that ensure their unnoticed and prolonged attachment to the host skin. Furthermore, ticks are very effective vectors of a diverse spectrum of pathogens. In order to feed, tick chelicerae cut the host epidermis and their hypostome penetrates through the layers of the skin. As a result of laceration of the skin and rupturing blood vessels, a pool of blood is formed in the dermis, serving for intermittent blood sucking and secretion of saliva. Cutaneous injury caused by tick mouthparts should normally elicit wound healing, a complex biological process coordinated by interaction among different host cells, numerous signalling pathways and by a variety of soluble factors including growth factors. Growth factors, endogenous signalling proteins involved in various biological events, are key players in all phases of the skin repair process. Maintaining feeding site integrity by overcoming sequential phases of wound healing is particularly important for ixodid ticks and is governed by bioactive molecules in their saliva. Tick saliva is a complex mixture of proteins, peptides, and non-peptide molecules and its composition depends on the feeding phase, tick developmental stage, gender and/or the presence/absence of microbial agents. In addition to already demonstrated anti-haemostatic, anti-cytokine and anti-chemokine activities, anti-growth factors activities were also detected in saliva of some tick species. In consequence of counteracting host defences by ticks, tick-borne pathogens can be transmitted to and disseminated in the host. Elucidation of the complex interplay between ticks - pathogens - host cutaneous immunity could lead to improved vector and pathogens control strategies. https://www.selleckchem.com/products/pf-8380.html Additionally, tick saliva bioactive molecules have a promising therapeutic perspective to cure some human diseases associated with dysregulation of specific cytokines/growth factors and alterations in their signalling pathways.Ureases are metalloenzymes that hydrolyze urea to ammonia and carbamate. The main urease isoforms present in the seeds of Canavalia ensiformis (jack bean urease - JBU and canatoxin) exert a variety of biological activities. The insecticidal activity of JBU is mediated, at least in part, by jaburetox (Jbtx), a recombinant peptide derived from the JBU amino acid sequence. In this article, we review the neurotoxicity of Jbtx in insects. The insecticidal activity of Jbtx has been investigated in a variety of insect orders and species, including Blattodea (the cockroaches Blatella germânica, Nauphoeta cinerea, Periplaneta americana e Phoetalia pallida), Bruchidae (Callosobruchus maculatus - cowpea weevil), Diptera (Aedes aegypti - mosquito), Hemiptera (Dysdercus peruvianus - cotton stainer bug; Oncopeltus fasciatus - large milkweed bug, and the kissing bugs Rhodnius prolixus and Triatoma infestans), Lepidoptera (Spodoptera frugiperda - fall army worm) and Orthoptera (Locusta migratoria - locust). In N. cinerea, the injection of Jbtx induces marked alteration of locomotor and grooming behavior, whereas in T.

Low-to-moderate risk preterm children as groups are disadvantaged in the development of intelligence and executive function as compared to healthy full-term children even until school-age. However, with appropriate protective factors they may have chances to develop comparably with their full-term, non-risk counterparts. Low-to-moderate risk preterm children as groups are disadvantaged in the development of intelligence and executive function as compared to healthy full-term children even until school-age. However, with appropriate protective factors they may have chances to develop comparably with their full-term, non-risk counterparts.The overall aim of this study is to examine vape shop business operations during COVID-19 among a cohort of 88 vape shops in the Greater Los Angeles area in Southern California, located in ethnically diverse communities. A total of six web- and/or phone-based assessments were conducted over a 12-week period (April 1, 2020-June 10, 2020), extending from the mandated closure of nonessential businesses (Stage 1; Assessments 1-3) to the reopening of nonessential sectors (Stage 2; Assessments 4-6), to evaluate business operations (open and closure statuses). The proportion of vape shops found to be noncompliant with the Governor's executive order (i.e., open) during Stage 1 gradually increased from 54 (61.4%) at Assessment 1 (week of April 1, 2020) to 58 (65.9%) at Assessment 3 (week of April 29, 2020). Moreover, vape shops located in Hispanic/Latino and Korean/Asian communities (vs. those in non-Hispanic White and African American communities) were more likely to stay open both during and after the shutdown at Assessments 1 and 6. More specifically, vape shops located in Hispanic/Latino communities were significantly more likely to offer walk-in service during Assessment 1 (during