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Abstract Background There is limited evidence regarding the modifying effects of parents’ age at childbirth on the relationship between air pollution and obesity in plateau areas. This study aimed to explore the association between particulate matter (PM) and child obesity, specifically investigating whether parents’ age at childbirth could modify this relationship in the Tibetan plateau, China. Methods Satellite-based random forest models were used to estimate the concentrations of PM2.5 (particulate matter with aerodynamic diameters ≤ 2.5 μm), PMc (particulate matter with aerodynamic diameters between 2.5 μm and 10 μm), and PM10 (particulate matter with aerodynamic diameters ≤ 10 μm). Linear and logistic regression models were employed to assess associations between PM exposure and obesity indicators, and effect estimates of PM across different particle sizes were compared. Results The study comprised 2,015 children under five years old. Postnatal exposure to PM was positively associated with overweight and obesity (OWO), waist-to-hip ratio (WHR) and body mass index (BMI). Among these pollutants, PM10 exhibited the strongest association with BMI and OWO, whereas PMc showed the strongest association with WHR. An interquartile range (IQR) increase in PM2.5 (5.67 µg/m3), PMc (5.25 µg/m3), and PM10 (11.06 µg/m3) was positively associated with OWO (odd ratio [OR] for PM2.5 = 1.52, 95% confidence interval [CI] for PM2.5 = 1.24 to 1.85; OR for PMc = 1.50, 95% CI for PMc = 1.19 to 1.88; OR for PM10 = 1.56, 95% CI for PM10 = 1.25 to 1.96), respectively. Stratified analysis by parents’ age at childbirth indicated that the effects of PM on obesity indicators were more pronounced in the advanced age group. Conclusions Long-term exposure to PM was positively associated with OWO, WHR, and BMI. Our findings also underscore the importance of examining the effects of ambient PM exposure on OWO, particularly in parents of advanced age at childbirth.

Abstract Background In clinical oncology practice, patient-reported outcomes (PROs) are essential for assessing the symptom burden, quality of life, and psychological status of patients. However, there remains a gap between the use of PROs in an oncologic setting and its implementation. Furthermore, numerous reviews in PRO implementation are often based on one particular technology, setting, or health condition, making it difficult to obtain a comprehensive and coherent summary of available evidence to help plan and undertake implementation. This systematic review aims to identify and integrate enablers and barriers to PRO implementation through the comprehensive framework for implementation research (CFIR) to provide a reference for implementing patient-reported outcomes management in oncology settings. Methods This review strictly observed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. PubMed, Web of Science, CINAHL, Embase, and PsycINFO databases were systematically searched using a three-step search strategy. The search was limited from the inception of each database to April 2024. Articles describing facilitators and barriers to implementing PROs in clinical oncology practice were included. Two researchers screened the literature independently, and the quality assessment of cross-sectional, qualitative, and mixed studies was completed using the critical appraisal tools recommended by Joanna Briggs Institute (JBI) and the mixed methods assessment tool, respectively. Basic information about the included studies and determinants affecting PRO implementation was extracted, and coding categorization of facilitators and barriers was completed based on the 48 constructs provided by the CFIR framework. Results We included 30 studies from 5,649 search results, including 25 original and 5 review studies. The quality of the literature for qualitative studies was generally good, and the quality for quantitative and mixed studies was assessed as fair. We identified 52 facilitators and 50 barriers in the included literature, covering the domains used in the CFIR framework and 39 constructs, mainly including "Innovation Evidence-Base", "Innovation Complexity", "Innovation Design", "Structural Characteristics", "Compatibility", "Incentive Systems", "Access to Knowledge & Information", "Innovation Deliverers", "Innovation Recipients", and "Planning". Conclusions This systematic review integrated facilitators and barriers affecting PRO implementation in routine oncology clinical practice settings and categorized them through the CFIR framework. These influencing factors should be fully considered in future clinical practice to ensure the successful implementation of PROs. Trial registration It has been registered prospectively in PROSPERO under the registration number 42024532983.

Abstract Gestational diabetes mellitus (GDM) is the first spontaneous hyperglycemia during pregnancy. Early diagnosis and intervention are important for the management of the disease. This study compared and analyzed the proteins of total plasma exosomes (T-EXO) and placental-derived exosomes (PLAP-EXO) in pregnant women who subsequently developed GDM (12–16 weeks), GDM patients (24–28 weeks) and their corresponding controls to investigate the pathogenesis and biomarkers of GDM associated with exosomes. The exosomal proteins were extracted and studied by proteomics approach, then bioinformatics analysis was applied to the differentially expressed proteins (DEPs) between the groups. At 12–16 and 24–28 weeks of gestation, 36 and 21 DEPs were identified in T-EXO, while 34 and 20 DEPs were identified in PLAP-EXO between GDM and controls, respectively. These proteins are mainly involved in complement pathways, immunity, inflammation, coagulation and other pathways, most of them have been previously reported as blood or exosomal proteins associated with GDM. The findings suggest that the development of GDM is a progressive process and that early changes promote the development of the disease. Maternal and placental factors play a key role in the pathogenesis of GDM. These proteins especially Hub proteins have the potential to become predictive and diagnostic biomarkers for GDM.

Purinergic signaling plays a causal role in the modulation of immune inflammatory response in the course of psoriasis, but its regulatory mechanism remains unclear. As a member of purinoceptors, P2Y6R mainly distributed in macrophages was significantly up-expressed in skin lesions from patients with psoriasis in the present study. Here, the severity of psoriasis was alleviated in imiquimod-treated mice with macrophages conditional knockout of P2Y6R, while the cell-chat algorithm showed there was a correlation between macrophage P2Y6R and Th1 cells mediated by IL-27. Mechanistically, P2Y6R enhanced PLCβ/p-PKC/MAPK activation to induce IL-27 release dependently, which subsequently regulated the differentiation of Th1 cells, leading to erythematous and scaly plaques of psoriasis. Interestingly, we developed a novel P2Y6R inhibitor FS-6, which bonds with the ARG266 side chain of P2Y6R, exhibited remarkable anti-psoriasis effects targeting P2Y6R. Our study provides insights into the role of P2Y6R in the pathogenesis of psoriasis and suggests its potential as a target for the development of therapeutic interventions. A novel P2Y6R inhibitor FS-6 could be developed as an anti-psoriasis drug candidate for the clinic.

Abstract Charge density waves (CDWs) in transition metal dichalcogenides are the subject of growing scientific interest due to their rich interplay with exotic phases of matter and their potential technological applications. Here, using density functional theory with advanced meta-generalized gradient approximations (meta-GGAs) and linear response time-dependent density functional theory (TDDFT) with state-of-the-art exchange-correlation kernels, we investigate the electronic, vibrational, and optical properties in 1T-TiSe2 with and without CDW. In both bulk and monolayer TiSe2, the electronic bands and phonon dispersions in either normal or CDW (semiconducting) phase are described well via meta-GGAs, which separate the valence and conduction bands just as HSE06 does but with significantly more computational feasibility. The experimentally observed humps of electron energy loss spectroscopy are successfully reproduced in TDDFT. Our work opens the door to simulating these complexities in CDW compounds from first principles by revealing meta-GGAs as an accurate low-cost alternative to HSE06.

Objective The constructor of Qingdao Metro Line 13 has a higher requirement for energy saving during operation. In the process of construction, in order to implement the concept of energy saving, environmental protection, and intelligence in rail transit and meet the actual demand, it is necessary to seek entry points for energy saving through the control system in metro electromechanical system. Method Ventilation and air conditioning, as the key energy consumers of metro, are the focus of the present energy saving. Therefore, in consideration of their characteristics, CCCC Second Highway Consultants Co. Ltd. creatively sets up an energy-saving energy management system and successfully launches it for online operation. The system for the first time opens up the information transmission channel between energy management and air-water linkage energy-saving control of environmental control system, coordinating the two independent systems. With ana-lysis, regulation and management of energy consumption, the linkage control of air and water systems within the environmental control system is realized by using the energy-saving energy management system model and control strategy, technically achieving the goal of energy saving. Result & Conclusion When the energy-saving mode and the non-energy-saving mode run alternately for the same period, the energy consumption of the air conditioning water and air systems at each testing station is tested, recorded and compared, and the energy-saving rate of the above management system is calculated. Based on the results, it is concluded that the energy-saving effect can fully meet the minimum energy-saving requirements during system design. By comparing the changes in the station internal environment under the two operating modes during the set time period, it is determined that the operation of the energy-saving energy management system can ensure stable and comfortable internal environment of the station under the premise of energy saving.

