Integrated physiological, transcriptomic and metabolomic analyses reveal the mechanism of peanut kernel weight reduction under waterlogging stress.

Waterlogging stress (WS) hinders kernel development and directly reduces peanut yield; however, the mechanism of kernel filling in response to WS remains unknown. The waterlogging-sensitive variety Huayu 39 was subjected to WS for 3 days at 7 days after the gynophores touched the ground (DAG). We found that WS affected kernel filling at 14, 21, and 28 DAG. WS decreased the average filling rate and kernel dry weight, while transcriptome sequencing and widely targeted metabolomic analysis revealed that WS inhibited the gene expression in starch and sucrose metabolism, which reduced sucrose input and transformation ability. Additionally, genes related to ethylene and melatonin synthesis and the accumulation of tryptophan and methionine were upregulated in response to WS. WS upregulated the expression of the gene encoding tryptophan decarboxylase (AhTDC), and overexpression of AhTDC in Arabidopsis significantly reduced the seed length, width, and weight. Therefore, WS reduced the kernel-filling rate, leading to a reduction in the 100-kernel weight. This survey informs the development of measures that alleviate the negative impact of WS on peanut yield and quality and provides a basis for exploring high-yield and high-quality cultivation, molecular-assisted breeding, and waterlogging prevention in peanut farming.

Influence factors of metagenomic next-generation sequencing negative results in diagnosed patients with spinal infection.

The aim of this study was to evaluate the influence factors of metagenomic next-generation sequencing (mNGS) negative results in the diagnosed patients with spinal infection. mNGS test was applied in a cohort of 114 patients with suspected spinal infection, among which 56 patients had a final diagnosis of spinal infection. mNGS achieved a sensitivity of 75.0% (95% CI, 61.6% to 85.6%) and a specificity of 84.5% (95% CI, 72.6% to 92.7%), using histopathology and culture results as reference. Diagnosed patients with a negative culture result had lower white blood cell account, percentage of neutrophilic granulocyte, C-reactive protein (all P<0.05) and relatively higher rate of prior antimicrobial treatment history (P=0.059). However, diagnosed patients with a negative mNGS result did not have such difference with mNGS-positive patients, suggesting that mNGS was not strictly limited by the above indicators, which presented the advantages of this technique from another point of view.

Transcatheter tricuspid valve replacement with LuX-valve device: Overview of key echocardiographic considerations.

Tricuspid regurgitation is a common valve disease with high incidence and poor prognosis. For elderly patients and those with a history of open heart surgery, second thoracotomy and valve replacement carry a high risk. Transcatheter tricuspid valve replacement (TTVR) has become an alternative treatment for patients with high surgical risk. LuX-Valve is a novel self-expandable valve that does not rely on radial force to anchor the valve annulus. The preliminary results have been satisfactory, and this technology is gradually being adopted in China and around the world. Successful implementation of this technique depends on echocardiographic preoperative screening, intraoperative guidance, and postoperative follow-up. The purpose of this article is to provide a state-of-the-art review of the key points and technical considerations for preoperative screening, intraoperative guidance, and postoperative follow-up for TTVR.

Myositis Autoantibody Profiles and Clinical Significance in Patients with Inflammatory Myopathies in Southwest China.

BACKGROUND: The purpose of this study is to analyze the distribution of myositis-specific autoantibodies (MSAs) and myositis-associated autoantibodies (MAAs) in patients with idiopathic inflammatory myopathies (IIMs) in southwest China and to explore the relevance between each subtype, each clinical feature, and to explore the relevance between the laboratory indexes. METHODS: For this study, 200 patients with IIMs were tested for myositis autoantibodies. Clinical manifestations and laboratory metrics were collected and the correlations between autoantibodies and clinical phenotypes were analyzed. RESULTS: MSAs were found in 73.5% of the patients. The most frequently MSAs were anti-MDA5 (26.8%), followed by anti-ARS (18.5%). Anti-Ro52 was the most prevalent in MAAs (46.2%). Interstitial lung disease (ILD) and arthralgia were more frequent in anti-MDA5 and anti-Jo-1 positive groups (each p < 0.05). Anti-TIF1-γ and anti-NXP2 were associated with dysphagia (each p < 0.05). Different antibody subtypes were associated with laboratory indicators of response to muscle damage and immune status. Logistic regression showed that anti-MDA5 and anti-Jo-1 were independent risk factors for ILD (OR = 4.542, p = 0.004; OR = 4.290, p = 0.018, respectively) and arthralgia (OR = 7.856, p = 0.000; OR = 5.731, p = 0.004, respectively), whereas anti-TIF1-γ and anti-NXP2 were independent risk factors for dysphagia (OR = 4.521, p = 0.009; OR = 6.889, p = 0.017, respectively). CONCLUSIONS: Different antibody subtypes were associated with specific clinical features. Anti-MDA5 and anti-Jo-1 were independent risk factors for ILD and arthralgia. Anti-TIF1-γ and anti-NXP2 were independent risk factors for dysphagia.

