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Heterosexuals have become the most prevalent group of HIV-1 in Kunming, Yunnan Province. Utilizing the principle of genetic similarity between their gene sequences, we built a molecular transmission network by gathering data from earlier molecular epidemiological studies. This allowed us to analyze the epidemiological features of this group and offer fresh concepts and approaches for the prevention and management of HIV-1 epidemics. Cytoscope was used to visualize and characterize the network following the processing of the sample gene sequences by BioEdit and HyPhy. The number of possible links and the size of the clusters were investigated as influencing factors using a zero-inflated Poisson model and a logistic regression model, respectively. A scikit-learn-based prediction model was developed to account for the dynamic changes in the HIV-1 molecular network. Six noteworthy modular clusters with network scores ranging from 4 to 9 were found from 150 clusters using Molecular Complex Detection analysis at a standard genetic distance threshold of 0.01. The size of the number of possible links and the network's clustering rate were significantly impacted by sampling time, marital status, and CD4+ T lymphocytes (all p < 0.05). The gradient boosting machine (GBM) model had the highest area under the curve value, 0.884 ± 0.051, according to scikit-learn. Though not all cluster subtypes grew equally, the network clusters were relatively specific and aggregated. The largest local transmission-risk group for HIV-1CRF08_BC is now the heterosexual transmission population. The most suitable model for constructing the HIV-1 molecular network dynamics prediction model was found to be the GBM model. [ABSTRACT FROM AUTHOR]

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease globally, with only one Food and Drug Administration (FDA)-approved drug for its treatment. Given MASLD's complex pathophysiology, therapies that simultaneously target multiple pathways are highly desirable. One promising approach is dual-modulation of the farnesoid X receptor (FXR), which regulates lipid and bile acid metabolism. However, FXR agonists alone are insufficient due to their limited anti-inflammatory effects. This study aimed to dto identify natural products capable of both FXR activation and inflammation inhibition to provide a comprehensive therapeutic approach for MASLD. Potential FXR ligands from the Natural Product Library were predicted via virtual screening using the Protein Preparation Wizard module in Schrodinger (2018) for molecular docking. Direct binding and regulation of candidate compounds on FXR were analyzed using surface plasmon resonance (SPR) binding assay, reporter gene analysis, and reverse transcription-polymerase chain reaction (RT-PCR). The anti-inflammatory properties of these compounds were evaluated in AML12 cells treated with tumor necrosis factor-alpha (TNF-α). Dual-function compounds with FXR agonism and inflammation inhibition were further identified in cells transfected with Fxr siRNA and treated with TNF-α. The effects of these dual-function compounds on lipid accumulation and inflammation were evaluated in cells treated with palmitic acid. Results revealed that 17 natural products were predicted via computational molecular docking as potential FXR agonists, with 15 exhibiting a strong affinity for FXR recombinant protein. Nine isoflavone compounds significantly enhanced FXR reporter luciferase activity and the mRNA expressions of Shp and Ostb. Structure-activity relationship analysis indicated that introducing isopropyl or methoxy groups at the C7 position or a methoxy group at the C6 position could enhance the agonistic efficacy of isoflavones. Three compounds (2 , 6 , and 8) were identified as dual-function natural products functioning as FXR agonists and inflammatory inhibitors, while one compound (12) acted as an FXR agonist to inhibit inflammation. These natural products protected hepatocytes against palmitic acid-induced lipid accumulation and inflammation. In conclusion, compounds 2 , 6 , and 8 (genistein, biochanin A, and 7-methoxyisoflavone, respectively) were identified as dual-function bioactive products that transactivate FXR and inhibit inflammation, serving as potential candidates or lead compounds for MASLD therapy. [ABSTRACT FROM AUTHOR]

