The inhibitor of apoptosis (IAP) proteins maintain a balance between cell proliferation and cell death by inhibiting caspase activity and facilitating immune responses. In this study, phylogenetic analysis revealed lineage-specific expansion and tandem duplication of IAPs in the Pacific oyster Crassostrea gigas. We then investigated a representative oyster-specific XIAP-like gene (CgIAP2) to understand how it regulates initiator caspase. Cloning of full-length CgIAP2 from oyster cDNA uncovered a deduced protein containing two BIR domains and a RING domain. Homolog comparison demonstrated that CgIAP2 clustered into the invertebrate branch. We found that CgIAP2 was likely involved in apoptosis inhibition and immune defense, based on high mRNA expression in the gills and labial palps, as well as increased mRNA expression after bacterial challenge. A yeast two-hybrid assay revealed that the BIR2 domain was necessary and sufficient to mediate interaction between CgIAP2 and Cgcaspase-2, providing direct evidence that CgIAP2 participates in apoptosis inhibition.

Endothelial cell injury leading to microvascular rarefaction is a characteristic feature of chronic kidney disease (CKD). However, the mechanism underlying endothelial cell dropout is poorly defined. Here, we show a central role of the extracellular microenvironment in controlling endothelial cell survival and proliferation in CKD. When cultured on a decellularized kidney tissue scaffold (KTS) from fibrotic kidney, endothelial cells increased the expression of proapoptotic proteins. Proteomics profiling identified fibrillin-1 (FBN1) as a key component of the fibrotic KTS, which was up-regulated in animal models and patients with CKD. FBN1 induced apoptosis of endothelial cells and inhibited their proliferation in vitro. RNA sequencing uncovered activated integrin αvβ6/transforming growth factor-β signaling, and blocking this pathway abolished FBN1-triggered endothelial injury. In a mouse model of CKD, depletion of FBN1 ameliorated renal fibrotic lesions and mitigated vascular rarefaction. These studies illustrate that FBN1 plays a role in mediating vascular rarefaction by orchestrating a hostile microenvironment for endothelial cells.

To compare the safety and efficiency of simple corneal topography-guided (T-CAT) photorefractive keratectomy (PRK) and T-CAT PRK combined with crosslinking (CXL) to correct myopia with borderline suspicious tomography.Eyes with suspicious tomography (not classified as forme fruste keratoconus) underwent PRK combined with CXL. The suspicious tomography showed irregular posterior corneal morphology or maximum elevation value of the central 6 mm zone of the posterior surface (MEL) >15 μm, or Belin/Ambrósio Enhanced Ectasia Index (BAD-D) was >1.6. The PRK group was generated and matched within 2 μm for MEL, 0.3 for BAD-D value, and 0.5 D for manifest refractive spherical equivalent (MRSE) compared with the PRK-CXL group.PRK-CXL exhibited a larger MRSE (0.09 ± 0.22 D vs -0.03 ± 0.24 D, P = .02) and a larger sphere (0.14 ± 0.22 D vs 0.01 ± 0.21 D, P = .002) compared with PRK alone at 18 months postoperatively. The magnitude change and relative change rate of stiffness parameter A1 in the PRK-CXL were smaller than in the PRK group (-15.72 ± 14.56 vs -19.95 ± 14.37, P = .04, for magnitude change and -0.16 ± 0.15 vs -0.20 ± 0.14, P = .02, for relative change rate). In the PRK-CXL and PRK groups, 4.8% and 6.9% of eyes suffered grade 0.5 haze at postoperative 18-month. No cases of ectasia were reported in either group.PRK in combination with prophylactic crosslinking showed comparable safety and efficacy, but higher biomechanical stability compared to PRK alone, thus, the additional CXL plays a measurable role in reducing the change in corneal biomechanical properties after PRK in suspicious eyes.

Heart failure (HF) affects over 26 million people worldwide, yet the pathologies of this complex syndrome have not been completely understood. Here, we investigated the involvement of deacetylase Sirtuin 1 (Sirt1) in HF and its downstream signaling pathways. A HF model was induced by the ligation of the left coronary artery in rats, where factors associated with left ventricular echocardiography, heart hemodynamics and ventricular mass indexes were recorded. Collagen volume fraction in heart tissues was determined by Masson's trichrome staining. Cell models of HF were also established (H2O2, 30 min) in cardiomyocytes harvested from suckling rats. HF rats presented with downregulated expressions of Sirt1, brain-derived neurotrophic factor (BDNF) and exhibited upregulated expressions of NF-κB p65 and miR-155. Repressed Sirt1 expression increased acetylation of NF-κB p65, resulting in the elevation of NF-κB p65 expression. NF-κB p65 silencing improved heart functions, decreased ventricular mass and reduced apoptosis in cardiomyocytes. MiR-155 inhibition upregulated its target gene BDNF, thereby reducing cardiomyocyte apoptosis. Sirt1 overexpression upregulated BDNF, improved heart function, and reduced apoptosis in cardiomyocytes. In conclusion, Sirt1 alleviates HF in rats through the NF-κB p65/miR-155/BDNF signaling cascade.

