Genome-Wide Identification and Expression Analysis of the BTB Gene Superfamily Provides Insight into Sex Determination and Early Gonadal Development of Alligator sinensis.

The BTB gene superfamily is widely distributed among higher eukaryotes and plays a significant role in numerous biological processes. However, there is limited knowledge about the structure and function of BTB genes in the critically endangered species Alligator sinensis, which is endemic to China. A total of 170 BTB genes were identified from the A. sinensis genome, classified into 13 families, and unevenly distributed across 16 chromosomes. Analysis of gene duplication events yielded eight pairs of tandem duplication genes and six pairs of segmental duplication genes. Phylogenetics shows that the AsBTB genes are evolutionarily conserved. The cis-regulatory elements in the AsBTB family promoter region reveal their involvement in multiple biological processes. Protein interaction network analysis indicates that the protein interactions of the AsBTB genes are centered around CLU-3, mainly participating in the regulation of biological processes through the ubiquitination pathway. The expression profile and protein interaction network analysis of AsBTB genes during sex differentiation and early gonadal development indicate that AsBTB genes are widely expressed in this process and involves numerous genes and pathways for regulation. This study provides a basis for further investigation of the role of the BTB gene in sex differentiation and gonadal development in A. sinensis.

Weight change and the risk of cardiovascular disease in patients with hypertension: A primary-care cohort study.

Background: Weight control is a cornerstone of hypertension management. Therefore, it is important to understand the relationship of weight change to risk of cardiovascular disease (CVD) among patients with hypertension. We aimed to investigate the association of weight change with the risk of CVD, stroke, and myocardial infarction (MI) among patients with hypertension. Methods: We obtained the data from medical records of the Hypertension Health Management Program (HMPH) in Shenzhen, China. The present study included 221 454 individuals with hypertension. Weight change over two years was divided into loss ≥10%, loss 5-10%, stable (-5 ~ 5%), gain 5-10%, and gain >10%. Cox regression analyses were applied to assess the associations of weight change groups with the risk of CVD, stroke, and MI. Results: Compared with the stable weight group (-5 ~ 5%), those with weight loss ≥10% had a higher risk of CVD (hazard ratio (HR) = 1.21; 95% confidence interval (CI) = 1.05-1.40) in the fully adjusted model. Weight gain >10% was significantly associated with a higher risk of CVD (HR = 1.17; 95% CI = 1.04-1.31). In the meanwhile, participants with weight loss ≥10% had significantly higher risks of stroke (HR = 1.20; 95% CI = 1.02-1.41). However, participants with weight gain >10% had an increased risk of MI (HR = 1.45; 95% CI = 1.15-1.82) in the fully adjusted model. Conclusions: Weight loss or weight gain were associated with higher risks of CVD. Management of patients with hypertension requires close monitoring and appropriate interventions to achieve optimal body weight to prevent adverse outcomes.

Novel metabolic indicators and the risk of cardiovascular disease in patients with hypertension: A primary-care cohort study.

BACKGROUND AND AIMS: Data are limited on whether several easily measured indices serve as effective tools for Cardiovascular disease (CVD) risk assessment in hypertensive patients. This study aimed to assess the associations of metabolic score for insulin resistance (METS-IR), lipid accumulation product (LAP), and visceral adiposity index (VAI) with CVD risk in hypertensive patients. METHODS AND RESULTS: Our data were drawn from the medical records of primary-care institutions in China. The present study included 306,680 individuals with hypertension attending primary healthcare centers. Cox regression analyses were applied to assess the associations of novel metabolic indicators with the risk of CVD. During a median follow-up of 1.98 years, 5820 participants developed CVD. When comparing with the lowest quartile of the indices, the highest quartile of METS-IR, LAP, and VAI was associated with 1.25-fold (95 % CI: 1.16-1.35), 1.15-fold (95 % CI: 1.05-1.25), and 1.19-fold (95 % CI: 1.10-1.28) risk of CVD after adjusting for potential confounders. CONCLUSION: This study provided additional evidence that novel metabolic indicators like METS-IR, LAP, and VAI were associated with the risk of CVD. These results suggest that proactive assessment of visceral adiposity and insulin resistance could be helpful for the effective clinical management of the hypertensive population.