Bacterial infection reprograms cellular metabolism and epigenetic status, but how the metabolic-epigenetic crosstalk empowers host antibacterial defense remains unclear. Here, we report that heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) is a sensor for metabolite adenine to launch an antimicrobial innate response through increasing Il1b transcription. Myeloid cell-specific Hnrnpa2b1 -cKO mice are more susceptible to bacterial infection, while interleukin 1 beta (IL-1β) supplementation rescues the phenotype. Through a large-scale metabolites-hnRNPA2B1 interaction screen, we reveal that adenine directly binds and activates hnRNPA2B1 to mediate innate antibacterial response. Mechanistically, adenine directly recruits hnRNPA2B1 to Il1b enhancers, and hnRNPA2B1 increases Il1b enhancer chromatin accessibility through binding and recruiting nucleolin and fat mass and obesity-associated protein (FTO) to mediate Il1b enhancer DNA N6-methyladenosine (6mA) demethylation. Furthermore, bacterial infection elevates nuclear adenine at the early stage of infection, and in vivo adenine administration protects mice from death upon bacterial infection through the hnRNPA2B1-IL-1β circuit. Our findings offer new insights into metabolic-epigenetic crosstalk relevant to antibacterial innate immunity and indicate potential approaches for treating bacterial infections. [Display omitted] • hnRNPA2B1 is an antibacterial innate factor via enhancing Il1b transcription • hnRNPA2B1 senses metabolite adenine to launch an antibacterial innate response • hnRNPA2B1/NCL/FTO mediates Il1b enhancer DNA 6mA demethylation • Adenine supplementation is a potential antibacterial strategy Zhang et al. demonstrate that nuclear adenine enhances antibacterial innate immunity by activating hnRNPA2B1-mediated Il1b transcription through enhancer-specific DNA modification, and adenine supplementation enhances host antibacterial innate immunity. [ABSTRACT FROM AUTHOR]

The study aimed to investigate the spatial distribution patterns of passing and receiving locations during the 2022 FIFA World Cup in different match stages, playing positions and team possession types. Eighteen types of spatial entropy were proposed to evaluate the heterogeneity of passing and receiving locations in 64 matches. T-tests of these entropies were made between teams at the group and knockout stages, and between distinct playing positions. The K-means clustering of each team's ball-possession per match was employed to divide all matches into two categories, and their differences in entropies were then analysed using one-way ANOVA. Results showed that the teams at the group and knockout stages had significant differences only in goalkeeper entropy (ES = 0.368). The spatial entropy of the goalkeeper exhibited significant differences in comparison to the other positions (ES: −6.71 ~ -4.69). Low ball-possession teams were significantly lower in 8 types of spatial entropies (ES: −1.02 ~ -0.41) compared to their high ball-possession counterparts. Furthermore, only two types of spatial entropies (ES: −0.58 ~ -0.54) differed significantly in the comparison between high and low ball-possession teams. These findings may provide coaches with guidance for implementing targeted defensive strategies and enhancing the team's passing performance. [ABSTRACT FROM AUTHOR]

The aim of this study was to comprehensively evaluate the links of genetic predisposition among 13 common circulating interleukins (ILs) and endodontic diseases by using a 2-sample Mendelian randomization method. Single nucleotide polymorphisms were chosen as instrumental variables from summary data of genome-wide association studies (GWASs), using the inverse-variance–weighted method as the primary analysis. In addition, a variety of sensitivity analyses was conducted to evaluate the resilience of the primary outcomes and identify any inherent pleiotropic effects. After multiple comparison corrections, 4 circulating ILs were genetically predicted to significantly play a role in endodontic diseases. Among these, circulating IL-17 (odds ratio [OR] IVW , 1.33; 95% confidence interval [CI], 1.15–1.54; P < 3.85 × 10−3) were significantly identified as potential risk-increasing factors toward pulp and periapical diseases, and circulating IL-16 (OR IVW , 0.89; 95% CI, 0.83 to 0.94; P < 3.85 × 10−3) may exert protective effects on the development of periapical abscess. In the reverse analyses, null significantly association was found between genetic liability to endodontics disorders and the corresponding circulating inflammatory biomarkers. Overall, sensitivity analyses were consistent with the estimates direction of primary analyses results, supporting the reliability of findings. Given the unavoidable limitations presented in this study, our findings provided significant evidence to support the identification of elevated IL-16 levels as a potential risk-mitigating factor, whereas elevated IL-17 levels exhibit potentially deleterious effects on endodontic disorders. Future validation is warranted to examine the conclusions of our study and to evaluate the potential application of these circulating ILs as lifestyle or pharmacological targets for oral health care. [ABSTRACT FROM AUTHOR]

