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Abstract Larynx cancer poses a significant public health challenge in China, with rising incidence and mortality rates over the past decades. Understanding the long-term trends and underlying factors is crucial for effective intervention and policy formulation. Data were utilized from the global burden of disease (GBD) Study 2021 to analyze the incidence, prevalence, mortality, disability-adjusted life years (DALYs), years lived with disability (YLDs), and years of life lost (YLLs) due to larynx cancer in China from 1990 to 2021. Joinpoint regression analysis identified key changes in trends, while age-period-cohort (APC) analysis and decomposition analysis quantified the contributions of aging, epidemiological changes, and population growth to these trends. Our study found a significant increase in the incidence and prevalence of larynx cancer in China, particularly among males. The age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) for males were substantially higher than those for females. Decomposition analysis revealed that aging was the primary driver of increasing incidence and mortality rates, while epidemiological changes had a mitigating effect. Joinpoint analysis identified periods of rapid urbanization and economic growth as key turning points for increased incidence. Bayesian APC models projected a continued upward trend in incidence rates up to 2030. The rising burden of larynx cancer in China underscores the need for targeted public health interventions, including smoking cessation programs, environmental pollution control, and early detection strategies. Addressing gender disparities and implementing effective prevention measures are crucial to mitigating the impact of larynx cancer in China.

Abstract This study aimed to explore the selection of induction chemotherapy (IC) cycles for stage N3 nasopharyngeal carcinoma (NPC). We employed propensity score matching (PSM) to categorize patients into 3-cycle and 4-cycle IC groups (IC = 3 and IC = 4). The log-rank and chi-squared tests were used respectively to evaluate the differences in survival and acute toxicities. Survival outcomes including overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS) were evaluated among the two groups. After PSM, each group comprised 99 patients. The IC = 4 group exhibited markedly improved survival outcomes compared with the IC = 3 group. Multivariate analysis revealed that pre-EBV DNA was an independent risk factor affecting PFS and DMFS. For high-risk patients with pre-EBV DNA ≥ 7800 copies/ml, the IC = 4 group demonstrated greater survival compared to the IC = 3 group. Among low-risk patients with pre-EBV DNA

Abstract The rapid rise of live-streaming selling and the increasing diversity of e-commerce channels have sparked ongoing debates regarding product pricing power. This price competition behaviour of online dual channels triggered by the supply-side pricing dilemma is a topic of significant research interest and forms the focal point of this paper. Therefore, we leverage the principles of game theory to construct a three-party evolutionary game model consisting of a brand, a steamer, and a traditional e-commerce platform. Within this framework, the brand holds the primary pricing authority. Our analysis examines the equilibrium strategies adopted by the various players under diverse scenarios and explores how the evolving behaviours of these parties impact the overall game system. Additionally, we employ the “people-goods-scene” perspective to deconstruct the intricate dynamics within this complex supply chain ecosystem. Our findings reveal two distinct evolutionary stable strategies: one in which brands maintain a stance against low-price negotiation, streamers avoid bargaining, and platforms avoid providing subsidies; the other in which brands are open to negotiating low prices, streamers engage in bargaining, and platforms provide subsidies. Notably, in most cases, brands tend to avoid explicitly stating their opposition to low-price negotiation. However, if a brand’s strategy shifts towards rejecting such negotiation, the negative implications of price wars across channels become a critical consideration. Conversely, when a brand opts for a more concessive pricing strategy, we need to consider the potential positive impacts of low-price competition.

As the direct microenvironment of assisted reproductive technology, the evaluation of culture medium for human assisted reproduction technology is particularly important. This paper discussed the classification management, technical review points, clinical evaluation and review thinking, focusing on the basic requirements, raw material control, biological evaluation, sterilization process of culture medium for human assisted reproduction technology, combined with some material limit, new added material and quality system control to thoroughly assess management risk of the whole life cycle of culture medium for human assisted reproduction technology.

ObjectiveTo examine differences in HIV-related behaviors among college students who are men who have sex with men (MSM) and of different sexual orientations. MethodsA total of 682 MSM students aged ≥18 years were recruited from colleges/universities in four cities (Hangzhou, Ningbo, Jiaxing and Jinhua) in Zhejiang province through convenience sampling with the help of NGO (non-governmental organization) for a web-based on-site survey with face-to-face instructions from interviewers from March to July 2022. Participants' information on household registration, campus location, years in college, public expression of sexual identity, online casual sex, substance abuse, HIV knowledge, pre-exposure and post-exposure prophylaxis, and HIV testing were collected using a self-compiled questionnaire. SPSS 25.0 software was used for data analysis. ResultsOf the 671 valid respondents, 73.3% reported a homosexual orientation and 26.7% reported a bisexual/unsure orientation. Compared to respondents with a homosexual orientation, respondents with a bisexual/uncertain orientation reported significantly lower rates of publicly expressing their sexual identity (50.8% vs. 60.2%), receiving health education about condom use from peers (70.9% vs. 79.1%), and self-testing for HIV once or more (64. 4% vs. 76.0%), but significantly higher rates of first homosexual behavior within the past year (48.8% vs. 37.4%), being seduced or coerced into first homosexual behavior (27.4% vs. 16.5%), and using sex-stimulating rush popper during their last online casual sexual encounter (40.7% vs. 27.1%) (P < 0.05 for all). ConclusionThere are significant differences between MSM college/university students with a homosexual orientation and those with a bisexual/unsure orientation in public expression of sexual identity, timing and type of first homosexual encounter, use of rush popper and other substances, receipt of peer education about condom use, and self-testing for HIV, suggesting that targeted interventions to reduce the risk of HIV infection in this population should be strengthened.

Abstract Background Circulating atherogenic index of plasma (AIP) levels has been proposed as a novel biomarker for dyslipidemia and as a predictor of insulin resistance (IR) risk. However, the association between AIP and the incidence of new-onset stroke, particularly in individuals with varying glucose metabolism status, remains ambiguous. Methods A total of 8727 participants aged 45 years or older without a history of stroke from the China Health and Retirement Longitudinal Study (CHARLS) were included in this study. The AIP was calculated using the formula log [Triglyceride (mg/dL) / High-density lipoprotein cholesterol (mg/dL)]. Participants were divided into four groups based on their baseline AIP levels: Q1 (AIP ≤ 0.122), Q2 (0.122 0.562). The primary endpoint was the occurrence of new-onset stroke events. The Kaplan–Meier curves, multivariate Cox proportional hazard models, and Restricted cubic spline analysis were applied to explore the association between baseline AIP levels and the risk of developing a stroke among individuals with varying glycemic metabolic states. Results During an average follow-up of 8.72 years, 734 participants (8.4%) had a first stroke event. The risk for stroke increased with each increasing quartile of baseline AIP levels. Kaplan–Meier curve analysis revealed a significant difference in stroke occurrence among the AIP groups in all participants, as well as in those with prediabetes mellitus (Pre-DM) and diabetes mellitus (DM) (all P values 0.05). Restricted cubic spline analysis also demonstrated that higher baseline AIP levels were associated with higher hazard ratios for stroke in all participants and those with glucose metabolism disorders. Conclusions An increase in baseline AIP levels was significantly associated with the risk of stroke in middle-aged and elderly individuals, and exhibited distinct characteristics depending on the individual’s glucose metabolism status.

Marine actinomycetes exhibit a high level of biodiversity and possess significant potential for the production of high-value secondary metabolites. During the course of investigation of marine actinobacteria from corals, two Saccharopolyspora strains, namely, HNM0983T and HNM0986T, were isolated from stony corals collected from the coastal area of Hainan Island. The 16S ribosomal RNA (rRNA) gene sequence analysis revealed that these two strains are putative novel taxa of the genus Saccharopolyspora. Whole-genome sequencing comparisons further confirmed the two strains as belonging to two novel Saccharopolyspora species, which can be distinguished phenotypically and chemically from their current closest phylogenetic relatives. Some genomic information of the genus Saccharopolyspora was compared for evaluating the production capacity of secondary metabolites. A total of 519 biosynthetic gene clusters (BGCs) from the genus Saccharopolyspora were used for analysis, and terpene BGCs were found to be widespread and most abundant in this genus. In addition, abundant novel BGCs in the genus Saccharopolyspora are not clustered with the known BGCs in the database, indicating that the metabolites of the genus Saccharopolyspora deserve further exploration. On the basis of these presented results, Saccharopolyspora montiporae sp. nov. (type strain = HNM0983T = CCTCC AA 2020014T = KCTC 49526T) and Saccharopolyspora galaxeae sp. nov. (type strain = HNM0986T = CCTCC AA 2020011T = KCTC 49524T) are proposed as the names for the new strains, respectively.