the shutdown), and vape shops in Hispanic/Latino and Korean/Asian were significantly more likely to offer walk-in service during Assessment 6 (after the re-opening). This study demonstrates high rates of noncompliance with shutdown orders among vape shops located in ethnic communities, thus suggesting higher contextual risk factors of COVID-19 exposure among certain ethnic communities.Aim To assess isorhamnetin efficacy for diabetic kidney disease in a Type 2 diabetes mellitus rat model, through investigating its effect at the epigenetic, mRNA and protein levels. Materials & methods Type 2 diabetes mellitus was induced in rats by streptozotocin and high-fat diet. Rats were treated with isorhamnetin (50 mg/kg/d) for 4 or 8 weeks. Fasting blood glucose, renal and lipid profiles were evaluated. https://www.selleckchem.com/products/sgc-cbp30.html Renal tissues were examined by light and electron microscopy. Autophagy genes (FYCO1, ULK, TECPR1 and WIPI2) and miR-15b, miR-34a and miR-633 were assessed by qRT-PCR, and LC3A/B by immunoblotting. Results Isorhamnetin improved fasting blood glucose, renal and lipid profiles with increased autophagosomes in renal tissues. It suppressed miRNA regulation of autophagy genes. Conclusion We propose a molecular mechanism for the isorhamnetin renoprotective effect by modulation of autophagy epigenetic regulators. Preclinical ovine model. To assess the efficacy and safety of the P-15 L bone graft substitute and compare its performance to autologous iliac crest bone graft (ICBG) for lumbar interbody fusion indications. Thirty skeletally mature sheep underwent lumbar interbody fusion surgery. Half of the sheep received autologous ICBG and the other half the peptide enhanced bone graft substitute (P-15 L). Following termination at 1, 3, and 6 months after surgery, the operated segments were analyzed using micro computed tomography (µCT), histology, and destructive mechanical testing. Additional systemic health monitoring was performed for the P-15 L group. One month after surgery, there was only minor evidence of bone remodeling and residual graft material could be clearly observed within the cage. There was active bone remodeling between 1 and 3 months after surgery. At 3 months after surgery significantly denser and stiffer bone was found in the P-15 L group, whereas at 6 months, P-15 L and ICBG gave similar fusion results. The P-15 L bone graft substitute did not have any adverse effects on systemic health. The drug device combination P-15 L was demonstrated to be effective and save for lumbar interbody fusion as evidenced by this ovine model. Compared to autologous ICBG, P-15 L seems to expedite bone formation and remodeling but in the longer-term fusion results were similar. The drug device combination P-15 L was demonstrated to be effective and save for lumbar interbody fusion as evidenced by this ovine model. Compared to autologous ICBG, P-15 L seems to expedite bone formation and remodeling but in the longer-term fusion results were similar. Retrospective Cohort Study. This study aimed to determine how the surgeon-determined and patient-rated location of predominant pain influences patient-rated outcomes at 1-year after posterior lumbar fusion in adult isthmic spondylolisthesis. We retrospectively reviewed consecutive patients prospectively enrolled in the Canadian Spine Outcomes and Research Network national registry between 2009 and 2017 that underwent posterior lumbar fusion for isthmic spondylolisthesis. Using longitudinal mixed-model repeated-measures analysis the change from baseline in patient-reported outcome measures (PROMs) at 1 year after surgery was compared between surgeon-determined groups (back vs. radicular) and between patient-rated pain groups (back, leg, and equal) derived from preoperative pain scores on the numerical rating scale (NRS). 83/252 (33%) patients had a surgeon-determined chief complaint of back pain, while 103 (41%) patients rated their back pain as the predominant pain location, and 78 (31%) rated their back and leg pain to be equal. At baseline patients in the surgeon-determined radicular group had worse NRS-leg pain than those in the back-pain group but equal NRS-back pain. At baseline patients in the patient-rated equal pain group had similar back pain compared to the patient-rated back pain group and similar leg pain compared to the patient-rated leg pain group. All PROMs improved post-operatively and were not different between the 2 groups at 1 year. Our study found no difference in outcome, irrespective of whether a surgeon determines the patient's primary pain complaint back or radicular dominant, or the patient rates pain in one location greater than another. Our study found no difference in outcome, irrespective of whether a surgeon determines the patient's primary pain complaint back or radicular dominant, or the patient rates pain in one location greater than another.

