Current syphilis infection in virally suppressed people living with HIV: a cross-sectional study in eastern China.

Background: Antiretroviral therapy (ART) has been shown to reduce human immunodeficiency virus (HIV) viral replication and ultimately achieve viral suppression and eliminate HIV transmission. However, little is known about the impact of viral suppression on high-risk behaviors and sexually transmitted infections (STIs). Objective: This study aimed to assess the rates of current syphilis infection in virally suppressed people living with HIV (PLWH) and whether with the duration of ART can reduce the current syphilis infection in eastern China. Method: We conducted a cross-sectional survey of PLWH in Zhejiang Province, China, in 2022. PLWH who were on ART >6 months and were virally suppressed (viral load <50 copies/mL) were included in the study. Data were collected from the National Epidemiological Database of Zhejiang Province and all participants were tested for viral load and current syphilis. Multivariable logistic regression was used to identify risk factors associated with current syphilis infection. Result: A total of 30,744 participants were included in the analysis. 82.7% of participants were male, the mean age was 44.9 ± 14.1 years, 84.9% had received ART in a hospital setting, the mean time on ART was 5.9 ± 3.1 years and 5.6% of participants were infected with current syphilis. Multivariable logistic regression showed that being male [adjusted odds ratio (aOR): 2.12, 95% confidence interval (CI): 1.69-2.66], high level of education (aOR: 1.23, 95% CI: 1.02-1.49), homosexual route of HIV infection (aOR: 1.80, 95% CI: 1.60-2.04), non-local registered residence (aOR: 1.29, 95% CI: 1.11-1.51), had history of STIs before HIV diagnosis (aOR: 1.95, 95 % CI: 1.75-2.18) and treatment provided by a municipal hospital (aOR: 2.16, 95% CI: 1.31-3.55) were associated with increased risk of current syphilis infection. Being married (aOR: 0.67, 95% CI: 0.58-0.76) was associated with a decreased risk of current syphilis infection. Conclusion: Our findings revealed a high rate of current syphilis infection among virally suppressed PLWH in eastern China. Duration of ART did not reduce the prevalence of current syphilis infection. Targeted interventions to reduce current syphilis infection should be prioritized for subgroups at higher risk.

CRISPR/Cas9-mediated Nap knockout affects female reproduction and egg shape in Bombyx mori.

Insect reproductive capacity can affect effective pest control and infertility studies and has become an important focus in recent molecular genetic research. Nucleosome assembly protein (Nap) is highly conserved across multiple species and is involved in forming the sperm nucleus in many species. We used clustered regularly interspaced palindromic repeats/Cas9 technology to knockout BmNap in Bombyx mori and observed that the mutations caused female infertility, whereas male fertility was not affected. BmNap mutants grew and mated normally; however, female mutants laid smaller eggs that could not be fertilised and did not hatch. In addition, female sterility produced by the mutation could be inherited stably via male mutants; therefore, Nap could be used as a potential target for lepidopteran pest control through population regulation. In the current study, we elucidated a new function of BmNap, increased the understanding of the oogenesis regulation network in Lepidoptera and promoted the development of insect sterility technologies.

Gut microbiota modulating intestinal stem cell differentiation.

Proliferation and differentiation of intestinal stem cell (ISC) to replace damaged gut mucosal epithelial cells in inflammatory states is a critical step in ameliorating gut inflammation. However, when this disordered proliferation continues, it induces the ISC to enter a cancerous state. The gut microbiota on the free surface of the gut mucosal barrier is able to interact with ISC on a sustained basis. Microbiota metabolites are able to regulate the proliferation of gut stem and progenitor cells through transcription factors, while in steady state, differentiated colonocytes are able to break down such metabolites, thereby protecting stem cells at the gut crypt. In the future, the gut flora and its metabolites mediating the regulation of ISC differentiation will be a potential treatment for enteropathies.

Antibacterial activity and mechanism of chelerythrine against Streptococcus agalactiae.

