Search

Abstract Background The correlation between serum cotinine and fatty liver index (FLI) needs further investigation for the early identification, prevention, and treatment of metabolic dysfunction-associated steatotic liver disease (MASLD). Methods Data from the NHANES database spanning from March 2017 to 2018 was used to perform the population-based study to assess the relationship between serum cotinine and FLI. A variance estimation strategy was applied to address the data volatility. To examine the correlation between serum cotinine and FLI, a weighted multivariate logistic regression model was used. Initial normality assessment through the Kolmogorov-Smirnov test indicated non-normal distribution. Median and interquartile range were employed for description of non-normally distributed measurement data, and group comparisons were made using the Kruskal-Wallis H test. Proportions were used for ordinal data description and comparisons, with the chi-square test used for categorical data. Smooth curve fittings and generalized additive models were used to explore the non-linear relationship between serum cotinine and FLI. Results Finally, 2350 subjects (mean age: 49.83 ± 18.30, 1135 males and 1215 females) were selected for analysis. After adjusting for confounders, serum cotinine showed positive correlation with FLI in adults (β = 0.009, 95% CI: 0.003 to 0.014, P = 0.001). Additionally, individuals in the unexposed and passively exposed groups had lower FLI compared to those in the actively exposed group (β = -3.041, 95% CI: -4.728 to -1.353, P

Abstract Soil nitrogen (N) transformation is an essential portion of the N cycle in wetland ecosystems, governing the retention status of soil N by controlling the effective soil N content. N deposition produced by human activities changes the physical characteristics of soil, affecting N fractions and enzyme activities. To characterize these influences, three different N addition levels (N5, 5 g/m2; N10, 10 g/m2; N15, 15 g/m2) were established using a wet meadow on the Qinghai-Tibet Plateau (QTP) as a control treatment (0 g/m2). We investigated the features of soil physical property alterations, N fractions contents, and enzyme activities under N addition conditions throughout the peak plant growth season. Our findings indicated that N addition significantly enhanced soil aeration, porosity, total nitrogen (TN), ammonium nitrogen (NH4 +), nitrate nitrogen (NO3 −) content, and urease activity. At the same time, it decreased soil dissolved organic nitrogen (DON) content and bulk density (BD). Additionally, N addition treatment exerted a significant seasonal impact on soil nitrogen component content. The nitrogen component content within the surface soil (0–10 cm) under four treatments is more sensitive to N addition, whereas the nitrogen component in the deep soil is relatively stable. Principal component analysis demonstrated that soil aeration and porosity were the primary factors affecting soil N fractions and enzyme activities. The findings suggested that lower levels of N addition promoted the transformation process of soil N pools in wet meadows and exacerbated the loss of N in wetland ecosystems. Our findings indicate that sustained increases in N deposition will accelerate soil microbial N cycling, potentially overcoming N limitation in alpine wetland ecosystems and exacerbating the risk of N loss and greenhouse gas emissions from alpine wetland surface soils.

ABSTRACT: Tea drinks have a long history and milk is often added to enhance the taste and nutritional value, whereas the interaction between the tea bioactive compounds with proteins has not been systematically investigated. In this study, a milk-tea model was prepared by mixing green tea solution with milk and then heating at 100°C for 15 min. The milk tea was then measured using biochemical assay, antioxidant detection kit, and microscopy, as well as HPLC-quadrupole time-of-flight-MS/MS after ultrafiltration. The study found that as the concentration of milk protein increased in the milk-tea system, the total phenol-protein binding rate rose from 19.63% to 51.08%, which led to a decrease in free polyphenol content. This decrease of polyphenol was also revealed in the antioxidant capacity, including 2,2-diphenyl-1-picrylhydrazyl radical scavenging ability and ferric ion reducing antioxidant power, in a dose-dependent manner. Untargeted metabolomics results revealed that the majority of small-molecule compounds/polyphenols in tea, such as epigallocatechin gallate, (-)-epicatechin gallate, and catechin 5,7,-di-O-gallate, bound to milk proteins and were removed by ultrafiltration after addition of milk and heat treatment. The SDS-PAGE and Native-PAGE results further indicated that small-molecule compounds in tea formed covalent and noncovalent complexes by binding to milk proteins. All of these results partially explained that milk proteins form conjugates with tea small-molecule compounds. Consistently, the particle size of the tea-milk system increased as the tea concentration increased, but the polymer dispersity index decreased, indicating a more uniform molecular weight distribution of the particles in the system. Addition of milk protein enhanced foam ability in the milk-tea system but reduced foam stability. In summary, our findings suggest that the proportion of milk added to tea infusion needs to be considered to maintain the quality of milk tea from multiple perspectives, including stability, nutritional quality, and antioxidant activity.

Abstract Antibodies are essential to immune homeostasis due to their roles in neutralizing pathogenic agents. However, failures in central and peripheral checkpoints that eliminate autoreactive B cells can undermine self-tolerance and generate autoantibodies that mistakenly target self-antigens, leading to inflammation and autoimmune diseases. While autoantibodies are well-studied in autoimmune and in some communicable diseases, their roles in chronic conditions, such as obesity and aging, are less understood. Obesity and aging share similar aspects of immune dysfunction, such as diminished humoral responses and heightened chronic inflammation, which can disrupt immune tolerance and foster autoantigen production, thus giving rise to autoreactive B cells and autoantibodies. In return, these events may also contribute to the pathophysiology of obesity and aging, to the associated autoimmune disorders linked to these conditions, and to the development of immunosenescence, an age-related decline in immune function that heightens vulnerability to infections, chronic diseases, and loss of self-tolerance. Furthermore, the cumulative exposure to antigens and cellular debris during obesity and aging perpetuates pro-inflammatory pathways, linking immunosenescence with other aging hallmarks, such as proteostasis loss and mitochondrial dysfunction. This review examines the mechanisms driving autoantibody generation during obesity and aging and discusses key putative antigenic targets across these conditions. We also explore the therapeutic potential of emerging approaches, such as CAR-T/CAAR-T therapies, vaccines, and BiTEs, to tackle autoimmune-related conditions in aging and obesity.

Abstract Aiming at problems such as slow cutting speed, poor cutting quality and inability to cut thick plates effectively with traditional single-layer nozzle structure, it is proposed to add an outer ring core to form a double-layer nozzle structure on the basis of the single-layer nozzle structure to improve its cutting performance. The three-dimensional entity of single- and double-layer nozzle is established, and the simulation model of auxiliary gas flow field is established by using N-S equation and SST k-ω turbulence model assisted by laser cutting in this paper. The simulation results show that under the same cutting parameters, the auxiliary gas flow rate, oxygen concentration, mass flow rate, shear force and dynamic pressure of the double-layer nozzle structure are higher than those of the single-layer nozzle structure. In addition, compared with the single-layer nozzle structure, the double-layer nozzle structure can effectively improve the attenuation of oxygen concentration in the direction of sheet thickness. Two nozzle structures were used to laser cutting carbon steel plates with a thickness of 20 mm in the experiment, and the experimental parameters of cutting speed were 1.2–1.6 m/min. The comparison results show that the cutting speed and cutting section quality of the double-layer nozzle are better than those of the single-layer nozzle, and the results of simulation analysis are consistent with the cutting test results.

