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In CB2 knockout mice, renal tubular cell senescence and kidney fibrosis were also significantly inhibited. CB2 overexpression or activation by the agonist AM1241 could sufficiently induce the decrease in PGC-1α and a variety of mitochondria-related proteins and trigger cellular senescence in cultured human renal proximal tubular cells. CB2-activated mitochondrial dysfunction and cellular senescence could be blocked by ICG-001, a blocker for β-catenin signalling. These results show CB2 plays a central role in renal tubular mitochondrial dysfunction and kidney ageing. The intrinsic mechanism may be related to its activation in β-catenin signalling.

Ethnicity, neighbourhood ethnic density, and four additional neighbourhood factors (urbanicity, crime, voting, and poverty) were examined in relation to the incidence of first episode of psychosis (FEP) in the Pacific Island of Guam.

All first contact patients seen at the Guam Department of Mental Health and Substance Abuse (DMHSA) between January 2005 and December 2007 that met DSM-IV criteria for the diagnosis of a psychotic disorder were included. At the time of the study, DMHSA was the only psychiatric facility in Guam.

After controlling for age and gender, Chamorros, the indigenous people of Guam, had a standardized incidence rate (IR=151/100 000 person-years, 95%CI=129-173) of FEP over twice that of Whites (IR=66/100 000 person-years, 95%CI=34-99). Individuals from Palau had the highest standardized incidence rate (IR=832/100 000 person-years, 95%CI=581-1083). Increased neighbourhood Chamorro density was associated with decreased incidence of FEP among Chamorro individuals (IRR=0.11, 95%CI=0.03-0.in neighbourhoods with few other indigenous individuals. Findings also suggest that even on a small island, with only ~150 000 people, urbanicity is associated with FEP. Finally, results are consistent with other research suggesting that the reduction of crime and social adversity can play a positive role in reducing the incidence of first episode psychosis.Setae, fibrils located on a gecko's feet, have been an inspiration of synthetic dry microfibrillar adhesives in the last two decades for a wide range of applications due to unique properties residue-free, repeatable, tunable, controllable and silent adhesion; self-cleaning; and breathability. However, designing dry fibrillar adhesives is limited by a template-based-design-approach using a pre-determined bioinspired T- or wedge-shaped mushroom tip. Here, a machine learning-based computational approach to optimize designs of adhesive fibrils is shown, exploring a much broader design space. A combination of Bayesian optimization and finite element methods creates novel optimal designs of adhesive fibrils, which are fabricated by two-photon-polymerization-based 3D microprinting and double-molding-based replication out of polydimethylsiloxane. Such optimal elastomeric fibril designs outperform previously proposed designs by maximum 77% in the experiments of dry adhesion performance on smooth surfaces. Furthermore, finite-element-analyses reveal that the adhesion of the fibrils is sensitive to the 3D fibril stem shape, tensile deformation, and fibril microfabrication limits, which contrast with the previous assumptions that mostly neglect the deformation of the fibril tip and stem, and focus only on the fibril tip geometry. The proposed computational fibril design could help design future optimal fibrils with less help from human intuition.Colletotrichum gloeosporioides is a hemibiotrophic ascomycete fungus that causes anthracnose on numerous plants worldwide and forms a specialized infection structure known as an appressorium in response to various plant surface signals. However, the associated mechanism of host surface signal recognition remains unclear. In the present study, three putative sensors, namely the mucin Msb2, the membrane sensor protein Sho1, and the G-protein-coupled receptor Pth11, were identified and characterized. The results showed that CgMsb2 plays a major role in the recognition of various host surface signals; deletion of CgMsb2 resulted in significant defects in appressorium formation, appressorium penetration, cellophane membrane penetration, and pathogenicity. CgSho1 plays a minor role and together with CgMsb2 cooperatively regulates host signal recognition, cellophane membrane penetration, and pathogenicity; deletion of CgSho1 resulted in an expansion defect of infection hyphae. Deletion of CgPth11 in wildtype, ΔCgMsb2, and ΔCgSho1 strains only resulted in a slight defect in appressorium formation at the early stage, and CgPth11 was dispensable for penetration and pathogenicity. However, exogenous cAMP failed to restore the defect of appressorium formation in ΔCgPth11 at the early stage. CgMsb2 contributed to the phosphorylation of the mitogen-activated protein kinase CgMk1, which is essential for infection-associated functions, while CgSho1 was unable to activate CgMk1 alone but rather cooperated with CgMsb2 to activate CgMk1. These data suggest that CgMsb2 contributes to the activation of CgMk1 and has overlapping functions with CgSho1 in plant surface sensing, appressorium formation, and pathogenicity.

Little is known about the external validity of the Data-collection on Adverse Effects of Anti-HIV Drugs (DAD) model for predicting cardiovascular disease (CVD) risk among people living with HIV (PLWH). We aimed to evaluate the performance of the updated DAD model for 5-year CVD risk in a diverse group of PLWH engaged in HIV care.

We used data from an institutional HIV registry, which includes PLWH engaged in care at a safety-net HIV clinic. Eligible individuals had a baseline clinical encounter between 1 January 2013 and 31 December 2014, with follow-up through to 31 December 2019. We estimated 5-year predicted risks of CVD as a function of the prognostic index and baseline survival of the DAD model, which were used to assess model discrimination (C-index), calibration and net benefit.