Streptococcus agalactiae (S.agalactiae), also known as group B Streptococcus (GBS), is a highly infectious pathogen. Prolonged antibiotic usage leads to significant issues of antibiotic residue and resistance. Chelerythrine (CHE) is a naturally occurring benzophenidine alkaloid and chelerythrine chloride (CHEC) is its hydrochloride form with diverse biological and pharmacological activities. However, the antibacterial mechanism of CHEC against GBS remains unclear. Thus, this study aims to investigate the in vitro antibacterial activity of CHEC on GBS and elucidate its underlying mechanism. The antibacterial effect of CHEC on GBS was assessed using inhibitory zone, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) assays, as well as by constructing a time-kill curve. The antibacterial mechanism of CHEC was investigated through techniques such as scanning electron microscopy (SEM) and transmission electron microscopy (TEM), measurement of alkaline phosphatase (AKP) activity, determination of Na+ K+, Ca2+ Mg2+-adenosine triphosphate (ATP) activity, observation of membrane permeability, and analysis of intracellular reactive oxygen species (ROS) and mRNA expression levels of key virulence genes. The results demonstrated that the inhibition zone diameters of CHEC against GBS were 14.32 mm, 12.67 mm, and 10.76 mm at concentrations of 2 mg/mL, 1 mg/mL, and 0.5 mg/mL, respectively. The MIC and MBC values were determined as 256 µg/mL and 512 µg/mL correspondingly. In the time-kill curve, 8 × MIC, 4 × MIC and 2 × MIC CHEC could completely kill GBS within 24 h. SEM and TEM analyses revealed significant morphological alterations in GBS cells treated with CHEC including shrinkage, collapse, and leakage of cellular fluids. Furthermore, the antibacterial mechanism underlying CHEC's efficacy against GBS was attributed to its disruption of cell wall integrity as well as membrane permeability resulting in extracellular release of intracellular ATP, AKP, Na+ K+, Ca2+ Mg2+. Additionally CHEC could increase the ROS production leading to oxidative damage and downregulating mRNA expression levels of key virulence genes in GBS cells. In conclusion, CHEC holds potential as an antimicrobial agent against GBS and further investigations are necessary to elucidate additional molecular mechanisms.

Adipose stem cell­derived exosomes promote high glucose-induced wound healing by regulating the TRIM32/STING axis.

Refractory diabetic wounds are still a clinical challenge that can cause persistent inflammation and delayed healing. Exosomes of adipose stem cells (ADSC-exos) are the potential strategy for wound repair; however, underlying mechanisms remain mysterious. In this study, we isolated ADSC-exos and identified their characterization. High glucose (HG) stimulated human umbilical vein endothelial cells (HUVECs) to establish in vitro model. The biological behaviors were analyzed by Transwell, wound healing, and tube formation assays. The underlying mechanisms were analyzed using quantitative real-time PCR, co-immunoprecipitation (Co-IP), IP, and western blot. The results showed that ADSC-exos promoted HG-inhibited cell migration and angiogenesis. In addition, ADSC-exos increased the levels of TRIM32 in HG-treated HUVECs, which promoted the ubiquitination of STING and downregulated STING protein levels. Rescue experiments affirmed that ADSC-exos promoted migration and angiogenesis of HG-treated HUVECs by regulating the TRIM32/STING axis. In conclusion, ADSC-exos increased the levels of TRIM32, which interacted with STING and promoted its ubiquitination, downregulating STING levels, thus promoting migration and angiogenesis of HG-treated HUVECs. The findings suggested that ADSC-exos could promote diabetic wound healing and demonstrated a new mechanism of ADSC-exos.

First Report of Colletotrichum aenigma Causing Anthracnose on Dragon Fruit in Korea.

