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Objective: The prospective relation of vitamin D status with the risk of chronic kidney diseases (CKD) remains uncertain. We aimed to examine the association of serum 25-hydroxyvitamin D (25OHD) with new-onset CKD in participants with and without diabetes at baseline and examine the potential modifications by genetic susceptibility on the association.Research Design and Methods: Included were 348,243 adults from the UK Biobank without prior CKD at baseline. Serum 25OHD concentrations were measured by chemiluminescent immunoassay method. Genetic risk score of CKD was calculated by 263 single nucleotide polymorphisms, which showed significant associations with estimated glomerular filtration rate. The primary outcome was new-onset CKD.Results: During a median follow-up duration of 12.1 years, 9,344 new-onset CKD were documented. Overall, there was a significant inverse association between baseline serum 25OHD and new-onset CKD in participants with diabetes (per SD increment, adjusted hazard ratio [HR] 0.91; 95% CI 0.86-0.96), but not in those without diabetes (per SD increment, adjusted HR 0.98; 95% CI 0.96-1.01; P-interaction between serum 25OHD and diabetes = 0.004). Accordingly, among participants with diabetes, compared with those baseline serum 25OHD <25 nmol/L, a significantly lower risk of new-onset CKD was found in those with 25OHD ≥50 nmol/L (adjusted HR 0.77; 95% CI 0.67-0.89). Moreover, the genetic risk of CKD did not significantly modify the association between baseline serum 25OHD and new-onset CKD among participants with diabetes (P-interaction = 0.127).Conclusions: There was an inverse association between baseline serum 25OHD and new-onset CKD in participants with diabetes. The inverse association was not found in participants without diabetes. [ABSTRACT FROM AUTHOR]

High levels of hepatitis B virus (HBV) surface antigen (HBsAg) in the blood of chronic HBV carriers are considered to drive the exhaustion of antigen-specific T and B lymphocytes and thus responsible for the persistence of infection. Accordingly, therapeutic elimination of HBsAg may facilitate the activation of adaptive antiviral immune responses against HBV and achieve a functional cure of chronic hepatitis B. We discovered recently that an amphipathic alpha helix spanning W156 to R169 of HBV small envelope (S) protein plays an essential role in the morphogenesis of subviral particles (SVPs) and metabolism of S protein. We thus hypothesized that pharmacological disruption of SVP morphogenesis may induce intracellular degradation of S protein and reduce HBsAg secretion. To identify inhibitors of SVP biogenesis, we screened 4417 bioactive compounds with a HepG2-derived cell line expressing HBV S protein and efficiently secreting small spherical SVPs. The screen identified 24 compounds that reduced intracellular SVPs and secreted HBsAg in a concentration-dependent manner. However, 18 of those compounds inhibited the secretion of HBsAg and HBeAg in HBV replicon transfected HepG2 cells at similar efficiency, suggesting each of those compounds may disrupt a common cellular function required for the synthesis and/or secretion of these viral proteins. Interestingly, lycorine more efficiently inhibited the secretion of HBsAg in HepG2 cells transfected with HBV replicons, HepG2.2.15 cells and HBV infected - HepG2 cells expressing sodium taurocholate cotransporting polypeptide (NTCP). The structure activity relationship and antiviral mechanism of lycorine against HBV have been determined. • Sustained clearance of HBsAg is essential for the functional cure of chronic hepatitis B. • A cell-based assay was developed for high throughput screen of compounds that inhibit HBsAg production. • Bioactive compounds were discovered to inhibit HBsAg production. • Lycorine inhibited HBsAg production by targeting cellular functions. [ABSTRACT FROM AUTHOR]

Objectives: The association between habitual glucosamine use and incident gout has not been examined in previous studies. We aimed to evaluate the association of habitual use of glucosamine with the risk of gout in general population. Methods: A total of 436,594 participants (55.4% female) without prior gout at baseline who completed a questionnaire on supplementation use, which included glucosamine, in the UK Biobank were enrolled. Incident gout was recorded from self-report, death register, primary care, and hospital admission data. Results: At baseline, 53,433 (22.1%) females and 30,685 (15.8%) males reported habitual glucosamine use. During a median follow-up period of 12.1 years, 1718 (0.7%) females and 5685 (2.9%) males developed gout. After multivariable adjustment for major risk factors, glucosamine use was associated with a significantly lower risk of incident gout in females (hazard ratio [HR], 0.81, 95% confidence interval [CI], 0.71–0.92), but not in males (HR, 1.05, 95% CI, 0.97–1.13), compared with non-use (P-interaction < 0.001). Among females, the inverse association between glucosamine use and gout was stronger in participants with diuretics use (HR, 0.64, 95% CI, 0.50–0.81) than those without diuretics use (HR, 0.89, 95% CI, 0.77–1.03) (P-interaction = 0.015). Moreover, gout genetic risk scores did not significantly modify the association between glucosamine use and the risk of incident gout in males (P-interaction = 0.548) or females (P-interaction = 0.183). Conclusions: Habitual glucosamine use to relieve osteoarthritis pain was related to lower risk of gout in females, but not in males. Highlights: Glucosamine use was associated with lower risk of incident gout in females. The inverse association between glucosamine use and gout was stronger in females with diuretics use. Gout genetic risk scores did not significantly modify the association. [ABSTRACT FROM AUTHOR]