Methodological Validation and Inter-Laboratory Comparison of Microneutralization Assay for Detecting Anti-AAV9 Neutralizing Antibody in Human.

Anti-AAV neutralizing Abs (NAbs) titer is usually measured by cell-based microneutralization (MN) assay and is crucial for patient screening in AAV-based gene therapy clinical trials. However, achieving uniform operation and comparable results among different laboratories remains challenging. Here, we established a standardized MN assay for anti-AAV9 NAbs in human sera or plasma and transferred the method to the other two research teams. Then, we validated its parameters and tested a set of eight human samples in blind across all laboratories. The end-point titer, defined by a transduction inhibition of 50% (IC50), was calculated using curve-fit modelling. A mouse neutralizing monoclonal antibody in human negative serum was used for system quality control (QC), requiring inter-assay titer variation of <4-fold difference or geometric coefficient of variation (%GCV) of <50%. The assay demonstrated a sensitivity of 54 ng/mL and no cross-reactivity to 20 µg/mL anti-AAV8 MoAb. The intra-assay and inter-assay variation for the low positive QC were 7-35% and 22-41%, respectively. The titers of the blind samples showed excellent reproducibility within and among laboratories, with a %GCV of 18-59% and 23-46%, respectively. This study provides a commonly transferrable MN assay for evaluating anti-AAV9 NAbs in humans, supporting its application in clinical trials.

Risk factors for patients with tracheal stenosis: a systematic review and meta-analysis.

OBJECTIVE: To systematically evaluate potential risk factors for tracheal stenosis and to provide a reference for the prevention and management of patients with this condition. METHODS: Databases were searched to identify studies of the risk factors for tracheal stenosis, from their inception to October 2023, then a meta-analysis was performed. The study was registered with PROSPERO under the registration number CRD42023428906. RESULTS: Ten studies of a total of 2525 patients were included. The meta-analysis showed that tracheotomy, diabetes, the duration of intubation, the duration of mechanical ventilation, respiratory tract infection, a high incision, and a ratio of intratracheal tube cuff diameter (C)/transverse diameter at the level of the clavicle (T) >150% were risk factors for the development of tracheal stenosis. CONCLUSION: Measures such as shortening the duration of mechanical ventilation and intubation, reducing and avoiding tracheotomy after prolonged intubation, early tracheotomy in patients with obesity who require prolonged mechanical ventilation, appropriate choices of incision location and catheter, the maintenance of appropriate C/T, the prevention of respiratory infection, and the control of diabetes mellitus should limit the risk of tracheal stenosis.

Association of handgrip strength with health care utilisation among older adults: A longitudinal study in China.

Background: Evidence on the association between handgrip strength (HGS) and health care utilisation among Chinese older adults is scarce. In this study, we aimed to investigate the association of HGS with health care utilisation and to identify whether these associations varied by gender. Methods: The analytic sample of this prospective cohort study included 6007 Chinese older adults (≥60 years) from 2011 to 2018 waves of the China Health and Retirement Longitudinal Study. A handgrip dynamometer was used to measure HGS. We measured health care utilisation by outpatient visits, inpatient visits, and unmet hospitalisation needs. We used covariates-adjusted general estimating equations for the analyses. Results: Longitudinal results showed that participants with weakness increased the likelihood of outpatient visits (odds ratio (OR) = 1.13; 95% confidence interval (CI) = 1.01-1.27), inpatient visits (OR = 1.51; 95% CI = 1.32-1.73), and unmet hospitalisation needs (OR = 1.44; 95% CI = 1.19-1.79) than their counterparts. Participants with weakness increased the number of outpatient visits (incidence rate ratio (IRR) = 1.29; 95% CI = 1.11-1.51) and the number of inpatient visits (IRR = 1.39; 95% CI = 1.10-1.61). Participants with HGS asymmetry increased the likelihood of unmet hospitalisation needs (OR = 1.19; 95% CI = 1.03-1.43) than their counterparts. The results of the impact of every one-kilogramme (kg) increase in HGS on health care utilisation indicated consistent results. The associations were similarly observed irrespective of gender. Conclusions: Chinese older adults with weakness or HGS asymmetry used more health care. Interventions for improving muscle strength and correcting strength asymmetry are highly recommended, with the potential to considerably save households and health care systems.