This study explores the impact of multi-scale urban morphology on solar radiation in high-density environments, focusing on Nanjing as a case study. Using Grasshopper, the research decomposed urban models into four scales—district, block group, block, and plot—and analyzed eight morphological indicators, including site coverage (SC), floor area ratio (FAR), and block surface ratio (BSR). Solar radiation was simulated for the entire year, the summer solstice, and the winter solstice. Key findings reveal that different scales exhibit varying influences on solar radiation. At the district scale, BSR shows the highest correlation with annual solar radiation (R 2 = 0.96), while at the neighborhood cluster scale, the minimum distance between buildings (DBmin) is most correlated (R 2 = 0.7). At the block scale, BSR significantly correlates with summer solar radiation (R 2 = 0.55). At the plot scale, no single indicator strongly correlates with solar radiation, but a combination of indicators is more relevant. These findings enable rapid solar performance assessments in urban design, promoting efficient solar energy use. [ABSTRACT FROM AUTHOR]

[Display omitted] • Early-life tobacco smoke exposure elevated osteoporosis (OP) in adulthood. • Early-life tobacco smoke exposure had joint effects with genetic risk on OP. • High genetic risk subjects with early-life smoke exposure had the highest OP risk. • Telomere length mediate early-life tobacco exposure and OP association. • Reducing smoking in early life might be an measure to curb the OP epidemic. The growing prevalence of osteoporosis (OP) in an aging global population presents a significant public health concern. Tobacco smoke negatively affects bone turnover, leading to reduced bone mass and heightened OP and fracture risk. However, the impact of early-life tobacco smoke exposure on later-life OP risk remains unclear. This study was to explore the effects of early-life tobacco smoke exposure on incident OP risk in later life. The mediating role of telomere length (TL) and the interaction with genetic predisposition were also studied. Data on in utero tobacco smoke exposure (IUTSE) status and age of tobacco use initiation from the UK Biobank were used to estimate early-life tobacco smoke exposure. Incident OP cases were identified according to health-related records. Linear, Cox, and Laplace regression models were mainly used for data analysis. Individuals with IUTSE showed a higher OP risk [hazard ratio (HR): 1.06, 95 % confidence interval (CI): 1.01, 1.11] and experienced earlier OP onset by 0.30 years [50th percentile difference = -0.30, 95 % CI: −0.51, −0.09] compared to those without. Participants initiating tobacco smoke in childhood, adolescence, and adulthood had 1.41 times (95 % CI: 1.23, 1.61), 1.17 times (95 % CI:1.10, 1.24), and 1.14 times (95 % CI: 1.07, 1.20) the risk of OP, respectively, compared to never smokers. They also experienced earlier OP onset by 2.16, 0.95, and 0.71 years, sequentially. The TL significantly mediated the early-life tobacco exposure and OP association. Significant joint and interactive effects were detected between early-life tobacco smoke exposure and genetic elements. Our findings implicate that early-life tobacco smoke exposure elevates the later-life OP risk, mediated by telomere length and interplayed with genetic predisposition. These findings highlight the importance of early-life intervention against tobacco smoke exposure and ageing status for precise OP prevention, especially in individuals with a high genetic risk. [ABSTRACT FROM AUTHOR]