Dragon fruit (Selenicereus undatus) is a valuable fruit crop in tropical and subtropical regions. It is renowned for its nutritional benefits, such as high sodium, potassium, and vitamin levels, and as a source of prebiotics and antioxidants (Balendres et al. 2019). In July 2023, anthracnose symptoms on stems were detected on dragon fruit plants in Jeju, South Korea. The typical anthracnose symptoms, such as sunken necrotic lesions (5-20 mm in diameter), were seen on the mature stems. The disease incidence ranged from 10% to 12% among the three surveyed greenhouses. To isolate the causative organism, infected stem samples were surface sterilized, cut into small pieces, and placed on potato dextrose agar (PDA). After two days of incubation at 24ºC, white hyphae appeared on the PDA around the plant tissues. Isolates CNU H23009 and CNU H23010 were purified from a single hypha under a stereoscope (e-Xtra Figure 1). Conidial morphology was examined from two-day-old fungal cultures grown on V8 juice agar. The conidia were transparent, aseptate, cylindrical to clavate, with a rounded apex and base, and measured 11.9 - 16.85 × 5.17 - 6.91 µm (mean = 15.28 × 5.93 µm, n = 30). No appressoria was observed. Morphological characteristics indicated the isolates were Colletotrichum sp. matching the description of the C. gloeosporioides species complex (Weir et al. 2012). To further identify the isolates, genomic DNA was extracted and the ribosomal internal transcribed spacer (ITS) region, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and actin (ACT) were amplified using ITS1/ITS4, GDF/GDR, and ACT-512F/ACT-783R, respectively (Weir et al. 2012). Based on phylogenetic analysis, the isolates clustered with C. aenigma (strains ICMP18608, ICMP18686, CSH2, and QSG1), with 71% bootstrap support, as determined using the maximum parsimony method in PAUP 4.0 (e-Xtra Figure 2). Based on morphological and molecular characteristics, isolates were identified as C. aenigma. Sequences of CNU H23009 and CNU H23010 were deposited in GenBank with accession numbers OR535144 and OR535145 for ITS, OR540725 and OR540726 for GAPDH, and OR540723 and OR540724 for ACT. The pathogenicity was tested on healthy dragon fruit stems using wound inoculation with mycelial plugs of the CNU H23009 isolate. Controls were inoculated with PDA plugs. The plants were covered with plastic bags to maintain humidity and incubated in a greenhouse at 25ºC. After two days, necrotic spots had developed on the inoculated tissues; after four days, black, irregular, and sunken necrotic lesions similar to those seen in the field were observed. No symptoms occurred in the controls. C. aenigma was re-isolated from the artificially inoculated plants and re-identified based on conidial morphology. The pathogenicity test was repeated three times with three replications for each treatment. Previous studies have reported that C. aenigma, C. gloeosoporioides, C. siamense, C. truncatum, and C. karsti cause anthracnose in dragon fruit. However, C. aenigma has been reported only in Thailand (Balendres et al. 2019; Meetum et al. 2015). To our knowledge, this is the first report of C. aenigma causing anthracnose in dragon fruit in Korea.

Unveiling fenpropathrin resistance levels in field populations of Tetranychus cinnabarinus (Boisduval): Insights, risks, and RNAi strategy.

Indoor cases of Tetranychus cinnabarinus displaying resistance have been documented, but the resistance level in field populations remains unexplored in China. This study delves into the resistance dynamics of T. cinnabarinus to fenpropathrin in various field populations across China, a pressing concern in contemporary agricultural pest control. The conventional bioassay and amplicon sequencing reveal a notable absence of significant fenpropathrin resistance in field populations, contrasting with known resistance in indoor cases. Current study highlights the limitations of traditional bioassays in detecting early-stage resistance and underscores the nuanced capabilities and constraints of amplicon sequencing in resistance gene frequency analysis. By employing an integrated approach, we combined dose-response bioassays, amplicon sequencing, and statistical modeling to assess resistance levels and investigate underlying genetic factors. The model with empirical data indicates that a 5% mutation frequency represents the threshold before resistance emerges. However, the detection of the kdr mutation in certain populations ranging from 0 to 1.2%, signals an early looming threat of future resistance emergence. Additionally, we further assessed a specific dsRNA targeting VGSC genes at two concentrations (10 ng/µL and 100 ng/µL), both inducing substantial mortality by silencing target genes effectively. The exploration of RNA interference (RNAi) as a novel, more environmentally friendly pest control measure opens new avenues, despite the ongoing challenge of resistance evolution. Overall, this study underscores the necessity for evolving pest management strategies, integrating advanced biotechnological approaches with traditional methods, to effectively counter pesticide resistance and ensure sustainable agricultural productivity.

Shared genetic basis connects smoking behaviors and bone health: Insights from a genome-wide cross-trait analysis.