Abstract Low-load resistance training with blood flow restriction (LRT-BFR) has shown potential to improve muscle strength and mass in different populations; however, there remains limited evidence in sarcopenic people diagnosed with sarcopenia criteria. This study systematically compared the effectiveness of LRT-BFR and conventional high-intensity resistance training (CRT) on clinical muscle outcomes (muscle mass, strength and performance), cardiovascular disease (CVD) risk factors and sarcopenia-related biomarkers of older people with sarcopenia. Twenty-one older individuals (aged 65 years and older) diagnosed with sarcopenia were randomly assigned to the LRT-BFR (20%–30% one-repetition maximum (1RM), n = 10) or CRT (60%–70% 1RM, n = 11) group. Both groups underwent a supervised exercise program three times a week for 12 weeks. The primary outcome was knee extensor strength (KES), and the secondary outcomes included body composition (body mass, body mass index and body fat percentage), muscle mass [appendicular skeletal muscle mass index (ASMI)], handgrip strength, physical performance [short physical performance battery (SPPB) and 6-m walk], CVD risk factors [hemodynamic parameters (systolic and diastolic blood pressure and heart rate (SBP, DBP and HR)) and lipid parameters (total cholesterol, triglyceride (TG), high-density lipoprotein (HDL) and low-density lipoprotein)], sarcopenia-related blood biomarkers [inflammatory biomarkers, hormones (growth hormone (GH) and insulin-like growth factor 1) and growth factors (myostatin and follistatin)] and quality of life [Short Form 36 Health Survey (SF-36)]. Both interventions remarkably improved the body composition, KES, 6-m walk, SBP, HDL, TG, GH, FST and SF-36 scores. CRT significantly improved the ASMI (p

Abstract Patients with schizophrenia with early onset age have been shown to exhibit more severe negative symptoms. Genetic, biomarker, postmortem brain, and imaging studies indicate the involvement of immune abnormalities in the pathophysiology of schizophrenia. In this study, we examined the moderating role of early onset on the associations between clinical symptoms and neutrophil-to-lymphocyte ratio (NLR) in medication-naïve first-episode schizophrenia (MNFES). A total of 97 MNFES patients were recruited. Neutrophil (NEU), LYM, and NLR values were compared between early-onset (EO) and non-early-onset (non-EO) patients with schizophrenia to explore the potential influence of EO on the correlations between NLR and symptoms. The results showed no differences in NEU and NLR values between the EO and non-EO groups. In the EO group, NEU and NLR values significantly correlated with general psychopathology and total score (all p

Glucose-like peptide-1 (GLP-1) is a vital hormone in the intestines that regulates glucose metabolism. Although pancreatic-derived factor (PANDER) overexpression is known to suppress GLP-1, the underlying mechanisms are unclear. Our study aims to uncover how PANDER influences GLP-1 synthesis and secretion. We established a PANDER overexpression model in STC-1 intestinal cells, confirming its inhibitory effect on GLP-1 secretion. This effect was reversed in PANDER-knockout cells. Additionally, a negative correlation between PANDER and GLP-1 was observed in patients with a history of gestational diabetes. Subsequently, through whole transcriptome gene sequencing in PANDER-overexpressed STC-1 cells, we discovered that the activation of IL-6 and its related STAT3 signaling pathway was significantly inhibited, and this finding was validated by Western blotting and quantitative reverse transcription PCR. Finally, rescue experiments confirmed that the IL-6-related STAT3/Akt/GSK3β/β-catenin signaling pathway mediates the negative regulatory effect of PANDER on GLP-1. Taken together, our data identify IL-6 as a bridge connecting PANDER and GLP-1 in the STC-1 cells, demonstrating potential therapeutic targets for diabetes treatment by targeting the PANDER–IL-6–GLP-1 axis.

ObjectiveTo analyze the current state of domestic and international research on primary cardiac malignant tumor and predict its future development trends using bibliometric methods. MethodsRelevant literature on “primary cardiac malignant tumor”, from January 1, 2004 to June 1, 2024 was retrieved from the the China National Knowledge Infrastructure (CNKI) and Web of Science (WOS) core collection databases. The number of publications in this field over the past 20 years was counted, and the national publication volume, author situation, keyword clustering and emergence, and co-occurrence of authors, institutions, and keywords in the included literature were analyzed using CiteSpace and VOSviewer software. ResultsA total of 312 and 775 papers were included in the CNKI and WOS core collections, respectively. WOS core collection data showed that China’s publication volume ranked second globally, but its international cooperation was relatively low with 0.01 of centrality. In the CNKI database, the authors with high publication volume were represented by Chen Dong, Xu Zhiyun, and Song Shutian, while in the WOS core collection, the authors were represented by Reardon Michael J and Gaudino Mario. Some publications included in the WOS core collection from Chinese researchers, but the Chinese researchers were short of research cooperation and continuous academic output. The keyword map analysis showed that “pathological typing”, “echocardiography”, and “surgical treatment” were the research focus in this field for decades. In recent years, research on chemotherapy and molecular mechanisms increased both domestically and internationally, and immune checkpoint inhibitors (ICIs) and other immunotherapy treatment options have gradually been applied to the disease. Compared with domestic research, foreign research focused more on refined imaging diagnosis, in-depth pathological typing, comprehensive treatment, prognosis management, and multicenter research cooperation. However, many studies were case reports. ConclusionsThe improvement of surgical plans and the renewal of imaging technology remain the research focus in the field of primary cardiac malignant tumor. Exploring targeted treatments and comprehensive treatments to improve patient prognosis based on molecular pathological mechanisms is the future research trend, and high-quality clinical research based on multicenter and multidisciplinary cooperation is imperative.

Abstract Purpose Colorectal cancer (CRC) surgery in elderly patients with hypertension poses challenges due to potential complications and prolonged recovery. This study aimed to assess the impact of multimodal opioid-sparing anesthesia on intestinal function and prognosis of elderly hypertension patients undergoing CRC surgery. Methods A total of 80 elderly hypertension patients who underwent open surgery for CRC in the People’s Hospital of Xinjiang Uygur Autonomous Region from October 2020 to October 2022 were selected and randomly divided into two group (A and B, n = 40) through the random number table method. Group A received multimodal opioid-sparing anesthesia, defined as low-dose opioid general anesthesia combined with a transversus abdominis plane block, incision infiltration with local anesthetics, and postoperative analgesia via a patient-controlled analgesia (PCA) pump, with the remifentanil dose set at one-third (± 10%) of the conventional group’s dose. Group B received conventional opioid anesthesia, involving standard general anesthesia maintained with remifentanil at 0.4–0.5 µg/(kg·min), incision infiltration with local anesthetics, and postoperative PCA. Primary outcomes included mean arterial pressure (MAP) and heart rate (HR), changes in albumin, C-reactive protein (CRP) and white blood cell (WBC), indicators of intestinal function recovery (the recovery time of bowel sounds, the first exhaust time, the first defecation time and the feeding recovery time), and visual analogue scale (VAS) pain scores. Second outcomes included postoperative complications and total hospital stays. Results After excluding 8 patients, 72 were included in the final analysis. Compared with patients in the B group, patients in the A group exhibited shorter recovery time of bowel sounds, first exhaust time and feeding recovery time (P

Abstract Background Axillary lymph node dissection (ALND) is the standard axillary management for breast cancer patients with positive sentinel lymph node biopsy (SLNB) after neoadjuvant therapy. Nevertheless, when that happens, the frequency of additional positive nodes is not properly evaluated. We aim to develop a prediction model to assess the frequency of additional nodal disease after a positive sentinel lymph node following neoadjuvant therapy. Methods We retrospectively analyzed the ultrasound and clinicopathological characteristics of breast cancer patients with 1–3 positive sentinel lymph nodes (SLN) undergoing mastectomy after neoadjuvant therapy (NAT) at our institution, and performed univariate and multivariate logistic analyses to confirm the factors affecting non-SLN metastasis. These factors were included to establish a nomogram, and the area under receiver operating characteristic curve (AUC) and decision curve analysis (DCA) were utilized to assess the validity of this model. Results A total of 126 breast cancer patients were ultimately included in our study, 38 (53.5%) patients were diagnosed with non-SLN metastases of all 71 patients in training set. The results of multifactorial logistic analysis suggested that lymph node metastasis ratio (LNR), short axis of lymph node and progesterone receptor (PR) were strongly associated with non-SLN metastasis. We established a nomogram using the above three variables as predictors, which yielded an area under the curve of 0.795, and validated with a favorable AUC of 0.876. Conclusion The nomogram we constructed can accurately predict the likelihood of non-SLN metastasis in our patients with 1–3 positive SLN after NAT, which may help guide decision making regarding axillary management.