The in vivo experiments further demonstrated that the antitumor effect of these nanotheranostics was significantly enhanced and that their toxicity and side effects against normal tissues were effectively suppressed. The FT@HA NPs can be applied for activated tumor combination therapy under the guidance of dual-mode imaging including fluorescence imaging and magnetic resonance imaging, providing an effective strategy for the design and preparation of TME-responsive multifunctional nanotheranostics for precise tumor imaging and combination therapy.Hemoglobin (Hb)-based oxygen carriers (HBOCs) present an alternative to red blood cells (RBCs) when blood is not available. However, the most widely used synthesis techniques have fundamental flaws, which may have contributed toward disappointing clinical application. Polymerized Hb contains a heterogeneous distribution of particle size and shape, while Hb encapsulation inside liposomes results in high lipid burden and low Hb content. https://www.selleckchem.com/products/Menadione.html Meanwhile, there are a variety of other nanoparticle synthetic techniques which, having found success as drug delivery vehicles, may be well suited to function as an HBOC. We synthesized desolvated Hb nanoparticles (Hb-dNPs) with diameters of approximately 250 nm by the controlled precipitation of Hb with ethanol. Oxidized dextran was found to be an effective surface stabilizing agent that maintained particle integrity. In vitro biophysical characterization showed a high-affinity oxygen delivery profile (P50 = 7.72 mm Hg), suggesting a potential for therapeutic use and opening a new avenue for HBOC research.The development of reliable ways of predicting the binding free energies of covalent inhibitors is a challenge for computer-aided drug design. Such development is important, for example, in the fight against the SARS-CoV-2 virus, in which covalent inhibitors can provide a promising tool for blocking Mpro, the main protease of the virus. This work develops a reliable and practical protocol for evaluating the binding free energy of covalent inhibitors. Our protocol presents a major advance over other approaches that do not consider the chemical contribution of the binding free energy. Our strategy combines the empirical valence bond method for evaluating the reaction energy profile and the PDLD/S-LRA/β method for evaluating the noncovalent part of the binding process. This protocol has been used in the calculations of the binding free energy of an α-ketoamide inhibitor of Mpro. Encouragingly, our approach reproduces the observed binding free energy. Our study of covalent inhibitors of cysteine proteases indicates that in the choice of an effective warhead it is crucial to focus on the exothermicity of the point on the free energy surface of a peptide cleavage that connects the acylation and deacylation steps. Overall, we believe that our approach should provide a powerful and effective method for in silico design of covalent drugs.Individual Maillard reaction products (MRPs), namely, free and protein-bound glycated amino acids as well as dicarbonyl compounds, were quantitated in various types of brewing malt using chromatographic means. Among the protein-bound glycated amino acids, which were analyzed following enzymatic hydrolysis, N-ε-fructosyllysine was the dominating compound in light (EBC less then 10) and dark (10 less then EBC less then 500) malts, accounting for up to 15.9% of lysine derivatization, followed by N-ε-maltulosyllysine (light malts, up to 4.9% lysine derivatization) or pyrraline (dark malts, up to 10.4% lysine derivatization). Roasting of malt led to the degradation of most of the protein-bound glycated amino acids. The same trends were visible for free glycated amino acids. A novel MRP-derived Strecker aldehyde, namely, 5-(2'-formyl-5'-hydroxymethylpyrrol-1'-yl)-pentanal (pyrralinal), was detected in dark malt. The most abundant 1,2-dicarbonyl compound in malt samples was 3-deoxyglucosone (up to 9 mmol/kg), followed by 3-deoxymaltosone (up to 2 mmol/kg). Only few MRPs such as 5-hydroxymethylfurfural, furfural, the dicarbonyl compounds glyoxal, methylglyoxal, and diacetyl as well as protein-bound rhamnolysine and MG-H1 correlated with the malt color. A comparison of MRPs present in malt with corresponding amounts in beer points to