Anchoring Single-Atomic Metal Sites in Metalloporphyrin-Based Covalent Organic Frameworks for Enhanced Photocatalytic Hydrogen Evolution.

A photoactive covalent organic framework (COF) was built from metalloporphyrin and bipyridine monomers and single-atomic Pt sites were subsequently installed. Integrating photosensitizing metalloporphyrin and substrate-activating Pt(bpy) moieties in a single solid facilitates multielectron transfer and accelerates photocatalytic hydrogen evolution with a maximum production rate of 80.4 mmol h-1 gPt-1 and turnover frequency (TOF) of 15.7 h-1 observed. This work demonstrates that incorporation of single-atomic metal sites with photoactive COFs greatly enhances photocatalytic activity and provides an effective strategy for the design and construction of novel photocatalysts.

Analysis of common differential gene expression in synovial cells of osteoarthritis and rheumatoid arthritis.

OBJECTIVE: To elucidate potential molecular mechanisms differentiating osteoarthritis (OA) and rheumatoid arthritis (RA) through a bioinformatics analysis of differentially expressed genes (DEGs) in patient synovial cells, aiming to provide new insights for clinical treatment strategies. MATERIALS AND METHODS: Gene expression datasets GSE1919, GSE82107, and GSE77298 were downloaded from the Gene Expression Omnibus (GEO) database to serve as the training groups, with GSE55235 being used as the validation dataset. The OA and RA data from the GSE1919 dataset were merged with the standardized data from GSE82107 and GSE77298, followed by batch effect removal to obtain the merged datasets of differential expressed genes (DEGs) for OA and RA. Intersection analysis was conducted on the DEGs between the two conditions to identify commonly upregulated and downregulated DEGs. Enrichment analysis was then performed on these common co-expressed DEGs, and a protein-protein interaction (PPI) network was constructed to identify hub genes. These hub genes were further analyzed using the GENEMANIA online platform and subjected to enrichment analysis. Subsequent validation analysis was conducted using the GSE55235 dataset. RESULTS: The analysis of differentially expressed genes in the synovial cells from patients with Osteoarthritis (OA) and Rheumatoid Arthritis (RA), compared to a control group (individuals without OA or RA), revealed significant changes in gene expression patterns. Specifically, the genes APOD, FASN, and SCD were observed to have lower expression levels in the synovial cells of both OA and RA patients, indicating downregulation within the pathological context of these diseases. In contrast, the SDC1 gene was found to be upregulated, displaying higher expression levels in the synovial cells of OA and RA patients compared to normal controls.Additionally, a noteworthy observation was the downregulation of the transcription factor PPARG in the synovial cells of patients with OA and RA. The decrease in expression levels of PPARG further validates the alteration in lipid metabolism and inflammatory processes associated with the pathogenesis of OA and RA. These findings underscore the significance of these genes and the transcription factor not only as biomarkers for differential diagnosis between OA and RA but also as potential targets for therapeutic interventions aimed at modulating their expression to counteract disease progression. CONCLUSION: The outcomes of this investigation reveal the existence of potentially shared molecular mechanisms within Osteoarthritis (OA) and Rheumatoid Arthritis (RA). The identification of APOD, FASN, SDC1, TNFSF11 as key target genes, along with their downstream transcription factor PPARG, highlights common potential factors implicated in both diseases. A deeper examination and exploration of these findings could pave the way for new candidate targets and directions in therapeutic research aimed at treating both OA and RA. This study underscores the significance of leveraging bioinformatics approaches to unravel complex disease mechanisms, offering a promising avenue for the development of more effective and targeted treatments.

Exploration of quantitative-effectiveness association between acupuncture temporal parameters and stable chronic obstructive pulmonary disease: A systematic review and dose-response meta-analysis of randomized controlled trials.