Assessing the importance of risk factors for diabetic retinopathy in patients with type 2 diabetes mellitus: Results from the classification and regression tree models.

BACKGROUND: Diabetic retinopathy (DR) is one of the serious complications of diabetes mellitus (DM). Many studies have identified the risk factors associated with DR, but there is not much evidence on the importance of these factors for DR. This study aimed to investigate the associated factors for patients with type 2 DM (T2DM) and calculate the importance of the identified factors. MATERIALS AND METHODS: Using probability proportionate to size sampling method in this community-based cross-sectional study, 22 community health service centers were selected from 10 administrative districts in Shenzhen, China. Approximately 60 T2DM patients were recruited from each center. The participants completed a structural questionnaire, had their venous blood collected, and underwent medical examinations and fundus photography. Logistic regression models were used to identify the risk factors of DR. The classification and regression tree (CART) model was used to calculate the importance of the identified risk factors. RESULTS: This study recruited 1097 T2DM patients, 266 of whom were identified as having DR, yielding a prevalence rate of 24.3% (95% confidence interval [CI]: 21.7%-26.9%). Results showed that a longer duration of DM, indoor-type lifestyle, and higher levels of hemoglobin A1c (HbA1c) or urea increased the risk of DR. Patients with HbA1c values ≥7% were about 2.45 times (odds ratio: 2.45; 95% CI: 1.83-3.29) more likely to have DR than their counterparts. The CART model found that the values of variable importance for HbA1c, DM duration, lifestyle (i.e., indoor type), and urea were 48%, 37%, 10%, and 4%, respectively. CONCLUSION: The prevalence of DR is high for T2DM patients who receive DM health management services from the primary healthcare system. HbA1c is the most important risk factor for DR. Integration of DR screening and HbA1c testing into the healthcare services for T2DM to reduce vision impairment and blindness is urgently warranted.

The Whole Genome DNA Methylation Signatures of Hindlimb Muscles in Chinese Alligators during Hibernation and Active Periods.

Many ectotherms hibernate to increase their chances of survival during harsh winter conditions. The role of DNA methylation in regulating gene expression related to hibernation in ectotherms remains unclear. Here, we employed whole-genome bisulfite sequencing (WGBS) technology to construct a comprehensive genome-wide DNA methylation landscape of the hindlimb muscles in the Chinese alligator during hibernation and active periods. The results indicated that methylation modifications were most abundant at CG sites, identifying 9447 differentially methylated regions (DMRs) and 2329 differentially methylated genes (DMGs). KEGG pathway enrichment analysis of the DMGs revealed significant enrichment in major pathways such as the neurotrophin signaling pathway, the MAPK signaling pathway, the GnRH signaling pathway, the biosynthesis of amino acids, and the regulation of the actin cytoskeleton, which are closely related to lipid metabolism, energy metabolism, and amino acid metabolism. Among these, 412 differentially methylated genes were located in promoter regions, including genes related to energy metabolism such as ATP5F1C, ATP5MD, PDK3, ANGPTL1, and ANGPTL2, and genes related to ubiquitin-proteasome degradation such as FBXO28, FBXO43, KLHL40, and PSMD5. These findings suggest that methylation in promoter regions may play a significant role in regulating the adaptive hibernation mechanisms in the Chinese alligator. This study contributes to a further understanding of the epigenetic mechanisms behind the hibernation of the Chinese alligator.

Identification of suitable habitats and priority conservation areas under climate change scenarios for the Chinese alligator (Alligator sinensis).