Intracranial-intracranial bypass is a crucial treatment for complex intracranial aneurysms, as it not only achieves aneurysm eradication but also ensures perfusion to the bypassed vascular territory. To ensure bypass vessels patency and postoperative neurological recovery in patients with aneurysm, it is necessary to consider multiple characteristics of the aneurysm, donor artery and recipient artery. This comprehensive evaluation enables the selection of appropriate surgical decisions and bypass techniques. In recent years, with the advancement of intracranial-intracranial bypass, several new options including donor artery and recipient artery, anastomosis techniques, graft vessels, and auxiliary techniques have been added for neurosurgeons to choose from. This review aims to introduce the technical advances, surgical experience of intracranial - intracranial bypass for complex intracranial aneurysms, with the intention of facilitating clinical application of intracranial-intracranial bypass.

Abstract Background The Correa’s cascade, encompassing chronic non-atrophic gastritis, atrophic gastritis, intestinal metaplasia, and dysplasia, represents the well-recognized pathway for the development of non-cardia gastric cancer. Population-based studies on all-cause and cause-specific mortalities among patients with gastric lesions in Correa’s cascade are scarce. Methods We compiled a cohort of 340 744 eligible patients who had undergone endoscopy with biopsy for non-malignant indications during the period 1979–2011, which was followed up until 2014. Standardized mortality ratios (SMRs) with 95% confidence intervals (CIs) provided estimation of the relative risk, using the general Swedish population as reference. Cox regression model was used to estimate hazard ratios (HRs) of death for internal comparison. Results A total of 306 117 patients were included in the final analysis, accumulating 3,049,009 person-years of follow-up. In total 106,625 deaths were observed during the study period. Compared to the general population, excess risks of overall mortality were noted in all subgroups, with SMRs ranging from 1.11 (95% CI 1.08–1.14) for the normal mucosa group to 1.54 (95% CI 1.46–1.62) for the dysplasia group. For cause-specific mortalities, mortality from gastric cancer gradually increased along Correa’s cascade, with excess risk rising from 105% for patients with chronic gastritis to more than 600% for the dysplasia group. These results were confirmed in the comparison with the normal mucosa group. For non-cancer conditions, increased death risks were noted for various diseases compared to the general population, especially among patients with more severe gastric precancerous lesions. But the results were confirmed only for “infectious diseases and parasitic diseases”, “respiratory system diseases”, and “digestive system disease”, when using the normal mucosa group as reference. Conclusions Increased mortality from gastric cancer suggests that early recognition and intervention of gastric precancerous lesions probably benefit the patients. Excess mortality due to non-cancer conditions should be interpreted with caution, and future studies are warranted.

Abstract Background Temperature fluctuations can impact the occurrence and progression of respiratory system diseases. However, the current understanding of the impact of temperature on acute exacerbation of chronic obstructive pulmonary disease (AECOPD) remains limited. Therefore, our study aims to investigate the relationship between daily mean temperature (DMT) and the risk of AECOPD hospitalizations within Panzhihua City. Methods We systematically collected data on AECOPD hospitalizations at Panzhihua Central Hospital from 2015 to 2020 and meteorological factors across Panzhihua City’s districts. A two-stage analysis method was used to establish a distributed lag non-linear model to elucidate the influence of DMT on the frequency of admissions for AECOPD. Subgroup analyses were conducted by gender and age to identify populations potentially susceptible to the impact of DMT. Results A total of 5299 AECOPD hospitalizations cases were included. The DMT and the risk of AECOPD hospitalization showed a non-linear exposure–response pattern, with low temperatures exacerbating the risk of hospitalizations. The lag effects of low temperature and relatively low temperature peaked at 2th day, with the lag effects disappearing at 16–17 days. Females and elders aged ≥ 65 years were more sensitive to effects of low and relatively low temperature at lag 0–4 days, while male AECOPD patients exhibited longer lasting lag effects. Conclusions Low temperatures are associated with an increased risk of AECOPD hospitalizations. Females or elders aged ≥ 65 years with chronic obstructive pulmonary disease should pay more attention to taking protective measures in cold environments. These findings are crucial for the formulation of public health policies, as they will help significantly alleviate the burden of AECOPD and improve respiratory health in the face of climate challenges.

Abstract The upper respiratory tract is the initial site of SARS-CoV-2 infection. Nasal spike-specific secretory immunoglobulin A (sIgA) correlates with protection against Omicron breakthrough infection. We report that intranasal vaccination using human adenovirus serotype 5 (Ad5) vectored Omicron spike in people who previously vaccinated with ancestral vaccine could induce robust neutralizing sIgA in the nasal passage. Nasal sIgA was predominantly present in dimeric and multimeric forms and accounted for nearly 40% of total proteins in nasal mucosal lining fluids (NMLFs). A low-level IgG could also be detected in NMLFs but not IgM, IgD, and IgE. After a complete nasal wash, sIgA in the nasal passage could be replenished rapidly within a few hours. A comparison of purified paired serum IgA, serum IgG, and nasal sIgA from the same individuals showed that sIgA was up to 3-logs more potent than serum antibodies in binding to spikes and in neutralizing Omicron subvariants. Serum IgG and IgA failed to neutralize XBB and BA.2.86, while nasal sIgA retained potent neutralization against these newly emerged variants. Further analysis showed that sIgA was more effective than IgG or IgA in blocking spike-mediated cell-to-cell transmission and protecting hACE2 mice from XBB challenge. Using a sIgA monoclonal antibody as a reference, we estimated that the total nasal sIgA contains about 2.6–3.9% spike-specific sIgA in NMLFs collected approximately one month after intranasal vaccination. Our study provided insights for developing intranasal vaccines that can induce sIgA to build an effective and mutation-resistant first-line immune barrier against constantly emerging variants.

Abstract The study of brain differences across Eastern and Western populations provides vital insights for understanding potential cultural and genetic influences on cognition and mental health. Diffusion MRI (dMRI) tractography is an important tool in assessing white matter (WM) connectivity and brain tissue microstructure across different populations. However, a comprehensive investigation into WM fiber tracts between Eastern and Western populations is challenged due to the lack of a cross-population WM atlas and the large site-specific variability of dMRI data. This study presents a dMRI tractography atlas, namely the East-West WM Atlas, for concurrent WM mapping between Eastern and Western populations and creates a large, harmonized dMRI dataset (n=306) based on the Human Connectome Project and the Chinese Human Connectome Project. The curated WM atlas, as well as subject-specific data including the harmonized dMRI data, the whole brain tractography data, and parcellated WM fiber tracts and their diffusion measures, are publicly released. This resource is a valuable addition to facilitating the exploration of brain commonalities and differences across diverse cultural backgrounds.

Alzheimer's disease (AD) is one of the most common age-related neurodegenerative diseases and the most devastating form of senile dementia. It has a complex mechanism and no effective treatment. Exploring the pathogenesis of AD and providing ideas for treatment can effectively improve the prognosis of AD. Microglia were incubated with β-amyloid protein 1-42 (Aβ1-42) to construct an AD cell model. After microglia were activated, cell morphology changed, the expression level of inflammatory factors increased, cell apoptosis was promoted, and the expression of microtubule-associated protein (Tau protein) and related proteins increased. By up-regulating and down-regulating Toll-like receptor 4 (TLR4), the cells were divided into TLR4 knockdown negative control group(Lv-NC group), TLR4 knockdown group(Lv-TLR4 group), TLR4 overexpression negative control group(Sh-NC group), and TLR4 overexpression group(Sh-TLR4 group). The expression of inflammatory factors was detected again. It was found that compared with the Lv-NC group, the expression of various inflammatory factors in the Lv-TLR4 group decreased, cell apoptosis was inhibited, and the expression of Tau protein and related proteins decreased. Compared with the Sh-NC group, the expression of inflammatory factors in the Sh-TLR4 group increased, cell apoptosis was promoted, and the expression of Tau protein and related proteins increased. These results indicate that Aβ1-42 may promote microglial activation and apoptosis by binding to TLR4. Reducing the expression of TLR4 can reduce the occurrence of inflammatory response in AD cells and slow down cell apoptosis. Therefore, TLR4 is expected to become a new target for the prevention and treatment of AD.