INTRODUCTION: Chronic Obstructive Pulmonary Disease (COPD) is a globally common chronic respiratory disease with a high morbidity and mortality rate. Acupuncture has been proven effective for COPD. A dose-response meta-analysis was conducted to assess the correlation between the acupuncture temporal parameters(session, frequency, and duration) and its effectiveness in patients with stable COPD. METHODS: Acupuncture randomized controlled trials on COPD were searched in eight databases from their inception to June 2023. The "doses" were defined as the acupuncture session, frequency, and duration. The outcomes mainly included Forced Expiratory Volume in one-second rate (FEV1%) and Six-minute Walking Distance (6MWD). The assessment of bias risk and literature quality were conducted independently using the Cochrane risk of bias tool and the Standards for reporting interventions in clinical trials of acupuncture. The dose-response relationship was modeled using robust error element regression, and meta-analysis was operated by R 4.3.1 and Stata 15.0. The protocol was registered in PROSPERO with the registration number CRD42023401406. RESULT: Out of 1669 records, 17 RCTs with 1165 participants were finally included in the meta-analysis. There was notable heterogeneity among the studies, but sensitivity analysis demonstrated good robustness. The findings revealed a significant improvement in the following outcomes for stable COPD patients in the acupuncture group: FEV1% (MD=3.50, 95%CI: 2.05-4.95), 6MWD (MD=47.39, 95%CI: 29.29-65.50), St. George's respiratory questionnaire (SGRQ; MD=-8.25, 95%CI: -11.38 to -5.12); COPD assessment test (CAT; MD=-2.91, 95%CI: -3.99 to -1.83). The relationship between the acupuncture session, duration, and FEV1%, 6MWD followed a "Λ" curve pattern, while the relationship between acupuncture frequency and FEV1%, 6MWD exhibited logarithmic growth. Firstly, After 12 acupuncture sessions, FEV1% and 6MWD increased by 7.06% (95%CI: 4.56-9.55) and 36.28 m (95%CI: 20.37-52.20), respectively. The peak improvement in FEV1% and 6MWD was observed after 18 acupuncture sessions (MD=7.89, 95% CI: 5.33-10.45) and 45 sessions (MD=125.43, 95% CI: 72.80-178.07) each. Additionally, weekly acupuncture resulted in a 4.14% improvement in FEV1% (95% CI: 2.55-5.72) and a 42.49 m increase in 6MWD (95%CI: 17.16-67.81). Notably, the maximum effects on FEV1% and 6MWD improvement were achieved with different acupuncture frequencies, specifically three times a week (MD=6.00, 95% CI: 5.34-6.66) and once a day(MD=112.41, 95% CI: 77.27-147.56), respectively. Furthermore, after a 28-day duration of acupuncture treatment, FEV1% increased by 4.74% (95% CI: 3.73-5.75) and 6MWD increased by 47.34 m (95%CI: 22.01-72.67). During 60 days of acupuncture treatment, the FEV1% and 6MWD improvement reached their highest levels at 8.76% (95% CI: 7.05-10.47) and 88.06 m (95% CI: 45.96-130.16), respectively. CONCLUSION: Acupuncture was effective in improving FEV1%, 6MWD, SGRQ, and CAT in patients with stable COPD. There was a dose-response relationship between the time parameters of acupuncture (session, frequency, and duration) and the efficacy of COPD treatment (FEV1% and 6MWD). The minimal clinically important difference could be achieved after 12 acupuncture sessions. Acupuncture with a medium-frequency (2-3 times per week) over 60 days may result in the greatest improvement in FEV1%, while higher-frequency acupuncture (5-7 times per week) for 2 months may lead to the maximum improvements in 6MWD. It indicated that the optimal acupuncture duration for different indicators remains consistent, while the optimal frequencies may differ. To confirm these results, it is necessary to conduct multicenter, large-scale randomized controlled trials. ETHICS AND DISSEMINATION: Ethical approval is not required for literature-based studies. The results will be published in peer-reviewed journals or conferences.

Evolution characteristics and performance evaluation of extended end-plate joints with single and double side connections under cyclic loading.