Limited evidence exists regarding the efficacy of preoperative exercise in reducing short-term complications after minimally invasive surgery in patients with non–small cell lung cancer. This study aims to investigate the impact of preoperative exercise on short-term complications after minimally invasive lung resection. In this prospective, open-label, randomized (1:1) controlled trial at Xiangya Hospital, China (September 2020 to February 2022), patients were randomly assigned to a preoperative exercise group with 16-day alternate supervised exercise or a control group. The primary outcome assessed was short-term postoperative complications, with a follow-up period of 30 days postsurgery. A total of 124 patients were recruited (preoperative exercise group n = 62; control n = 62). Finally, 101 patients (preoperative exercise group; n = 51 and control; n = 50) with a median age of 56 years (interquartile range, 50-62 years) completed the study. Compared with the control group, the preoperative exercise group showed fewer postoperative complications (preoperative exercise 3/51 vs control 10/50; odds ratio, 0.17; 95% CI, 0.04-0.86; P =.03) and shorter hospital stays (mean difference, −2; 95% CI, −3 to −1; P =.01). Preoperative exercise significantly improved depression, stress, functional capacity, and quality of life (all P <.05) before surgery. Furthermore, preoperative exercise demonstrated a significantly lower minimum blood pressure during surgery and lower increases in body temperature on day 2 after surgery, neutrophil-to-lymphocyte ratio, and neutrophil count after surgery (all P <.05). Exploratory research on lung tissue RNA sequencing (5 in each group) showed downregulation of the tumor necrosis factor signaling pathway in the preoperative exercise group compared with the control group. Preoperative exercise training decreased short-term postoperative complications in patients with non–small cell lung cancer. [Display omitted] [ABSTRACT FROM AUTHOR]

There remains a progressive projected deficit in the vascular surgery (VS) workforce for decades. Despite the expanding integrated VS residency pathway, the fellowship training model remains critical in supporting our future workforce. Therefore, it is imperative to understand the resident and program-specific factors that influence VS specialization among general surgery (GS) residents. Data from the United States Resident OPerative Experience (ROPE) Consortium, which comprises 20 Accreditation Council for Graduate Medical Education-accredited GS residency programs across the United States, were queried for resident demographics and residency program-related details. Logistic regression analysis was used to identify factors associated with VS specialization. From 2010 to 2020, a total of 1343 graduating GS residents were included in the study. Of these, 135 (10.1%) pursued VS fellowship training. Residents pursuing VS were more frequently male (80.7% vs 62.8%; P <.0001) and younger (median age, 32 vs 33 years; P =.03) compared with other GS residents. Racial and ethnic group, underrepresented in medicine status, and international medical graduate status were similar between the VS and non-VS groups. Residency program-level details were also similar between groups, including program type (university vs community-based), region, size, resident volume, dedicated research experience, and National Institutes of Health funding. Dedicated vascular rotations were common among all GS programs (95.4%), and total months spent on a VS rotation (median, 4 vs 4.5 months; P =.11) did not differ among residents pursuing VS and all other residents. The presence of a collocated traditional (5 + 2) VS fellowship (91.1% vs 90.4%; P =.79) or integrated (0 + 5) VS residency (56.3% vs 55.0%; P =.77) were also similar between groups. On multivariate analysis, only male sex (odds ratio, 2.34; 95% confidence interval, 1.50-3.81; P <.001) was associated with pursuing VS fellowship. Factors that did not impact VS specialization included resident age, underrepresented in medicine status, international medical graduate status, program volume, dedicated research experience, or total months spent on a VS rotation. In this multi-institutional study, we did not find any program-specific factors that influence VS specialization among GS residents. Notably, the presence of a collocated 0 + 5 residency or 5 + 2 fellowship program did not appear to deter GS residents from pursuing a VS fellowship. These data suggest that individual factors, such as mentorship, may be more impactful in recruiting GS residents to the VS specialty. [ABSTRACT FROM AUTHOR]