Our evaluable population comprised 1029 PLWH, of whom 30% were female, 50% were non-Hispanic black, and median age was 45years. The C-index was 0.70 [95% confidence limits (CL) 0.64-0.75]. The predicted 5-year CVD risk was 3.0% and the observed 5-year risk was 8.9% (expected/observed ratio=0.33, 95% CL 0.26-0.54). The model had a greater net benefit than treating all or treating none at a risk threshold of 10%.

The DAD model was miscalibrated for CVD risk among PLWH engaged in HIV care at an urban safety-net HIV clinic, which may be related to differences in case-mix and baseline CVD risk. Nevertheless, the HIV DAD model may be useful for decisions about CVD intervention for high-risk patients.

The DAD model was miscalibrated for CVD risk among PLWH engaged in HIV care at an urban safety-net HIV clinic, which may be related to differences in case-mix and baseline CVD risk. Nevertheless, the HIV DAD model may be useful for decisions about CVD intervention for high-risk patients.Child undernutrition in Cambodia is a persistent public health problem requiring low-cost and scalable solutions. Rising cellphone use in low-resource settings represents an opportunity to replace in-person counselling visits with phone calls; however, questions remain on relative effectiveness. Our objective was to evaluate the impact of two options for delivering a World Vision infant and young child feeding (IYCF) counselling programme (1) traditional Positive Deviance/Hearth (PDH) programme with in-person visits or (2) PDH with Interactive Voice Calling (PDH-IVC) which integrates phone calls to replace 62.5% of face-to-face interaction between caregivers and volunteers, compared to the standard of care (SOC). We conducted a longitudinal cluster-randomised controlled trial in 361 children 6-23 months. We used an adjusted difference-in-difference approach using baseline, midline (3 months) and endline (12 months) surveys to evaluate the impact on child growth among the three groups. At baseline, nearly a third of children were underweight, and over half were food insecure. At midline the PDH group and the PDH-IVC groups had improved weight-for-age z-scores (0.13 DID, p = 0.011; 0.13 DID, p = 0.02, respectively) and weight-for-height z-score (0.16 DID, p = 0.038; 0.24 DID, p = 0.002), relative to SOC. There were no differences in child height-for-age z-scores. At endline, the impact was sustained only in the PDH-IVC group for weight-for-age z-score (0.14 DID, p = 0.049), and the prevalence of underweight declined by 12.8 percentage points (p = 0.036), relative to SOC. Integration of phone-based IYCF counselling is a potentially promising solution to reduce the burden of in-person visits; however, the modest improvements suggest the need to combine it with other strategies to improve child nutrition.High-energy-density lithium (Li) metal batteries suffer from a short lifespan owing to apparently ceaseless inactive Li accumulation, which is accompanied by the consumption of electrolyte and active Li reservoir, seriously deteriorating the cyclability of batteries. Herein, a triiodide/iodide (I3 - /I- ) redox couple initiated by stannic iodide (SnI4 ) is demonstrated to reclaim inactive Li. The reduction of I3 - converts inactive Li into soluble LiI, which then diffuses to the cathode side. The oxidation of LiI by the delithiated cathode transforms cathode into the lithiation state and regenerates I3 - , reclaiming Li ion from inactive Li. The regenerated I3 - engages the further redox reactions. Furthermore, the formation of Sn mitigates the corrosion of I3 - on active Li reservoir sacrificially. In working Li | LiNi0.5 Co0.2 Mn0.3 O2 batteries, the accumulated inactive Li is significantly reclaimed by the reversible I3 - /I- redox couple, improving the lifespan of batteries by twice. This work initiates a creative solution to reclaim inactive Li for prolonging the lifespan of practical Li metal batteries.Self-harm definition is an important focus of academic research and clinical practice. The precise definition of self-harm has been contested for decades, and current terminology varies across, and sometimes within, countries. This commentary has been written to highlight the problematic use of the term 'deliberate' self-harm (i.e. DSH) and to clarify the terminology currently recommended by clinical agencies in the United Kingdom. Comparisons will be made to other definitions in the field, such as non-suicidal self-injury (NSSI), with the aim of contributing to the worldwide discussion about how we conceptualise, discuss and treat suicidal and non-suicidal behaviours. The commentary concludes by highlighting the findings of Ward and Curran (2021). Cyclopamine research buy It is suggested that undiagnosed ADHD may be a potential driver for self-harm, particularly among girls, further highlighting the ongoing challenges in identifying and predicting which youth are at risk for self-harm and suicidal behaviours. Central to this challenge has been the long-standing confusion around the best way to define self-harm.During evolution, plants have developed sophisticated ways to cope with different biotic and abiotic stresses. Phytohormones and secondary metabolites are known to play pivotal roles in defence responses against invading pathogens. One of the key hormones involved in plant immunity is salicylic acid (SA), of which the role in plant defence is well established and documented. Plants produce an array of secondary metabolites categorized in different classes, with the phenylpropanoids as major players in plant immunity. Both SA and phenylpropanoids are needed for an effective immune response by the plant. To successfully infect the host, pathogens secrete proteins, called effectors, into the plant tissue to lower defence. Secreted effectors can interfere with several metabolic or signalling pathways in the host to facilitate infection. In this review, we will focus on the different strategies pathogens have developed to affect the levels of SA and phenylpropanoids to increase plant susceptibility.