Microglia-associated neuroinflammation plays essential roles in pathology of acute stroke. Cedrol, a natural compound extracted from ginger, has been shown to confer inhibitory effects on inflammation in various diseases. However, whether Cedrol suppresses neuroinflammation and protects brains from acute ischemic injury still remains unclear. In this study, we found that Cedrol inhibited microglia activation and the production of inflammatory factors in LPS-challenged microglia and the penumbra region of middle cerebral artery occlusion (MCAO) mice. We also found that Cedrol reduced the infarct size and mNSS scores and improved acute cerebral ischemia-induced behavioral outcomes, suggesting remarked neuroprotection of Cedrol. Molecular docking analysis showed that Cedrol bound to estrogen receptor β (ERβ) with moderate-strong affinity. Intriguingly, treatment with fulvestrant, an ER blocker, abolished the anti-inflammatory effects of Cedrol. Cedrol significantly reversed the LPS- and MCAO-induced increases in phosphorylation levels of IκB and NF-κB P65 in primary microglia and MCAO mice, respectively. Additionally, Cedrol was observed to rescue LPS-induced shuttling of NF-κB P65 from cytoplasm to nuclei in primary microglia, indicating inhibitory effects of Cedrol on NF-κB signaling. These results suggest microglia associated neuroinflammation may be mediated by ERβ-NF-κB signaling pathway. Together, our study reveals that Cedrol protected brain function from acute cerebral ischemia through inhibition of microglia-associated neuroinflammation via ERβ-NF-κB signaling pathways, and Cedrol may serve as an alternative option for treatment of acute stroke injury.

ObjectiveTo assess the clinical impact of unilateral laminotomy for bilateral decompression (ULBD) in managing patients with adjacent vertebrae following lumbar fusion.MethodsA retrospective analysis was conducted on 21 patients, with a mean age of 67.4 years, who underwent ULBD for adjacent vertebra disease at our department from January 2021 to November 2023. We reviewed demographic data, surgical techniques, imaging studies, and patient-reported outcomes. The study compared Visual Analog Scale (VAS) scores, Numeric Rating Scale (NRS) scores, Japanese Orthopaedic Association (JOA) scores, Short Form-36 (SF-36) scores, and imaging outcomes before surgery, immediately post-surgery, and at 1 month, 6 months, and 12 months post-surgery.ResultsEvaluation of 21 patients with adjacent segment disease (ASD) (13 males, 8 females; mean age 67.42 years) was performed with follow-ups at various intervals post-surgery. Postoperative VAS, NRS, JOA, and SF-36 scores showed significant improvements compared to preoperative scores. Immediately after surgery, there were significant improvements in NRS score (2.76 ± 0.70 vs. 3.71 ± 0.85, P

BackgroundHIV notification and testing integrated into partner service (PS) practices among HIV-positive individuals have been proven to be an efficient approach for case finding, although it remains a weak link in China. Although nonmarital sexual activities accounted for a large proportion of newly diagnosed HIV-positive cases in China, little is known about PS uptake and associated factors within nonmarital partnerships. ObjectiveThis study aimed to describe HIV PS utilization and its associated factors among HIV-positive individuals with nonmarital sexual partners. MethodsWe recruited newly diagnosed HIV-positive individuals who had nonmarital sexual partners in 2022 in Zhejiang Province and offered them PS. We described the PS uptake cascade within sexual partner categories and analyzed the associated factors with 3 primary outcomes from the participants’ perspective: nonmarital partner enumeration, HIV testing, and HIV positivity. ResultsIn this study, 3509 HIV-positive individuals were recruited as participants, and they enumerated 2507 nonmarital sex partners (2507/14,556, 17.2% of all nonmarital sex partners) with contact information. Among these, 43.1% (1090/2507) underwent an HIV test, with an HIV-positive rate of 28.3% (309/1090). Heterosexual commercial partners were the least likely of being enumerated (441/4292, 10.3%) and had the highest HIV-positive rate (40/107, 37.4%). At the participant level, 48.1% (1688/3509) of the participants enumerated at least one nonmarital sex partner with contact information, 52.7% (890/1688) had a sex partner tested for HIV, and 31% (276/890) had at least one nonmarital sex partner who tested positive. Multivariate analysis indicated that gender and transmission route were associated with both nonmarital sex partner enumeration and HIV testing. Age and occupation were associated with nonmarital sex partner enumeration and HIV positivity. Compared with participants who had no regular nonmarital sex partner, those who had a regular nonmarital sex partner were more likely to enumerate nonmarital sex partners (adjusted odds ratio [aOR] 3.017, 95% CI 2.560-3.554), have them get tested for HIV (aOR 1.725, 95% CI 1.403-2.122), and have an HIV-positive nonmarital sex partner (aOR 1.962, 95% CI 1.454-2.647). ConclusionsThe percentage of partner enumeration was low, and HIV testing rate was moderate among nonmarital partnerships of HIV-positive individuals. More efforts should be made to improve PS practices among HIV-positive individuals and address the gap in partner enumeration, especially for heterosexual commercial nonmarital partnerships. Additionally, enhancing PS operational skills among health care personnel could increase the overall efficiency of PS uptake in China.

Summary: Nasopharyngeal carcinoma (NPC) has high metastatic potential and is hard to detect early. This study aims to develop a deep learning model for NPC diagnosis using optical imagery. From April 2008 to May 2021, we analyzed 12,087 nasopharyngeal endoscopic images and 309 videos from 1,108 patients. The pretrained model was fine-tuned with stochastic gradient descent on the final layers. Data augmentation was applied during training. Videos were converted to images for malignancy scoring. Performance metrics like AUC, accuracy, and sensitivity were calculated based on the malignancy score. The deep learning model demonstrated high performance in identifying NPC, with AUC values of 0.981 (95% confidence of interval [CI] 0.965–0.996) for the Fujian Cancer Hospital dataset and 0.937 (0.905–0.970) for the Jiangxi Cancer Hospital dataset. The proposed model effectively diagnoses NPC with high accuracy, sensitivity, and specificity across multiple datasets. It shows promise for early NPC detection, especially in identifying latent lesions.

Background: Microglia-mediated inflammation is a critical factor in the progression of ischemic stroke. Consequently, mitigating excessive microglial activation represents a potential therapeutic strategy for ischemic injury. Thymol, a monophenol derived from plant essential oils, exhibits diverse beneficial biological activities, including anti-inflammatory and antioxidant properties, with demonstrated protective effects in various disease models. However, its specific effects on ischemic stroke and microglial inflammation remain unexplored. Methods: Rodent transient middle cerebral artery occlusion (tMCAO) model was established to simulate ischemic stroke. TTC staining, modified neurological function score (mNSS), and behavioral tests were used to assess the severity of neurological damage. Then immunofluorescence staining and cytoskeleton analysis were used to determine activation of microglia. Lipopolysaccharide (LPS) was utilized to induce the inflammatory response of primary microglia in vitro. Quantitative real-time polymerase chain reaction (qRT-PCR), western blot, and enzyme-linked immunosorbent assay (ELISA) were performed to exam the expression of inflammatory cytokines. And western blot was used to investigate the mechanism of the anti-inflammatory effect of thymol. Results: In this study, we found that thymol treatment could ameliorate post-stroke neurological impairment and reduce infarct volume by mitigating microglial activation and pro-inflammatory response (IL-1β, IL-6, and TNF-α). Mechanically, thymol could inhibit the phosphorylation of phosphatidylinositol-3-kinase (PI3K), sink serine/threonine kinase (Akt), and mammalian target of rapamycin (mTOR), thereby suppressing the activation of nuclear factor-κB (NF-κB). Conclusions: Our study demonstrated that thymol could reduce the microglial inflammation by targeting PI3K/Akt/mTOR/NF-κB signaling pathway, ultimately alleviating ischemic brain injury. These findings suggest that thymol is a promising candidate as a neuroprotective agent against ischemic stroke.