Experimental studies were conducted on four extended end-plate joints subjected to cyclic loading at the column top, investigating the evolving patterns of the joints' mechanical performance. The paper provides a detailed analysis and discussion of the test joints' failure modes, ductility, stiffness degradation, and energy dissipation capacity. The Mann-Kendall (M - K) trend analysis tool was applied to the mechanical response curves, identifying key performance evolution points (evolution initiation point P and overall yield point Q). The trends in bolt forces, deformations, and strains at critical joints were effectively validated, revealing the transition of the energy system from quantitative to qualitative changes and the component's failure process from stability to instability. Additionally, based on the experimental joints' hysteresis curves and energy dissipation capacity, a theoretical hysteresis model was established to predict the joint's hysteresis curve and cumulative dissipated energy accurately. According to EC3 requirements, joints were classified as partially rigid connections. The experimental results of the initial rotational stiffness and plastic moment were further used to evaluate the calculated values in existing standards EN 1993-1-8, ANSI/AISC 358-16, and GB 51017-2017. The results indicate that extended end-plate connections possess sufficient strength, joint rotational stiffness, ductility, and energy dissipation capacity, making them suitable for seismic moment frames.

Critical role of the gut microbiota in immune responses and cancer immunotherapy.

The gut microbiota plays a critical role in the progression of human diseases, especially cancer. In recent decades, there has been accumulating evidence of the connections between the gut microbiota and cancer immunotherapy. Therefore, understanding the functional role of the gut microbiota in regulating immune responses to cancer immunotherapy is crucial for developing precision medicine. In this review, we extract insights from state-of-the-art research to decipher the complicated crosstalk among the gut microbiota, the systemic immune system, and immunotherapy in the context of cancer. Additionally, as the gut microbiota can account for immune-related adverse events, we discuss potential interventions to minimize these adverse effects and discuss the clinical application of five microbiota-targeted strategies that precisely increase the efficacy of cancer immunotherapy. Finally, as the gut microbiota holds promising potential as a target for precision cancer immunotherapeutics, we summarize current challenges and provide a general outlook on future directions in this field.

Sensitive and rapid identification of pathogens by droplet digital PCR in a cohort of septic patients: a prospective diagnostic study.

BACKGROUND: There is a critical need for a rapid and sensitive pathogen detection method for septic patients. This study aimed to investigate the diagnostic efficacy of Digital droplet polymerase chain reaction (ddPCR) in identifying pathogens among suspected septic patients. METHODS: We conducted a prospective pilot diagnostic study to clinically validate the multiplex ddPCR panel in diagnosing suspected septic patients. A total of 100 sepsis episodes of 89 patients were included in the study. RESULTS: In comparison to blood culture, the ddPCR panel exhibited an overall sensitivity of 75.0% and a specificity of 69.7%, ddPCR yielded an additional detection rate of 17.0% for sepsis cases overall, with a turnaround time of 2.5 h. The sensitivity of ddPCR in the empirical antibiotic treatment and the non-empirical antibiotic treatment group were 78.6% versus 80.0% (p > 0.05). Antimicrobial resistance genes were identified in a total of 13 samples. Whenever ddPCR detected the genes beta-lactamase-Klebsiella pneumoniae carbapenemase (blaKPC) or beta-lactamase-New Delhi metallo (blaNDM), these findings corresponded to the cultivation of carbapenem-resistant gram-negative bacteria. Dynamic ddPCR monitoring revealed a consistent alignment between the quantitative ddPCR results and the trends observed in C-reactive protein and procalcitonin levels. CONCLUSIONS: Compared to blood culture, ddPCR exhibited higher sensitivity for pathogen diagnosis in suspected septic patients, and it provided pathogen and drug resistance information in a shorter time. The quantitative results of ddPCR generally aligned with the trends seen in C-reactive protein and procalcitonin levels, indicating that ddPCR can serve as a dynamic monitoring tool for pathogen load in septic patients.

The role of gut microbiota in mediating increased toxicity of nano-sized polystyrene compared to micro-sized polystyrene in mice.

Microplastics (MPs) are widespread environmental contaminants that have been detected in animals and humans. However, their toxic effects on terrestrial mammals and the underlying mechanisms are still not well understood. Herein, we explored the role of gut microbiota in mediating the toxicity of micro- and nano-sized polystyrene plastics (PS-MPs/PS-NPs) using an antibiotic depleted mice model. The results showed that PS-MPs and PS-NPs exposure disrupted the composition and structure of the gut microbiota. Specifically, these particles led to an increase in pathogenic Esherichia-shigella, while depleting probiotics such as Akkermansia and Lactobacillus. Comparatively, PS-NPs particles had more pronounced effect, leading to obviously shifted the colon transcriptional profiles characterized by inducing the enrichment of colon metabolism and immune-related pathways (i.e., upregulated in genes like udgh, ugt1a1, ugt1a6a, ugt1a7c and ugt2b34). Additionally, both PS-MPs and PS-NPs induced oxidative stress, gut-liver damage and systemic inflammation in mice. Mechanistically, we confirmed that PS particles disturbed gut microbiota, activating TLR2-My88-NF-κB pathway to trigger the release of inflammatory cytokine IL-1ß and TNF-α. The damage and inflammation caused by both size of PS particles was alleviated when the gut microbiota was depleted. In conclusion, our findings deepen the understanding of the molecule mechanisms by which gut microbiota mediate the toxicity of PS particles, informing health implications of MPs pollution.