Abstract Research on outdoor, mobile, and self-powered temperature-control devices has always been highly regarded. These devices can reduce energy consumption for cooling and heating, and they have broad market prospects. On this basis, a rotary disc-shaped triboelectric nanogenerator (TENG) with a maximum open-circuit voltage of 6913 V, a maximum short-circuit current of 85 μA, and a maximum transferred charge of 1.3 μC was prepared. We synthesized a ferroelectric ceramic composed of 0.15PbTiO3–0.85PbSc0.5Ta0.5O3 (0.15PT–0.85PST), which exhibited excellent electrothermal effects at room temperature. By quenching, the electrothermal effect ( $$\Delta$$ Δ T max) and energy harvesting properties of the device were 1.574 K and 0.542 J/cm3, respectively. Then, for the first time, we proposed a self-powered temperature quantification control system with a rotary disc-shaped TENG. This device effectively harnessed wind and water energy, in addition to other types of energy. The system consisted of energy collecting cups, a rotating disc-shaped FEP–rabbit fur TENG, a circuit management module, and a ferroelectric ceramic chip array. Through the circuit management module, the system converted external wind energy into a high-voltage electric field at the two ends of the 0.15PT–0.85PST ceramic chip to fully stimulate the electrothermal effect. At a speed of 200 rpm, the temperature change in the insulated cup within 276 s was 0.49 K, and the volume of the insulated cup was 300 times greater than that of the 0.15PT–0.85PST ceramic chip. Compared with the results reported in previous work, the cooling and heating times were both reduced by 31%, and the temperature changes for both cooling and heating increased by 81%. Moreover, the heating and cooling temperatures of the device optimized on this basis were increased to 1.19 K and 0.93 K, respectively. The great improvement in the temperature variation performance confirmed the great potential of the device for commercialization. This research could serve as a reference for reducing energy consumption for cooling and heating, and it meets the international energy policies of carbon dioxide emission peaking and carbon neutrality.

Abstract Carbon peaking and achieving carbon neutrality have emerged as pivotal strategic imperatives in China. These objectives not only drive a shift in production, lifestyle, and consumption patterns but also illuminate a path towards a comprehensive green metamorphosis in China’s economic and social development landscape. The distinctive nature of museums as quintessential public edifices, requiring sustained regulation of temperature and humidity alongside attracting substantial foot traffic, positions them as crucial pioneers in the pursuit of carbon peaking and neutrality. It is essential for museums to leverage their leadership and advocacy roles to catalyze low-carbon construction practices across society. This study delves into the energy dynamics specific to the museum sector, delving into the recycling of exhibition materials, methodologies for carbon footprint assessments of visitors and museum staff, and the establishment of a standardized carbon emission accounting framework tailored to the museum industry. Through meticulous examination of representative cases and subsequent analysis, this research delineates decarbonization strategies, offering indispensable technical scaffolding for carbon assessment and emission reduction efforts within the museum realm.

Abstract Respiratory pathogens infecting the human respiratory system are characterized by their diversity, high infectivity, rapid transmission, and acute onset. Traditional detection methods are time-consuming, have low sensitivity, and lack specificity, failing to meet the needs of rapid clinical diagnosis. Nucleic acid aptamers, as an emerging and innovative detection technology, offer novel solutions with high specificity, affinity, and broad target applicability, making them particularly promising for respiratory pathogen detection. This review highlights the progress in the research and application of nucleic acid aptamers for detecting respiratory pathogens, discussing their selection, application, potential in clinical diagnosis, and future development. Notably, these aptamers can significantly enhance the sensitivity and specificity of detection when combined with detection techniques such as fluorescence, colorimetry and electrochemistry. This review offers new insights into how aptamers can address the limitations of traditional diagnostic methods and advance clinical diagnostics. It also highlights key challenges and future research directions for the clinical application of nucleic acid aptamers.

Abstract Background and aims Despite concerns on the adverse health outcomes of sarcopenic obesity (SO), exploration regarding the applicability of different diagnostic criteria and the optimal screening methods is still lacking. This study aims to compare the prevalence and diagnostic agreement of SO under four diagnostic criteria in Chongming, Shanghai, China and assess the diagnostic value of nine screening methods for SO. Methods The study population included older people aged ≥ 65 years. The Asian Working Group for Sarcopenia-2019 (AWGS-2019) was used to diagnose sarcopenia. Obesity was defined using percentage of body fat (PBF), percent of body fat exceeding the 60th percentile (60% PBF), body mass index (BMI) and waist circumference (WC). The four diagnostic criteria for SO were AWGS + PBF, AWGS + 60% PBF, AWGS + BMI and AWGS + WC. Nine screening methods were the sarcopenia questionnaire [the questionnaire with five items to screen for sarcopenia (SARC-F), the addition of calf circumference to the SARC-F (SARC-CalF), and the addition of elderly age and BMI to the SARC-F (SARC-F + EBM)] combined with commonly used obesity indicators. Cohen’s kappa compared agreement between diagnostic criteria, whilst sensitivity, specificity, receiver operating characteristics (ROC) and area under the ROC curve (AUC) compared the diagnostic value of nine screening methods. Results A total of 1407 older people were enrolled. The prevalence of SO ranged from 0.3 to 9.9%. The highest agreement between AWGS + 60% PBF and AWGS + PBF. When the AWGS + PBF was used as the ‘gold standard’ (due to its high agreement and high prevalence), SARC-CalF + PBF had the highest AUC value, and SARC-F + BMI had the highest sensitivity. The recommended cut-off values for SARC-F + BMI are SARC-F ≥ 1 score and BMI ≥ 19.845 kg/m², and the recommended cut-off values for SARC-CalF + PBF are SARC-CalF ≥ 5 score and PBF ≥ 34.55%. Conclusion The prevalence of SO varied greatly amongst the four diagnostic criteria. AWGS + PBF is recommended for diagnosing SO in older people. SARC-F + BMI and SARC-CalF + PBF can be used as screening methods for SO.

Most of the pyroptosis inhibitors targeted Gasdermin D (GSDMD) are functioning by restraining GSDMD-N (p30) oligomerization. For the first time, this work discovered a pyroptosis inhibitor taking effect by degrading p30 and GSDMD. As the principal bioactive constituent in Erigeron breviscapus, scutellarin (SCU) assumes a pivotal role in the realm of anti-inflammatory processes. In this study, SCU demonstrated efficacy in hindering pyroptosis mediated by the NOD-like receptor protein 3 (NLRP3) inflammasome, absent in melanoma 2 (AIM2) inflammasome, NLR-family CARD-containing protein 4 (NLRC4) inflammasome, and that activated through the non-canonical pathway. The inhibitory effect is achieved by thwarting apoptosis-associated speck-like protein containing CARD (ASC) oligomerization and inducing the ubiquitin-dependent selective autophagy of p30/GSDMD. Throughout the autophagic process, SCU facilitates selective autophagy of the pyroptosis executor p30/GSDMD through K33-linked polyubiquitination at Lys51 catalyzed by the E3 ligase tripartite motif-containing 21 (TRIM21). This process contributes to the recognition of p30/GSDMD by the cargo receptor sequestosome 1 (SQSTM1)/p62. The characteristic positions SCU as a prospective clinical intervention for a broader spectrum of inflammatory-related disorders.