Our previous research showed the antioxidant activity of anthocyanins extracted from Aronia melanocarpa of black chokeberry in vitro. Ischemia acute kidney injury is a significant risk in developing progressive and deterioration of renal function leading to clinic chronic kidney disease. There were many attempts to protect the kidney against this progression of renal damage. Current study was designed to examine the effect of pretreatment with three anthocyanins named cyanidin-3-arabinoside, cyanidin-3-glucodise, and cyaniding-3-galactoside against acute ischemia-reperfusion injury in mouse kidney.

Undergraduate students participating in the UCLA Undergraduate Research Consortium for Functional Genomics (URCFG) have conducted a two-phased screen using RNA interference (RNAi) in combination with fluorescent reporter proteins to identify genes important for hematopoiesis in Drosophila. This screen disrupted the function of approximately 3500 genes and identified 137 candidate genes for which loss of function leads to observable changes in the hematopoietic development. Targeting RNAi to maturing, progenitor, and regulatory cell types identified key subsets that either limit or promote blood cell maturation. Bioinformatic analysis reveals gene enrichment in several previously uncharacterized areas, including RNA processing and export and vesicular trafficking. Lastly, the participation of students in this course-based undergraduate research experience (CURE) correlated with increased learning gains across several areas, as well as increased STEM retention, indicating that authentic, student-driven research in the form of a CURE represents an impactful and enriching pedagogical approach.

The endoplasmic reticulum (ER)-resident E3 ligase HRD1 and its co-activator Sel1L are major components of ER-associated degradation (ERAD) machinery. Here, we investigated the molecular mechanism and functional significance underlying the circadian regulation of HRD1/Sel1L-mediated protein degradation program in hepatic energy metabolism.

Stairs are among the most hazardous locations, and stair descending contributes to a high risk of falls among the elderly under dual-task (DT) conditions. The purpose of this study was to determine whether the practitioners of Tai Chi (TC), one type of mind-body exercise, have lower fall risks under DT conditions during stair descending, compared with their no-exercise (NE) counterparts. Fifteen TC practitioners with at least 10 years of experience in TC and fifteen NE participants were recruited in this study. They were asked to descend a six-step staircase under single-task (ST) and DT conditions. An eight-camera motion analysis system and two force plates were used for data collection. Results showed group by DT interactions in walking velocity (p = 0.016) and center of mass-center of pressure inclination angle (COM-COP IA) in the anteroposterior directions (p = 0.026). Group effects observed with foot clearance (p = 0.031), trunk (p = 0.041) and head (p = 0.002) tilt angles, and COM-COP IA in the mediolateral (p = 0.006) directions. Significant DT effects only detected in foot clearance (p = 0.004). Although both groups of participants adopted a more cautious gait strategy under the dual-task condition, the TC practitioners were less influenced by the DT paradigm than their NE counterparts. Our observations indicated that TC practitioners have lower fall risks under DT conditions during stair descending.

The 129sv mouse strain is particularly sensitive to experimental immune-mediated nephritis. Previous studies have indicated that transforming growth factor-β (TGF-β) plays a critical role in both immune modulation and tissue fibrogenesis in various diseases and that its biological activities are exerted via the SMAD family. In this study, we aimed to determine whether TGF-β/SMAD signaling is essential for the development of immune-mediated nephritis in 129sv mice. Relative to C57BL/6J control mice with anti-glomeruli basement membrane (GBM) nephritis, 129sv mice with anti-GBM nephritis exhibited increased renal collagen deposition. Additionally, higher mRNA levels of pro-collagen and collagen IV, higher serum levels of active and total TGF-β1, and increased TGF-β1, TGF-βIIR, and phosphorylated SMAD expression were detected in these mice. Deletion of Smad3 in 129sv mice ameliorated anti-GBM induced nephritis, including crescentic glomerulonephritis. Collectively, these findings indicate that the heightened experimental nephritis and fibrotic disease in the 129sv strain of mice are regulated by SMAD3, which could be a potential therapeutic target for immune-mediated nephritis.