Although the negative association of tobacco smoking with osteoporosis is well-documented, little is known regarding the shared genetic basis underlying these conditions. In this study, we aim to investigate a shared genetic architecture between smoking and heel estimated bone mineral density (eBMD), a reliable proxy for osteoporosis. We conducted a comprehensive genome-wide cross-trait analysis to identify genetic correlation, pleiotropic loci and causal relationship of smoking with eBMD, leveraging summary statistics of the hitherto largest genome-wide association studies conducted in European ancestry for smoking initiation (Nsmoker = 1 175 108, Nnonsmoker = 1 493 921), heaviness (cigarettes per day, N = 618 489), cessation (Ncurrent smoker = 304 244, Nformer smoker = 843 028), and eBMD (N = 426 824). A significant negative global genetic correlation was found for smoking cessation and eBMD (${r}_g$ = -0.051, P = 0.01), while we failed to identify a significant global genetic correlation of smoking initiation or heaviness with eBMD. Partitioning the whole genome into independent blocks, we observed six significant shared local signals for smoking and eBMD, with 22q13.1 showing the strongest regional genetic correlation. Such a genetic overlap was further supported by 71 pleiotropic loci identified in the cross-trait meta-analysis. Mendelian randomization identified no causal effect of smoking initiation (beta = -0.003 g/cm2, 95%CI = -0.033-0.027) or heaviness (beta = -0.017 g/cm2, 95%CI = -0.072-0.038) on eBMD, but a putative causal effect of genetic predisposition to being a current smoker was associated with a lower eBMD compared to former smokers (beta = -0.100 g/cm2, 95%CI = -0.181- - 0.018). Our study demonstrates a pronounced biological pleiotropy as well as a putative causal link between current smoking status and eBMD, providing novel insights into the primary prevention and modifiable intervention of osteoporosis by advocating individuals to avoid, reduce or quit smoking as early as possible.

We conducted a comprehensive genome-wide cross-trait analysis to investigate the shared genetic basis and causal relationship underlying smoking and osteoporosis. Our findings revealed that smoking and eBMD are inherently linked through biological pleiotropy. Importantly, our study discovered that quitting smoking significantly reduced the risk of lower eBMD. We recommend individuals to avoid, reduce, or quit smoking as early as possible to protect bone health.

Retinitis pigmentosa with iris coloboma due to miR-204 gene variant in a Chinese family.

PURPOSE: To characterize the phenotype and genotype of a Chinese family with autosomal-dominant retinitis pigmentosa (RP) accompanied by iris coloboma. METHODS: The proband, a 34-year-old male, was examined with his family by using fundus photography, optical coherence tomography (OCT), autofluorescence, and full-field electroretinography (ffERG). Genetic analyses were conducted through whole-exome sequencing (WES) to screen for variations. RESULTS: Three members of this Chinese family were shown to be bilateral iris coloboma. The male proband and his mother exhibited typical RP feature. The proband's late grandfather had been documented manifestation of iris coloboma. The mode of inheritance was confirmed to be autosomal dominance. Through linkage analysis and WES, a heterozygous variation in the miR-204 gene (n.37C>T), a noncoding RNA gene, was identified in these three members. CONCLUSIONS: In this third independent and the first Asian family, the existence of a miR-204 variant associated with RP accompanied by iris coloboma was confirmed. Our findings reinforce the significance of miR-204 as an important factor influencing visual function in the retina. When phenotypes like RP accompanied by iris coloboma in an autosomal-dominant pattern, including in Chinese patients, miR-204 aberrations should be considered.

Performance of preimplantation genetic testing for aneuploidy for patients with unexplained recurrent pregnancy loss and repeated implantation failure.

Objective: The primary objective was to investigate whether the utilization of next-generation sequencing (NGS) for preimplantation genetic testing for aneuploidy (PGT-A) could enhance the reproductive outcomes in patients with unexplained recurrent pregnancy loss (uRPL) or unexplained repeated implantation failure (uRIF) undergoing intracytoplasmic sperm injection (ICSI) cycles. Materials and methods: We studied the reproductive outcomes of uRPL or uRIF sufferers in Chengdu women and children's central hospital from July 2020 to Jan 2024 retrospectively. These patients were categorized into two groups based on whether they underwent PGT-A or not. As the patients in the PGT-A group all had ICSI and frozen-thawed embryo transfer (FET), only patients who underwent ICSI and FET were included in the non-PGT-A group for comparison. Demographic characteristics and reproductive outcomes were compared in uRPL or uRIF sufferers. Results: For uRPL group, a significant increased ongoing pregnancy rate (63.6 % vs 26.1 %, p = 0.002) and reduced pregnancy loss rate (18.4 % vs 73.3 %, p < 0.001) were found in the PGT-A group in comparison with those in the non-PGT-A group. For uRIF group, no significant difference was noted in the HCG-positive rate, ongoing pregnancy rate, or pregnancy loss rate between the two groups. It is noteworthy that the maternal age in the PGT-A group was significantly higher than that in the non-PGT-A group (p = 0.048). Conclusions: NGS-based PGT-A effectively optimized the reproductive outcomes in uRPL sufferers. Although its benefits in uRIF appeared to be limited, there is a potential advantage for those with advanced maternal age. Considering the small sample size, further randomized controlled trials are warranted to validate these findings.