The best management of symptomatic chronic internal carotid artery occlusion (CICAO) has been controversial. This systematic review and meta-analysis were to compare the outcomes of different treatment strategies for symptomatic CICAO. Two independent researchers conducted a search of articles on the treatment of CICAO published between January 2000 and October 2023 in PubMed, Web of Science, Embase, and The Cochrane Library. Twenty-two articles were eligible for meta-analysis using a random effects model to combine and analyze the data for the pooled rates of stroke and death, and the rates of procedural success and significant restenosis/occlusion. A total of 1193 patients from 22 publications were included in this study. Six of them had bilateral internal carotid artery occlusion. The 30-day stroke and death rates were 1.1% (95% confidence interval [CI], 0%-4.4%) in the best medical treatment (BMT) group, 4.1% (95% CI, 0.7%-9.3%; I2 = 71.4%) in the extracranial-intracranial (EC-IC) bypass group, 4.4% (95% CI, 2.4%-6.8%; I2 = 0%) in the carotid artery stenting (CAS) group, and 1.2% (95% CI, 0%-3.4%; I2 = 0%) in the combined carotid endarterectomy (CEA) and stenting (CEA + CAS) group. During follow-up of 16.5 (±16.3) months, the stroke and death rates were 19.5%, 1.2%, 6.6%, and 2.4% in the BMT, EC-IC, CAS, and CEA + CAS groups respectively. The surgical success rate was 99.7% (95% CI, 98.5%-100%; I2 = 0%) in the EC-IC group, 70.1% (95% CI, 62.3%-77.5%; I2 = 64%) in the CAS group, and 86.4% (95% CI, 78.8%-92.7%; I2 = 60%) in the CEA + CAS group. The rate of post-procedural significant restenosis or occlusion was 3.6% in the EC-IC group, 18.7% in the CAS group, and 5.7% in the CEA + CSA group. The surgical success rate was negatively associated by the length of internal carotid artery (ICA) occlusion. Surgical success rate was significantly higher in the patients with occlusive lesion within C1 to C4 segments, compared with those with occlusion distal to C4 segment (odds ratio, 11.3; 95% CI, 5.0-25.53; P <.001). A proximal stump of ICA is a favorable sign for CAS. The success rate of CAS was significantly higher in the patients with an ICA stump than that in the patients without (odds ratio, 11.36; 95% CI, 4.84-26.64; P <.01). However, the success rate of CEA + CAS was not affected by the proximal ICA stump. For the management of symptomatic CICAO, BMT alone is associated with the highest risk of mid- and long-term stroke and death. EC-IC bypass surgery and CEA + CAS should be considered as the choice of treatment based on operator's expertise and patient's anatomy. CAS may be employed as an alternative option in high surgical risk patients, especially when proximal ICA stump exists. [ABSTRACT FROM AUTHOR]

The contact area between the turning tool and the chip (workpiece) experiences friction, normal composite forces, and high temperatures under severe working conditions. Optimizing the tool geometry at the contact point with the chip is crucial for enhancing the comprehensive cutting performance of the turning tool. This study proposes a tool segmentation optimization design method within a hybrid optimization framework. Initially, a three-segment parametric geometric model of the tool, comprising the rake face shape, transition zone length, and tool edge radius, is constructed. Subsequently, a two-dimensional cutting simulation model based on thermal-mechanical coupling is developed. Utilizing Python, the model inputs and data response outputs from the ABAQUS cutting simulation process are redeveloped to facilitate direct, automatic iterative optimization of the tool structure using a genetic algorithm. The study explores the impact of varying cutting thicknesses on the optimal rake face shape, revealing that increased feed rates expand the optimization potential for minimizing cutting forces. The methodology was applied to the design of a cemented carbide turning tool for H13 steel, and comprehensive cutting performance tests were conducted. The findings indicate that the optimized tool significantly reduces temperatures and strain in the shear and friction zones, diminishes plastic deformation of the chip, and cuts the cutting force by approximately 8 %. Additionally, it lowers the adhesion of workpiece material on the rake face, reduces the contact area between the tool and the chip, and improves the workpiece's surface finish. The proposed method can provide a new automatic optimization design framework for the effective upgrading of the turning tool structure of traditional difficult-to-cut materials and the efficient development of the turning tool structure of new materials. [Display omitted] • The segmented design concept of cutting tool is put forward. • The optimal rake face surface structure has good potential in reducing cutting force. • There are significant differences in the optimal shape of the tool rake face under different tool-chip contact lengths. • The optimal tool reduces the cutting force, chip plastic deformation, tool-chip contact wear area and chip adhesion. • It can quickly design the effective shape of the tool with wide applicability for specific workpiece materials. [ABSTRACT FROM AUTHOR]