The purpose of this study was to investigate the relationship between childhood chronic stress(CCS), Protein kinase C beta (PRKCB) methylation and adolescent major depressive disorder (MDD). After recruiting 100 adolescents with MDD and 50 healthy controls (HCs), we evaluated the severity of CCS. PRKCB methylation was assessed by pyrosequencing using whole blood-derived DNA. To explore the relationship between CCS, PRKCB and adolescent MDD, we conducted correlation analysis and regression analysis, and constructed multiplicative interaction models and generalized linear models. PRKCB methylation and CCS were both found to be associated with MDD, and CCS was associated with PRKCB methylation. No significant CCS-PRKCB methylation interactions were observed. However, we found the interaction of CCS and MDD on PRKCB methylation. Our results found that PRKCB methylation was influenced by CCS and the disease itself, and PRKCB methylation was significantly positively associated with MDD severity, suggesting that PRKCB methylation may be a potential biomarker for adolescent MDD. This study is a cross-sectional observational study, which cannot draw the conclusion of causality. Prospective cohort studies are needed to further examine the relationship between CCS, adolescent MDD, and PRKCB methylation.

The continuous emergence of highly immune-evasive SARS-CoV-2 variants has challenged vaccine efficacy. A vaccine that can provide broad protection is desirable. We evaluated the immunogenicity of a series of monovalent and bivalent adenovirus-vectored vaccines containing the spikes of Wildtype (WT), Beta, Delta, Omicron subvariants BA.1, BA.2, BA.2.12.1, BA.2.13, BA.3, BA.5, BQ.1.1, and XBB. Vaccination in mice using monovalent vaccines elicited the highest neutralizing titers against each self-matched strain, but against other variants were reduced 2− to 73-fold. A bivalent vaccine consisting of WT and BA.5 broadened the neutralizing breadth against pre-Omicron and Omicron subvariants except XBB. Among bivalent vaccines based on the strains before the emergence of XBB, a bivalent vaccine consisting of BA.2 and BA.5 elicited the most potent neutralizing antibodies against Omicron subvariants, including XBB. In mice primed with injected WT vaccine, intranasal booster with a bivalent vaccine containing XBB and BA.5 could elicit broad serum and respiratory mucosal neutralizing antibodies against all late Omicron subvariants, including XBB. In mice that had been sequentially vaccinated with WT and BA.5, intranasal booster with a monovalent XBB vaccine elicited greater serum and mucosal XBB neutralizing antibodies than bivalent vaccines containing XBB. Both monovalent and bivalent XBB vaccines induced neutralizing antibodies against EG.5. Unlike the antibody response, which is highly variant-specific, mice receiving either monovalent or bivalent vaccines elicited comparable T-cell responses against all variants. Furthermore, intranasal but not intramuscular booster induced antigen-specific lung resident T cells. This study provides insights into the design of the COVID-19 vaccine and vaccination strategies.

Soil acidification poses a significant environmental challenge in China’s southern red soil regions, impacting the abundance of soil microbes and their capacity for carbon fixation. The effect of vegetation types on soil’s biological and abiotic components under acidification, and their regulatory role on the CO2 fixation mechanisms of soil autotrophic microorganisms, is difficult to examine. This gap in understanding constrains the assessment of the carbon fixation potential of red soils. To address this, indoor cultivation coupled with 13C stable isotope labeling was employed to evaluate the disparate abilities of autotrophic microorganisms to assimilate and store CO2 across five vegetation soils from the Qianyanzhou acidic red soil experimental station in China. Findings indicate that carbon fixation rates in these soils spanned from 4.25 to 18.15 mg C kg−1 soil d−1, with paddy field soils demonstrating superior carbon fixation capabilities compared to orchard, coniferous forest, broad-leaved forest, and wasteland soils. The 13C fixation rate in the 0–10 cm soil stratum surpassed that of the 10–30 cm layer across all vegetation types. High-throughput sequencing of 16S rRNA, following cbbL gene purification and amplification, identified Bradyrhizobium, Azospirillum, Burkholderia, Paraburkholderia, and Thermomonospora as the predominant autotrophic carbon-fixing microbial genera in the soil. PERMANOVA analysis attributed 65.72% of the variance in microbial community composition to vegetation type, while soil depth accounted for a mere 8.58%. Network analysis of microbial co-occurrence suggested the soil microbial interactions and network complexity changed with the change of vegetation types. Additionally, multiple linear regression analysis pinpointed the Shannon index and soil organic carbon (SOC) content as primary influencers of carbon fixation rates. Structural equation modeling suggested that iron enrichment and acidification indirectly modulated carbon fixation rates by altering SOC and autotrophic bacterial diversity. This investigation shows the spatial dynamics and mechanisms underpinning microbial carbon fixation across varying vegetation types in southern China’s red soil regions.

Objective: The objective of this study was to elucidate the molecular mechanisms underlying the potential contribution of commonly utilized plasticizers, including Diethyl phthalate (DEP), Dimethyl phthalate (DMP), and Dioctyl phthalate (DOP), to the pathogenesis of breast cancer. This study aimed to highlight the complex interactions between these environmental chemicals and key molecular pathways implicated in tumorigenesis. Methods: We employed network toxicology and molecular docking techniques to analyze the interactions between plasticizers and key proteins implicated in breast cancer. Utilizing databases such as the TCGA, we performed an expression analysis of selected key genes in breast cancer tissue compared to normal controls. Enrichment analysis was conducted to identify the biological pathways associated with these genes. Results: Enrichment analysis highlighted the association of these plasticizer-targeted genes with pathways integral to adenocarcinoma development, suggesting a broad impact of plasticizers on hormone-dependent and other forms of cancers. Subsequent expression analysis using data from the TCGA breast cancer database indicated significant upregulation or downregulation of these genes in breast cancer tissues compared to normal controls, confirming their pivotal roles in tumor biology. Furthermore, the molecular docking analysis revealed that plasticizers, including DEP, DMP, and DOP, exhibit specific binding interactions with key proteins such as MAPK1, AKT1, SRC, ESR1, and ALB, which are crucial in the regulation of breast cancer pathogenesis. Conclusion: The study provides evidence that exposure to plasticizers may influence breast cancer pathogenesis through interactions with critical proteins and signaling pathways. By employing network pharmacology, protein interactions, and molecular docking, our findings highlight the potential risks posed by plasticizers. These results underscore the need for further epidemiological and clinical research to fully understand the implications of plasticizer exposure on breast cancer risk, thus informing future preventive and therapeutic strategies.

Abstract Background In knee osteoarthritis (KOA), treatments involving knee injections of bone marrow-derived mesenchymal stem cells (BM-MSC), adipose tissue-derived mesenchymal stem cells (AD-MSC), or umbilical cord-derived mesenchymal stem cells (UC-MSC) have shown promise in alleviating symptoms. However, which types of mesenchymal stem cells (MSCs) have the best therapeutic outcomes remain uncertain. Method We systematically searched PubMed, OVID, Web of Science, and the Cochrane Library until January 1, 2024. The study evaluated five endpoints: Visual Analog Score (VAS) for Pain, Range of Motion (ROM), Whole-Organ Magnetic Resonance Imaging Score (WORMS), Western Ontario McMaster Universities Osteoarthritis Index (WOMAC), and adverse events (ADs). Standard meta-analysis and network meta-analysis were performed using Stata 16.0. Results Fifteen studies involving 585 patients were included in the meta-analysis. Standard meta-analysis revealed significant improvements with MSCs in VAS score (P

Abstract In chronic kidney disease (CKD), renal fibrosis is an unavoidable result of various manifestations. However, its pathogenesis is not yet fully understood. Here, we revealed the novel role of Homeobox D10 (HOXD10) in CKD-related fibrosis. HOXD10 expression was downregulated in CKD-related in vitro and in vivo fibrosis models. UUO model mice were administered adeno-associated virus (AAV) containing HOXD10, and HOXD10 overexpression plasmids were introduced into human proximal tubular epithelial cells induced by TGF-β1. The levels of iron, reactive oxygen species (ROS), lipid ROS, the oxidized glutathione/total glutathione (GSSG/GSH) ratio, malonaldehyde (MDA), and superoxide dismutase (SOD) were determined using respective assay kits. Treatment with AAV–HOXD10 significantly attenuated fibrosis and renal dysfunction in UUO model mice by inhibiting NOX4 transcription, ferroptosis pathway activation, and oxidative stress. High levels of NOX4 transcription, ferroptosis pathway activation and profibrotic gene expression induced by TGF-β1/erastin (a ferroptosis agonist) were abrogated by HOXD10 overexpression in HK-2 cells. Moreover, bisulfite sequencing PCR result determined that HOXD10 showed a hypermethylated level in TGF-β1-treated HK-2 cells. The binding of HOXD10 to the NOX4 promoter was confirmed by chromatin immunoprecipitation (ChIP) analysis and dual-luciferase reporter assays. Targeting HOXD10 may represent an innovative therapeutic strategy for fibrosis treatment in CKD.