Risk factors for the recurrence of left atrioventricular valvular regurgitation after surgical repair of partial and transitional atrioventricular septal defect.

Background: Left atrioventricular valvular regurgitation (LAVVR) recurrence after partial and transitional atrioventricular septal defect (AVSD) repair is the main risk factor associated with reoperation or mortality. The purpose of this study was to identify risk factors associated with the recurrence of LAVVR after surgical repair of transitional and partial AVSD at a single institution. Methods: A hundred and fifty-seven patients who underwent anatomical repair for partial and transitional AVSD from January 2013 to December 2021 were included in our institutional database. Demographic characteristics, operative information, comorbidities, complications, and outcomes were retrieved from electronic medical records. Echocardiographic evaluations included cardiac dimensions, the degree of LAVVR, and the anatomy of the atrioventricular valve. Results: After a median follow-up period of 5.8 years, 40 patients had recurrent moderate or even more severe LAVVR. Compared with patients without recurrent LAVVR, those experiencing LAVVR recurrence were more likely to have larger preoperative left atrial (LA) size and larger left ventricular (LV) size after standardization, larger left atrioventricular valve (LAVV) cleft width, higher proportions of preoperative moderate or even more severe LAVVR, and immediately postoperative mild to moderate or even more severe LAVVR. Univariate Cox regression analysis showed that age at first repair, height, LA size after standardization, LV size after standardization, the severity of preoperative LAVVR, immediately postoperative LAVVR, and the LAVV cleft width more than 1cm were risk factors for recurrent LAVVR (P<0.05 for all). Multivariable Cox regression analysis showed that mild to moderate or even more severe LAVVR postoperatively [hazard ratio (HR) 9.53, 95% confidence interval (CI): 3.78-24.01; P<0.001], the width of LAVV cleft more than 1 cm (HR: 3.90, 95% CI: 1.80-8.48; P<0.001) and age at first repair (HR: 0.45, 95% CI: 0.31-0.66; P<0.001) were independently associated with the recurrence of LAVVR. Conclusions: The width of LAVV cleft, mild to moderate or even more severe LAVVR immediately after surgery, and age at initial surgery are risk factors for recurrent LAVVR. The presence of recurrent LAVVR necessitates proactive surveillance to facilitate timely reintervention.

Short-term effects of kinesiology taping on static and dynamic balance in healthy subjects.

Background: As a therapeutic tool, kinesiology taping (KT) has become increasingly popular for musculoskeletal injuries utilized by physiotherapists. KT has been found to have effects on facilitating muscle strength by generating a concentric pull on the fascia. However, little is known about KT in the improvement of dynamic and static balance. This study aims to explore whether KT on the quadriceps muscle has any immediate effects on static and dynamic balance. Methodology: Twenty-seven healthy individuals (13 males and 14 females, aged 22 to 29) were recruited in a crossover study with two conditions: KT and no taping. KT was applied to the quadriceps muscle for the taping group, with the control receiving no taping. Pre- and post-test measurements were taken to give an indication of the effect of the tape on balance performance. Center of Pressure Excursion (COPE) and Time to Stabilization (TTS) when landing from a hop test and Y Balance test combined score (YBTCS) were used to assess a stabilizing balance activity and a dynamic balance. The pre- and post-intervention were collected, with differences explored using repeated measures ANOVA with time and condition (tape) factor analysis. Results: We found a significant improvement (p ≤ 0.05) with a moderate to large effect size in YBTCS between KT and no taping, indicating enhanced balance performance in the KT group. However, no significant difference (p ≥ 0.05) with small to moderate effect size was found in COPE or TTS between the two conditions during landing tests, suggesting similar balance capabilities in these specific measures. Conclusion: The use of KT shows no significant immediate effect on static balance in healthy individuals when applied to the quadriceps muscles; however, it demonstrates a positive immediate effect on dynamic balance.

Hydrogen-rich water alleviates constipation by attenuating oxidative stress through the sirtuin1/nuclear factor-erythroid-2-related factor 2/heme oxygenase-1 signaling pathway.