Insulin resistance and its relationship with long-term exposure to ozone: Data based on a national population cohort.

The relationship of ozone (O3), particularly the long-term exposure, with impacting metabolic homeostasis in population was understudied and under-recognised. Here, we used data from ChinaHEART, a nationwide, population-based cohort study, combined with O3 and PM2.5 concentration data with high spatiotemporal resolution, to explore the independent association of exposure to O3 with the prevalence of insulin resistance (IR). Among the 271 540 participants included, the crude prevalence of IR was 39.1%, while the age and sex standardized prevalence stood at 33.0%. Higher IR prevalence was observed with each increase of 10.0 µg/m3 in long-term O3 exposure, yielding adjusted odds ratios (OR) of 1.084 (95% CI: 1.079-1.089) in the one-pollutant model and 1.073 (95% CI: 1.067-1.079) in the two-pollutant model. Notably, a significant additive interaction between O3 and PM2.5 on the prevalence of IR was observed (P for additive interaction < 0.001). Our main findings remained consistent and robust in the sensitivity analyses. Our study suggests long-term exposure to O3 was independently and positively associated with prevalence of IR. It emphasized the benefits of policy interventions to reduce O3 and PM2.5 exposure jointly, which could ultimately alleviate the health and economic burden related to DM.

An overview of the cholesterol metabolism and its proinflammatory role in the development of MASLD.

Cholesterol is an essential lipid molecule in mammalian cells. It is not only involved in the formation of cell membranes but also serves as a raw material for the synthesis of bile acids, vitamin D, and steroid hormones. Additionally, it acts as a covalent modifier of proteins and plays a crucial role in numerous life processes. Generally, the metabolic processes of cholesterol absorption, synthesis, conversion, and efflux are strictly regulated. Excessive accumulation of cholesterol in the body is a risk factor for metabolic diseases such as cardiovascular disease, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease (MASLD). In this review, we first provide an overview of the discovery of cholesterol and the fundamental process of cholesterol metabolism. We then summarize the relationship between dietary cholesterol intake and the risk of developing MASLD, and also the animal models of MASLD specifically established with a cholesterol-containing diet. In the end, the role of cholesterol-induced inflammation in the initiation and development of MASLD is discussed.

The pattern of tumor progression on first-line immune checkpoint inhibitor-based systemic therapy for Chinese advanced hepatocellular carcinoma -CLEAP 004 study.