[Display omitted] • Lithium-rich strata with hydrothermal overprinting found in Wumishan Formation. • Lithium mainly occupies octahedral sites in authigenic illite and I/S structures. • K-feldspar illitization and illite smectitization form Li-bearing clay minerals. Lithium (Li), as a strategic critical metal, plays a pivotal role in the emerging energy landscape, particularly in the context of Li-ion batteries driving the new energy economy. Recently, Li-rich strata (with Li 2 O > 0.3 wt%) have been discovered in the Mesoproterozoic Wumishan Formation in Hebei Province, North China, suggesting a prospective Li reservoir. This study investigates these Li-rich strata using geochemical and in-situ micro-analytical techniques to explore the occurrence of Li and the formation mechanism of Li-host minerals, aiming for a comprehensive understanding of the supernormal enrichment of Li. The Li-rich samples are predominantly composed of dolomite and quartz, followed by clay minerals such as illite, interstratified illite–smectite (I/S), and chlorite, with minor amounts of K-feldspar, albite, biotite, calcite, baryte, fluorite and fluorapatite. In-situ analysis and 7Li NMR spectroscopy reveal that Li predominantly occupies the octahedral sites within the structures of authigenic illite and I/S, while its absence in clastic illite, clastic chlorite, unaltered K-feldspar, and dolomite. The presence of veined minerals (e.g., fluorite, baryte, and calcite) and a strong positive correlation between Li and F imply that post-depositional hydrothermal fluids have significantly contributed to the formation of Li-host minerals. The paragenesis of these minerals suggests that Li-bearing illite has formed through the hydrothermal alteration of K-feldspar. These Li-bearing illites subsequently transformed into Li-bearing I/S, consisting of illite-rich I/S and smectite-rich I/S, under continuous hydrothermal alteration. Lithium could have been leached from the surrounding carbonate rock and tuff through water–rock interaction and subsequently enriched by post-depositional hydrothermal fluids in specific regions, leading to mineralization. These findings provide valuable insights for targeting exploration of this promising Li resource. [ABSTRACT FROM AUTHOR]

Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most harmful pathogens in the swine industry. Our previous studies demonstrated that the small extracellular domain (ECL2) of CLDN4 effectively blocks PRRSV infection. In this study, we explored the in vivo administration of swine ECL2 (sECL2) and found that it blocked HP-PRRSV infection and alleviated histopathological changes in organs. Notably, sECL2 stimulated cytokine production in the lungs. We observed that CLDN4 upregulated the expression of IFN-β at low doses of GP3. While high doses of GP3 inhibited the activity of the IFN-β promotor, regardless of whether CLDN4 was present. GP3 also downregulated IFN-β by decreasing the phosphorylation of TBK1 and IRF3. These findings highlight functional differences in GP3 under quantity control, which account for the variations in IFN-β induction during the early and late stages of infection. Our results indicate that sECL2 is a promising candidate drug for developing treatments to control PRRS. [ABSTRACT FROM AUTHOR]