Alzheimer's disease (AD) is a complex neurodegenerative disorder, which is characterized by memory loss and cognitive deficits. The neuroprotective role of milrinone on the injury of spinal cord or cerebral ischemia-reperfusion has been confirmed. However, the accurate function of milrinone on AD pathogeny is still unclear.

The diagnostic efficiency of radiation encephalopathy (RE) remains heterogeneous, and prediction of RE is difficult at the pre-symptomatic stage. We aimed to analyze the whole-brain resting-state functional connectivity density (FCD) of individuals with pre-symptomatic RE using multivariate pattern analysis (MVPA) and explore its prediction efficiency. Resting data from NPC patients with nasopharyngeal carcinoma (NPC; consisting of 20 pre-symptomatic RE subjects and 26 non-RE controls) were collected in this study. We used MVPA to classify pre-symptomatic RE subjects from non-RE controls based on FCD maps. Classifier performances were evaluated by accuracy, sensitivity, specificity, and area under the characteristic operator curve. Permutation tests and leave-one-out cross-validation were applied for assessing classifier performance. MVPA was able to differentiate pre-symptomatic RE subjects from non-RE controls using global FCD as a feature, with a total accuracy of 89.13%. The temporal lobe as well as regions involved in the visual processing system, the somatosensory system, and the default mode network (DMN) revealed robust discrimination during classification. Our findings suggest a good classification efficiency of global FCD for the individual prediction of RE at a pre-symptomatic stage. Moreover, the discriminating regions may contribute to the underlying mechanisms of sensory and cognitive disturbances in RE.

Melasma is a chronic and recurrent skin problem for which an effective therapy is currently lacking. Platelet-rich plasma (PRP) has recently emerged as a novel treatment for melasma, but to date there has been no systematic evaluation of its efficacy and safety.

Recently, the benefits of cognitive behavioral therapy (CBT)-based interventions for patients with hypertension have been recognized, but there has been no systematic review that has comprehensively analyzed the efficacy of CBT on health outcomes in this population. We aimed to explore the therapeutic effect of CBT-based interventions on hypertension patients through a meta-analysis. Relevant randomized controlled trials (RCTs) were obtained by searching electronic databases. The primary outcomes were physiological indicators (blood pressure, blood lipid profile). Secondary outcomes were psychological indicators (anxiety, depression), and the quality of sleep. Stata version 15.0 software was used to analyze the results. A total of 15 RCTs were included. The main analysis revealed that CBT-based interventions reduced systolic pressure: -8.67 (95% CI: -10.67 to -6.67, P = 0.000); diastolic pressure: -5.82 (95% CI: -7.82 to -3.81, P = 0.000); total cholesterol levels: -0.43 (95% CI: -0.76 to -0.10, P = 0.010); depressive symptoms: -3.13 (95% CI: -4.02 to -2.24, P = 0.000); anxiety symptoms: -3.63 (95% CI: -4.40 to -2.87, P = 0.000); and improved quality of sleep: -2.93 (95% CI: -4.40 to -1.47, P = 0.000). Additionally, the results of subgroup analysis indicated that long-term group-based CBT-based interventions were particularly beneficial for blood pressure management in hypertension patients. CBT-based interventions are effective in reducing systolic pressure, diastolic pressure, total cholesterol levels, anxiety symptoms, depressive symptoms, and improving quality of sleep in hypertension patients.

Microcephalic osteodysplastic primordial dwarfism type II (MOPD II) is a rare autosomal recessive disorder characterized by severe pre- and postnatal growth restrictions, microcephaly, skeletal dysplasia, severe teeth deformities, and typical facial features. Previous studies have shown that MOPD II is associated with mutations in the pericentrin (PCNT) gene.

Hepatocellular carcinoma (HCC) is a liver malignancy which lacks effective treatment and has a poor prognosis. β-Elemene refers to a natural Curcuma wenyujin-derived single molecular entity, which exhibits various biological activities, and is especially well-known for it's antitumor properties.

Scientific findings and policy guidelines recommend integrating HIV and drug addiction prevention and care into community-based settings. Systematic capacity-building efforts are warranted to provide technical support for community health workers and improve their confidence in the integrated service provision. An intervention trial was conducted between 2018 and 2019 with 120 community health workers (CHW) from 60 communes in Vietnam's four provinces. The 60 intervention CHW received in-person training to enhance their HIV/addiction-related service knowledge and skills. Online support groups were established between trained CHW and local HIV and addiction specialists. The intervention outcomes were assessed using mixed-effects regression models with the data collected at baseline and every 3 months for 1 year. Adjusted analyses showed that intervention CHW reported a significant increase in the interaction with other treatment providers than the control group at 6 months and remained at the 12-month follow-up. The difference in the improvement of confidence in HIV/addiction-related service delivery between the intervention and control groups was significant at 6-month but became insignificant at the 12-month. Male CHW were more confident in providing services than female CHW at baseline, and gender differences in the changing patterns were observed over time. This capacity-building intervention demonstrated promising outcomes on CHW inter-agency collaborations and confidence in service delivery. Gender divides in healthcare professionals should be attended to in future studies.