Abstract Solution coating of organic semiconductors offers great potential for achieving low‐cost and high‐throughput manufacturing of large‐area and flexible electronics. However, the solution processability of semiconducting small molecules for fabricating uniform and reliable thin‐film devices poses challenges due to the low viscosities of small‐molecule solutions. Here, we report a universal approach employing a primer template (PT) to enhance the spreadability of small‐molecule solutions on silicon wafers, enabling the spin‐coating fabrication of uniform thin films composed of millimeter‐scale grains with complete large‐area coverage and well‐ordered molecular packing. Using PT, we fabricated organic thin‐film transistors (OTFTs) using solutions containing various small molecules such as rubrene and 2‐decyl‐7‐phenyl‐[1]benzothieno[3,2‐b][1]benzothiophene. The device yield of all fabricated OTFTs is consistently 100% while achieving a high average mobility of 1.62 cm2 V−1 s−1 with a device‐to‐device variation of 7.7% measured in ambient air condition. In addition, the utilization of PT resulted in a batch‐to‐batch variation of 12.5% in device performance over dozens of OTFT devices. The key industrial manufacturing metrics, such as device yield, reproducibility, and performance uniformity of the PT OTFTs, are among the best for devices fabricated using solution spin‐coating techniques.

Background B-Raf proto-oncogene, serine/threonine kinase (BRAF)V600E-mutant microsatellite stable (MSS) colorectal cancer (CRC) constitutes a distinct CRC subgroup, traditionally perceived as minimally responsive to standard therapies. Recent clinical attempts, such as BRAF inhibitors (BRAFi) monotherapy and combining BRAFi with other inhibitors, have yielded unsatisfactory efficacy. This study aims to identify a novel therapeutic strategy for this challenging subgroup.Methods We first performed a large-scale drug screening using patient-derived organoid models and cell lines to pinpoint potential therapies. Subsequently, we investigated the synergistic effects of identified effective inhibitors and probed their cooperative mechanisms. Concurrently, we explored the immune characteristics of BRAFV600E MSS CRC using RNA sequencing and multiplex immunohistochemistry. Finally, we established a CT26 BRAFV637E mouse cell line and validated the efficacy of combining these inhibitors and programmed death 1 (PD-1) blockades in immunocompetent mice.Results Drug screening identified histone deacetylase (HDAC) inhibitor and mitogen-activated protein kinase kinase (MEK) inhibitor as significantly effective against BRAFV600E MSS CRC. Further research revealed that these two inhibitors have superior synergistic effects by comprehensively inhibiting the activation of the epidermal growth factor receptor, mitogen-activated protein kinase, and phosphoinositide 3-kinase-protein kinase B pathways and suppressing the key target homeobox C6 (HOXC6). HOXC6, overexpressed in BRAFV600E MSS CRC, regulates the MYC gene and contributes to treatment resistance, tumor growth, and metastasis. Moreover, the combination therapy demonstrated the ability to enhance antitumor immunity by synergistically upregulating the expression of immune activation-related genes, activating the cyclic guanosine monophosphate–adenosine monophosphate synthase/stimulator of interferon genes (cGAS/STING) pathway, and diminishing the tumor cells’ DNA mismatch repair capacity. Notably, BRAFV600E MSS CRC was identified to exhibit a distinct immune microenvironment with increased PD-1+ cell infiltration and potential responsiveness to immunotherapy. Echoing the above findings, in vivo, HDAC and MEK inhibitors significantly improved PD-1 blockade efficacy, accompanied by increased CD8+ T-cell infiltration.Conclusions Our findings indicate that combining HDAC inhibitor, MEK inhibitor, and PD-1 blockade is a potential strategy for treating BRAFV600E-mutant MSS CRC, warranting further investigation in clinical settings.

ObjectiveThis study aims to explore the differences in ocular parameters among adult myopic patients with different degrees of myopia and axial lengths, and to investigate the correlations between these ocular parameters.MethodsThis single-center observational study collected clinical data from myopic patients aged 18–45 years who visited the Eye Hospital of Nanjing Medical University between January and June 2023. The data included laterality, diopter of spherical power (DS), diopter of cylindrical power (DC), spherical equivalent (SE), axial length (AL), central corneal thickness (CCT), flat meridian keratometry (K1), steep meridian keratometry (K2), mean keratometry (Km), anterior chamber depth (ACD), corneal radius of curvature (CRC), and axial length/corneal radius of curvature ratio (AL/CRC). Following predefined inclusion and exclusion criteria, 1,026 eyes were included in the study. Patients were grouped based on SE and AL parameters into different degrees of myopia. Analysis of variance (ANOVA) and Welch ANOVA were used to compare intergroup differences. Spearman correlation coefficients were calculated to analyze the correlations between parameters, and linear regression and ROC curve analyses were performed.ResultsSignificant differences (p

We present a highly challenging case of brainstem hemorrhage complicated with pneumonia in a 41-year-old male patient. The patient had intermittent and recurrent fever for nearly two months from June 24, 2022 to August 22, 2022, along with extremely unstable vital signs. Multiple consultations were conducted among clinicians and pharmacists. In view of the patient's actual situation, they initially carried out empirical treatment and then comprehensively considered factors such as the characteristics of anti-infective drugs, interactions, susceptibility testing, and blood drug concentration to analyze and adjust the types and dosages of drugs and implement individualized therapy. Eventually, the patient's body temperature returned to normal, vital signs stabilized, and the patient was discharged smoothly. The author presents this case with the intention of providing a valuable reference for the treatment of patients with cerebral hemorrhage and pneumonia.

BackgroundNT-proBNP (N-terminal pro-B-type natriuretic peptide), high-sensitivity cardiac troponin T (hs-troponin T), and high-sensitivity cardiac troponin I (hs-troponin I) have been widely recognized as significant cardiac biomarkers, and are increasingly being recommended for early risk identification in cardiovascular high-risk populations. The aim of our study was to evaluate the prevalence of elevated cardiac biomarkers (NT-proBNP, hs-troponin T, hs-troponin I) and their association with the risk of hyperuricemia in the general US adults without known cardiovascular disease. We further studied whether elevated cardiac biomarkers are associated with an increased risk of all-cause and cardiovascular mortality in individuals with or without hyperuricemia.MethodsThe study population came from the adults (age ≥20y) without prevalent cardiovascular disease in NHANES (National Health and Nutrition Examination Survey) 1999 to 2004. We evaluated the prevalence of elevated cardiac biomarkers among adults with or without hyperuricemia, and conducted a comprehensive multivariate logistic regression analysis to ascertain the association between elevated cardiac biomarkers and hyperuricemia risk. Multivariate Cox regression model and Kaplan-Meier curve, risk competition model and Cumulative Incidence Function(CIF) were used respectively to examine the associations between elevated cardiac biomarkers with all-cause and cardiovascular mortality.ResultsIn general US adults without known cardiovascular disease, the prevalence of hyperuricemia was 16.35%. The age-adjustd prevalence of elevated NT-proBNP (≥125 pg/mL), hs-troponin T (≥6 ng/L), and hs-troponin I (male ≥6, female ≥4 ng/L) was 16.70%, 49.80%, and 11.91%, respectively, among adults with hyperuricemia. Adjusted multivariable logistic regression analysis revealed a statistically significant association between elevated levels of NT-proBNP, hs-troponin T, and hs-troponin I and hyperuricemia, and different clinical categories observed grade differences on the same cardiac biomarker. Elevated NT-proBNP, hs-troponinT and hs-troponinI were each significantly positively associated with the cumulative incidence of all-cause and cardiovascular mortality in adults with or without hyperuricemia. Compared to those with elevated cardiac biomarkers only, adults with hyperuricemia and elevated cardiac biomarkers faced the highest risk of all-cause and cardiovascular mortality.ConclusionsOur study identified that elevated cardiac biomarkers pose a high burden on hyperuricemia risk in the general population without known cardiovascular disease, and further provides important information on long-term mortality risk in these populations. Routine testing of cardiac biomarkers may be useful for early risk identification and prognostic assessment in adults with hyperuricemia.