Background: We aimed to investigate the joint effect of visit-to-visit variability (VVV) in low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides and glycosylated hemoglobin (HbA1c) on cardiovascular mortality and total mortality in patients with diabetes. Methods: Among 5194 participants with type 2 diabetes enrolled in the ACCORD lipid trial, VVVs of LDL-C, triglycerides, HDL-C, and HbA1c were assessed from baseline to 2 years of follow-up and expressed as coefficient of variation (CV). The study outcomes included cardiovascular mortality and all-cause mortality. Results: Over a median follow-up of 3.0 years from the end of variability measurements at years 2, there were 305 (5.9%) cases of all-cause mortality, of which, 144 were cardiovascular causes. The positive relations between LDL-C CV and cardiovascular mortality were significantly stronger among participants with higher HDL-C CV (P for interaction = 0.023), and higher HbA1c CV (P for interaction = 0.015). However, there were no significant interactions between LDL-C CV and triglycerides CV (P for interaction = 0.591). Similar trends were found for all-cause mortality. Consistently, there were graded trends in the risk of mortality with the increasing numbers of higher CV of the three variables: LDL-C, HbA1c, and HDL-C (P for trend = 0.008 for cardiovascular mortality, and P for trend < 0.001 for all-cause mortality). Conclusion: VVVs in LDL-C, HDL-C, and HbA1c may jointly affect the risks of cardiovascular and all-cause mortality in diabetes patients. Those with higher CVs of all three variables had the highest risks of cardiovascular and all-cause mortality. [ABSTRACT FROM AUTHOR]

In the process of drilling CFRP sheets by industrial robots, the contact stiffness between the terminal actuator and the sheet is poor, which causes the hole position to vibrate during processing. The design of a presser foot device in front of the terminal actuator can effectively solve this problem. The Navier method is used to solve the allowable range of the pressing force of the presser foot. A numerical simulation model for drilling CFRP sheets is established, the influence of different pressing forces within the allowable range on the drilling quality is studied, and the recommended value of the pressing force of the presser foot is obtained. Drilling experiments are carried out under different pressing forces. The experimental results show that the optimized pressing force of the presser foot can effectively reduce the vibration of the CFRP sheet during the drilling process, and the surface roughness of the drilling hole wall can reach 1.8 μm. At the same time, the surface morphology at the exit of the machined hole is improved. [ABSTRACT FROM AUTHOR]

The Chinese government has launched a series of health reforms to establish universal health insurance coverage, particularly for vulnerable groups, including middle-aged and older adults. However, the current public health insurance system is highly fragmented, consisting of different programs with different levels of premiums and benefits. We analyse whether the universal health insurance system increases the life satisfaction of middle-aged and older Chinese people and to what extent the type of health insurance affects the life satisfaction of this group. Our study is based on data from the China Health and Retirement Longitudinal Study, a nationally representative longitudinal survey of Chinese aged 45 and above, in 2011, 2013, and 2015. We find that the life satisfaction of middle-aged and older adults does not depend on having any health insurance coverage but varies with the type of health insurance coverage, controlling for potential confounding variables such as health status, occupation, hukou status, and other demographic variables. Individuals covered by the most generous program, the Government Medical Insurance, reported a higher life satisfaction. In comparison, individuals covered by the Urban Employee Medical Insurance, the Urban Resident Medical Insurance, and the New Rural Cooperative Scheme reported a lower life satisfaction by 0.155, 0.106, and 0.112 standard deviations, respectively. Our results suggest that establishing a more equitable health insurance system should be the next step in health reforms in China. [ABSTRACT FROM AUTHOR]