Amphibians and reptiles, especially the critically endangered Chinese alligators, are vulnerable to climate change. Historically, the decline in suitable habitats and fragmentation has restricted the distribution of Chinese alligators to a small area in southeast Anhui Province in China. However, the effects of climate change on range-restricted Chinese alligator habitats are largely unknown. We aimed to predict current and future (2050s and 2070s) Chinese alligator distribution and identify priority conservation areas under climate change. We employed species distribution models, barycenter migration analyses, and the Marxian model to assess current and future Chinese alligator distribution and identify priority conservation areas under climate change. The results showed that the lowest temperature and rainfall seasonality in the coldest month were the two most important factors affecting the distribution of Chinese alligators. Future predictions indicate a reduction (3.39%-98.41%) in suitable habitats and a westward shift in their distribution. Further, the study emphasizes that suitable habitats for Chinese alligators are threatened by climate change. Despite the impact of the Anhui Chinese Alligator National Nature Reserve, protection gaps persist, with 78.27% of the area lacking priority protected area. Our study provides crucial data for Chinese alligator adaptation to climate change and underscores the need for improved conservation strategies. Future research should refine conservation efforts, consider individual plasticity, and address identified limitations to enhance the resilience of Chinese alligator populations in the face of ongoing climate change.

High-resolution magnetic resonance vessel wall imaging in ischemic stroke and carotid artery atherosclerotic stenosis: A review.

Ischemic stroke is a significant burden on human health worldwide. Carotid Atherosclerosis stenosis plays an important role in the comprehensive assessment and prevention of ischemic stroke patients. High-resolution vessel wall magnetic resonance imaging has emerged as a successful technique for assessing carotid atherosclerosis stenosis. This advanced imaging modality has shown promise in effectively displaying a wide range of characteristics associated with the condition, leading to a comprehensive evaluation. High-resolution vessel wall magnetic resonance imaging not only enables a comprehensive evaluation of the instability of carotid atherosclerosis stenosis plaques but also provides valuable information for understanding the pathogenesis and predicting the prognosis of ischemic stroke patients. The purpose of this article is to review the application of high-resolution magnetic resonance imaging in ischemic stroke and carotid atherosclerotic stenosis.

A rhodium-catalyzed cascade C-H activation/annulation strategy for the expeditious assembly of pyrrolidinedione-fused 1,2-benzothiazines.

A cascade annulation strategy triggered by rhodium(III)-catalyzed C-H activation has been reported for the expeditious assembly of pyrrolidinedione-fused 1,2-benzothiazines from free NH-sulfoximines with maleimides under mild conditions. Without the need for inert atmosphere protection, a broad range of sulfoximines with maleimides were well tolerated, producing diverse fused-thiazine derivatives in moderate to good yields. Additionally, the late-stage transformation of the target product demonstrated the potential synthetic value of this protocol.

Tandem Acidic CO2 Electrolysis Coupled with Syngas Fermentation: A Two-Stage Process for Producing Medium-Chain Fatty Acids.

The tandem application of CO2 electrolysis with syngas fermentation holds promise for achieving heightened production rates and improved product quality. However, the significant impact of syngas composition on mixed culture-based microbial chain elongation remains unclear. Additionally, effective methods for generating syngas with an adjustable composition from acidic CO2 electrolysis are currently lacking. This study successfully demonstrated the production of medium-chain fatty acids from CO2 through tandem acidic electrolysis with syngas fermentation. CO could serve as the sole energy source or as the electron donor (when cofed with acetate) for caproate generation. Furthermore, the results of gas diffusion electrode structure engineering highlighted that the use of carbon black, either alone or in combination with graphite, enabled consistent syngas generation with an adjustable composition from acidic CO2 electrolysis (pH 1). The carbon black layer significantly improved the CO selectivity, increasing from 0% to 43.5% (0.05 M K+) and further to 92.4% (0.5 M K+). This enhancement in performance was attributed to the promotion of K+ accumulation, stabilizing catalytically active sites, rather than creating a localized alkaline environment for CO2-to-CO conversion. This research contributes to the advancement of hybrid technology for sustainable CO2 reduction and chemical production.

Delineating cathodic extracellular electron transfer pathways in microbial electrosynthesis: Modulation of polarized potential and Pt@C addition.