ABSTRACTThe air quality in China has changed due to the implementation of clean air actions since 2013. Evaluating the spatial pattern of PM2.5 and the effectiveness of reducing anthropogenic emissions in urban and nonurban areas is crucial. Therefore, the China Long-term Air Pollutant dataset for PM2.5 (CLAP_PM2.5) was generated from 2010 to 2022 with a daily 0.1° resolution using the random forest model and integrating multiple data sources, including extensive in-situ PM2.5 measurements, visibility, satellite retrievals, surface and upper-level meteorological data and other ancillary data. The CLAP_PM2.5 dataset is more reliable and accurate than other public datasets. Analysis of CLAP_PM2.5 from 2010 to 2022 reveals the decrease in positive urban-nonurban PM2.5 differences and higher decreasing rates of PM2.5 in most city clusters in eastern China. Furthermore, separating meteorological and emission contributions to the PM2.5 variability by a meteorological normalization approach indicates that meteorological contribution gradually changed from unfavorable to PM2.5 reduction during 2013–2017 to favorable to decline enhancement during 2018–2022, and in urban regions, meteorological contribution is higher than that in nonurban areas. Overall, the reduction in deweathered PM2.5 concentrations highlights China's significant achievements in terms of comprehensive clean air actions.

Background During the acute heart failure (AHF), acute kidney injury (AKI) is highly prevalent in critically ill patients. The occurrence of the latter condition increases the risk of mortality in patients with acute heart failure. The current research on the relationship between nutritional risk and the occurrence of acute kidney injury in patients with acute heart failure is very limited.Methods This retrospective cohort study utilized data from the Medical Information Mart for Intensive Care IV (MIMIC-IV, version 2.1) database. We included adult patients with AHF who were admitted to the intensive care unit in the study. Results: A total of 1310 critically ill patients with acute heart failure were included. The AUC of geriatric nutritional risk index (GNRI) (0.694) is slightly superior to that of controlling nutritional status (CONUT) (0.656) and prognostic nutritional index (PNI) (0.669). The Log-rank test revealed a higher risk of acute kidney injury in patients with high nutritional risk (p

Background During the run-in phase of the TESTING study, approximately half of patients with IgA nephropathy (IgAN) were excluded due to proteinuria below 1 g/24 h after intensive supportive therapy. The long-term prognosis of these patients needs further investigation.Methods 112 screening failed patients in the TESTING study from 10 centers in China were enrolled in this retrospective study. The prognosis of 88 patients, who were excluded because of proteinuria below 1 g/24 h, was analyzed by Landmark Kaplan-Meier analysis. The composite kidney endpoint was defined by a ≥ 50% reduction in eGFR, ESKD (eGFR

Introduction KMT2A rearrangement (KMT2Ar) is a common genomic alteration in acute leukemia that can be effectively targeted by menin inhibitors. While FISH is the standard laboratory test for KMT2Ar, false positives can occur.Case Report We present a case of AML in which both RUNX1::RUNX1T1 and KMT2Ar were identified by karyotype analysis and FISH. Although a targeted RNA next generation sequencing (NGS) assay confirmed the presence of the RUNX1::RUNX1T1 fusion, it did not detect a KMT2A fusion transcript. To investigate the discrepancy between the positive KMT2A FISH result and the negative fusion transcript, we performed whole-genome mate-pair DNA NGS to examine the KMT2A locus on chromosome 11q23. This analysis revealed a breakpoint located 5.8 kb downstream of KMT2A, which did not disrupt the gene itself. Given that KMT2A FISH probes cover approximately 1 Mb around KMT2A, this subtle shift led to a split-apart signal pattern mimicking a genuine KMT2A rearrangement, resulting in a false positive FISH interpretation.Conclusion This case highlights a false positive KMT2Ar in primary AML, indicating the need for additional molecular testing for confirmation.

Abstract For the polarization multiplexing requirements in all-optical networks, this work presents a compact all-fiber polarization beam splitter (PBS) based on dual-core photonic crystal fiber (PCF) and an elliptical gold layer. Numerical analysis using the finite element method (FEM) demonstrates that the mode modulation effect of the central gold layer effectively reduces the dimensions of the proposed PBS. By determining reasonable structural parameters of the proposed PCF, the coupling length ratio (CLR) between X- and Y-polarized super-modes can approach 2, achieving a minimal device length of 0.122 mm. The PBS exhibits a maximum extinction ratio (ER) of − 65 dB at 1.55 μm, with an operating bandwidth spanning 100 nm (1.5–1.6 μm) and a stable insertion loss (IL) of ~ 1.5 dB at 1.55 μm. Furthermore, the manufacture feasibility and performance verification scheme are also investigated. It is widely anticipated that the designed PBS will play a crucial role in the ongoing development process of miniaturization and integration of photonic devices.

Abstract Introduction Sepsis is a life-threatening condition that poses a globally high mortality rate. Identifying risk factors is crucial. Insulin resistance and the TYG index, associated with metabolic disorders, may play a role. This study explores their correlation with mortality in non-diabetic septic patients. Methods This retrospective cohort study used data from the MIMIC-IV (version 2.1) database, which includes over 50,000 ICU admissions from 2008 to 2019 at Beth Israel Deaconess Medical Center in Boston. We included adult patients with sepsis who were admitted to the intensive care unit in the study. The primary outcome was to evaluate the ability of TYG to predict death at 28-day of hospital admission in patients with sepsis. Results The study included 2213 patients with sepsis, among whom 549 (24.8%) died within 28 days of hospital admission. We observed a non-linear association between TYG and the risk of mortality. Compared to the reference group (lower TYG subgroup), the 28-day mortality increased in the higher TYG subgroup, with a fully adjusted hazard ratio of 2.68 (95% CI: 2.14 to 3.36). The area under the curve (AUC) for TYG was 67.7%, higher than for triglycerides alone (AUC = 64.1%), blood glucose (AUC = 62.4%), and GCS (AUC = 63.6%), and comparable to SOFA (AUC = 69.3%). The final subgroup analysis showed no significant interaction between TYG and each subgroup except for the COPD subgroup (interaction P-values: 0.076–0.548). Conclusion In our study, TYG can be used as an independent predictor for all-cause mortality due to sepsis within 28 days of hospitalization.

Abstract Background Peritoneal dialysis (PD) and conventional in‐center hemodialysis (HD) are treatment options for patients with end‐stage kidney disease (ESKD). However, their impact on all‐cause mortality is unclear. Methods We conducted a multicenter, open‐label, randomized, non‐inferiority trial to determine the effect of dialysis modality on mortality in patients with ESKD. Eligible patients were recruited from 30 sites across China and assigned to receive either PD or HD in a ratio of 1:1. The primary outcome was all‐cause mortality. Non‐inferiority was defined as the upper bound of the one‐sided 95% confidence interval (CI) for the hazard ratio (HR) being ≤1.25. Results A total of 414 patients with incident ESKD were randomly assigned to PD (n = 213) or HD (n = 201). During a median follow‐up of 1.7 years, 37 patients in the PD group and 31 in the HD group died, giving respective event rates per patient‐year of 0.061 and 0.071. The HR for mortality on PD in comparison with HD was 0.76 (95% CI 0.47–1.24) after adjustment for age, sex, and diabetes status, achieving the limit for non‐inferiority. There were more adverse events (p = 0.003), serious adverse events (p = 0.009), and adverse events leading to hospitalization (p = 0.003) in the PD group than in the HD group; however, there was no significant between‐group difference in adverse events leading to death or discontinuation of treatment. Conclusions PD was non‐inferior to conventional in‐center HD in terms of survival in patients with ESKD. Our findings underscore the need for shared decision‐making between physicians and patients regarding the selection of dialysis modality. Trial registration Registered at ClinicalTrials.gov (NCT01413074).

Abstract The amount of actively cultivated land in China is increasingly threatened by rapid urbanization and rural population aging. Quantifying the extent and changes of active cropland and cropping intensity is crucial to global food security. However, national-scale datasets for smallholder agriculture are limited in spatiotemporal continuity, resolution, and precision. In this paper, we present updated annual Cropland Use Intensity maps in China (China-CUI10m) with descriptions of the extent of fallow/abandoned, actively cropped fields and cropping intensity at a 10-m resolution in recent six years (2018–2023). The dataset is produced by robust algorithms with no requirements for regional adjustments or intensive training samples, which take full advantage of the Sentinel-1 (S1) SAR and Sentinel-2 (S2) MSI time series. The China-CUI10m maps have achieved high accuracy when compared to ground truth data (Overall accuracy = 90.88%) and statistical data (R2 > 0.94). This paper provides the recent trends in cropland abandonment and agricultural intensification in China, which contributes to facilitating geographic-targeted cropland use control policies towards sustainable intensification of smallholder agricultural systems in developing countries.