In recent years, tourism has flourished in ethnic areas of China as an important tool for rural revitalization and has become an important stimulus to promote the transformation of rural residents’ livelihood. However, rural residents in tourist villages in ethnic areas still face various livelihood risks, and academic literature has paid little attention to the mechanism’s substrate these household livelihood decision-making behaviors, and the differences in adaptive capacity and decision-making behaviors between mountainous minority villages and non-tourist villages are not sufficiently clear. Based on survey data of 284 rural residents in tourist and non-tourist villages in ethnic areas of western Sichuan, this study analyzed the adaptive capacity and differences of rural households using the comprehensive index method and Kruskal-Wallis test, and constructed a disordered multi-classification logistic regression model to explore the mechanism of rural residents’ livelihood behavior decisions. The results indicate that: (1) The adaptive capacity of rural residents in tourist villages in western Sichuan ethnic areas is slightly higher than that of non-tourist villages. (2) Tibetan households have the strongest adaptive capacity, and there is a significant difference between the adaptive capacity of Tibetan households and the rest of the minority households except Han Chinese. (3) The households with tourism-oriented livelihood strategy have the highest adaptive capacity, followed by households with tourism expansion livelihood strategy, while households with other types of livelihood strategies had the lowest livelihood adaptive capacity.(4) Compared to other types of livelihood strategies, when the policies are favorable and the ethnic culture is more primitive, rural residents are more inclined to choose tourism-oriented livelihood strategies, followed by tourism expansion livelihood strategies. When rural residents have higher adaptive capacity and more advantages in the market economy, they prefer tourism expansion strategies, followed by tourism-oriented strategies.

Abstract Background Macrophages are key inflammatory immune cells that orchestrate the initiation and progression of autoimmune diseases. The characters of macrophage in diseases are determined by its phenotype in response to the local microenvironment. Ficolins have been confirmed as crucial contributors to autoimmune diseases, with Ficolin-2 being particularly elevated in patients with autoimmune diseases. However, whether Ficolin-A stimulates macrophage polarization is still poorly understood. Methods We investigated the transcriptomic expression profile of murine bone marrow-derived macrophages (BMDMs) stimulated with Ficolin-A using RNA-sequencing. To further confirm a distinct phenotype activated by Ficolin-A, quantitative RT-PCR and Luminex assay were performed in this study. Additionally, we assessed the activation of underlying cell signaling pathways triggered by Ficolin-A. Finally, the impact of Ficolin-A on macrophages were investigated in vivo through building Collagen-induced arthritis (CIA) and Dextran Sulfate Sodium Salt (DSS)-induced colitis mouse models with Fcna-/- mice. Results Ficolin-A activated macrophages into a pro-inflammatory phenotype distinct to LPS-, IFN-γ- and IFN-γ + LPS-induced phenotypes. The transcriptomic profile induced by Ficolin-A was primarily characterized by upregulation of interleukins, chemokines, iNOS, and Arginase 1, along with downregulation of CD86 and CD206, setting it apart from the M1 and M2 phenotypes. The activation effect of Ficolin-A on macrophages deteriorated the symptoms of CIA and DSS mouse models, and the deletion of Fcna significantly alleviated the severity of diseases in mice. Conclusion Our work used transcriptomic analysis by RNA-Seq to investigate the impact of Ficolin-A on macrophage polarization. Our findings demonstrate that Ficolin-A induces a novel pro-inflammatory phenotype distinct to the phenotypes activated by LPS, IFN-γ and IFN-γ + LPS on macrophages.

Abstract Background Drug resistance poses a significant challenge in cancer treatment, particularly as a leading cause of therapy failure. Cisplatin, the primary drug for lung adenocarcinoma (LUAD) chemotherapy, shows effective treatment outcomes. However, the development of resistance against cisplatin is a major obstacle. Therefore, identifying genes resistant to cisplatin and adopting personalized treatment could significantly improve patient outcomes. Methods By examining transcriptome data of cisplatin-resistant LUAD cells from the GEO database, 181 genes associated with cisplatin resistance were identified. Using univariate regression analysis, random forest and multivariate regression analyses, two prognostic genes, E2F7 and FAM83A, were identified. This study developed a prognostic model utilizing E2F7 and FAM83A as key indicators. The Cell Counting Kit 8 assay, Transwell assay, and flow cytometry were used to detect the effects of E2F7 on the proliferation, migration, invasiveness and apoptosis of A549/PC9 cells. Western blotting was used to determine the effect of E2F7 on AKT/mTOR signaling pathway. Results This study has pinpointed two crucial genes associated with cisplatin resistance, E2F7 and FAM83A, and developed a comprehensive model to assist in the diagnosis, prognosis, and evaluation of relapse risk in LUAD. Analysis revealed that patients at higher risk, according to these genetic markers, had elevated levels of immune checkpoints (PD-L1 and PD-L2). The prognostic and diagnosis values of E2F7 and FAM83A were further confirmed in clinical data. Furthermore, inhibiting E2F7 in lung cancer cells markedly reduced their proliferation, migration, invasion, and increased apoptosis. In vivo experiments corroborated these findings, showing reduced tumor growth and lung metastasis upon E2F7 suppression in lung cancer models. Conclusion Our study affirms the prognostic value of a model based on two DEGs, offering a reliable method for predicting the success of tumor immunotherapy in patients with LUAD. The diagnostic and predictive model based on these genes demonstrates excellent performance. In vitro, reducing E2F7 levels shows antitumor effects by blocking LUAD growth and progression. Further investigation into the molecular mechanisms has highlighted E2F7’s effect on the AKT/mTOR signaling pathway, underscoring its therapeutic potential. In the era of personalized medicine, this DEG-based model promises to guide clinical practice.

Abstract Excessive iron accumulation in the brain cortex increases the risk of cognitive deterioration. However, interregional relationships (defined as susceptibility connectivity) of local brain iron have not been explored, which could provide new insights into the underlying mechanisms of cognitive decline. Seventy-six healthy controls (HC), 58 participants with mild cognitive impairment due to probable Alzheimer’s disease (MCI-AD) and 66 participants with white matter hyperintensity (WMH) were included. We proposed a novel approach to construct a brain susceptibility network by using Kullback‒Leibler divergence similarity estimation from quantitative susceptibility mapping and further evaluated its topological organization. Moreover, sparse logistic regression (SLR) was applied to classify MCI-AD from HC and WMH with normal cognition (WMH-NC) from WMH with MCI (WMH-MCI).The altered susceptibility connectivity in the MCI-AD patients indicated that relatively more connectivity was involved in the default mode network (DMN)-related and visual network (VN)-related connectivity, while more altered DMN-related and subcortical network (SN)-related connectivity was found in the WMH-MCI patients. For the HC vs. MCI-AD classification, the features selected by the SLR were primarily distributed throughout the DMN-related and VN-related connectivity (accuracy = 76.12%). For the WMH-NC vs. WMH-MCI classification, the features with high appearance frequency were involved in SN-related and DMN-related connectivity (accuracy = 84.85%). The shared and specific patterns of the susceptibility network identified in both MCI-AD and WMH-MCI may provide a potential diagnostic biomarker for cognitive impairment, which could enhance the understanding of the relationships between brain iron burden and cognitive decline from a network perspective.

ObjectiveThe distribution of the photon energy spectrum in isocenter plane of the medical linear accelerator and the influence of secondary collimator on the photon energy spectrum are studied. Methods Use the BEAMnrc program to simulate the transmission of the 6 MeV electrons and photons in 5 cm×5 cm,10 cm×10 cm,15 cm×15 cm and 20 cm×20 cm fields in treatment head of the medical linear accelerator, where a phase space file was set up at the isocenter plane to record the particle information passing through this plane. The BEAMdp program is used to analyze the phase space file, in order to obtain the distribution of the photon energy spectrum in isocenter plane and the influence of secondary collimator on the photon energy spectrum. Results By analyzing the photon energy spectrum of a medical linear accelerator with a nominal energy of 6 MV, it is found that the secondary collimator has little effect on the photon energy spectrum; different fields have different photon energy spectrum distributions; the photon energy spectrum in different central regions of the same field have the same normalized distribution. Conclusion In the dose calculation of radiation therapy, the influence of photon energy spectrum should be carefully considered.

In recent years, new degradable materials have been applied to cardiovascular implants. Cardiovascular implants with different physicochemical properties and degradation properties have special endpoints for their biological evaluation. In this study, the end points of biological evaluation of degradable cardiovascular implants were reviewed by taking vascular stents and occluders as examples.