Abstract Background Osteonecrosis of the femoral head (ONFH) is a common clinical disease. Improper treatment can lead to femoral head collapse and hip joint dysfunction. Core decompression is particularly important for early ONFH. However, subtrochanteric fractures after core decompression cause some clinical problems. Case presentation This article describes a 34-year-old male patient with early ONFH. After core decompression, he suffered a subtrochanteric fracture of the femur while bearing weight on the affected limb when going up stairs. He was subsequently treated with open reduction and intramedullary nail fixation. Conclusion When core decompression is used to treat ONFH, the location or size of the drill hole, whether a tantalum rod or bone is inserted, and partial weight-bearing of the affected limb may directly affect whether a fracture occurs after surgery. It is hoped that this case report can provide a reference for clinical orthopedic surgeons in the treatment of early ONFH.

Abstract Introduction Incontinentia pigmenti (IP) is a rare neuroectodermal dysplasia caused by a defect in the IKBKG gene. The pathogenesis of central nervous system injury is believed to be related to microvascular ischemia. Currently, few treatment strategies are available for the inflammatory phase. Materials and methods This retrospective descriptive analysis included the clinical data of 41 children with IP collected from 2007 to 2021 in Xi’an, China, comprising clinical characteristics, imaging findings, blood cell analysis, skin histopathology, and genetic data. Results Fourteen children (34%) aged 4 days to 5 months exhibited clinical signs and symptoms, including convulsions, delayed psychomotor development following neurological damage, and revealed significant MRI abnormalities, including ischemia, hypoxia, cerebral hypoperfusion, hemorrhage, encephalomalacia, and cerebral atrophy. Eight of the 24 patients (33%) presented with retinal vascular tortuosity and telangiectasis, accompanied by neovascularization and hemorrhage. Thirty-eight children (93%) had elevated eosinophils (mean: 3.63 ± 4.46 × 109), and 28 children (68%) had significantly elevated platelets (mean: 420.16 ± 179.43 × 109). Histopathology of skin revealed microvascular extravasation and vasodilation with perivascular and intravascular eosinophilic infiltration. Conclusion Brain injury in IP occurs during infancy until 5 months of age, which is also the acute dermatitis phase accompanied by eosinophilia and an increased platelet count. This study provides evidence of microvascular damage to the skin and fundus during the inflammatory phase. The mechanism of microvascular damage may be similar to that in the brain.

Abstract Background As the greenhouse effect intensifies, global temperatures are steadily increasing, posing a challenge to bread wheat (Triticum aestivum L.) production. It is imperative to comprehend the mechanism of high temperature tolerance in wheat and implement breeding programs to identify and develop heat-tolerant wheat germplasm and cultivars. Results To identify quantitative trait loci (QTL) related to heat stress tolerance (HST) at seedling stage in wheat, a panel of 253 wheat accessions which were re-sequenced used to conduct genome-wide association studies (GWAS) using the factored spectrally transformed linear mixed models (FaST-LMM). For most accessions, the growth of seedlings was found to be inhibited under heat stress. Analysis of the phenotypic data revealed that under heat stress conditions, the main root length, total root length, and shoot length of seedlings decreased by 47.46%, 49.29%, and 15.19%, respectively, compared to those in normal conditions. However, 17 varieties were identified as heat stress tolerant germplasm. Through GWAS analysis, a total of 115 QTLs were detected under both heat stress and normal conditions. Furthermore, 15 stable QTL-clusters associated with heat response were identified. By combining gene expression, haplotype analysis, and gene annotation information within the physical intervals of the 15 QTL-clusters, two novel candidate genes, TraesCS4B03G0152700/TaWRKY74-B and TraesCS4B03G0501400/TaSnRK3.15-B, were responsive to temperature and identified as potential regulators of HST in wheat at the seedling stage. Conclusions This study conducted a detailed genetic analysis and successfully identified two genes potentially associated with HST in wheat at the seedling stage, laying a foundation to further dissect the regulatory mechanism underlying HST in wheat under high temperature conditions. Our finding could serve as genomic landmarks for wheat breeding aimed at improving adaptation to heat stress in the face of climate change.

Here we have shown the novel biosynthesis of silver nanoparticles (Ag NPs) encapsulated by chitosan polymers in the presence of Achillea millefolium aqueous extract (Ag NPs@CHI). The Ag ions were first embedded over the chitosan surface enriched with polar organofunctions like amines (NH2) and hydroxyls, and subsequently the ions were reduced green-metrically by the electron rich phytochemicals of the plant extract. After the synthesis numerous techniques, including the UV-vis spectrum, transmission electron microscopy, FE-SEM, EDS-elemental mapping, and ICP-AES, were used to study the physicochemical characteristics of the nanocomposite biomaterial. Next, we explored the material biologically in the anti-cutaneous squamous cell carcinoma effects against the corresponding cell lines like PM1, MET1, MET 4, SCC T9, SCC IC1MET, SCC IC19, SCC T8, and SCC T11. The related IC50 values of the nanocomposite against them were 182, 158, 177, 178, 177, 99, 62, and 183 µg/mL, respectively. The cytotoxicity in terms of percentage cell viability of cancer cells were decreased with the increase in the nanocomposite doses.

Abstract Glioblastoma multiforme (GBM), the most aggressive form of primary brain tumor, poses a considerable challenge in neuro-oncology. Despite advancements in therapeutic approaches, the prognosis for GBM patients remains bleak, primarily attributed to its inherent resistance to conventional treatments and a high recurrence rate. The primary goal of this study was to acquire molecular insights into GBM by constructing a gene co-expression network, aiming to identify and predict key genes and signaling pathways associated with this challenging condition. To investigate differentially expressed genes between various grades of Glioblastoma (GBM), we employed Weighted Gene Co-expression Network Analysis (WGCNA) methodology. Through this approach, we were able to identify modules with specific expression patterns in GBM. Next, genes from these modules were performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis using ClusterProfiler package. Our findings revealed a negative correlation between biological processes associated with neuronal development and functioning and GBM. Conversely, the processes related to the cell cycle, glomerular development, and ECM-receptor interaction exhibited a positive correlation with GBM. Subsequently, hub genes, including SYP, TYROBP, and ANXA5, were identified. This study offers a comprehensive overview of the existing research landscape on GBM, underscoring the challenges encountered by clinicians and researchers in devising effective therapeutic strategies.

Abstract Tumour medical image segmentation plays a crucial role in clinical imaging diagnosis. Existing research has achieved good results, enabling the segmentation of three tumour regions in MRI brain tumour images. Existing models have limited focus on the brain tumour areas, and the long‐term dependency of features is weakened as the network depth increases, resulting in blurred edge segmentation of the targets. Additionally, considering the excellent segmentation performance of the Swin Transformer(Swin‐T) network, its network structure and parameters are relatively large. To address these limitations, this paper proposes a brain tumour segmentation framework with deep nuanced reasoning and Swin‐T. It is mainly composed of the backbone hybrid network (BHN) and the deep micro texture extraction module (DMTE). The BHN combines the Swin‐T stage with a new downsampling transition module called dual path feature reasoning (DPFR). The entire network framework is designed to extract global and local features from multi‐modal data, enabling it to capture and analyze deep texture features in multi‐modal images. It provides significant optimization over the Swin‐T network structure. Experimental results on the BraTS dataset demonstrate that the proposed method outperforms other state‐of‐the‐art models in terms of segmentation performance. The corresponding source codes are available at https://github.com/CurbUni/Brain‐Tumor‐Segmentation‐Framework‐with‐Deep‐Nuanced‐Reasoning‐and‐Swin‐T.