neoformation of MRPs such as MG-H1 and 3-deoxygalactosone during the brewing process.Constructing the nanostructure of transition metal oxides for high energy density lithium-ion batteries has been widely studied recently. Prompted by the idea that the transition metal can serve as a catalyzer influence on the reversibility of solid-electrolyte interphase films, Co/MnO@C composite nanofibers were designed by electrospinning and chemical vapor deposition methods. The Co/MnO@C electrode showed superior electrochemical performance with a large capacity increase for the first 400 cycles and a high rate performance of 1345 mA h g-1 at 1000 mA g-1. There was no obvious decay of capacity over the whole 1000 cycles, demonstrating the excellent cycling stability of the samples. The new design and synthesis of the anodic materials may offer a prototype for high-performance and strong-stability batteries.Building on our previous free-energy map (J. Phys. Chem. A2018, 122, 6769-6779) examining the reactions of monomeric glycolonitrile, we explore the formation of its dimers and trimers in aqueous solution under neutral conditions. While 5-membered rings are kinetically favored, open-chain oligomers with ester or amide linkages are thermodynamically favored. Accessing the 5-membered rings also provides a potential route to glyoxal that bypasses preforming glycolamide, the thermodynamic sink for monomers. However, finding a kinetically accessible route to glycine starting from glycolonitrile in the absence of added ammonia at room temperature proved challenging; the best case involved an intramolecular nucleophilic substitution reaction in a dimer containing neighboring imine and amide groups. Our free-energy map also examines routes to experimentally proposed moieties, explaining why some are observed in low yield or not at all.

These results provide insights into glucagon biology and suggest that INSP3R1 may represent a target for therapies that aim to reverse nonalcoholic fatty liver disease and type-2 diabetes.In mammalian cells, mitochondrial dysfunction triggers the integrated stress response, in which the phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) results in the induction of the transcription factor ATF41-3. However, how mitochondrial stress is relayed to ATF4 is unknown. Here we show that HRI is the eIF2α kinase that is necessary and sufficient for this relay. In a genome-wide CRISPR interference screen, we identified factors upstream of HRI OMA1, a mitochondrial stress-activated protease; and DELE1, a little-characterized protein that we found was associated with the inner mitochondrial membrane. Mitochondrial stress stimulates OMA1-dependent cleavage of DELE1 and leads to the accumulation of DELE1 in the cytosol, where it interacts with HRI and activates the eIF2α kinase activity of HRI. In addition, DELE1 is required for ATF4 translation downstream of eIF2α phosphorylation. Blockade of the OMA1-DELE1-HRI pathway triggers an alternative response in which specific molecular chaperones are induced. The OMA1-DELE1-HRI pathway therefore represents a potential therapeutic target that could enable fine-tuning of the integrated stress response for beneficial outcomes in diseases that involve mitochondrial dysfunction.Mitochondrial fidelity is tightly linked to overall cellular homeostasis and is compromised in ageing and various pathologies1-3. Mitochondrial malfunction needs to be relayed to the cytosol, where an integrated stress response is triggered by the phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) in mammalian cells4,5. eIF2α phosphorylation is mediated by the four eIF2α kinases GCN2, HRI, PERK and PKR, which are activated by diverse types of cellular stress6. However, the machinery that communicates mitochondrial perturbation to the cytosol to trigger the integrated stress response remains unknown1,2,7. Here we combine genome engineering and haploid genetics to unbiasedly identify genes that affect the induction of C/EBP homologous protein (CHOP), a key factor in the integrated stress response. We show that the mitochondrial protease OMA1 and the poorly characterized protein DELE1, together with HRI, constitute the missing pathway that is triggered by mitochondrial stress. Mechanistically, stress-induced activation of OMA1 causes DELE1 to be cleaved into