Abstract Background Nasopharyngeal carcinoma (NPC) is prevalent in southern China. EBV DNA is the most useful biomarker in NPC. However, the value of EBV DNA in posttreatment NPC patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains unclear. Methods Sixty-four eligible NPC patients were enrolled between December 2022 and February 2023. Patients who met the following criteria were included: had non-metastatic NPC, completed radical treatment, were first firstly infected with SARS-CoV-2 and their EBV DNA changed from undetectable to detectable. Results At the end of follow-up, 81.25% (52/64) of patients were confirmed not to relapse with undetectable EBV DNA (no-relapse). In addition, 18.75% (12/64) of patients experienced relapse with consistent detection of EBV DNA (yes-relapse). For all 64 patients, the average time from diagnosis of coronavirus disease 2019 (COVID-19) to detection of detectable EBV DNA was 35.41 days (2 to 139 days). For 52 no-relapse patients, the average time from EBV DNA changing from detectable to undetectable was 63.12 days (6 to 147 days). The levels of EBV DNA were greater in yes-relapse patients than that in no-relapse patients, and the average of EBV DNA levels were 1216 copies/ml and 53.18 copies/ml, respectively. Using 62.3 copies/mL as the threshold, the area under the curve for EBV DNA was 0.88 for distinguishing yes-relapse patients from no-relapse patients. The sensitivity and specificity were 81.97% (95% CI 0.71–0.95) and 86.67% (95% CI 0.70–0.95), respectively. Conclusion For NPC patients infected with SARS-CoV-2, EBV DNA alone is insufficient for monitoring relapse after radical therapy. Long-term follow-up and underlying mechanistic investigations of EBV DNA changes are urgently needed.

Decisions regarding adjuvant therapy in patients with stage II colon cancer remains controversial and challenging. We aimed to determine novel biomarkers that help to predict relapse free survival (RFS) and identify a subset of patients with stage II colon cancer who could gain survival benefits from adjuvant chemotherapy. Public microarray datasets of stage II colon cancer samples were extracted from Gene Expression Omnibus database. Global gene expression changes were then analyzed between the paired early relapse and long-term survival group to identify the differentially expressed mRNAs and lncRNAs. Based on Lasso Cox regression modeling analysis, a total of 30 mRNAs and 2 lncRNAs were finally identified. With specific formula, stage II patients in training and validation sets were divided into low and risk groups with significantly different RFS. PAX8-AS1 is the novel lncRNA which showed the highest upregulation in early relapse group. Patients with high PAX8-AS1 expression level showed notably poorer RFS in both meta GEO cohort (P = 0.04, Figure 4B) and FUSCC cohort (P < 0.001, Figure 4C). Among the stage II patients with high PAX8-AS1 level, administration of fluorouracil-based adjuvant chemotherapy provided a substantial improvement in RFS (P = 0.002, Figure 3C). Further mechanistic study unveiled that PAX8-AS1 increases the response of CRC cells to chemotherapy in vitro and in vivo by maintaining the mRNA stability of PAX8. In conclusion, PAX8-AS1 as a novel and reliable biomarker for predicting prognosis and identification of patients with stage II disease who could gain survival benefit from fluorouracil-based adjuvant chemotherapy.

Abstract Graphitic carbon nitride (CN), as a nonmetallic photocatalyst, has gained considerable attention for its cost‐effectiveness and environmentally friendly nature in catalyzing solar‐driven CO2 conversion into valuable products. However, the photocatalytic efficiency of CO2 reduction with CN remains low, accompanied by challenges in achieving desirable product selectivity. To address these limitations, a two‐step hydrothermal‐calcination tandem synthesis strategy is presented, introducing carbon quantum dots (CQDs) into CN and forming ultra‐thin CQD/CN nanosheets. The integration of CQDs induces a distinct work function with CN, creating a robust interface electric field after the combination. This electric field facilitates the accumulation of photoelectrons in the CQDs region, providing an abundant source of reduced electrons for the photocatalytic process. Remarkably, the CQD/CN nanosheets exhibit an average CO yield of 120 µmol g−1, showcasing an outstanding CO selectivity of 92.8%. The discovery in the work not only presents an innovative pathway for the development of high‐performance photocatalysts grounded in non‐metallic CN materials employing CQDs but also opens new avenues for versatile application prospects in environmental protection and sustainable cleaning energy.

Background Observational studies show that patients with chronic obstructive pulmonary disease (COPD) tend to be sedentary during leisure time. Physical activity (PA) may reduce the risk of COPD, but the causal relationship is unclear. We used a Mendelian randomisation (MR) method to elucidate the association of leisure sedentary behaviours (LSB) and PA with lung function and COPD.Methods Data on LSB (n=422 218), PA (n=608 595), COPD (n=299 929) and lung function (n=79 055) were obtained from the large-scale genome-wide association study. Causal inference used inverse variance-weighted, MR-Egger and weighted median. Sensitivity analysis was performed to assess heterogeneity and pleiotropy, and radial MR was used to distinguish outliers. The primary outcome was analysed by multifactorial MR adjusted for daily smoking.Results The inverse variance weighted analysis indicated that increased moderate-to-vigorous PA (MVPA) is associated with higher levels of forced vital capacity (FVC) (beta=0.27, 95% CI 0.12 to 0.42; p=3.51×10–4). For each increment of 2.8 hours in television watching, the odds of COPD were 2.25 times greater (OR=2.25; 95% CI 1.84 to 2.75; p=2.38×10–15). For early-onset COPD, the odds were 2.11 times greater (OR=2.11; 95% CI 1.56 to 2.85; p=1.06×10–6), and for late-onset COPD, the odds were 2.16 times greater (OR=2.16; 95% CI 1.64 to 2.84; p=3.12×10–8). Similarly, the odds of hospitalisation for COPD were 2.02 times greater with increased television watching (OR=2.02; 95% CI 1.59 to 2.55; p=4.68×10–9). Television watching was associated with lower FVC (beta=−0.19, 95% CI −0.28 to −0.10; p=1.54×10–5) and forced expiratory volume in the 1 s (FEV1) (beta=−0.16, 95% CI −0.25 to −0.08; p=1.21×10–4) levels. The results remained significant after adjustment for smoking.Conclusions Our study suggests a potential association with LSB, particularly television watching, is associated with higher odds of COPD and lower indices of lung function as measured continuously, including FEV1 and FVC. Conversely, an increase in MVPA is associated with higher indices of lung function, particularly reflected in increased FVC levels.

The resonance enhanced InAs/GaSb type-II Superlattices (T2SLs) infrared detectors with diffraction rings is designed, and the photoelectric characteristics are calculated and studied in this paper. The diffraction rings are designed on the top surface of T2SLs detector to control the incident light inside the device by forming the resonant cavity. We designed the structure of the conventional PIN InAs/GaSb T2SLs photodetector, calculated the energy band structure of the absorption layer, and analyzed the influence of the thickness of the absorption layer on the photoelectric performance. It is proved that blindly increasing the thickness of the absorption layer cannot effectively improve the device performance. We further studied the quantum efficiency (QE) and electric field distribution of the device after adding the diffraction ring structure. The results show that the structure with diffraction rings can significantly improve the QE of the photodetector without increasing the dark current. The interaction between the diffraction ring and the metal contact layer will enhance the localization of the electric field and further increase the light absorption between the semiconductor layers.

Chitosan nanoparticles (NPs) possess great potential in biomedical fields. Orifice-induced hydrodynamic cavitation (HC) has been used for the enhancement of fabrication of size-controllable genipin-crosslinked chitosan (chitosan-genipin) NPs based on the emulsion cross-linking (ECLK). Experiments have been performed using various plate geometries, chitosan molecular weight and under different operational parameters such as inlet pressure (1–3.5 bar), outlet pressure (0–1.5 bar) and cross-linking temperature (40–70 °C). Orifice plate geometry was a crucial factor affecting the properties of NPs, and the optimized geometry of orifice plate was with single hole of 3.0 mm diameter. The size of NPs with polydispersity index of 0.359 was 312.6 nm at an optimized inlet pressure of 3.0 bar, and the maximum production yield reached 84.82 %. Chitosan with too high or too low initial molecular weight (e.g., chitosan oligosaccharide) was not applicable for producing ultra-fine and narrow-distributed NPs. There existed a non-linear monotonically-increasing relationship between cavitation number (Cv) and chitosan NP size. Scanning electron microscopy (SEM) test indicated that the prepared NPs were discrete with spherical shape. The study demonstrated the superiority of HC in reducing particle size and size distribution of NPs, and the energy efficiency of orifice type HC-processed ECLK was two orders of magnitude than that of ultrasonic horn or high shear homogenization-processed ECLK. In vitro drug-release studies showed that the fabricated NPs had great potential as a drug delivery system. The observations of this study can offer strong support for HC to enhance the fabrication of size-controllable chitosan-genipin NPs.