Abstract Background Osteoarthritis (OA), the most common joint disease, is linked with chondrocyte apoptosis and extracellular matrix (ECM) degradation. Charged multivesicular body protein 5 (CHMP5), a member of the multivesicular body, has been reported to serve as an anti-apoptotic protein to participate in leukemia development. However, the effects of CHMP5 on apoptosis and ECM degradation in OA remain unclear. Methods In this study, quantitative proteomics was performed to analyze differential proteins between normal and OA patient articular cartilages. The OA mouse model was constructed by the destabilization of the medial meniscus (DMM). In vitro, interleukin-1 beta (IL-1β) was used to induce OA in human chondrocytes. CHMP5 overexpression and silencing vectors were created using an adenovirus system. The effects of CHMP5 on IL-1β-induced chondrocyte apoptosis were investigated by CCK-8, flow cytometry, and western blot. The effects on ECM degradation were examined by western blot and immunofluorescence. The potential mechanism was explored by western blot and Co-IP assays. Results Downregulated CHMP5 was identified by proteomics in OA patient cartilages, which was verified in human and mouse articular cartilages. CHMP5 overexpression repressed cell apoptosis and ECM degradation in OA chondrocytes. However, silencing CHMP5 exacerbated OA chondrocyte apoptosis and ECM degradation. Furthermore, we found that the protective effect of CHMP5 against OA was involved in nuclear factor kappa B (NF-κB) signaling pathway. Conclusions This study demonstrated that CHMP5 repressed IL-1β-induced chondrocyte apoptosis and ECM degradation and blocked NF-κB activation. It was shown that CHMP5 might be a novel potential therapeutic target for OA in the future.

Abstract Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development.

ObjectiveThe clinical management of catatonia has always been a focus of psychiatric nursing. Unfortunately, there is still limited research on the risk factors and nursing methods for patients with catatonia and bacterial pneumonia. Few studies have identified and analyzed the clinical risk factors for catatonia patients with bacterial pneumonia. This study aims to explore the risk factors and preventive nursing measures for pneumonia in patients with catatonia.MethodsA total of 88 patients with catatonia treated in the emergency department of a psychiatric hospital from January 2019 to October 2021 were selected. They were divided into bacterial pneumonia group (n=17) and non-pneumonia group (n=71) based on whether they had pneumonia. The demographic data and clinical characteristics of the two groups were compared. Logistic regression analysis and point-biserial correlation were used to analyze the risk factors for developing pneumonia in patients with catatonia.ResultsThe incidence of pneumonia in patients with catatonia was 19.32%. Correlation analysis showed that age (r=0.216, p=0.043), The Activities of Daily Living Scale (ADL) score (r=0.265, p=0.013), cell count of white blood (r=0.591, p

IntroductionHIV-exposed uninfected (HEU) infants exhibit elevated pro-inflammatory biomarkers that persist after birth. However, comprehensive assessments of bioprofiles associated with immune regulation and development in pregnant women with HIV (PWH) and HEU infants has not been performed. Maternal immunity in PWH may be imprinted on their HEU newborns, altering immune bioprofiles during early immune development.MethodsCryopreserved paired plasma samples from 46 HEU infants and their mothers enrolled in PACTG 316, a clinical trial to prevent perinatal HIV-1 transmission were analyzed. PWH received antiretrovirals (ARV) and had either fully suppressed or unsuppressed viral replication. Maternal blood samples obtained during labor and infant samples at birth and 6 months were measured for 21 biomarkers associated with germinal centers (GC), macrophage activation, T-cell activation, interferon gamma (IFN-γ)-inducible chemokines, and immune regulatory cytokines using Mesoscale assays. Pregnant women without HIV (PWOH) and their HIV unexposed uninfected (HUU) newborns and non-pregnant women without HIV (NPWOH) served as reference groups. Linear regression analysis fitted for comparison among groups and adjusted for covariant(s) along with principal component analysis performed to assess differences among groups.ResultsCompared with NPWOH, PWOH displayed higher levels of GC, macrophage, and regulatory biomarkers. PWH compared to PWOH displayed elevated GC, T cell activation, and IFN-γ-inducible chemokines biomarkers at delivery. Similar to their mothers, HEU infants had elevated GC, macrophage, and IFN-γ-inducible chemokines, as well as elevated anti-inflammatory cytokines, IL-10 and IL-1RA. Across all mother/newborn dyads, multiple biomarkers positively correlated, providing further evidence that maternal inflammation imprints on newborn bioprofiles. By 6 months, many HEU biomarkers normalized to levels similar to HUU infants, but some GC and inflammatory biomarkers remained perturbed. Bioprofiles in PWH and HEU infants were similar regardless of the extent of maternal viral suppression by ARV.ConclusionsGC immune pathways are perturbed in HEU newborns, but immune regulatory responses down regulate inflammation during early infancy, indicating a transient inflammatory effect. However, several GC biomarkers that may alter immune development remain perturbed.

African swine fever virus (ASFV) is a large double-stranded DNA virus with a complex structural architecture and encodes more than 150 proteins, where many are with unknown functions. E184L has been reported as one of the immunogenic ASFV proteins that may contribute to ASFV pathogenesis and immune evasion. However, the antigenic epitopes of E184L are not yet characterized. In this study, recombinant E184L protein was expressed in prokaryotic expression system and four monoclonal antibodies (mAbs), designated as 1A10, 2D2, 3H6, and 4C10 were generated. All four mAbs reacted specifically with ASFV infected cells. To identify the epitopes of the mAbs, a series of overlapped peptides of E184L were designed and expressed as maltose binding fusion proteins. Accordingly, the expressed fusion proteins were probed with each E184L mAb separately by using Western blot. Following a fine mapping, the minimal linear epitope recognized by mAb 1A10 was identified as 119IQRQGFL125, and mAbs 2D2, 3H6, and 4C10 recognized a region located between 153DPTEFF158. Alignment of amino acids of E184L revealed that the two linear epitopes are highly conserved among different ASFV isolates. Furthermore, the potential application of the two epitopes in ASFV diagnosis was assessed through epitope-based ELISA using 24 ASFV positive and 18 negative pig serum and the method were able to distinguish positive and negative samples, indicating the two epitopes are dominant antigenic sites. To our knowledge, this is the first study to characterize the B cell epitopes of the antigenic E184L protein of ASFV, offering valuable tools for future research, as well as laying a foundation for serological diagnosis and epitope-based marker vaccine development.

BackgroundAstrocytic activation in the spinal dorsal horn contributes to the central sensitization of neuropathic pain. Bone morphogenetic protein (BMP) 10, one of the BMPs highly expressed in the central nervous system, has been demonstrated to have an accelerated effect on astrocytic activation. This study aimed to investigate the functional effects of BMP10 on the activation of astrocytes in the spinal dorsal horn of animal model of neuropathic pain and to explore potential mechanisms involved in this process.MethodsA neuropathic pain mice model was established using the spared nerve injury (SNI). Western blot analysis was performed to detect the expressional levels of BMP10, activin receptor-like receptor 2 (ALK2), Smad1/5/8, phosphorylated Smad1/5/8, and glial fibrillary acidic protein (GFAP). Immunofluorescence staining was used to detect BMP10, ALK2, and GFAP distribution and expression. The behavioral changes in mice were evaluated using paw withdrawal threshold (PWT), thermal withdrawal latency (TWL), and open field test (OFT). The BMP10 siRNA, Smad1 siRNA, BMP10 peptide, and ALK2-IN-2 (ALK2 inhibitor) were intrathecally administrated to mice. A model of lipopolysaccharide (LPS)-stimulated astrocytes was established to investigate the effect of Smad1. The transfection efficiency of siRNAs was detected by western blot and qRT-PCR analysis.ResultsBMP10 levels were increased in the L4-6 ipsilateral spinal dorsal horn of SNI mice and particularly elevated in astrocytes. Consistently, GFAP and phosphorylated Smad1/5/8 were upregulated in the L4-6 ipsilateral spinal dorsal horn after SNI, indicating the activation of astrocytes and Smad1/5/8 signaling. An intrathecal injection of BMP10 siRNA abrogated pain hypersensitivity and astrocytic activation in SNI mice. In addition, intrathecal administration of BMP10 peptide evoked pain hypersensitivity and astrocytic activation in normal mice, and this action was reversed by inhibiting the ALK2. Furthermore, targeting Smad1 in vitro with the help of siRNA inhibited the activation of astrocytes induced by LPS. Finally, targeting Smad1 abrogated BMP10-induced hypersensitivity and activation of astrocytes.ConclusionThese findings indicate that the BMP10/ALK2/Smad1/5/8 axis plays a key role in pain hypersensitivity after peripheral nerve injury, which indicates its stimulative ability toward astrocytes.