a short form that accumulates in the cytosol, where it binds to and activates HRI via its C-terminal portion. Obstruction of this pathway can be beneficial or adverse depending on the type of mitochondrial perturbation. In addition to the core pathway components, our comparative genetic screening strategy identifies a suite of additional regulators. Together, these findings could be used to inform future strategies to modulate the cellular response to mitochondrial dysfunction in the context of human disease.Condensin, a key component of the structure maintenance of chromosome (SMC) protein complexes, has recently been shown to be a motor that extrudes loops of DNA1. It remains unclear, however, how condensin complexes work together to collectively package DNA into chromosomes. Here we use time-lapse single-molecule visualization to study mutual interactions between two DNA-loop-extruding yeast condensins. We find that these motor proteins, which, individually, extrude DNA in one direction only are able to dynamically change each other's DNA loop sizes, even when far apart. When they are in close proximity, condensin complexes are able to traverse each other and form a loop structure, which we term a Z-loop-three double-stranded DNA helices aligned in parallel with one condensin at each edge. Z-loops can fill gaps left by single loops and can form symmetric dimer motors that pull in DNA from both sides. These findings indicate that condensin may achieve chromosomal compaction using a variety of looping structures.Studies of two-dimensional electron systems in a strong magnetic field revealed the quantum Hall effect1, a topological state of matter featuring a finite Chern number C and chiral edge states2,3. Haldane4 later theorized that Chern insulators with integer quantum Hall effects could appear in lattice models with complex hopping parameters even at zero magnetic field. The ABC-trilayer graphene/hexagonal boron nitride (ABC-TLG/hBN) moiré superlattice provides an attractive platform with which to explore Chern insulators because it features nearly flat moiré minibands with a valley-dependent, electrically tunable Chern number5,6. https://www.selleckchem.com/products/bapta-am.html Here we report the experimental observation of a correlated Chern insulator in an ABC-TLG/hBN moiré superlattice. We show that reversing the direction of the applied vertical electric field switches the moiré minibands of ABC-TLG/hBN between zero and finite Chern numbers, as revealed by large changes in magneto-transport behaviour. For topological hole minibands tuned to have a finite Chern number, we focus on quarter filling, corresponding to one hole per moiré unit cell. The Hall resistance is well quantized at h/2e2 (where h is Planck's constant and e is the charge on the electron), which implies C = 2, for a magnetic field exceeding 0.4 tesla. The correlated Chern insulator is ferromagnetic, exhibiting substantial magnetic hysteresis and a large anomalous Hall signal at zero magnetic field. Our discovery of a C = 2 Chern insulator at zero magnetic field should open up opportunities for discovering correlated topological states, possibly with topological excitations7, in nearly flat and topologically nontrivial moiré minibands.Structurally intact tropical forests sequestered about half of the global terrestrial carbon uptake over the 1990s and early 2000s, removing about 15 per cent of anthropogenic carbon dioxide emissions1-3. Climate-driven vegetation models typically predict that this tropical forest 'carbon sink' will continue for decades4,5. Here we assess trends in the carbon sink using 244 structurally intact African tropical forests spanning 11 countries, compare them with 321 published plots from Amazonia and investigate the underlying drivers of the trends. The carbon sink in live aboveground biomass in intact African tropical forests has been stable for the three decades to 2015, at 0.66 tonnes of carbon per hectare per year (95 per cent confidence interval 0.53-0.79), in contrast to the long-term decline in Amazonian forests6. Therefore the carbon sink responses of Earth's two largest expanses of tropical forest have diverged. The difference is largely driven by carbon losses from tree mortality, with no detectable multi-decadal trend in Africa and a long-term increase in Amazonia.