Abstract Background Patients with Alzheimer’s disease (AD) are often co-morbid with unprovoked seizures, making clinical diagnosis and management difficult. Although it has an important role in both AD and epilepsy, abnormal γ-aminobutyric acid (GABA)ergic transmission is recognized only as a compensative change for glutamatergic damage. Neuregulin 1 (NRG1)-ErbB4 signaling can promote GABA release and suppress epileptogenesis, but its effects on cognition in AD are still controversial. Methods Four-month-old APPswe/PS1dE9 mice (APP mice) were used as animal models in the early stage of AD in this study. Acute/chronic chemical-kindling epilepsy models were established with pentylenetetrazol. Electroencephalogram and Racine scores were performed to assess seizures. Behavioral tests were used to assess cognition and emotion. Electrophysiology, western blot and immunofluorescence were performed to detect the alterations in synapses, GABAergic system components and NRG1-ErbB4 signaling. Furthermore, NRG1 was administrated intracerebroventricularly into APP mice and then its antiepileptic and cognitive effects were evaluated. Results APP mice had increased susceptibility to epilepsy and resulting hippocampal synaptic damage and cognitive impairment. Electrophysiological analysis revealed decreased GABAergic transmission in the hippocampus. This abnormal GABAergic transmission involved a reduction in the number of parvalbumin interneurons (PV+ Ins) and decreased levels of GABA synthesis and transport. We also found impaired NRG1-ErbB4 signaling which mediated by PV+ Ins loss. And NRG1 administration could effectively reduce seizures and improve cognition in four-month-old APP mice. Conclusion Our results indicated that abnormal GABAergic transmission mediated hippocampal hyperexcitability, further excitation/inhibition imbalance, and promoted epileptogenesis in the early stage of AD. Appropriate NRG1 administration could down-regulate seizure susceptibility and rescue cognitive function. Our study provided a potential direction for intervening in the co-morbidity of AD and epilepsy.

Abstract Objective To develop a clinical learning environment scale for Chinese nursing students and test its reliability and validity. Methods Based on Moos social environment theory, qualitative interviews and expert consultations were used to develop a pretest version of the Chinese Nursing Students’ Clinical Learning Environment Scale. With a convenience sampling method, 255 and 1582 Chinese nursing students were selected as the prediction and validation samples, respectively, from December 2022 to March 2023. Exploratory and confirmatory factor analyses were conducted to determine the construct validity. Results The scale consisted of 19 items. Exploratory factor analysis revealed three sub-scales, named goal orientation, interpersonal relation, and learning support, which explained 71.500% of the total variance. The results of the confirmatory factor analysis showed that the GFI was 0.848, the AGFI was 0.806, the RMSEA was 0.090, the RMR was 0.041, the NFI was 0.910, the IFI was 0.916, the CFI was 0.916, the PCFI was 0.798, and the PNFI was 0.793. The reliability values of the three dimensions were 0.870, 0.858, and 0.943, respectively, and the convergent validity values were 0.574, 0.603, and 0.625, respectively. Conclusion The reliability and validity of the dimensions of the Chinese Nursing Students’ Clinical Learning Environment Scale are acceptable, and the scale can be used as a useful tool for measuring the clinical learning environment of Chinese nursing students.

Abstract Background Microglia is the major contributor of post-stroke neuroinflammation cascade and the crucial cellular target for the treatment of ischemic stroke. Currently, the endogenous mechanism underlying microglial activation following ischemic stroke remains elusive. Serglycin (SRGN) is a proteoglycan expressed in immune cells. Up to now, the role of SRGN on microglial activation and ischemic stroke is largely unexplored. Methods Srgn knockout (KO), Cd44-KO and wild-type (WT) mice were subjected to middle cerebral artery occlusion (MCAO) to mimic ischemic stroke. Exogenous SRGN supplementation was achieved by stereotactic injection of recombinant mouse SRGN (rSRGN). Cerebral infarction was measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Neurological functions were evaluated by the modified neurological severity score (mNSS) and grip strength. Microglial activation was detected by Iba1 immunostaining, morphological analysis and cytokines’ production. Neuronal death was examined by MAP2 immunostaining and FJB staining. Results The expression of SRGN and its receptor CD44 was significantly elevated in the ischemic mouse brains, especially in microglia. In addition, lipopolysaccharide (LPS) induced SRGN upregulation in microglia in vitro. rSRGN worsened ischemic brain injury in mice and amplified post-stroke neuroinflammation, while gene knockout of Srgn exerted reverse impacts. rSRGN promoted microglial proinflammatory activation both in vivo and in vitro, whereas Srgn-deficiency alleviated microglia-mediated inflammatory response. Moreover, the genetic deletion of Cd44 partially rescued rSRGN-induced excessed neuroinflammation and ischemic brain injury in mice. Mechanistically, SRGN boosted the activation of NF-κB signal, and increased glycolysis in microglia. Conclusion SRGN acts as a novel therapeutic target in microglia-boosted proinflammatory response following ischemic stroke.

Abstract HBV-miR-3 is encoded by HBV and takes part in pathogenesis of HBV-related liver disease. Whether HBV-miR-3 has a relationship with HBV replication and is predictive of PegIFN-α treatment response is still unknown. HBV-miR-3 quantification is based on qRT-PCR. The relationship of HBV-miR-3 and HBV replication, and predictive value of HBV-miR-3 were evaluated in a cohort of 650 HBeAg positive patients from a multi-center, randomized phase III clinical trial for the study of PegIFN-a2b. HBV-miR-3 is significantly positively related to HBVDNA, HBVpgRNA, HBeAg and HBsAg at baseline and at all the different time points during PegIFN-α treatment. Both univariate regression analyses and multivariate logistic regression analyses showed HBV-miR-3 is a predictor of HBeAg seroconversion in the patients treated with PegIFN-α at weeks of 0, 12, and 24. 70.0% of patients with HBV-miR-3 6log at week 12 no patient obtained HBeAg seroconversion. Conbination of HBV-miR-3 and HBeAg is more strongly predictive of HBeAg seroconversion (83.64%) at week 12. HBV-miR-3 is new biomarker for HBV replication and positively correlated to HBV replication. HBV-miR-3 is also an early predictor of HBeAg seroconversion in the patients treated with PegIFN-α.

Abstract Background Damage in the ischemic core and penumbra after stroke affects patient prognosis. Microglia immediately respond to ischemic insult and initiate immune inflammation, playing an important role in the cellular injury after stroke. However, the microglial heterogeneity and the mechanisms involved remain unclear. Methods We first performed single-cell RNA-sequencing (scRNA-seq) and spatial transcriptomics (ST) on middle cerebral artery occlusion (MCAO) mice from three time points to determine stroke-associated microglial subclusters and their spatial distributions. Furthermore, the expression of microglial subcluster-specific marker genes and the localization of different microglial subclusters were verified on MCAO mice through RNAscope and immunofluorescence. Gene set variation analysis (GSVA) was performed to reveal functional characteristics of microglia sub-clusters. Additionally, ingenuity pathway analysis (IPA) was used to explore upstream regulators of microglial subclusters, which was confirmed by immunofluorescence, RT-qPCR, shRNA-mediated knockdown, and targeted metabolomics. Finally, the infarct size, neurological deficits, and neuronal apoptosis were evaluated in MCAO mice after manipulation of specific microglial subcluster. Results We discovered stroke-associated microglial subclusters in the brains of MCAO mice. We also identified novel marker genes of these microglial subclusters and defined these cells as ischemic core-associated (ICAM) and ischemic penumbra-associated (IPAM) microglia, according to their spatial distribution. ICAM, induced by damage-associated molecular patterns, are probably fueled by glycolysis, and exhibit increased pro-inflammatory cytokines and chemokines production. BACH1 is a key transcription factor driving ICAM generation. In contrast, glucocorticoids, which are enriched in the penumbra, likely trigger IPAM formation, which are presumably powered by the citrate cycle and oxidative phosphorylation and are characterized by moderate pro-inflammatory responses, inflammation-alleviating metabolic features, and myelinotrophic properties. Conclusions ICAM could induce excessive neuroinflammation, aggravating brain injury, whereas IPAM probably exhibit neuroprotective features, which could be essential for the homeostasis and survival of cells in the penumbra. Our findings provide a biological basis for targeting specific microglial subclusters as a potential therapeutic strategy for ischemic stroke.