Background: For decades, stratification criteria for first-line clinical studies have been highly uniform. However, there is no principle or consensus for restratification after systemic treatment progression based on immune checkpoint inhibitors (ICIs). The aim of this study was to assess the patterns of disease progression in patients with advanced hepatocellular carcinoma (HCC) who are not eligible for surgical intervention, following the use of immune checkpoint inhibitors. Methods: This is a retrospective study that involved patients with inoperable China liver stage (CNLC) IIIa and/or IIIb. The patients were treated at eight centers across China between January 2017 and October 2022. All patients received at least two cycles of first-line treatment containing immune checkpoint inhibitors. The patterns of disease progression were assessed using RECIST criteria 1.1. Different progression modes have been identified based on the characteristics of imaging progress. The study's main outcome measures were post-progression survival (PPS) and overall survival (OS). Survival curves were plotted using the Kaplan-Meier method to compare the difference among the four groups. Subgroup analysis was conducted to compare the efficacy of different immunotherapy combinations. Variations in the efficacy of immunotherapy have also been noted across patient groups exhibiting alpha-fetoprotein (AFP) levels equal to or exceeding 400ng/mL, in contrast to those with AFP levels below 400ng/mL. Results: The study has identified four distinct patterns of progress, namely p-IIb, p-IIIa, p-IIIb, and p-IIIc. Diverse patterns of progress demonstrate notable variations in both PPS and OS. The group p-IIb had the longest PPS of 12.7m (95% 9.3-16.1) and OS 19.6m (95% 15.6-23.5), the remaining groups exhibited p-IIIb at PPS 10.5 months (95%CI: 7.9-13.1) and OS 19.2 months (95%CI 15.1-23.3). Similarly, p-IIIc at PPS 5.7 months (95%CI: 4.2-7.2) and OS 11.0 months (95%CI 9.0-12.9), while p-IIIa at PPS 3.4 months (95%CI: 2.7-4.1) and OS 8.2 months (95%CI 6.8-9.5) were also seen. Additional stratified analysis was conducted and showed there were no differences of immunotherapy alone or in combination in OS (HR= 0.92, 95%CI: 0.59-1.43, P=0.68) and PPS (HR= 0.88, 95%CI: 0.57-1.36, P=0.54); there was no significant difference in PPS (HR=0.79, 95% CI: 0.55-1.12, P=0.15) and OS (HR=0.86, 95% CI: 0.61-1.24, P=0.39) for patients with AFP levels at or over 400ng/mL. However, it was observed that patients with AFP levels above 400ng/mL experienced a shorter median progression of PPS (8.0 months vs. 5.0 months) after undergoing immunotherapy. Conclusion: In this investigation of advanced hepatocellular carcinoma among Chinese patients treated with immune checkpoint inhibitors, we identified four distinct progression patterns (p-IIb, p-IIIa, p-IIIb and p-IIIc) that showed significant differences in PPS and OS. These findings demonstrate the heterogeneity of disease progression and prognosis after immunotherapy failure. Further validation in large cohorts is necessary to develop prognostic models that integrate distinct progression patterns to guide subsequent treatment decisions. Additionally, post-immunotherapy progression in patients with AFP levels ≥400ng/mL indicates a shortened median PPS. These findings provide valuable insights for future personalized treatment decisions.

Polygenic risk-stratified screening for nasopharyngeal carcinoma in high-risk endemic areas of China: a cost-effectiveness study.

Background: Nasopharyngeal carcinoma (NPC) has an extremely high incidence rate in Southern China, resulting in a severe disease burden for the local population. Current EBV serologic screening is limited by false positives, and there is opportunity to integrate polygenic risk scores for personalized screening which may enhance cost-effectiveness and resource utilization. Methods: A Markov model was developed based on epidemiological and genetic data specific to endemic areas of China, and further compared polygenic risk-stratified screening [subjects with a 10-year absolute risk (AR) greater than a threshold risk underwent EBV serological screening] to age-based screening (EBV serological screening for all subjects). For each initial screening age (30-34, 35-39, 40-44, 45-49, 50-54, 55-59, 60-64, and 65-69 years), a modeled cohort of 100,000 participants was screened until age 69, and then followed until age 79. Results: Among subjects aged 30 to 54 years, polygenic risk-stratified screening strategies were more cost-effective than age-based screening strategies, and almost comprised the cost-effectiveness efficiency frontier. For men, screening strategies with a 1-year frequency and a 10-year absolute risk (AR) threshold of 0.7% or higher were cost-effective, with an incremental cost-effectiveness ratio (ICER) below the willingness to pay (¥203,810, twice the local per capita GDP). Specifically, the strategies with a 10-year AR threshold of 0.7% or 0.8% are the most cost-effective strategies, with an ICER ranging from ¥159,752 to ¥201,738 compared to lower-cost non-dominated strategies on the cost-effectiveness frontiers. The optimal strategies have a higher probability (29.4-35.8%) of being cost-effective compared to other strategies on the frontier. Additionally, they reduce the need for nasopharyngoscopies by 5.1-27.7% compared to optimal age-based strategies. Likewise, for women aged 30-54 years, the optimal strategy with a 0.3% threshold showed similar results. Among subjects aged 55 to 69 years, age-based screening strategies were more cost-effective for men, while no screening may be preferred for women. Conclusion: Our economic evaluation found that the polygenic risk-stratified screening could improve the cost-effectiveness among individuals aged 30-54, providing valuable guidance for NPC prevention and control policies in endemic areas of China.

Associations of CBC-Derived inflammatory indicators with sarcopenia and mortality in adults: evidence from Nhanes 1999 ∼ 2006.