BACKGROUND: Constipation, a highly prevalent functional gastrointestinal disorder, induces a significant burden on the quality of patients' life and is associated with substantial healthcare expenditures. Therefore, identifying efficient therapeutic modalities for constipation is of paramount importance. Oxidative stress is a pivotal contributor to colonic dysmotility and is the underlying pathology responsible for constipation symptoms. Consequently, we postulate that hydrogen therapy, an emerging and promising intervention, can serve as a safe and efficacious treatment for constipation. AIM: To determine whether hydrogen-rich water (HRW) alleviates constipation and its potential mechanism. METHODS: Constipation models were established by orally loperamide to Sprague-Dawley rats. Rats freely consumed HRW, and were recorded their 24 h total stool weight, fecal water content, and charcoal propulsion rate. Fecal samples were subjected to 16S rDNA gene sequencing. Serum non-targeted metabolomic analysis, malondialdehyde, and superoxide dismutase levels were determined. Colonic tissues were stained with hematoxylin and eosin, Alcian blue-periodic acid-Schiff, reactive oxygen species (ROS) immunofluorescence, and immunohistochemistry for cell growth factor receptor kit (c-kit), PGP 9.5, sirtuin1 (SIRT1), nuclear factor-erythroid-2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1). Quantitative real-time PCR and western blot analysis were conducted to determine the expression level of SIRT1, Nrf2 and HO-1. A rescue experiment was conducted by intraperitoneally injecting the SIRT1 inhibitor, EX527, into constipated rats. NCM460 cells were induced with H2O2 and treated with the metabolites to evaluate ROS and SIRT1 expression. RESULTS: HRW alleviated constipation symptoms by improving the total amount of stool over 24 h, fecal water content, charcoal propulsion rate, thickness of the intestinal mucus layer, c-kit expression, and the number of intestinal neurons. HRW modulated intestinal microbiota imbalance and abnormalities in serum metabolism. HRW could also reduce intestinal oxidative stress through the SIRT1/Nrf2/HO-1 signaling pathway. This regulatory effect on oxidative stress was confirmed via an intraperitoneal injection of a SIRT1 inhibitor to constipated rats. The serum metabolites, ß-leucine (ß-Leu) and traumatic acid, were also found to attenuate H2O2-induced oxidative stress in NCM460 cells by up-regulating SIRT1. CONCLUSION: HRW attenuates constipation-associated intestinal oxidative stress via SIRT1/Nrf2/HO-1 signaling pathway, modulating gut microbiota and serum metabolites. ß-Leu and traumatic acid are potential metabolites that upregulate SIRT1 expression and reduce oxidative stress.

Polyoxometalates based catalysts for carbonylation reactions: a review.

As a type of diverse and structurally adjustable metal-oxo clusters, polyoxometalates (POMs) based materials have been extensively applied as a catalysis in various valuable reactions. This review summarized recent progress in the application of POMs-based catalysts for various carbonylation reactions including (1). Carbonylation of olefins, (2). Carbonylation of formaldehyde, (3). Carbonylation of methanol or dimethyl ether, (4). Oxidative carbonylation of methane, (5). Oxidative carbonylation of phenol and (6). Reductive carbonylation of nitrobenzene. A brief perspective on POMs-based catalysts for the carbonylation reactions is proposed.

Examining HIV Testing Coverage and Factors Influencing First-Time Testing Among Men Who Have Sex With Men in Zhejiang Province, China: Cross-Sectional Study Based on a Large Internet Survey.

BACKGROUND: Men who have sex with men (MSM) constitute a significant population of patients infected with HIV. In recent years, several efforts have been made to promote HIV testing among MSM in China. OBJECTIVE: This study aimed to assess HIV testing coverage and factors associated with first-time HIV testing among MSM to provide a scientific basis for achieving the goal of diagnosing 95% of patients infected with HIV by 2030. METHODS: This cross-sectional study was conducted between July 2023 and December 2023. MSM were recruited from the "Sunshine Test," an internet platform that uses location-based services to offer free HIV testing services to MSM by visiting the WeChat official account in Zhejiang Province, China. Participants were required to complete a questionnaire on their demographic characteristics, sexual behaviors, substance use, and HIV testing history. A logistic regression model was used to analyze first-time HIV testing and its associated factors. RESULTS: A total of 7629 MSM participated in the study, with 87.1% (6647) having undergone HIV testing before and 12.9% (982) undergoing HIV testing for the first time. Multivariate logistic regression analysis revealed that first-time HIV testing was associated with younger age (adjusted odds ratio [aOR] 2.55, 95% CI 1.91-3.42), lower education (aOR 1.39, 95% CI 1.03-1.88), student status (aOR 1.35, 95% CI 1.04-1.75), low income (aOR 1.55, 95% CI 1.16-2.08), insertive anal sex role (aOR 1.28, 95% CI 1.05-1.56), bisexuality (aOR 1.69, 95% CI 1.40-2.03), fewer sex partners (aOR 1.44, 95% CI 1.13-1.83), use of rush poppers (aOR 2.06, 95% CI 1.70-2.49), unknown HIV status of sex partners (aOR 1.40, 95% CI 1.17-1.69), lack of awareness of HIV pre-exposure prophylaxis (aOR 1.39, 95% CI 1.03-1.88), and offline HIV testing uptake (aOR 2.08, 95% CI 1.80-2.41). CONCLUSIONS: A notable 12.9% (982/7629) of MSM had never undergone HIV testing before this large internet survey. We recommend enhancing HIV intervention and testing through internet-based platforms and gay apps to promote testing among MSM and achieve the target of diagnosing 95% of patients infected with HIV by 2030.