Background: Osteoarthritis (OA) is the most common form of joint diseases, with hallmark of cartilage degeneration. Recent studies have shown that the pathogenesis of OA is associated with chondrocyte necroptosis. Methods: In this study, we used single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing data to analyze necroptosis regulation in OA chondrocytes. We performed enrichment analysis, carried out experimental validation, constructed machine learning models, and docked drug molecules. Results: After least absolute shrinkage and selection operator (LASSO) algorithm screening, 4 hub genes (RIPK3, CYBB, HSP90AB1, and TRAF5) with diagnostic characteristics were obtained. Following the comparison of multiple models, the Bayesian model with an average area under curve (AUC) value of 0.944 was finally selected. We found that nimesulide exhibited strong binding affinity to CYBB and HSP90AB1, and experimentally verified that nimesulide reduced the expression of RIPK3 and CYBB, suggesting its potential as an inhibitor of chondrocyte necroptosis. Furthermore, scRNA-seq results showed that necroptosis in OA was significantly upregulated on regulatory chondrocytes (RegC) compared to other chondrocyte subtypes. Conclusions: The results indicate that nimesulide might be used to treat OA by inhibiting chondrocyte necroptosis through down-regulation of RIK3 and CYBB genes. This study reveals the role of chondrocyte necroptosis in OA, and suggests a potential therapeutic strategy by regulating necroptosis with nimesulide.

Summary: Background: In non-high-risk individuals, risk-category-based atherosclerotic cardiovascular disease (ASCVD) screening strategies may be more cost-effective than one-size-fits-all approaches. However, current decisions are constrained by a lack of research evidence. We aimed to explore appropriate risk-category-based screening interval strategies for non-high-risk individuals in ASCVD primary prevention in the Chinese population. Methods: We used data from 28,624 participants in the China Kadoorie Biobank (CKB) who had completed at least two field surveys. The risk assessment tools were the 10-year ASCVD risk prediction models developed based on the CKB cohort. We constructed multistate Markov models to model disease progression and estimate transition probabilities between different risk categories. The total person-years spent unidentified in the high-risk state over a 10-year period were calculated for each screening interval protocol. We also estimated the number of ASCVD events prevented, quality-adjusted life years (QALYs) gained, and costs saved when compared to the 3-yearly screening protocol. Findings: When compared to the uniform 3-yearly protocol, most risk-category-based screening interval protocols would identify more high-risk individuals timely, thus preventing more ASCVD events and gaining QALYs. A few of them would reduce total health-care costs. The protocol, which used 6-year, 3-year, and 2-year screening intervals for low-risk, intermediate-low-risk, and intermediate-high risk individuals, was optimal, and would reduce the person-years spent unidentified in the high-risk category by 17.9% (95% CI: 13.1%–21.9%), thus preventing an estimated 113 thousand (95% CI: 83–138) hard ASCVD events for Chinese adults aged 30–79 over a 10-year period. When using a lower cost of statin therapy, more screening protocols would gain QALYs while saving costs. Interpretation: For the primary prevention of ASCVD, risk-category-based screening protocols outperformed the one-size-fits-all approach in the Chinese population. Funding: This work was supported by National Natural Science Foundation of China (82192904, 82388102, 82192900) and grants (2023YFC2509400) from the National Key R&D Program of China. The CKB baseline survey and the first re-survey were supported by a grant from the Kadoorie Charitable Foundation in Hong Kong. The long-term follow-up is supported by grants from the UK Wellcome Trust (212946/Z/18/Z, 202922/Z/16/Z, 104085/Z/14/Z, 088158/Z/09/Z), grants (2016YFC0900500) from the National Key R&D Program of China, National Natural Science Foundation of China (81390540, 91846303, 81941018), and Chinese Ministry of Science and Technology (2011BAI09B01).

The restoration of cartilage injuries remains a formidable challenge in orthopedics, chiefly attributed to the absence of vascularization and innervation in cartilage. Decellularized extracellular matrix (dECM) derived from cartilage, following antigenic removal through decellularization processes, has exhibited remarkable biocompatibility and bioactivity, rendering it a viable candidate for cartilage repair. Additionally, extracellular vesicles (EVs) generated from cartilage have demonstrated a synergistic effect when combined with dECM, potentially mitigating the inhibitory impact on protein synthesis by phosphorylating 4ebp, thereby promoting the synthesis of cartilage-related proteins such as collagen. In pursuit of this objective, we have innovated a novel bioink and repair scaffold characterized by exceptional biocompatibility, bioactivity, and biodegradability, establishing a tissue-specific microenvironment conducive to chondrogenesis. Within rat osteochondral defects, the biologically active scaffold successfully prompted the formation of transparent cartilage, featuring adequate mechanical strength, favorable elasticity, and dECM deposition indicative of cartilage. In summary, this study has effectively engineered a hydrogel bioink tailored for cartilage repair and devised a bioactive cartilage repair scaffold proficient in instigating cell differentiation and fostering cartilage repair.

BackgroundPleomorphic xanthoastrocytoma (PXA) is a rare brain tumor that accounts for

Abstract Objective This study aimed to compare hospital and long-term clinical outcomes associated with various treatment methods for Stanford A type aortic intramural hematoma (IMH) to provide a reference for clinical decision-making. Methods In this single-center cohort study, we retrospectively analyzed 73 patients with Type A IMH treated at our center from August 1, 2018 to August 1, 2021. Among these patients, 26 were treated conservatively, and 47 underwent surgical intervention. We next compared this IMH cohort with 154 patients with acute type A aortic dissection (AD) who were treated surgically during the same study period. Results Computed tomography angiography revealed that the diameter of the ascending aorta of IMH patients treated with surgery was higher than IMH patients treated with conservative therapy (44.92 ± 7.58 mm vs. 51.22 ± 11.85 mm, P

Abstract Background Peripheral vertigo is often comorbid with psychiatric disorders. However, no longitudinal study has quantified the association between peripheral vertigo and risk of psychiatric disorders. Furthermore, it remains unknown how the white matter integrity of frontal-limbic network relates to the putative peripheral vertigo-psychiatric disorder link. Methods We conducted a cohort study including 452,053 participants of the UK Biobank with a follow-up from 2006 through 2021. We assessed the risks of depression and anxiety disorders in relation to a hospitalization episode involving peripheral vertigo using Cox proportional hazards models. We also examined the associations of peripheral vertigo, depression, and anxiety with MRI fractional anisotropy (FA) in a subsample with brain MRI data (N = 36,087), using multivariable linear regression. Results Individuals with an inpatient diagnosis of peripheral vertigo had elevated risks of incident depression (hazard ratio (HR) 2.18; 95% confidence interval (CI) 1.79–2.67) and anxiety (HR 2.11; 95% CI 1.71–2.61), compared to others, particularly within 2 years after hospitalization (HR for depression 2.91; 95% CI 2.04–4.15; HR for anxiety 4.92; 95% CI 3.62–6.69). Depression was associated with lower FA in most studied white matter regions, whereas anxiety and peripheral vertigo did not show statistically significant associations with FA. Conclusions Individuals with an inpatient diagnosis of peripheral vertigo have increased subsequent risks of depression and anxiety disorders, especially within 2 years after hospitalization. Our findings further indicate a link between depression and lower microstructural connectivity as well as integrity beyond the frontal-limbic network.

Abstract Since thermoelectric materials have different physical and chemical properties, the design of contact layers requires dedicated efforts, and the welding temperatures are distinctly different. Therefore, a general interface design and connection technology can greatly facilitate the development of thermoelectric devices. Herein, we proposed a screening strategy for the contact materials based on the calculation of phase diagram method, and Mg2Ni has been identified as a matched contact layer for n-type Mg3Sb2-based materials. And this screening strategy can be effectively applied to other thermoelectric materials. By adopting the low-temperature sintering silver nanoparticles technology, the Zintl phase thermoelectric device can be fabricated at low temperature but operate at medium temperature. The single-leg n-type Mg3.15Co0.05SbBi0.99Se0.01 device achieves an efficiency of ~13.3%, and a high efficiency of ~11% at the temperature difference of 430 K has been realized for the Zintl phase thermoelectric device comprised together with p-type Yb0.9Mg0.9Zn1.198Ag0.002Sb2. Additionally, the thermal aging and thermal cycle experiments proved the long-term reliability of the Mg2Ni/Mg3.15Co0.05SbBi0.99Se0.01 interface and the nano-silver sintering joints. Our work paves an effective avenue for the development of advanced devices for thermoelectric power generation.