In an era marked by rapid digitalization and the convergence of media platforms, gender equality, particularly within journalism, has gained prominence. However, gender discrimination remains a challenge for female journalists. This research collected 387 valid responses from Spanish media professionals through digital and other channels. Data analysis, including statistical methods like frequency analysis and chi-square tests, aims to uncover factors affecting the careers of Spanish female journalists. The goal is to provide empirically supported recommendations for gender equality in the dynamic Spanish media landscape.

Fusion of hyperspectral image (HSI) and multispectral image (MSI) is a prevalent scheme to generate a HSI with enhanced spatial resolution. Current methods often fail to sufficiently leverage the effective spectral and spatial priors existing in the observed HSI and MSI to further enhance the fusion performance. To address this limitation, this paper proposes a novel HSI-MSI fusion approach, which integrates Sparse and Low Rank with a CNN denoiser (SLRCNN) while considering spectral dictionary optimization. Firstly, an initialized spectral dictionary is derived from the HSI. Next, the spatial coefficients optimization model is established by incorporating the sparse prior, local low-rank prior, and plugged image prior simultaneously, where the l1 norm is imposed to promote the sparse prior, and the super-pixel segmentation strategy is conducted on the MSI to impose the local low-rank prior while a well-trained CNN denoiser is plugged in to enforce the image prior. Then, the spectral dictionary optimization model is constructed to refine the initial spectral dictionary, capturing more detailed spectral characteristics to further improve the fusion results. Finally, the optimization process involves applying the split-augmented Lagrangian shrinkage method and the alternating direction method of multipliers. Experimental results on simulated and real datasets, namely the Pavia University dataset, the Indian Pines dataset, and the EO-1 dataset, indicate that SLRCNN outperforms existing state-of-the-art approaches at 4x, 5x, and 6x resolutions in both qualitative and quantitative evaluation results. Specifically, the peak signal-to-noise ratio (PSNR) of SLRCNN is improved by more than 0.9 dB, 0.9 dB, and 0.2 dB while the spectral angle mapper (SAM) is decreased by more than 0.1, 0.2, and 0.2 in degree compared to other state-of-the-art methods across three datasets, respectively, which underscores the effectiveness of SLRCNN in leveraging both spatial detail reconstruction and spectral preservation.

Purpose: To evaluate the efficacy of retinal massage combined with autologous blood covering in the treatment of persistent macular holes following vitrectomy in eyes with high myopia. Settings and Design: Retrospective, consecutive case series in a tertiary eye center. Methods: A total of 12 highly myopic eyes with persistent macular holes after vitrectomy and internal limiting membrane peeling received combined retinal massage, air/fluid exchange, autologous blood covering, and gas/silicone oil tamponade. Best-corrected visual acuity, axial length, and optical coherence tomographic images before and after the treatment were compared. Results: The mean hole diameter before this intervention was 931.58 ± 244.58 μm (range, 508–1270), and the axial length was 30.39 ± 2.13 mm (range, 27.08–34.64). During the 6-month follow-up period, hole closure was achieved in eight eyes (66.67%). The mean best-corrected visual acuity improved significantly from 1.40 ± 0.50 logarithm of the minimum angle of resolution (logMAR) at baseline to 1.10 ± 0.30 logMAR (P < 0.05). No complications were observed. Conclusions: Combined retinal massage and autologous blood covering, which is easy to manipulate, can promote the closure of persistent macular holes after vitrectomy and improve vision in high myopia with an axial length less than 29 mm.

The novel gelling polysaccharides (NPGP) were extracted and characterized from Nicandra physalodes (Linn.) Gaertn. seeds, while properties and potential application of NPGP gels with tea polyphenols were further explored. NPGP was composed of GalA, Glc, Rha, Gal, Xyl, Ara, and Man at a molar ratio of 71.87:17.13:3.10:2.55:2.19:1.64:1.52, with molecular weight of 6.32 × 104 Da and low methoxylation degree of 45.21%. The gelling properties of NPGP gel induced by tea polyphenols showed that tea polyphenols significantly improved the structural and rheological properties of NPGP gel, due to the formation of dense network by hydrogen bonds and the increase of crystalline degree of NPGP. NPGP gels with tea polyphenols could significantly ameliorated the texture, water-holding capacity, aggregation, leading force, and moisture distribution of surimi during freeze-thaw cycles. All results suggest that NPGP gels with tea polyphenols has fine properties and show potential to be applied as natural additives in food industry.

Abstract Hyperuricemia (HUA) is a common metabolic disease and kidney injury is one of its main complications. As a typical natural flavonoid, puerarin (PEA) has a range of pharmacological activity but the antihyperuricemic mechanism of PEA has not been reported. Herein, the inhibitory activity of PEA against xanthine oxidase (XOD) was evaluated by in vitro enzymatic reaction, and kinetic analysis, the antihyperuricemic activity, and nephroprotective effect of PEA were studied in HUA mice. The enzymatic reaction showed that the inhibitory effect of PEA (half maximal inhibitory concentration [IC50] = 4.39 µmol/L) on XOD was at the same level as allopurinol (IC50 = 4.05 µmol/L), and kinetic analysis indicated that PEA was a mixed competitive inhibitor. In vivo studies demonstrated that PEA exhibited excellent antihyperuricemic activity by inhibiting XOD and urate transporter 1 (URAT1), to reduce uric acid level. At the same time, PEA reduced the level of inflammatory cytokines and exerted significant nephroprotective effect through anti‐inflammatory activity. Molecular docking indicated that PEA closely bind to both XOD and URAT1, which had the potential to become an inhibitor of XOD and URAT1. In summary, PEA has important application value in developing novel functional food and medicine for the treatment of HUA and its complications.

Abstract Background Gastric cancer patients with peritoneal metastasis (GCPM) experience a rapidly deteriorating clinical trajectory characterized by therapeutic resistance and dismal survival, particularly following the development of malignant ascites. However, the intricate dynamics within the peritoneal microenvironment (PME) during the treatment process remain largely unknown. Methods Matched samples from primary tumours (PT), peritoneal metastases (PM), and paired pre‐treatment and post‐chemo/immunotherapy (anti‐PD‐1/PD‐L1) progression malignant ascites samples, were collected from 48 patients. These samples were subjected to single‐cell RNA sequencing (n = 30), multiplex immunofluorescence (n = 30), and spatial transcriptomics (n = 3). Furthermore, post hoc analyses of a phase 1 clinical trial (n = 20, NCT03710265) and an in‐house immunotherapy cohort (n = 499) were conducted to validate the findings. Results Tracing the evolutionary trajectory of epithelial cells unveiled the terminally differentially MUC1+ cancer cells with a high epithelial‐to‐mesenchymal transition potential, and they demonstrated spatial proximity with fibroblasts and endothelial cells, correlating with poor prognosis. A significant expansion of macrophage infiltrates, which exhibited the highest proangiogenic activity, was observed in the ascites compared with PT and PM. Besides, higher C1Q+ macrophage infiltrates correlated with significantly lower GZMA+ T‐lymphocyte infiltrates in therapeutic failure cases, potentially mediated by the LGALS9‐CD45 and SPP1‐CD44 ligand–receptor interactions. In the chemoresistant group, intimate interactions between C1Q+ macrophages and fibroblasts through the complement activation pathway were found. In the group demonstrating immunoresistance, heightened TGF‐β production activity was detected in MUC1+ cancer cells, and they were skewed to interplay with C1Q+ macrophages through the GDF15‐TGF‐βR2 axis. Ultimately, post hoc analyses indicated that co‐targeting TGF‐β and PDL1 pathways may confer superior clinical benefits than sole anti‐PD‐1/PD‐L1 therapy for patients presenting with GCPM at the time of diagnosis. Conclusions Our findings elucidated the cellular differentiation trajectories and crucial drug resistance features within PME, facilitating the exploration of effective targets for GCPM treatment. Highlights MUC1+ cancer cells with a high epithelial‐to‐mesenchymal transition potential and exhibiting spatial proximity to fibroblasts and endothelial cells constitute the driving force of gastric cancer peritoneal metastasis (GCPM). Higher C1Q+ macrophage infiltrates correlated with significantly lower GZMA+ T‐lymphocyte infiltrates within the peritoneal microenvironment in therapeutic failure cases. Co‐targeting TGF‐β and PDL1 pathways may confer superior clinical benefits than sole anti‐PD‐1/PD‐L1 therapy for patients presenting with GCPM at diagnosis.