BACKGROUND: It has been proposed that inflammation plays a role in the development of sarcopenia. This study aimed to investigate the links of complete blood cell count (CBC) parameters and CBC-derived inflammatory indicators with sarcopenia and mortality. METHODS: Data pertaining to sarcopenia were extracted from the 1999-2006 National Health and Nutrition Examination Survey (NHANES), and mortality events were ascertained through the National Death Index up to December 31, 2019. The CBC-derived inflammatory indicators assessed in this study included the neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), monocyte-to-lymphocyte ratio (MLR), neutrophil-monocyte to lymphocyte ratio (NMLR), systemic inflammatory response index (SIRI), and systemic immune-inflammation index (SII). The prognostic significance of these CBC-derived inflammatory indicators was evaluated using the random survival forests (RSF) analysis. RESULTS: The study encompassed a cohort of 12,689 individuals, among whom 1,725 were diagnosed with sarcopenia. Among individuals with sarcopenia, 782 experienced all-cause mortality, and 195 succumbed to cardiovascular causes. Following adjustment for confounding variables, it was observed that elevated levels of NLR, dNLR, NMLR, SIRI, and SII were associated with an increased prevalence of sarcopenia. Among participants with sarcopenia, those in the highest quartile of NLR (HR = 1.336 [1.095-1.631]), dNLR (HR = 1.274 [1.046-1.550]), MLR (HR = 1.619 [1.290-2.032]), NMLR (HR = 1.390 [1.132-1.707]), and SIRI (HR = 1.501 [1.210-1.862]) exhibited an elevated risk of all-cause mortality compared to those in the lowest quartile of these inflammation-derived indicators. These associations were similarly observed in cardiovascular mortality (HR = 1.874 [1.169-3.003] for MLR, HR = 1.838 [1.175-2.878] for SIRI). The RSF analysis indicated that MLR exhibited the highest predictive power for both all-cause and cardiovascular mortality among individuals with sarcopenia. CONCLUSIONS: Our findings underscore the association between CBC-derived inflammatory indicators and mortality in adults with sarcopenia. Of note, MLR emerged as the most robust predictor of all-cause and cardiovascular mortality in this population.

Kinetic Evaluation on Lithium Polysulfide in Weakly Solvating Electrolyte toward Practical Lithium-Sulfur Batteries.

Lithium-sulfur (Li-S) batteries are highly considered as next-generation energy storage techniques. Weakly solvating electrolyte with low lithium polysulfide (LiPS) solvating power promises Li anode protection and improved cycling stability. However, the cathodic LiPS kinetics is inevitably deteriorated, resulting in severe cathodic polarization and limited energy density. Herein, the LiPS kinetic degradation mechanism in weakly solvating electrolytes is disclosed to construct high-energy-density Li-S batteries. Activation polarization instead of concentration or ohmic polarization is identified as the dominant kinetic limitation, which originates from higher charge-transfer activation energy and a changed rate-determining step. To solve the kinetic issue, a titanium nitride (TiN) electrocatalyst is introduced and corresponding Li-S batteries exhibit reduced polarization, prolonged cycling lifespan, and high actual energy density of 381 Wh kg-1 in 2.5 Ah-level pouch cells. This work clarifies the LiPS reaction mechanism in protective weakly solvating electrolytes and highlights the electrocatalytic regulation strategy toward high-energy-density and long-cycling Li-S batteries.

Unravelling the molecular landscape of endometrial cancer subtypes: insights from multi-omics analysis.

BACKGROUND: Endometrial cancer (EC) as one of the most common gynecologic malignancies is increasing in incidence during the past 10 years. Genome-Wide Association Studies (GWAS) extended to metabolic and protein phenotypes inspired us to employ multi-omics methods to analyze the causal relationships of plasma metabolites and proteins with EC to advance our understanding of EC biology and pave the way for more targeted approaches to its diagnosis and treatment by comparing the molecular profiles of different EC subtypes. METHODS: Two-sample Mendelian randomization (MR) was performed to investigate the effects of plasma metabolites and proteins on risks of different subtypes of EC (endometrioid and non-endometrioid). Pathway analysis, transcriptomic analysis, and network analysis were further employed to illustrate gene-protein-metabolites interactions underlying the pathogenesis of distinct EC histological types. RESULTS: We identified 66 causal relationships between plasma metabolites and endometrioid EC, and 132 causal relationships between plasma proteins and endometrioid EC. Additionally, 40 causal relationships between plasma metabolites and non-endometrioid EC, and 125 causal relationships between plasma proteins and non-endometrioid EC were observed. Substantial differences were observed between endometrioid and non-endometrioid histological types of EC at both the metabolite and protein levels. We identified 7 overlapping proteins (RGMA, NRXN2, EVA1C, SLC14A1, SLC6A14, SCUBE1, FGF8) in endometrioid subtype and 6 overlapping proteins (IL32, GRB7, L1CAM, CCL25, GGT2, PSG5) in non-endometrioid subtype and network analysis of above proteins and metabolites to identify coregulated nodes. CONCLUSIONS: Our findings observed substantial differences between endometrioid and non-endometrioid EC at the metabolite and protein levels, providing novel insights into gene-protein-metabolites interactions that could influence future EC treatments.