Abstract Objective The aim of this study is to investigate the potential association between a history of gestational diabetes mellitus (GDM) and lumbar bone mineral density (BMD) among premenopausal women, with an additional examination of the mediating role of serum total cholesterol (TC). Methods In this cross-sectional study, 1809 women aged 20–49 years with at least one live birth between 2011 and 2018, drawn from the NHANES dataset, were analyzed. GDM history was identified through questionnaires. Using weighted multiple linear regression, we assessed the relationship between GDM history and lumbar BMD. Additionally, mediation analysis was performed to investigate the potential mediating role of TC. Results The fully adjusted linear regression model revealed a negative association between a history of GDM and lumbar BMD, indicating a reduction in lumbar BMD (β = -0.023, 95% CI: -0.043, -0.003, P = 0.0275). Subgroup analysis highlighted a more pronounced trend in individuals aged ≥ 35 years and with a body mass index ≥ 30 kg/m². Furthermore, mediation analysis demonstrated a significant direct effect of a history of GDM on lumbar BMD (P

In the context of extended probabilistic automata, this study focuses on an information flow property, called opacity, of discrete event systems. The achievement of this research is the formulation and in-depth analysis of what is termed sequential k-opacity. This metric, through its detailed assessment, marks an explicit and visible advancement beyond the existing paradigms for measuring system opacity. It introduces an improved method for analyzing the probability of event sequences leading to confidential states within a system. An approach of such a comprehensive nature is essential for a detailed analysis of opacity in systems typified by deterministic and stochastic elements. Furthermore, this work incorporates a numerical case study that provides a baseline for further investigations in practical applications, thereby validating the proposed framework’s usefulness. The research progresses to explore novel approaches to the reinforcement and persistence of system opacity within extended probabilistic automata. Among these approaches, the strategic use of fake events is critical as it is a fundamental tool for enhancing system security and secrecy, which plays an important role in protecting sensitive and secret data by effectively hiding the real status of the system from outside inspection.

Abstract Objective The purpose of this meta-analysis was to evaluate the effect of exercise training intervention in patients with abdominal aortic aneurysm (AAA). Methods Eight randomized controlled trials (RCTs) that recruited 588 AAA patients were extracted using 4 databases (PubMed, Embase, Wanfang Data, and Cochrane Library). Physiological and biochemistry parameters that included in this study are high-sensitivity C-reactive protein (hs-CRP), respiratory peak oxygen uptake rate (VO2peak), triglyceride (TG), total cholesterol (TC), anaerobic threshold (AT), the diameter of AAA, high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL), and matrix metalloproteinase-9 (MMP-9). Standard mean difference (SMD) was used to assess the between group effect. Results This meta-analysis was synthesized with findings from RCTs and found that hs-CRP (SMD, − 0.56 mg/dL; 95% CI: − 0.90 to 0.22; P = 0.001), VO2peak (SMD, 0.4 mL/kg/min; 95% CI, 0.21 to 0.60; P

Abstract Background Osteoarthritis (OA) is a chronic and low-grade inflammatory disease associated with metabolism disorder and multiple cell death types in the synovial tissues. Sulfur metabolism has not been studied in OA. Methods First, we calculated the single sample gene set enrichment analysis score of sulfur metabolism-associated annotations (i.e., cysteine metabolism process, regulation of sulfur metabolism process, and disulfidptosis) between healthy and synovial samples from patients with OA. Sulfur metabolism-related differentially expressed genes (DEGs) were analyzed in OA. Least absolute shrinkage and selection operator COX regression were used to identify the sulfur metabolism-associated gene signature for diagnosing OA. Correlation and immune cell deconvolution analyses were used to explore the correlated functions and cell specificity of the signature gene, TM9SF2. TM9SF2’s effect on the phagocytosis of macrophages M2 was analyzed by coculturing macrophages with IgG-coated beads or apoptotic Jurkat cells. Results A diagnostic six gene signature (i.e., MTHFD1, PDK4, TM9SF2, POU4F1, HOXA2, NCKAP1) was identified based on the ten DEGs, validated using GSE12021 and GSE1919 datasets. TM9SF2 was upregulated in the synovial tissues of OA at both mRNA and protein levels. The relationship between TM9SF2 and several functional annotations, such as antigen processing and presentation, lysosome, phagosome, Fcγ-mediated phagocytosis, and tyrosine metabolism, was identified. TM9SF2 and macrophages M2 were significantly correlated. After silencing TM9SF2 in THP-1-derived macrophages M2, a significantly reduced phagocytosis and attenuated activation of PLC-γ1 were observed. Conclusion A sulfur metabolism-associated six-gene signature for OA diagnosis was constructed and upregulation of the phagocytosis-associated gene, TM9SF2, was identified. The findings are expected to deepen our understanding of the molecular mechanism underlying OA development and be used as potential therapeutic targets.

AIM: To evaluate the pathogenic variants of the SCO2(OMIM 604272)gene in patients with high myopia from Enshi Tujia and Miao Autonomous Prefecture of China.METHODS: A total of 384 patients with high myopia whose spherical refractive error was ≤ -6.00 D and whose axial length was ≥26.00 mm in at least one eye were recruited. DNA was extracted by the phenol-chloroform method from 5 mL of peripheral venous blood. Sanger sequencing was performed to identify pathogenic variants in exon 2 of SCO2. The detected variants were evaluated via in silico prediction software. A total of 288 people from the same district were included as the normal control cohort.RESULTS: Seven variants were detected, namely, four synonymous variants(c.201C>T/p.=, c.576C>T/p.=, c.633A>C/p.=, c.780T>C/p.=.), two missense variants(c.187A>G/p.Ile63Val, c.59G>C/p.Arg20Pro)and one nonsense variant(c.544C>T/p.Gln182*). The two missense variants were not damaging, as predicted by PolyPhen2, SIFT and Provean. The novel nonsense variant(c.544C>T/p.Gln182*)cannot be found in the 1000 Genomes Project and was not identified in 288 normal controls. Variant Taster suggested that the nonsense variant site was conserved.CONCLUSION: The newly identified nonsense mutation may be responsible for high myopia of the patients in our cohort. SCO2 is associated with high myopia, while the incidence of SCO2 variants in high myopia in this cohort was as low as 1/384; the nonsense mutation may be a scarce variant of high myopia in the Enshi Tujia and Miao Autonomous Prefecture of China.

The search for efficient, environmentally friendly adsorbents is critical for purifying dye wastewater. In this study, we produced a first-of-its-kind effective biomimetic amorphous calcium carbonate (BACC) using bacterial processes and evaluated its capacity to adsorb a hazardous organic cationic dye—methylene blue (MB). BACC can adsorb a maximum of 494.86 mg/g of MB, and this excellent adsorption performance was maintained during different solution temperature (10–55 °C) and broad pH (3–12) conditions. The favorable adsorption characteristics of BACC can be attributable to its hydrophobic property, porosity, electronegativity, and perfect dispersity in aqueous solution. During adsorption, MB can form Cl-Ca, S-O, N-Ca, and H-bonds on the surface of BACC. Since BACC has excellent resistance to adsorption interference in different water bodies and in real dye wastewater, and can also be effectively recycled six times, our study is an important step forward in dye wastewater treatment applications.