3-Methylpyridine: Synthesis and Applications.

3-Methylpyridine holds a pivotal role in organic chemistry as it constitutes a fundamental structure in numerous biologically active compounds. Its significance is underscored by its involvement in synthesizing vitamin B3 and developing pyridine insecticides, garnering considerable attention. Consequently, chemists have dedicated efforts to devising efficient and environmentally friendly methods for its preparation. This review systematically reviews several synthetic routes to 3-methylpyridine, alongside recent advancements, while summarizing its application progress in various organic transformations.

Expression and clinical significance of NKG2A and HLA-E in advanced laryngeal carcinoma.

OBJECTIVES: The purpose was to detected features of the expression levels of NKG2A and its ligand HLA-E, a new member of the immune checkpoints, in advanced laryngeal carcinoma and their clinicopathologic significance. MATERIAL AND METHODS: We analyzed the expression levels of HLA-E and NKG2A in multiple types of tumors utilizing the Tumor Immune Estimation Resource (TIMER) database and immunohistochemistry and qRT-PCR analysis of paraffin embedded tissue samples to reveal the correlations of the clinicopathological factors with the expression of these two proteins in advanced laryngeal carcinoma as well as their prognostic significance. RESULTS: KLRC1 (the coding gene of NKG2A) and HLA-E are substantially overexpressed in various human cancers than normal tissues. HNSCC is also included. KLRC1 is differentially expressed in different HPV subgroups of patients, with higher expression in the HPV-positive group. Consistent with this, immunohistochemical results also revealed the high expression of these two proteins in tumor tissue. In addition, immunohistochemical staining also displayed a preference for the distribution of NKG2A-positive cells in tumor tissue. Clinicopathological analyses also displayed that the density of NKG2A-positive cells of the HPV-positive group infiltrating laryngeal carcinoma tissue was larger than that in the HPV-negative group. Prognostic analyses indicated that the expression of this immune checkpoint does not affect the overall survival length of patients, but the highly expressed HLA-E is significantly correlated with local recurrence in the patients. CONCLUSIONS: The findings suggest that the expression levels of HLA-E and NKG2A is upregulated in advanced laryngeal carcinoma. The NKG2A-positive cells infiltrating the tumor are mainly distributed in the cancer nest, while infiltrating cell number may be regulated by HPV. The highly expressed HLA-E may promote local recurrence in patients with advanced laryngeal carcinoma.

Functional analysis of SDR112C1 associated with fenpropathrin tolerance in Tetranychus cinnabarinus (Boisduval).

Short-chain dehydrogenases/reductases (SDRs) are ubiquitously distributed across diverse organisms and play pivotal roles in the growth, as well as endogenous and exogenous metabolism of various substances, including drugs. The expression levels of SDR genes are reportedly upregulated in the fenpropathrin (FEN)-resistant (FeR) strain of Tetranychus cinnabarinus. However, the functions of these SDR genes in acaricide tolerance remain elusive. In this study, the activity of SDRs was found to be significantly higher (2.26-fold) in the FeR strain compared to the susceptible strain (SS) of T. cinnabarinus. A specific upregulated SDR gene, named SDR112C1, exhibited significant overexpression (3.13-fold) in the FeR population compared with that in the SS population. Furthermore, the expression of SDR112C1 showed a significant increase in the response to FEN induction. Additionally, knockdown of the SDR112C1 gene resulted in decreased SDR activity and reduced mite viability against FEN. Importantly, heterologous expression and in vitro incubation assays confirmed that recombinant SDR112C1 could effectively deplete FEN. Moreover, the overexpression of the SDR112C1 gene in Drosophila melanogaster significantly decreased the toxicity of FEN to transgenic fruit flies. These findings suggest that the overexpression of SDR SDR112C1 is a crucial factor contributing to FEN tolerance in T. cinnabarinus. This discovery not only enhances our understanding of SDR-mediated acaricide tolerance but also introduces a new family of detoxification enzymes to consider in practice, beyond cytochrome P450s, carboxyl/choline esterases and glutathione S-transferases.