Background/Objectives: Urinary tract infection (UTI) is a prevalent microbial infection in medical practise, leading to significant patient morbidity and increased treatment costs, particularly in developing countries. This retrospective study, conducted at a tertiary care hospital in Dhaka, Bangladesh, aims to examine the antimicrobial resistance (AMR) patterns of uropathogens and evaluate whether these patterns are influenced by demographic factors such as gender, age, or patient status. Methods: Standard microbiological techniques were used to identify uropathogens, and AMR patterns were determined using the Kirby–Bauer disc diffusion method. Results: Out of 6549 urine samples, 1001 cultures were positive. The infection was more prevalent in females compared to males. The incidence of UTIs in children aged 0–10 years accounted for 12.59% of the total cases, with this age group also exhibiting the highest rate of polymicrobial infections. Among the bacterial uropathogens, 71.19% of isolates were multidrug resistant (MDR) and 84.27% were resistant to at least one antibiotic. Escherichia coli (n = 544, 73.90% MDR) and Klebsiella species (n = 143, 48.95% MDR) were the most common Gram-negative uropathogens, while Enterococcus species (n = 78, 94.87% MDR) was the predominant Gram-positive isolate in this study. Our results indicate that most uropathogens showed resistance against ceftazidime, followed by cefuroxime, trimethoprim-sulfamethoxazole, amoxicillin-clavulanate, and netilmicin. Moderate levels of resistance were observed against ciprofloxacin, levofloxacin, aztreonam, and cefpodoxime. Conclusions: Amikacin was observed to be effective against Gram-negative uropathogens, whereas cefixime was more active against Gram-positive microorganisms, such as Enterococcus species. Moreover, a principal coordinate analysis (PCoA) depicted no significant influence of gender, patient status, or age on AMR patterns. For the continued usefulness of most antibiotics, periodic analysis of the AMR patterns of uropathogens can help assess the rise of MDR bacteria, and therefore guide the selection of appropriate antibiotic treatment strategies.

The detection of Cerebral Microbleeds (CMBs) is crucial for diagnosing cerebral small vessel disease. However, due to the small size and subtle appearance of CMBs in susceptibility-weighted imaging (SWI), manual detection is both time-consuming and labor-intensive. Meanwhile, the presence of similar-looking features in SWI images demands significant expertise from clinicians, further complicating this process. Recently, there has been a significant advancement in automated detection of CMBs using a Convolutional Neural Network (CNN) structure, aiming at enhancing diagnostic efficiency for neurologists. However, existing methods still show discrepancies when compared to the actual clinical diagnostic process. To bridge this gap, we introduce a novel multimodal detection and classification framework for CMBs’ diagnosis, termed MM-UniCMBs. This framework includes a light-weight detection model and a multi-modal classification network. Specifically, we proposed a new CMBs detection network, CMBs-YOLO, designed to capture the salient features of CMBs in SWI images. Additionally, we design an innovative language–vision classification network, CMBsFormer (CF), which integrates patient textual descriptions—such as gender, age, and medical history—with image data. The MM-UniCMBs framework is designed to closely align with the diagnostic workflow of clinicians, offering greater interpretability and flexibility compared to existing methods. Extensive experimental results show that MM-UniCMBs achieves a sensitivity of 94% in CMBs’ classification and can process a patient’s data within 5 s.

WRKY transcription factor (TF) plays a crucial role in plant abiotic stress response, but it is rarely reported in Michelia crassipes. Our studies have found that the transcription factor McWRKY43, a member of the IIc subgroup, is strongly upregulated under cold stress. In this study, we cloned the full length of McWRKY43 to further investigate the function of McWRKY43 in resistance to cold stress and its possible regulatory pathways in M. crassipes. Under cold stress, the seed-germination rate of transgenic tobacco was significantly higher than that of the wild type, and the flavonoid content, antioxidant enzyme activities, and proline content of transgenic tobacco seedlings were significantly increased, which promoted the expression of flavonoid pathway structural genes. In addition, the transient transformation of McWRKY43 in the M. crassipes leaves also found the accumulation of flavonoid content and the transcription level of flavonoid structural genes, especially McLDOX, were significantly increased under cold stress. Yeast one-hybrid (Y1H) assay showed that McWRKY43 could bind to McLDOX promoter, and the transcription expression of McLDOX was promoted by McWRKY43 during cold stress treatment. Overall, our results indicated that McWRKY43 is involved in flavonoid biosynthetic pathway to regulate cold stress tolerance of M. crassipes, providing a basis for molecular mechanism of stress resistance in Michelia.

Summary: Background: Both defects in mismatch repair (dMMR) and high microsatellite instability (MSI-H) have been recognised as crucial biomarkers that guide treatment strategies and disease management in colorectal cancer (CRC). As MMR and MSI tests are being widely conducted, an increasing number of MSI-H tumours have been identified in CRCs with mismatch repair proficiency (pMMR). The objective of this study was to assess the clinical features of patients with pMMR/MSI-H CRC and elucidate the underlying molecular mechanism in these cases. Methods: From January 2015 to December 2018, 1684 cases of pMMR and 401 dMMR CRCs were enrolled. Of those patients, 93 pMMR/MSI-H were identified. The clinical phenotypes and prognosis were analysed. Frozen and paraffin-embedded tissue were available in 35 patients with pMMR/MSI-H, for which comprehensive genomic and transcriptomic analyses were performed. Findings: In comparison to pMMR/MSS CRCs, pMMR/MSI-H CRCs exhibited significantly less tumour progression and better long-term prognosis. The pMMR/MSI-H cohorts displayed a higher presence of CD8+ T cells and NK cells when compared to the pMMR/MSS group. Mutational signature analysis revealed that nearly all samples exhibited deficiencies in MMR genes, and we also identified deleterious mutations in MSH3-K383fs. Interpretation: This study revealed pMMR/MSI-H CRC as a distinct subgroup within CRC, which manifests diverse clinicopathological features and long-term prognostic outcomes. Distinct features in the tumour immune-microenvironment were observed in pMMR/MSI-H CRCs. Pathogenic deleterious mutations in MSH3-K383fs were frequently detected, suggesting another potential biomarker for identifying MSI-H. Funding: This work was supported by the Science and Technology Commission of Shanghai Municipality (20DZ1100101).

In recent years, environmental factors have received attention in the pathogenesis of neurodegenerative diseases. Other than genetic factors, the identification of environmental factors and modifiable risk factors may create opportunities to delay the onset or slow the progression of Lewy body disease. Researchers have made significant progress in understanding environmental and modifiable risk factors over the past 30 years. To date, despite the increasing number of articles assessing risk factors for Lewy body disease, few reviews have focused on their role in its onset. In this review, we reviewed the literature investigating the relationship between Lewy body disease and several environmental and other modifiable factors. We found that some air pollutants, exposure to some metals, and infection with some microorganisms may increase the risk of Lewy body disease. Coffee intake and the Mediterranean diet are protective factors. However, it is puzzling that low educational levels and smoking may have some protective effects. In addition, we proposed specific protocols for subsequent research directions on risk factors for neurodegenerative diseases and improved methods. By conducting additional case-control studies, we could explore the role of these factors in the etiopathogenesis of Lewy body disease, establishing a foundation for strategies aimed at preventing and reducing the onset and burden of the disease.

BackgroundLimited studies have explored the impact of the Omicron variant on SARS-CoV-2 infection, hospitalization, and associated factors among people living with HIV, particularly in China. The adjustment of preventive policies since December 2022 in China presents an opportunity to evaluate the real-world factors influencing SARS-CoV-2 infection and related hospitalization among people living with HIV. ObjectiveThis study aimed to investigate SARS-CoV-2 infection, hospitalization rates, and associated factors among people living with HIV following the adjustment of preventive policies from December 2022 to February 2023 in southeastern China. MethodsA cross-sectional telephone or web-based survey was conducted among people living with HIV in 5 cities in southeastern China from December 2022 to February 2023. Demographic information, SARS-CoV-2 infection and related hospitalization, and HIV-specific characteristics were collected from existing databases and special investigations. Multivariate logistic regression analyses were conducted to determine the associated factors for infection and hospitalization rates of SARS-CoV-2. Additionally, subgroup analyses were conducted for the association between vaccination and infection across different vaccination statuses and time since the last vaccination. ResultsAmong people living with HIV with a COVID-19 testing history, the SARS-CoV-2 infection rate was 67.13% (95% CI 65.81%-68.13%), whereas the hospitalization rate was 0.71% (95% CI 0.46%-0.97%). Factors such as age, latest CD4 cell count, latest HIV viral load, and transmission route were found to be associated with SARS-CoV-2 infection, while age, cancer, latest CD4 cell count, and latest HIV viral load were associated with SARS-CoV-2 hospitalization. In terms of SARS-CoV-2 vaccination, compared to unvaccinated people living with HIV, there was a lower infection rate among those who had been vaccinated for