ObjectiveTo investigate the prevalence and associated factors of suicidal ideation and suicide attempts among adolescent and young adults in China from December 14, 2022 to February 28, 2023, when COVID-19 restrictions were lifted.MethodsStudents in middle and high schools and colleges and universities in the province of Sichuan, China were asked to complete on-line cross-sectional surveys. Information was collected about sociodemographics, experiences related to the COVID-19 pandemic, suicidal ideation and suicide attempts. Participants also filled out the Patient Health Questionnaire-9, the Generalized Anxiety Disorder-7 and the Social Support Rate Scale surveys. Factors associated with suicidal ideation or suicide attempts were explored using logistic regression.ResultsOf the 82,873 respondents (aged 12 to 24 years), 21,292 (25.7%) reported having thought of suicide at least once in their lifetime, 10,382 (12.5%) reported having thought about suicide within the previous 12 months, and 1,123 (1.4%) reported having attempted it within the previous 12 months. Risk of lifetime suicidal ideation was higher among middle school students than among older students. Risk of suicidal ideation and risk of suicide attempts correlated directly with severity of symptoms of depression and anxiety, and inversely with level of social support. Greater risk of suicidal ideation and suicidal attempts was associated with: being female, living in an urban environment, attending a boarding school, currently being in love, having parents who divorced or remarried, having parents who exhibit non-authoritative parenting behavior, having higher family income, having been COVID-19 infected, having been quarantined for a long time, and being dissatisfied with one’s education.ConclusionsSuicidal ideation and suicide attempts remain prevalent among young people in China. The potential associated factors identified in our study may be useful for targeting appropriate psychosocial interventions and developing mental health policies.

Osteosarcoma, as the most prevalent primary malignant bone tumor, has consistently shown suboptimal clinical treatment outcomes. In this manuscript, we proposed an efficacious and novel phototherapy strategy for osteosarcoma based on a photoresponsive near-infrared (NIR) material, CaCO3-ICG-DDP-PEG-PT (CIDP-PT), which contained calcium carbonate (CaCO3) and Cisplatin (DDP) via the gas dispersion method, and indocyanine green (ICG) was encapsulated through a nanoprecipitation reaction by employing DSPE-PEG2000-COOH to enhance the stability and hydrophilicity. The targeting oligopeptide (PT) for osteosarcoma cells was inserted into the outer membrane of nanoparticles, thereby further enhancing the tumor-targeting capability through receptor-mediated binding. The prepared CIDP-PT nanoparticles exhibited high targeting efficiency and multifunctionality. In vitro and in vivo experiments demonstrated that CIDP-PT significantly enhanced the therapeutic efficacy for osteosarcoma via the NIR-II photoresponsive and tumor-targeting approach. It achieves efficient tumor cell eradication through multiple modalities while maintaining an exceptional level of biocompatibility. Hence, the CIDP-PT nanocarriers possess considerable practical value for future clinical applications in adjunct osteosarcoma phototherapy.

BackgroundNutrients are crucial for dialysis patients, especially elderly patients. Nutrition-related complications in dialysis patients are often closely related to cardiovascular aging. However, we know little about the effect of different nutrients on the commonly used outcome predictor, health-related quality of life (HRQOL). Therefore, this study investigated the associations between different nutrients and HRQOL among dialysis patients.MethodsA cross-sectional study was conducted on 123 dialysis adults at multiple dialysis centers. The Short Form-36 Health Survey (SF-36) assesses HRQOL. Modified quantitative subjective global assessment (MQSGA) evaluates nutritional status. A 3-day dietary record evaluated nutrient intakes.ResultsAmong the 123 participants, 79 received hemodialysis (HD), and 44 were on peritoneal dialysis (PD). Patients with PD had a higher SF-36 score than HD (525 ± 136 vs. 375 ± 179, P

Abstract Vascular calcification is a strong predictor of cardiovascular events. Essential metals play critical roles in maintaining human health. However, the association of essential metal levels with risk of aortic arch calcification (AoAC) remains unclear. We measured the plasma concentrations of nine essential metals in a cross‐sectional population and evaluated their individual and combined effects on AoAC risk using multiple statistical methods. We also explored the mediating role of fasting glucose. In the logistic regression model, higher quartiles of magnesium and copper were associated with the decreased AoAC risk, while higher quartile of manganese was associated with higher AoAC risk. The least absolute shrinkage and selection operator penalized regression analysis identified magnesium, manganese, calcium, cobalt, and copper as key metals associated with AoAC risk. The weighted quantile sum regression suggested a combined effect of metal mixture. A linear and positive dose–response relationship was found between manganese and AoAC in males. Moreover, blood glucose might mediate a proportion of 9.38% of the association between manganese exposure and AoAC risk. In summary, five essential metal levels were associated with AoAC and showed combined effect. Fasting glucose might play a significant role in mediating manganese exposure‐associated AoAC risk.

The objective of this study was to determine the effects of heat stress (HS) on physiological, blood biochemical, and energy metabolism in Dazu black goats. Six wether adult Dazu black goats were subjected to 3 experimental periods: high HS (group H, temperature-humidity index [THI] > 88) for 15 d, moderate HS (group M, THI was 79-88) for 15 d, and no HS (group L, THI < 72) for 15 d. Rectal temperature (RT) and respiratory rate (RR) were determined on d 7 and 15 of each period, and blood samples were collected on d 15 of each period. All goats received glucose (GLU) tolerance test (GTT) and insulin (INS) tolerance test on d 7 and d 10 of each period. The results showed that HS decreased dry matter intake (DMI) and INS concentrations (p 0.05) and 40.78% (p 0.05) during the ITT. A total of 60 differentially expressed metabolites were identified in response to groups H and M. In HS, changes in metabolites related to carbohydrate metabolism and glycolysis were identified (p

Background: The SARS-CoV-2 pandemic drove global vaccination. However, breakthrough infections raised concerns about vaccine performance, leading the World Health Organization (WHO) to recommend investigations thereof. This study aimed to evaluate the clinical outcomes (time to breakthrough infection, intensive care unit [ICU] admission, and in-hospital mortality) of hospitalised patients with SARS-CoV-2 breakthrough infection. This was the primary outcome and the risk factors associated with its severity were the secondary outcomes. Methods: This retrospective cohort study at a multispecialty tertiary hospital in Selangor, Malaysia included 200 fully adult vaccinated patients, with confirmed SARS-CoV-2 infection, admitted from September 2021 to February 2022. Participants were selected by simple random sampling. Infection severity was categorised as CAT 2–3 (mild–moderate) and 4–5 (severe–critical). Results: The time to breakthrough infection was significantly longer for BNT162B2 recipients (128.47 ± 46.21 days) compared to CoronaVac (94.09 ± 48.71 days; P = 0.001) and ChAdOx1-S recipients (90.80 ± 37.59 days; P = 0.019). No significant associations were found between SARS-CoV-2-related ICU admission, mortality, and the vaccines. Multivariable analysis identified vaccine type, variant of concern, ethnicity, and hypertension as significant predictors of severity. BNT162b2 and ChAdOx1-S recipients had significantly (81 % and 74 %, respectively) lower odds of CAT 4–5 infection compared to CoronaVac recipients. Indian patients had a significantly (83 %) lower chance of CAT 4–5 infection compared to Malay patients. Patients with breakthrough infections during the Omicron period had a significantly (58 %) lower risk of CAT 4–5 compared to those in the Delta period. The CAT 4–5 risk was significantly (nearly threefold) higher in hypertensive patients. Conclusion: The results support the Malaysian Ministry of Health's recommended booster three months after primary vaccination and the WHO's recommended heterologous booster following CoronaVac. Certain ethnic groups, hypertensive patients, and viral variants may require attention in future pandemics.

An eleven-wavelength-switchable thulium-doped fiber laser was proposed and demonstrated, incorporating an improved geta-shaped cavity providing bidirectional amplification, and a sandwich four-mode fiber Mach–Zehnder interferometer filter with curvature sensitivity. The filter was fabricated by splicing a segment of four-mode fiber (FMF) between two segments of a no-core fiber (NCF), with two segments of a single mode fiber (SMF) fused outside the two NCFs, and the structural order was SMF-NCF-FMF-NCF-SMF (SNFNS). The mode interference of the SNFNS filter was investigated theoretically in detail. The curvature characteristic was measured experimentally, and the maximum curvature sensitivity of the filter was 5.83 dB/m−1 in the ranges of 1.51 ∼ 2.26 m−1. By adjusting the curvature of the filter and polarization controllers, switchable eleven single-wavelength output can be obtained. The stability of the single-wavelength output was monitored with the fluctuations of the center wavelength and output power being less than 0.05 nm and 0.90 dB, respectively. Additionally, a slope efficiency of 9.797 % was achieved using a bidirectional amplifier configuration. The proposed laser may be suitable for mode-division multiplexing systems and optical sensor applications.