Recently, developed vaccination vehicles were repurposed and deployed for coronavirus disease 2019 (COVID-19) vaccination in China. We described the vehicles and reported an evaluation of vaccination throughput of these vehicles for COVID-19 vaccination in China.

Abiotic stresses, including cold and drought, negatively affect maize (Zea mays L.) seed field emergence and later yield and quality. In order to reveal the molecular mechanism of maize seed resistance to abiotic stress at seed germination, the global transcriptome of high- vigour variety Zhongdi175 exposed to cold- and drought- stress was analyzed by RNA-seq. In the comparison between the control and different stressed sample, 12,299 differentially expressed genes (DEGs) were detected, of which 9605 and 7837 DEGs were identified under cold- and drought- stress, respectively. Functional annotation analysis suggested that stress response mediated by the pathways involving ribosome, phenylpropanoid biosynthesis and biosynthesis of secondary metabolites, among others. Of the obtained DEGs (12,299), 5,143 genes are common to cold- and drought- stress, at least 2248 TFs in 56 TF families were identified that are involved in cold and/or drought treatments during seed germination, including bHLH, NAC, MYB and WRKY families, which suggested that common mechanisms may be originated during maize seed germination in response to different abiotic stresses. This study will provide a better understanding of the molecular mechanism of response to abiotic stress during maize seed germination, and could be useful for cultivar improvement and breeding of high vigour maize cultivars.

A rapid and high-throughput fluorescence detection method for zearalenone (ZEN) based on a CuO nanoparticle (NP)-assisted signal amplification immunosensor was developed using an automated sample pretreatment and signal conversion system. CuO NPs with high stability and biocompatibility were used as carriers to immobilize anti-ZEN antibodies. The obtained CuO NP-anti-ZEN can maintain the ability to recognize target toxins and act as both a signal source and carrier to achieve signal conversion using automated equipment. In this process, target toxin detection is indirectly transformed to Cu2+ detection because of the large number of Cu2+ ions released from CuO NPs under acidic conditions. Finally, a simple and high-throughput fluorescence assay based on a fluorescent tripeptide molecule was employed to detect Cu2+, using a multifunctional microporous plate detector. A good linear relationship was observed between the fluorescence signal and the logarithm of ZEN concentration in the range of 16.0-1600.0 μg/kg. Additionally, excellent accuracy with a high recovery yield of 99.2-104.9% was obtained, which was concordant with the results obtained from LC-MS/MS of naturally contaminated samples. The CuO NP-based assay is a powerful and efficient screening tool for ZEN detection and can easily be modified to detect other mycotoxins.

Background: Adolescent non-suicidal self-injury (NSSI) is becoming a serious public health concern worldwide. In recent years, there has seen a significant increase in both the growth rate and cases of NSSI in Eastern countries, such as Japan, India, and China. In China, most schools have a mental health office that comprises mental health professionals (MHPs), who are the first to respond to student mental health problems, which include NSSI. MHPs possess comprehensive knowledge as well as unique insight into adolescent NSSI. However, very few studies on NSSI have incorporated their perspectives. In this work, we seek to add novel insight by conducting a study focusing on adolescent NSSI from the perspective of MHPs. Methods: We recruited a total of 24 MHPs from different schools using purposive sampling and conducted a semi-structured interview on NSSI-related issues. Each interview was voice recorded and lasted ~30 min. A thematic analysis was performed for the responses to study the most common and concerning issues underlying NSSI. Results: We extracted three major themes and eight sub-themes from the interview records, which included (1) the impact of Chinese culture on NSSI (sex-bias discrimination, overly high expectations, and inappropriate parenting style); (2) life events in school (internet use, academic pressure, and romantic relationships); and (3) opinions on the status quo of NSSI in China (ignorance and stigma). Conclusion: Results showed that culturally sensitive influential factors, such as sex-bias discrimination, the imposing of unrealistic expectations for personal achievement, and inappropriate parenting style, should be given more attention to prevent, assess, and intervene in NSSI. Emerging factors of modern society and adolescent lifestyles, such as academic pressure, internet use, and romantic relationships, should also be considered for treatments.