BackgroundThe underlying molecular pathways of idiopathic pulmonary fibrosis (IPF), a progressive lung condition with a high death rate, are still mostly unknown. By using microarray datasets, this study aims to identify new genetic targets for IPF and provide light on the genetic factors that contribute to the development of IPF.MethodWe conducted a comprehensive analysis of three independent IPF datasets from the Gene Expression Omnibus (GEO) database, employing R software for data handling and normalization. Our evaluation of the relationships between differentially expressed genes (DEGs) and IPF included differential expression analysis, expression quantitative trait loci (eQTL) analysis, and Mendelian Randomization(MR) analyses. Additionally, we used Gene Set Enrichment Analysis (GSEA) and Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to explore the functional roles and pathways of these genes. Finally, we validated the results obtained for the target genes.ResultsWe identified 486 highly expressed genes and 468 lowly expressed genes that play important roles in IPF. MR analysis identified six significantly co-expressed genes associated with IPF, specifically C12orf75, SPP1, ZG16B, LIN7A, PPP1R14A, and TLR2. These genes participate in essential biological processes and pathways, including macrophage activation and neural system regulation. Additionally, CIBERSORT analysis indicated a unique immune cell distribution in IPF, emphasized the significance of immunological processes in the disease. The MR analysis was consistent with the results of the analysis of variance in the validation cohort, which strengthens the reliability of our MR findings.ConclusionOur findings provide new insights into the molecular basis of IPF and highlight the promise of therapeutic interventions. They emphasize the potential of targeting specific molecular pathways for the treatment of IPF, laying the foundation for further research and clinical work.

Heart failure is a continuously developing syndrome of cardiac insufficiency caused by diseases, which becomes a major disease endangering human health as well as one of the main causes of death in patients with cardiovascular diseases. The occurrence of heart failure is related to hemodynamic abnormalities, neuroendocrine hormones, myocardial damage, myocardial remodeling etc, lead to the clinical manifestations including dyspnea, fatigue and fluid retention with complex pathophysiological mechanisms. Currently available drugs such as cardiac glycoside, diuretic, angiotensin-converting enzyme inhibitor, vasodilator and β receptor blocker etc are widely used for the treatment of heart failure. In particular, natural products and related active ingredients have the characteristics of mild efficacy, low toxicity, multi-target comprehensive efficacy, and have obvious advantages in restoring cardiac function, reducing energy disorder and improving quality of life. In this review, we mainly focus on the recent advance including mechanisms and active ingredients of natural products for the treatment of heart failure, which will provide the inspiration for the development of more potent clinical drugs against heart failure.

Abstract The TMEM63 family proteins (A, B, and C), calcium-permeable channels in animals that are preferentially activated by hypo-osmolality, have been implicated in various physiological functions. Deficiency of these channels would cause many diseases including hearing loss. However, their structures and physiological roles are not yet well understood. In this study, we determine the cryo-electron microscopy (cryo-EM) structure of the mouse TMEM63C at 3.56 Å, and revealed structural differences compared to TMEM63A, TMEM63B, and the plant orthologues OSCAs. Further structural guided mutagenesis and calcium imaging demonstrated the important roles of the coupling of TM0 and TM6 in channel activity. Additionally, we confirm that TMEM63C exists primarily as a monomer under physiological conditions, in contrast, TMEM63B is a mix of monomer and dimer in cells, suggesting that oligomerization is a regulatory mechanism for TMEM63 proteins.

Abstract Background Emerging evidence has shown that myeloid cells that infiltrate into the peri-infarct region may influence the progression of ischemic stroke by interacting with microglia. Properdin, which is typically secreted by immune cells such as neutrophils, monocytes, and T cells, has been found to possess damage-associated molecular patterns (DAMPs) properties and can perform functions unrelated to the complement pathway. However, the role of properdin in modulating microglia-mediated post-stroke neuroinflammation remains unclear. Methods Global and conditional (myeloid-specific) properdin-knockout mice were subjected to transient middle cerebral artery occlusion (tMCAO). Histopathological and behavioral tests were performed to assess ischemic brain injury in mice. Single-cell RNA sequencing and immunofluorescence staining were applied to explore the source and the expression level of properdin. The transcriptomic profile of properdin-activated primary microglia was depicted by transcriptome sequencing. Lentivirus was used for macrophage-inducible C-type lectin (Mincle) silencing in microglia. Conditioned medium from primary microglia was administered to primary cortex neurons to determine the neurotoxicity of microglia. A series of cellular and molecular biological techniques were used to evaluate the proinflammatory response, neuronal death, protein–protein interactions, and related signaling pathways, etc. Results The level of properdin was significantly increased, and brain-infiltrating neutrophils and macrophages were the main sources of properdin in the ischemic brain. Global and conditional myeloid knockout of properdin attenuated microglial overactivation and inflammatory responses at the acute stage of tMCAO in mice. Accordingly, treatment with recombinant properdin enhanced the production of proinflammatory cytokines and augmented microglia-potentiated neuronal death in primary culture. Mechanistically, recombinant properdin served as a novel ligand that activated Mincle receptors on microglia and downstream pathways to drive primary microglia-induced inflammatory responses. Intriguingly, properdin can directly bind to the microglial Mincle receptor to exert the above effects, while Mincle knockdown limits properdin-mediated microglial inflammation. Conclusion Properdin is a new medium by which infiltrating peripheral myeloid cells communicate with microglia, further activate microglia, and exacerbate brain injury in the ischemic brain, suggesting that targeted disruption of the interaction between properdin and Mincle on microglia or inhibition of their downstream signaling may improve the prognosis of ischemic stroke.

Multi-source data-fusion approaches have been developed for estimating regional precipitation. However, studies considering the specific upper limits of the improved gridded rainfall data for different fusion approaches are limited. Here, the potential ranges of accuracy improvement for satellite and reanalysis rainfall products were addressed using various machine learning fusion approaches, including multivariate linear regression (MLR), feedforward neural network (FNN), random forest (RF), and long short-term memory (LSTM), over the Chinese mainland. All four fusion methods reduce errors in the original precipitation products. The upper limits of accuracy improvement in terms of correlation coefficient (CC) and root mean square error (RMSE) were 30.65 and 15.27%, respectively. M-RF showed the best average CC (0.828) and RMSE (4.62 mm/day) in the four seasons. LSTM performed the best under light rainfall events, whereas MLR and RF exhibited better performance under moderate and heavy rainfall events, respectively. Overall, these results serve as a basis for the fusion approach and technique selection, based on the comprehensive validation in different climate zones, altitudes, and seasons over the Chinese mainland. HIGHLIGHTS Machine learning fusion approaches were used for precipitation product estimation.; Four different models were used: MLR, feedforward neural network, RF, and LSTM.; All four fusion methods reduced errors in the original precipitation products.; LSTM showed the best performance for light rainfall events.; MLR and RF performed better for moderate and heavy rainfall events.;

Abstract Fusarium oxysporum f. sp. cubense (Foc) causes Fusarium wilt of banana (Musa spp.), a notorious soil-borne vascular fungal disease threatening the global banana industry. Phytopathogens secrete effectors to suppress plant immunity. However, little is known about the effectors of Foc race 4 (Foc4). In this study, we built a streamlined screening system (candidate effector prediction, RNA-seq-based expression level analysis, and cell death manipulative activity assessment based on transient expression in Nicotiana benthamiana) to identify candidate virulence-related effectors. In total, 80 candidate effector genes (CEGs) differentially expressed during plant colonization were predicted; 12 out of 15 characterized CEGs, including FoSSP17, could suppress BAX-triggered programmed cell death (PCD) in N. benthamiana and were induced during the infection of plants. FoSSP17 encodes a novel protein conserved in the Fusarium genus. FoSSP17 gene deletion mutants were not affected in vegetative growth and conidiation but showed reduced virulence. Furthermore, the deletion mutants triggered higher expression levels of host defense-related genes including PR1, PR3, PR5, and PR10. Signal peptide activity assay and subcellular localization assay suggested that FoSSP17 is a conventional secretory protein that exerts cell-death-suppressive activity inside plant cells. In addition, FoSSP17 suppressed pattern-triggered immunity in plants by inhibiting reactive oxygen species (ROS) accumulation, reducing callose deposition, and suppressing the expression of NbLOX and NbERF1 genes related to jasmonic acid (JA)-pathway and ethylene (ET)-pathway, respectively. Overall, a systemic screening of Foc4 candidate effectors reveals that FoSSP17 contributes to the virulence of Foc4 and suppresses pattern-triggered immunity in plants.