The performance of a post-induction fentanyl-test in predicting postoperative respiratory adverse events in children after adenotonsillectomy.

STUDY OBJECTIVES: Postoperative respiratory adverse events (PRAE) occurred more frequently in children having adenotonsillectomy than the general surgical population, and can require escalation of care. This study aims to assess the usefulness of post-induction fentanyl-test to predict PRAE in children with obstructive sleep apnea (OSA) after adenotonsillectomy. METHODS: Two hundred and forty patients with OSA undergoing adenotonsillectomy were included in this study. The oxygen saturation during sleep was monitored the night before adenotonsillectomy. Fentanyl-test was conducted under spontaneous breath after anesthesia induction with sevoflurane. Fentanyl-induced reduction in respiratory rate (FRR) was defined as the percentage of reduction in respiratory rate after 1 mcg/kg fentanyl administration. PRAE in the post-anesthesia care unit (PACU) included both respiratory complications and medical interventions. Receiver operating characteristic (ROC) analysis was used to assess the usefulness of fentanyl-test in predicting PRAE. RESULTS: Of the 240 children undergoing elective adenotonsillectomy, 38 children (16%) experienced PRAE in PACU. The areas under ROC curve for FRR and Nadir SpO2 were 0.756 and 0.692, respectively. FRR greater than 53% best predicted PRAE in PACU, with a sensitivity of 68% and a specificity of 72%. Patients with FRR > 53% exhibited a significantly longer duration of desaturation requiring supplementary oxygen than those with FRR ≦ 53% (p < 0.001). CONCLUSIONS: We suggest that post-induction fentanyl-test is a feasible evaluation for children undergoing adenotonsillectomy to predict early PRAE, especially for those who have not undergone polysomnography. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Effects of Individualized Opioid Analgesia Versus Conventional Opioid Analgesia After Adenotonsillectomy in Children; URL: https://clinicaltrials.gov/study/NCT04527393; Identifier: NCT04527393.

The Contribution of Mosaic Chromosomal Alterations to Schizophrenia.

BACKGROUND: Mosaic chromosomal alterations (mCAs) are implicated in neuropsychiatric disorders, yet the contribution to schizophrenia (SCZ) risk for somatic copy number variations (sCNVs) emerging in early developmental stages is not fully established. METHODS: We analyzed blood-derived genotype arrays from 9,715 SCZ patients and 28,822 controls of Chinese descent using a computational tool (MoChA) based on long-range chromosomal information to detect mCAs. We focused on probable early developmental sCNVs through stringent filtering. We assessed the sCNVs' burden across varying cell fraction (CF) cutoffs, as well as the frequency with which genes were involved in sCNVs. We integrated this data with the Psychiatric Genomics Consortium (PGC) dataset, which comprises 12,834 SCZ cases and 11,648 controls of European descent, and complemented it with genotyping data from postmortem brain tissue of 936 subjects (449 cases and 487 controls). RESULTS: Patients with SCZ had a significantly higher somatic losses detection rate than control subjects (1.00% vs 0.52%; odds ratio (OR) = 1.91; 95% CI, 1.47-2.49; two-sided Fisher's exact test, p=1.49×10-6). Further analysis indicated that the ORs escalated proportionately (from 1.91 to 2.78) with the increment in CF cutoffs. Recurrent sCNVs associated with SCZ (OR>8; Fisher's exact test, p<0.05) were identified, including notable regions at 10q21.1 (ZWINT), 3q26.1 (SLITRK3), 1q31.1 (BRINP3) and 12q21.31-21.32 (MGAT4C and NTS) in the Chinese cohort, some regions validated with PGC data. Cross-tissue validation pinpointed somatic losses at loci like 1p35.3-35.2 and 19p13.3-13.2. CONCLUSIONS: The study highlights mCAs' significant impact on SCZ, suggesting their pivotal role in the disorder's genetic etiology.