Microbial electrosynthesis (MES) is an innovative technology that employs microbes to synthesize chemicals by reducing CO2. A comprehensive understanding of cathodic extracellular electron transfer (CEET) is essential for the advancement of this technology. This study explores the impact of different cathodic potentials on CEET and its response to introduction of hydrogen evolution materials (Pt@C). Without the addition of Pt@C, H2-mediated CEET contributed up to 94.4 % at -1.05 V. With the addition of Pt@C, H2-mediated CEET contributions were 76.6 % (-1.05 V) and 19.9 % (-0.85 V), respectively. BRH-c20a was enriched as the dominated microbe (>80 %), and its relative abundance was largely affected by the addition of Pt@C NPs. This study highlights the tunability of MES performance through cathodic potential control and the addition of metal nanoparticles.

Using an In Vivo Mouse Model to Determine the Exclusion Criteria of Preexisting Anti-AAV9 Neutralizing Antibody Titer of Pompe Disease Patients in Clinical Trials.

The efficacy of adeno-associated virus (AAV)-based gene therapy is dependent on effective viral transduction, which might be inhibited by preexisting immunity to AAV acquired from infection or maternal delivery. Anti-AAV neutralizing Abs (NAbs) titer is usually measured by in vitro assay and used for patient enroll; however, this assay could not evaluate NAbs' impacts on AAV pharmacology and potential harm in vivo. Here, we infused a mouse anti-AAV9 monoclonal antibody into Balb/C mice 2 h before receiving 1.2 × 1014 or 3 × 1013 vg/kg of rAAV9-coGAA by tail vein, a drug for our ongoing clinical trials for Pompe disease. The pharmacokinetics, pharmacodynamics, and cellular responses combined with in vitro NAb assay validated the different impacts of preexisting NAbs at different levels in vivo. Sustained GAA expression in the heart, liver, diaphragm, and quadriceps were observed. The presence of high-level NAb, a titer about 1:1000, accelerated vector clearance in blood and completely blocked transduction. The AAV-specific T cell responses tended to increase when the titer of NAb exceeded 1:200. A low-level NAbs, near 1:100, had no effect on transduction in the heart and liver as well as cellular responses, but decreased transduction in muscles slightly. Therefore, we propose to preclude patients with NAb titers > 1:100 from rAAV9-coGAA clinical trials.

Surface coating combined with in situ cyclic voltammetry to enhance the stability of gas diffusion electrodes for electrochemical CO2 reduction.

Electrochemical CO2 reduction (CO2RR), fueled by clean and renewable energy, presents a promising method for utilizing CO2 effectively. The electrocatalytic reduction of CO2 to CO using a gas diffusion electrode (GDE) has shown great potential for industrial applications due to its high reaction rate and selectivity. However, guaranteeing its long-term stability still poses a significant challenge. In this study, we conducted a comprehensive investigation into various strategies to enhance the stability of the GDE. These strategies involved modifying the structure of the substrate, such as the gas diffusion layer (GDL) and the back side of the GDL (macroporous layer side). Additionally, we explored modifications to the catalyst layer (CL) and the front of the CL. To address these stability concerns, we proposed a practical approach that involved surface coating using carbon black in combination with in situ cyclic voltammetry (CV) cycles on Ag/Ag300/polytetrafluoroethylene (PTFE). The partial Faradaic efficiency exceeded 80 % within a span of 70 h. Electron microscopy and electrochemical characterization revealed that the implementation of in situ CV led to a reduction in catalyst particle size and the formation of a porous surface structure. By enhancing the stability of the GDE, this research opens up possibilities for the advancement of hybrid systems that focus on the production and utilization of syngas.

Associations between Chinese visceral adiposity index and risks of all-cause and cause-specific mortality: A population-based cohort study.