This paper presents an integrated framework for aircraft engines, which consists of three phases: modeling, control, and experimental testing. The engine is formulated as an uncertain T–S fuzzy model. By a hierarchical dynamical parameter clustering, the number and premise variables of fuzzy rules are optimized, which keeps the engine’s prime and representative dynamics. For each fuzzy rule, a global stability-guaranteed method is developed for the identification of the consequent uncertain dynamic model. The resulting stable T–S fuzzy model accurately approximates the actual engine dynamics in the operation space. Based on this fuzzy model, a new robust control is constructed with hierarchical compensators. The control parameters take advantage of the fuzzy blend of engine prime dynamics and uncertainty thresholds. Extensive hardware-in-loop (HIL) experimental tests in the flight envelope and a flight task cycle demonstrate the effectiveness and real-time performance of the proposed control. The settling times and overshoots of engine response are suppressed to be under 2.5 s and 10%, respectively.

Sepsis is a life-threatening condition arising from a dysregulated host immune response to infection, leading to a substantial global health burden. The accurate identification of bacterial pathogens in sepsis is essential for guiding effective antimicrobial therapy and optimising patient outcomes. Traditional culture-based bacterial typing methods present inherent limitations, necessitating the exploration of alternative diagnostic approaches. This study reports the successful application of Fourier-transform infrared (FT-IR) spectroscopy in combination with chemometrics as a potent tool for the classification and discrimination of microbial species and strains, primarily sourced from individuals with invasive infections. These samples were obtained from various children with suspected sepsis infections with bacteria and fungi originating at different sites. We conducted a comprehensive analysis utilising 212 isolates from 14 distinct genera, comprising 202 bacterial and 10 fungal isolates. With the spectral analysis taking several weeks, we present the incorporation of quality control samples to mitigate potential variations that may arise between different sample plates, especially when dealing with a large sample size. The results demonstrated a remarkable consistency in clustering patterns among 14 genera when subjected to principal component analysis (PCA). Particularly, Candida, a fungal genus, was distinctly recovered away from bacterial samples. Principal component discriminant function analysis (PC-DFA) allowed for distinct discrimination between different bacterial groups, particularly Gram-negative and Gram-positive bacteria. Clear differentiation was also observed between coagulase-negative staphylococci (CNS) and Staphylococcus aureus isolates, while methicillin-resistant S. aureus (MRSA) was also separated from methicillin-susceptible S. aureus (MSSA) isolates. Furthermore, highly accurate discrimination was achieved between Enterococcus and vancomycin-resistant enterococci isolates with 98.4% accuracy using partial least squares-discriminant analysis. The study also demonstrates the specificity of FT-IR, as it effectively discriminates between individual isolates of Streptococcus and Candida at their respective species levels. The findings of this study establish a strong groundwork for the broader implementation of FT-IR and chemometrics in clinical and microbiological applications. The potential of these techniques for enhanced microbial classification holds significant promise in the diagnosis and management of invasive bacterial infections, thereby contributing to improved patient outcomes.

Gas control in the upper corner of the natural coal mining face with high gas is always a difficult problem that troubles the safe production of the working face. Among them, a high gas-prone natural coal mining face with ground air leakage is more likely to cause gas and CO to exceed limits in the corner of the working surface and is difficult to control. The traditional treatment methods often have some problems; for example, it is easy to increase air leakage in the gob with the method of gas extraction in the gob, which is not conducive to the prevention and control of spontaneous combustion of coal in the gob. At present, the more effective method is the pressure-equalization method. However, the pressure-equalization measures need to establish a complex pressure-equalization system, and close cooperation between the systems is required; once the system power fails or equipment failure occurs, the pressure-equalization state changes randomly, and it is easy to cause gas over-limits and other faults. Therefore, this paper presents a new method to control gas in the gob of a coal seam by pumping the gob of the upper-adjacent layer, using the negative pressure of pumping, and balancing the negative pressure of the upper-adjacent layer and the gob of the coal seam to form a new pressure-equalization relationship. This method can prevent the toxic and harmful gases in the goaf of the upper-adjacent layer from escaping into the passageway of the gob of the local coal seam, reduce the air leakage in the goaf, and benefit the gas control and spontaneous coal combustion prevention in the goaf.

Abstract Background Hypothyroidism (HT) and subclinical HT after radiotherapy is frequent in nasopharyngeal carcinoma (NPC) patients, results in negative impact on patients' quality of life. The percentage of thyroid volume receiving more than 40 Gy (V40) ≤ 85% was reported to be a useful dose constraint to adopt during intensity-modulated radiation therapy (IMRT) planning. This study aims to verify whether V40 ≤ 85% can be used as an effective dose constraint in IMRT planning in a randomized clinical trial. Methods This single-center 1:1 randomized clinical trial was conducted in Fujian province hospital between March 2018 and September 2022. All patients were treated with IMRT and randomized to induction chemo followed by concurrent chemo-IMRT or concurrent chemo-IMRT alone. Ninety-two clinically NPC patients were included in this study. The thyroid function tests were performed for all patients before and after radiation at regular intervals. Thyroid dose-constraint was defined as V40 ≤ 85%. The primary outcome in this study was subclinical HT. Results Median follow up was 34 months. Significant difference in the incidence of subclinical HT between the thyroid dose-constraint group and unrestricted group was observed (P = 0.023). The risk of subclinical HT in the thyroid dose-constraint group was lower than that in the unrestricted group (P = 0.022). Univariate and multivariate cox regression analysis indicated that thyroid dose-constraint was a protective effect of subclinical HT (HR = 0.408, 95% CI 0.184–0.904; HRadjusted = 0.361, 95% CI 0.155–0.841). Conclusion V40 ≤ 85% can be used as an effective dose constraint in IMRT planning to prevent radiation-induced subclinical HT.

To further clarify the proppant transport and placement law in multi-branched fractures induced by volume fracturing, proppant transport simulation experiments were performed with different fracture shapes, sand ratios, branched fracture opening time and injection sequence of proppants in varied particle sizes. The results show that the settled proppant height increases and the placement length decreases in main fractures as the fracturing fluid diverts gradually to the branched fractures at different positions. The flow rate in branched fractures is the main factor affecting their filling. The diverion to branched fractures leads to low flow rate and poor filling of far-wellbore branched fractures. The inclined fracture wall exerts a frictional force on the proppant to slow its settlement, thus enhancing the vertical proppant distribution in the fracture. The increase of sand ratio can improve the filling of near-wellbore main fracture and far-wellbore branched fracture and also increase the settled proppant height in main fracture. Due to the limitation of fracture height, when the sand ratio increases to a certain level, the increment of fracture filling decreases. When branched fracture is always open (or extends continuously), the supporting effect on the branched fractures is the best, but the proppant placement length within the main fractures is shorter. The fractures support effect is better when it is first closed and then opened (or extends in late stage) than when it is first opened and then closed (or extends in early stage). Injecting proppants with different particle sizes in a specific sequence can improve the placement lengths of main fracture and branched fracture. Injection of proppants in an ascending order of particle size improves the near-wellbore fracture filling, to a better extent than that in a descending order of particle size.

Abstract Background Obesity has been confirmed to be associated with infertility. However, the association between metabolically healthy obesity (MHO), a subset of obesity with no metabolic abnormalities, and female infertility has not yet been investigated. This study aimed to examine the association between MHO and the risk of female infertility among United States. Methods This study utilized a cross-sectional design and included 3542 women aged 20–45 years who were selected from the National Health and Nutrition Examination Survey (NHANES) 2013–2020 database. The association between MHO and the risk of infertility was evaluated using risk factor–adjusted logistic regression models. Results Higher BMI and WC were associated with increased infertility risk after adjusting for potential confounding factors (OR (95% CI): 1.04(1.02, 1.06), P = 0.001; OR (95% CI): 1.02 (1.01, 1.03), P

Abstract Background Anti-NMDA receptor (NMDAR) encephalitis is an autoimmune disease characterized by complex neuropsychiatric syndrome and cerebrospinal fluid (CSF) NMDAR antibodies. Triggering receptor expressed on myeloid cells 2 (TREM2) has been reported to be associated with inflammation of the central nervous system (CNS). Matrix metalloproteinase-9 (MMP9) and cluster of differentiation (CD44) were measured to evaluate blood‒brain barrier (BBB) permeability in anti-NMDAR encephalitis. The roles of microglial activation and BBB disruption in anti-NMDAR encephalitis are not well known. Findings In this work, we detected increased expression levels of CSF sTREM2, CSF and serum CD44, and serum MMP9 in anti-NMDAR encephalitis patients compared with controls. CSF sTREM2 levels were positively related to both CSF CD44 levels (r = 0.702, p