ObjectiveThis study explores the relationship between social support and sporting activities of Muslim women and constructs a mediation model through role of psychological adjustment.MethodsUsing stratified cluster sampling, 301 Muslim women were measured in group psychology using the Social Support Scale and the Sports Activities and Psychological Adjustment Scale. The statistical software SPSS 24.0 and SPSS PROCESS 3.3 were used for statistical processing. The common-method variation test was carried out using the Harman single-factor control test. Finally, the Bootstrap sampling test method and process plug-in were used to test the significance of the intermediary effect.Results(1) Social support has a significant predictive effect on sports activities (β = 0.32, p

Objectives To analyse annual trends of the under-five mortality rate (U5MR) and main cause-specific U5MR in China from 1996 to 2020 and to assess the potential correlation of the healthcare system and health expenditure with the U5MR in China.Design A retrospective observational study using national data from 1996 to 2020. Joinpoint regression was employed to model U5MR trends and Pearson correlation analysis was conducted to examine the relationship between healthcare system factors, health expenditure and U5MR.Setting Nationwide study covering both rural and urban populations across China over a 25-year period.Results The U5MR in China experienced a three-stage decline from 1996 to 2020 with an average annual percentage rate change (AAPC) of −7.27 (p

Abstract Cardiovascular function and adipose metabolism were markedly influenced under high altitudes. However, the interplay between adipokines and heart under hypoxia remains to be elucidated. We aim to explore alterations of adipokines and underlying mechanisms in regulating cardiac function under high altitudes. We investigated the cardiopulmonary function and five adipokines in Antarctic expeditioners at Kunlun Station (4,087 m) for 20 days and established rats exposed to hypobaric hypoxia (5,000 m), simulating Kunlun Station. Antarctic expeditioners exhibited elevated heart rate, blood pressure, systemic vascular resistance, and decreased cardiac pumping function. Plasma creatine phosphokinase-MB (CK-MB) and platelet-endothelial cell adhesion molecule-1 (sPecam-1) increased, and leptin, resistin, and lipocalin-2 decreased. Plasma leptin significantly correlated with altered cardiac function indicators. Additionally, hypoxic rats manifested impaired left ventricular systolic and diastolic function, elevated plasma CK-MB and sPecam-1, and decreased plasma leptin. Chronic hypoxia for 14 days led to increased myocyte hypertrophy, fibrosis, apoptosis, and mitochondrial dysfunction, coupled with reduced protein levels of leptin signaling pathways in myocardial tissues. Cardiac transcriptome analysis revealed leptin was associated with downregulated genes involved in rhythm, Na+/K+ transport, and cell skeleton. In conclusion, chronic hypoxia significantly reduced leptin signaling pathways in cardiac tissues along with significant pathological changes, thus highlighting the pivotal role of leptin in regulation of cardiac function under high altitudes.

Steel containers used for geological disposal of high-level radioactive waste will be gradually thinned or even perforated due to corrosion, which will lead to radiolysis of nuclides when they contact with infiltrated groundwater and produce H2O2. This work focused on investigating the influence of H2O2 concentration (0%, 0.001%, 0.01%, 0.1% and 1% by volume) on the corrosion behavior of NiCu low alloy steel as the candidate material for containers was comparatively studied by combining corrosion weight loss test, corrosion product analysis, morphology characterization, thermodynamic analysis and electrochemical measurements. As [H2O2] = 0.001%, H2O2 inhibited the formation of γ-FeOOH and enhanced the compactness of rust layer, which effectively blocked the migration of aggressive ions and slowed down the cathodic reduction reaction of rust, thus improving the corrosion resistance of NiCu steel. With the increase of [H2O2] (0.01%→1%), the cathodic process of NiCu steel corrosion was promoted by the increase of dissolved oxygen involved in cathodic depolarization. Meanwhile, the relative content of Fe3O4 in the rust increased, while Fe6(OH)12SO4 and Fe6(OH)12CO3 decreased obviously, which led to the loose and porous rust layer, thus accelerating the corrosion of NiCu steel.

Abstract Background Numerous previous reports have demonstrated the efficacy of Lactic acid bacteria (LAB) in promoting growth and preventing disease in animals. In this study, Enterococcus faecium ZJUIDS-R1 and Ligilactobaciiius animalis ZJUIDS-R2 were isolated from the feces of healthy rabbits, and both strains showed good probiotic properties in vitro. Two strains (108CFU/ml/kg/day) were fed to weaned rabbits for 21 days, after which specific bacterial infection was induced to investigate the effects of the strains on bacterial diarrhea in the rabbits. Results Our data showed that Enterococcus faecium ZJUIDS-R1 and Ligilactobaciiius animalis ZJUIDS-R2 interventions reduced the incidence of diarrhea and systemic inflammatory response, alleviated intestinal damage and increased antibody levels in animals. In addition, Enterococcus faecium ZJUIDS-R1 restored the flora abundance of Ruminococcaceae1. Ligilactobaciiius animalis ZJUIDS-R2 up-regulated the flora abundance of Adlercreutzia and Candidatus Saccharimonas. Both down-regulated the flora abundance of Shuttleworthia and Barnesiella to restore intestinal flora balance, thereby increasing intestinal short-chain fatty acid content. Conclusions These findings suggest that Enterococcus faecium ZJUIDS-R1 and Ligilactobaciiius animalis ZJUIDS-R2 were able to improve intestinal immunity, produce organic acids and regulate the balance of intestinal flora to enhance disease resistance and alleviate diarrhea-related diseases in weanling rabbits.

Abstract Apple moldy core is a fungus-infested disease that is extremely insidious, usually occurring inside the fruit, making it very difficult to distinguish from the exterior with the naked eye. Using VIS/NIR transmission spectroscopy, this study successfully detected moldy core apples. By combining four wavelength selection algorithms (CARS, CARS-SPA, MC-UVE, and MC-UVE-SPA) with four classifiers (SVM, ELM, KNN, and LDA-KNN), discrimination models were established for two-class and three-class classifications. MC-UVE-SPA-LDA-KNN achieved an AUC of 0.99 and an accuracy of 98.82% for two-class classification, while MC-UVE-SPA achieved an AUC of 0.99 and an accuracy of 97.64% for three-class classification. This confirms MC-UVE-SPA as an effective tool for selecting wavelengths specific to moldy core apples, facilitating precise identification and differentiation of apple states. This study advances dynamic online detection of early-stage moldy core conditions in apples, reducing post-harvest disease occurrence and preserving fruit quality effectively. Graphical Abstract