Cohort profile of an early life observational cohort in China: Bone and MicroBiOme onset (BAMBOO) study.

PURPOSE: The Bone And MicroBiOme Onset (BAMBOO) study is an ongoing prospective observational cohort study conducted in Tianjin, China, aiming to determine age-appropriate trajectories for microbiome maturation and bone development and to identify the influence of dietary factors in the process. PARTICIPANTS: The recruitment started in September 2021 and was completed in February 2023. A total of 1380 subjects were recruited, 690 at birth (group 1) and 690 at 6 months of age (group 2). Groups 1 and 2 will be followed up for 12 months and 36 months, respectively. FINDINGS TO DATE: The age of the mothers was 31.1±3.7 (mean±SD), and the birth weight of infants was 3.3±0.5 kg with an incidence of caesarean section 50.4%. Food diary information of the first 100 subjects showed that 64 food items were introduced by 6 months. A pilot microbiome analysis revealed that at the species level, bacterial communities were composed of mostly Bacteroides dorei, Bacteroides vulgatus and Escherichia coli, which were consistent with that of previous reports. Feasibility assessments of breast milk vitamin D and human milk oligosaccharides were validated through certified reference measurements. The early data assessment showed a high reliability of the data generated from this study. FUTURE PLANS: Data collection will be completed in August 2025. Four stage-statistical analyses will be performed as the cohort reaches certain age thresholds before the final report. Analysis of BAMBOO data will be used to develop age-appropriate trajectories for microbiome maturation and bone development for children aged 0-3 years and investigate the contribution of dietary factors in the process. TRIAL REGISTRATION NUMBER: ChiCTR2100049972.

Evaluation of left ventricular flow field changes after stress in patients with nonobstructive coronary artery disease using ultrasonic flow vector imaging.

Purpose: Vector flow mapping and treadmill exercise stress echocardiography were used to evaluate and explore changes in the left ventricular (LV) flow field of patients with nonobstructive coronary artery disease. Methods: Overall, 34 patients with nonobstructive (<50%) left anterior descending coronary artery stenosis (case group) and 36 patients with no coronary artery stenosis (control group) were included. Apical four-, three-, and two-chamber echocardiographic images were collected at rest and during early recovery from treadmill exercise. LV flow field, vortex area, and circulation (cir) changes were recorded in different phases: isovolumetric systole (S1), rapid ejection (S2), slow ejection (S3), isovolumetric diastole (D1), rapid filling (D2), slow filling (D3), and atrial systole (D4). Intra- and inter-group differences were compared before and after exercise loading. Results: The control and case groups demonstrated regular trends of eddy current formation and dissipation at rest and under stress. Compared with the control group, the case group had irregular streamline distributions. Abnormal vortices formed in the S1 and D3 apical segments and D1 left ventricular middle segment in the resting group. Compared with the control group, the resting group had decreased left ventricular S1 vortex areas and increased S3 vortex areas. The post-stress D1 and D3 vortex areas and D1 and D2 cir increased. Compared with at rest, after stress, the control group had decreased S1, S3, D2, and D3 vortex areas; increased S2, D1, D3, and D4 cir; and decreased D2 cir. After stress, the case group had decreased S3 and D2 vortex areas, increased D1 vortex areas, and increased S2, D1, D3, and D4 cir (P all < 0.001). Logistic regression and ROC curve analyses show that increased D1 vortex area after stress is an independent risk factor for stenosis in nonobstructive stenosis of coronary arteries (OR: 1.007, 95% CI: 1.005-1.010, P < 0.05). A D1 vortex area cutoff value of 82.26 had an AUC, sensitivity, and specificity of 0.67, 0.655, and 0.726, respectively. Conclusion: The resting left ventricular flow field changed in patients with nonobstructive left anterior descending coronary artery stenosis. Both groups had more disordered left ventricular blood flow after stress. The increased D1 vortex area after stress is an independent risk factor for mild coronary stenosis and may contribute to the assessment of nonobstructive coronary stenosis. VFM combined with treadmill stress is useful in evaluating left ventricular flow field changes in patients with nonobstructive coronary artery disease, which is valuable in the early evaluation of coronary heart disease.