This study examines the changing role of traditional employment sector and the access to employment‐related citizenship rights in affecting migrant workers' settlement intentions in China. Traditionally, migrants who are informally employed were viewed as unsettled groups in Chinese cities. However, the expanded employment‐related citizenship rights provide more diverse channels for pursuing permanent urban settlement. We use data from China Migrants Dynamic Survey in 2013 to investigate migrant workers' permanent settlement intentions, taking into account their access to employment‐related citizenship rights, employment sector, hukou status, social‐economic attachments at the places of destination and origin, and regional variations. We found that self‐employed and informally employed migrants held a stronger intention to pursue permanent settlement if they were protected by the local urban insurance schemes, the so‐called "de facto" employment‐related citizenship. The study suggests that the dichotomy of employment sectors, formal versus informal, in understanding migrants' settlement decision has been weakened in China. [ABSTRACT FROM AUTHOR]

The study explored the impact of fragmented sDNA on anthracnose rot in postharvest loquat fruit and the underlying mechanisms. The findings revealed that the perception of fragmented sDNA triggered pattern-triggered immunity (PTI) defense, effectively inhibiting Colletotrichum gloeosporioide infection in postharvest loquat fruit. Transcriptome sequencing showed that fragmented sDNA activated ethylene-mediated induced systemic resistance (ISR), linked to increased transcription of genes in phenylpropanoid metabolism. Y2H and Co-IP experiments demonstrated a significant interaction between EjERF39 and EjRAV2. Furthermore, DLR and EMSA assays showed that EjRAV2 enhanced the activation of EjERF39-mediated transcription of genes related to phenylpropanoid metabolism (EjPAL1 , Ej4CH , EjC4L1 , EjCAD1 , and EjCCR1), leading to increased accumulation of phenolics and lignin. Accordingly, overexpression of EjRAV2 in Arabidopsis thaliana increased the expression of genes related to phenylpropanoid metabolism and enhanced resistance to C. gloeosporioides compared to the wild type. Therefore, DAMP signals from fragmented sDNA activate PTI-driven ISR, with the EjRAV2-EjERF39 module regulating phenylpropanoid metabolism in loquat fruit. [Display omitted] • sDNA effectively inhibits anthracnose rot in postharvest loquat fruit. • sDNA acts as a DAMP that induces PTI defense in loquat fruit. • sDNA activates the ET-mediated induced systemic resistance. • EjRAV2-EjERF39 module upregulates phenylpropanoid metabolism through ISR. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, with high rates of recurrence and death. Surgical resection and ablation therapy have limited efficacy for patients with advanced HCC and poor liver function, so pharmacotherapy is the first-line option for those patients. Traditional antitumor drugs have the disadvantages of poor biological distribution and pharmacokinetics, poor target selectivity, high resistance, and high toxicity to nontargeted tissues. Recently, the development of nanotechnology has significantly improved drug delivery to tumor sites by changing the physical and biological characteristics of drugs and nanocarriers to improve their pharmacokinetics and biological distribution and to selectively accumulate cytotoxic agents at tumor sites. Here, we systematically review the tumor microenvironment of HCC and the recent application of nanotechnology in HCC. 4yR9ZE2akgJiF2XmjN2GAm Video Abstract. [ABSTRACT FROM AUTHOR]

Background: Spinal tumor surgery usually involved long operation time, large area of soft tissue resection and long wound, and was prone to hypothermia during the operation. Therefore, actively promoting insulation and optimizing the intraoperative insulation program have great potential in reducing the incidence of hypothermia and reducing the incidence of postoperative complications. In this study, we compared patients who did not implement multi-mode nursing insulation program (MNIP) with those who implemented MNIP, observing and comparing clinical outcomes, and complications in both groups, with the aim of developing an optimal management plan for the preoperative, intraoperative, and postoperative periods, respectively. Methods: We selected 2 periods of 1 year, before (n = 120 patients) and after MINP implementation (n = 120 patients). Data were collected on patient demographics, operative, perioperative details, temperature changes, anesthesia recovery effect, incidence of postoperative wound infection, length of hospital stay and complications. PS analyses were used for dealing with confounding bias in this retrospective observational study. Results: After PS matching, the outcomes of 120 well-balanced pairs of patients were compared (No-MNIP vs MNIP). There was no significant difference concerning the satisfaction survey. The results indicated that the MNIP had better insulation effect at 90 min, 120 min, 150 min after anesthesia induction and after surgery. There were 16 cases of complications in the No-MNIP group and 5 cases in the MNIP group postoperative, which have significant statistical difference. Conclusion: In this study, the incidence of intraoperative hypothermia was effectively reduced by adopting the multi-mode insulation scheme, thus reducing the incidence of incision infection and shortening the length of hospital stay of patients. [ABSTRACT FROM AUTHOR]