AIM: To determine the associations between the Chinese visceral adiposity index (CVAI) and the risks of all-cause and cause-specific mortality. MATERIALS AND METHODS: A total of 3 916 214 Chinese adults were enrolled in a nationwide population cohort covering all 31 provinces of mainland China. The CVAI was calculated based on age, body mass index, waist circumference, and triglyceride and high-density lipoprotein cholesterol concentrations. We used a Cox proportional hazards regression model to determine the hazard ratios and 95% confidence intervals (CIs) for risk of mortality associated with different CVAI levels. RESULTS: The median follow-up duration was 3.8 years. A total of 86 158 deaths (34 867 cardiovascular disease [CVD] deaths, 29 884 cancer deaths, and 21 407 deaths due to other causes) were identified. In general, after adjusting for potential confounding factors, a U-shaped relationship between CVAI and all-cause mortality was observed by restricted cubic spline (RCS). Compared with participants in CVAI quartile 1, those in CVAI quartile 4 had a 23.0% (95% CI 20.0%-25.0%) lower risk of cancer death, but a 23.0% (95% CI 19.0-27.0) higher risk of CVD death. In subgroup analysis, a J-shaped and inverted U-shaped relationship for all-cause mortality and cancer mortality was observed in the group aged < 60 years. CONCLUSIONS: The CVAI, an accessible indicator reflecting visceral obesity among Chinese adults, has predictive value for all-cause, CVD, and cancer mortality risks. Moreover, the CVAI carries significance in the field of health economics and secondary prevention. In the future, it could be used for early screening purposes.

AAV-mediated hepatic LPL expression ameliorates severe hypertriglyceridemia and acute pancreatitis in Gpihbp1 deficient mice and rats.

GPIHBP1 plays an important role in the hydrolysis of triglyceride (TG) lipoproteins by lipoprotein lipases (LPLs). However, Gpihbp1 knockout mice did not develop hypertriglyceridemia (HTG) during the suckling period but developed severe HTG after weaning on a chow diet. It has been postulated that LPL expression in the liver of suckling mice may be involved. To determine whether hepatic LPL expression could correct severe HTG in Gpihbp1 deficiency, liver-targeted LPL expression was achieved via intravenous administration of the adeno-associated virus (AAV)-human LPL gene, and the effects of AAV-LPL on HTG and HTG-related acute pancreatitis (HTG-AP) were observed. Suckling Gpihbp1-/- mice with high hepatic LPL expression did not develop HTG, whereas Gpihbp1-/- rat pups without hepatic LPL expression developed severe HTG. AAV-mediated liver-targeted LPL expression dose-dependently decreased plasma TG levels in Gpihbp1-/- mice and rats, increased post-heparin plasma LPL mass and activity, decreased mortality in Gpihbp1-/- rat pups, and reduced the susceptibility and severity of both Gpihbp1-/- animals to HTG-AP. However, the muscle expression of AAV-LPL had no significant effect on HTG. Targeted expression of LPL in the liver showed no obvious adverse reactions. Thus, liver-targeted LPL expression may be a new therapeutic approach for HTG-AP caused by GPIHBP1 deficiency.

Achieving renewable energy transition through financial stability of renewable energy companies and banking facility.

Investing heavily in the transition to renewable energy is essential for global sustainability. Companies in the renewable energy sector often use bank financing for day-to-day operations and capital expenditures. This research looks at the effect of financial ties between renewable energy companies and banks on both industries' viability as they make the switch to renewable power sources. We analyze a large worldwide sample of renewable energy firms and banks to see how these interdependencies affect the long-term viability of both industries. According to our findings, the effectiveness of the shift is heavily impacted by the degree of interconnection between renewable energy businesses and banks. Financing costs are reduced and investments in renewable energy projects are encouraged when banks have a higher exposure to renewable energy enterprises. In addition to highlighting the importance of these linkages, our research also emphasizes the possible hazards associated with them, such as financial contagion and systemic risk, and underscores the necessity for effective risk management methods. In conclusion, this study highlights the need for a coordinated strategy to the renewable energy transition that weighs the advantages and disadvantages of interconnection. We show that there are both positive and negative outcomes that can result from the relationship between financial institutions and renewable energy enterprises, and we highlight the duty of policymakers and regulators to ensure that banks have adequate exposure to the industry while closely monitoring associated risks.