Water hammer protection is one of the key factors for the safe operation of the long-distance water delivery systems, which has lots of useful results. However, the protection experiences for bidirectional water delivery systems using the same pipeline are lacking. In this study, the protection method with one-way surge tanks in the bidirectional water delivery system is investigated. The theoretical formula for one-way surge tank setting is derived based on the theory of water hammer propagation, and the pump head and bidirectional water hammer protection constraints. Subsequently, the pump trip transient processes in an actual system are simulated. Finally, different kinds of one-way surge tank protection schemes are compared. The results show that the pressure along the pipeline after the pump trip can meet the standard when using the one-way surge tank protection scheme calculated by the theoretical formula. The proposed method can provide the effective protection strategy for the bidirectional water delivery systems. HIGHLIGHTS Negative pressure protection for the bidirectional water delivery systems in the same pipeline is studied.; The theoretical formula for one-way surge tank setting in bidirectional water delivery system is presented.; The proposed one-way surge tank setting strategy can provide effective water hammer protection for the system.;

The conditional Gaussian nonlinear system (CGNS) is a broad class of nonlinear stochastic dynamical systems. Given the trajectories for a subset of state variables, the remaining follow a Gaussian distribution. Despite the conditionally linear structure, the CGNS exhibits strong nonlinearity, thus capturing many non-Gaussian characteristics observed in nature through its joint and marginal distributions. Desirably, it enjoys closed analytic formulae for the time evolution of its conditional Gaussian statistics, which facilitate the study of data assimilation and other related topics. In this paper, we develop a martingale-free approach to improve the understanding of CGNSs. This methodology provides a tractable approach to proving the time evolution of the conditional statistics by deriving results through time discretization schemes, with the continuous-time regime obtained via a formal limiting process as the discretization time-step vanishes. This discretized approach further allows for developing analytic formulae for optimal posterior sampling of unobserved state variables with correlated noise. These tools are particularly valuable for studying extreme events and intermittency and apply to high-dimensional systems. Moreover, the approach improves the understanding of different sampling methods in characterizing uncertainty. The effectiveness of the framework is demonstrated through a physics-constrained, triad-interaction climate model with cubic nonlinearity and state-dependent cross-interacting noise.

Abstract Previous studies have shown a bidirectional communication between human gut microbiota and the brain, known as the microbiota–gut–brain axis (MGBA). The MGBA influences the host's nervous system development, emotional regulation, and cognitive function through neurotransmitters, immune modulation, and metabolic pathways. Factors like diet, lifestyle, genetics, and environment shape the gut microbiota composition together. Most research have explored how gut microbiota regulates host physiology and its potential in preventing and treating neurological disorders. However, the individual heterogeneity of gut microbiota, strains playing a dominant role in neurological diseases, and the interactions of these microbial metabolites with the central/peripheral nervous systems still need exploration. This review summarizes the potential role of gut microbiota in driving neurodevelopmental disorders (autism spectrum disorder and attention deficit/hyperactivity disorder), neurodegenerative diseases (Alzheimer's and Parkinson's disease), and mood disorders (anxiety and depression) in recent years and discusses the current clinical and preclinical gut microbe‐based interventions, including dietary intervention, probiotics, prebiotics, and fecal microbiota transplantation. It also puts forward the current insufficient research on gut microbiota in neurological disorders and provides a framework for further research on neurological disorders.

Summary: Pyrrolidine (PyD) has an important impact on the environment and human health. However, there is currently no method for trace detection of PyD. Here, we successfully designed diaminomethylene-4H-pyran (1) as the first specific fluorescent probe for PyD. Only by adding PyD to probe 1, there is blue fluorescence at 455 nm, and the color of the solution changes from colorless to yellow. The detection limit is 1.12 × 10−6 M, and the response time is less than 5 min. Meanwhile, probe 1 can also sense the gaseous PyD and detect PyD in actual water samples. Moreover, due to the low biological toxicity, probe 1 can detect the exogenous PyD in zebrafish. The preliminary mechanism shows that probe 1 and PyD undergo a combination-type chemical reaction to generate a new substance 1-PyD. Therefore, the 100% atom utilization reaction enables probe 1 to exhibit specific adsorption and removal of PyD.

ABSTRACT Hypermucoviscosity (HMV) is a phenotype that is commonly associated with hypervirulence in Klebsiella pneumoniae. The factors that contribute to the emergence of HMV subpopulations remain unclear. In this study, eight K. pneumoniae strains were recovered from an inpatient who had been hospitalized for 20 days. Three of the isolates exhibited a non-HMV phenotype, which was concomitant with higher biofilm formation than the other five HMV isolates. All eight isolates were highly susceptible to serum killing, albeit HMV strains were remarkably more infective than non-HMV counterparts in a mouse model of infection. Whole genome sequencing (WGS) showed that the eight isolates belonged to the K57-ST412 lineage. Average nucleotide identity (FastANIb) analysis indicated that eight isolates share 99.96% to 99.99% similarity and were confirmed to be the same clone. Through comparative genomics analysis, 12 non-synonymous mutations were found among these isolates, eight of which in the non-HMV variants, including rmpA (c.285delG) and wbaP (c.1305T > A), which are assumed to be associated with the non-HMV phenotype. Mutations in manB (c.1318G > A), dmsB (c.577C > T) and tkt (c.1928C > A) occurred in HMV isolates only. RNA-Seq revealed transcripts of genes involved in energy metabolism, carbohydrate metabolism and membrane transport, including cysP, cydA, narK, tktA, pduQ, aceB, metN, and lsrA, to be significantly dysregulated in the non-HMV strains, suggesting a contribution to HMV phenotype development. This study suggests that co-occurrence of HMV and non-HMV phenotypes in the same clonal population may be mediated by mutational mechanisms as well as by certain genes involved in membrane transport and central metabolism.IMPORTANCEK. pneumoniae with a hypermucoviscosity (HMV) phenotype is a community-acquired pathogen that is associated with increased invasiveness and pathogenicity, and underlying diseases are the most common comorbid risk factors inducing metastatic complications. HMV was earlier attributed to the overproduction of capsular polysaccharide, and more data point to the possibility of several causes contributing to this bacterial phenotype. Here, we describe a unique event in which the same clonal population showed both HMV and non-HMV characteristics. Studies have demonstrated that this process is influenced by mutational processes and genes related to transport and central metabolism. These findings provide fresh insight into the mechanisms behind co-occurrence of HMV and non-HMV phenotypes in monoclonal populations as well as potentially being critical in developing strategies to control the further spread of HMV K. pneumoniae.

Introduction: Previous studies have shown that rituximab (RTX) and cyclic oral corticosteroid-cyclophosphamide (CTX) regimens have similar effects on Primary Membranous Nephropathy. However, no studies have compared RTX with an intravenous CTX regimen, which is more commonly used in China and requires fewer cumulative CTX doses. Methods: We prospectively assigned 141 PMN patients with baseline proteinuria ≥ 4 g/24 h, serum albumin < 30 g/L, and eGFR ≥ 30 mL/min × 1.73 m2 despite at least 3 months of treatment with ACEI and/or ARB to the RTX group (375 mg/m2 per injection per week × 4 injections) or to the CTX group (prednisone 0.8 mg/kg/d and intravenous CTX 500 mg/m2 per month until the total dose reached 6–8 g). The primary endpoint was defined as a combination of partial remission or complete remission at 12 months. Results: By the end of 12 months, 43 of 70 patients (61.43%) in the RTX group and 54 of 71 patients (76.06%) in the CTX group reached the primary endpoint(P=0.06). Significantly fewer patients in the RTX group achieved complete remission than the CTX group (14.29% vs. 33.80%, P=0.01). The adverse events rate was similar between the RTX group and the CTX group (28.57% vs. 40.85%, P=0.13). In subgroup analysis, we found that fewer patients from the RTX group achieved the primary endpoint than the CTX group (48.65% vs. 74.29%, P=0.03) among patients with massive proteinuria (urine protein ≥ 8 g/24 h). During the observational phase, 61 patients in the RTX group and 58 in the CTX group completed 24 months of follow-up, exhibiting similar remission rates (RTX vs. CTX: 75.41% vs. 68.97%, P=0.54). Conclusions: Our results show that the intravenous CTX regimen has similar safety and efficacy with higher rates of early complete remission than RTX in the treatment of PMN patients.