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Abstract Background The combination of rituximab and chemotherapy is a first-line treatment for patients with B-cell non-Hodgkin lymphoma. Lenalidomide is an immunomodulatory drug that has shown promising properties and activity in a variety of hematological malignancies. This study evaluated the efficacy and safety of lenalidomide-based regimens in the treatment of B-cell non-Hodgkin lymphoma. Methods The PubMed, Science Direct, ClinicalTrials.gov, and Web of Science databases were searched for relevant studies published up to May 2022. Studies with patients diagnosed with non-Hodgkin B-cell lymphoma, who were randomly assigned to a lenalidomide treatment group or a non-lenalidomide control group were considered for inclusion in this review and meta-analysis. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) of the time-to-event outcomes and risk ratios (RRs) with 95% CIs of dichotomous data were estimated. Results A total of 3593 patients from 10 studies were evaluated. The results of the pooled analysis indicated that the lenalidomide-based regimen was associated with prolonged overall survival (HR, 0.85; 95% CI 0.74–0.97; P = 0.02) and progression-free survival (HR, 0.70; 95% CI 0.57–0.88; P = 0.002). Significant differences were found in the overall response rate (RR, 1.18; 95% CI 1.04–1.33; P = 0.01) and complete response rate (RR, 1.18; 95% CI 1.00–1.39; P = 0.05) between the treatment and control groups. Conclusions Lenalidomide appears to be a promising therapeutic agent that offers the possibility of a novel combination of chemotherapy free regimen for patients with B-cell non-Hodgkin lymphoma.

The uncertainty principle for vector-valued functions of $ L^2({\mathbb{R}}^n, {\mathbb{R}}^m) $ with $ n\ge 2 $ are studied. We provide a stronger uncertainty principle than the existing one in literature when $ m\ge 2 $. The phase and the amplitude derivatives in the sense of the Fourier transform are considered when $ m = 1 $. Based on these definitions, a generalized uncertainty principle is given.

Abstract Objectives This study aims to compare the efficacy of peripheral add multifocal soft contact lenses (SCLs) (excluding bifocal SCLs) with single vision contact lenses or spectacles in controlling myopia progression. Method A comprehensive literature search was conducted in the Pubmed, EMBASE, Web of Science, and Cochrane Library databases until October 2023. The literature was thoroughly screened based on predetermined eligibility criteria. Pooled odds ratios (ORs) were calculated for dichotomous data and weighted mean differences (WMD) for continuous data. Results A total of 11 articles comprising 787 participants were included in this meta-analysis. Our pooled results demonstrated that the peripheral add multifocal SCLs groups exhibited significantly reduced refraction progression (MD = 0.20; 95%CI, 0.14 ∼ 0.27; P

Abstract Background Polycystic ovary syndrome (PCOS) is an endocrinological and metabolic disorder that can lead to female infertility. Lipid metabolomics and proteomics are the new disciplines in systems biology aimed to discover metabolic pathway changes in diseases and diagnosis of biomarkers. This study aims to reveal the features of PCOS to explore its pathogenesis at the protein and metabolic level. Methods We collected follicular fluid samples and granulosa cells of women with PCOS and normal women who underwent in vitro fertilization(IVF) and embryo transfer were recruited. The samples were for the lipidomic study and the proteomic study based on the latest metabolomics and proteomics research platform. Results Lipid metabolomic analysis revealed abnormal metabolism of glycerides, glycerophospholipids, and sphingomyelin in the FF of PCOS. Differential lipids were strongly linked with the rate of high-quality embryos. In total, 144 differentially expressed proteins were screened in ovarian granulosa cells in women with PCOS compared to controls. Go functional enrichment analysis showed that differential proteins were associated with blood coagulation and lead to follicular development disorders. Conclusion The results showed that the differential lipid metabolites and proteins in PCOS were closely related to follicle quality,which can be potential biomarkers for oocyte maturation and ART outcomes.

Abstract Purpose To determine the correlation between HPV (human papillomavirus) 52 viral load, multiple infections and ThinPrep cytology test (TCT), to inform clinical management of HPV52-positive women after cervical cancer screening. Methods A total of 1,882 female patients who had positive quantitative HPV tests at Yuebei People's Hospital from January 2020 to December 2022, of whom 533 tested positive for HPV52. We excluded patients who combined HPV16 and/or HPV 18 positivity and whom HPV52 viral load could not be calculated. The final enrollment was 488 patients, including 400 NILM, 48 ASC-US, 28 LSIL and 12 HSIL. The HPV test is a quantitative multiplexed fluorescent PCR assay that provides both HPV genotyping and viral load. Results In our study, there were differences in the median distribution of viral loads among various cytological class categories. The risk of TCT results (LSIL or worse) was increased with the increase of HPV52 viral load, for every LOG unit increase in HPV52 viral load, the risk increased by 26.6%. More importantly, we found a nonlinear relationship between HPV52 viral load and TCT results (LSIL or worse) in both single and multiple infections. When the viral load reaches a threshold, the risk of abnormal cytological results increases significantly. Conclusion HPV52 viral load is an independent risk factor for TCT results (LSIL or worse). The relationship between HPV52 viral load and TCT results (LSIL or worse) is not linear. Viral load may be used as a triage indicator for HPV52-positive patients, thus improving the post-screening clinical management of HPV52-positive women.

Abstract Emerging evidence has highlighted that dysregulation of lipid metabolism in clear cell renal cell carcinoma (ccRCC) is associated with tumor development and progression. HIF-2α plays an oncogenic role in ccRCC and is involved in abnormal lipid accumulation. However, the underlying mechanisms between these two phenomena remain unknown. Here, MED15 was demonstrated to be a dominant factor for HIF-2α-dependent lipid accumulation and tumor progression. HIF-2α promoted MED15 transcriptional activation by directly binding the MED15 promoter region, and MED15 overexpression significantly alleviated the lipid deposition inhibition and malignant tumor behavior phenotypes induced by HIF-2α knockdown. MED15 was upregulated in ccRCC and predicted poor prognosis. MED15 promoted lipid deposition and tumor progression in ccRCC. Mechanistic investigations demonstrated that MED15 acts as SREBP coactivator directly interacting with SREBPs to promote SREBP-dependent lipid biosynthesis enzyme expression, and promotes SREBP1 and SREBP2 activation through the PLK1/AKT axis. Overall, we describe a molecular regulatory network that links MED15 to lipid metabolism induced by the SREBP pathway and the classic HIF-2α pathway in ccRCC. Efforts to target MED15 or inhibit MED15 binding to SREBPs as a novel therapeutic strategy for ccRCC may be warranted.

This study aimed to develop an artificial neural network (ANN) capable of predicting the molar concentration of diisobutylene (DIB), 3, 4, 4-trimethyl-1-pentene (DIM), and tert-butyl alcohol (TBA) in the distillate and residue streams within three specific columns: reactive (CDC), high pressure (ADC), and low pressure (TDC). The process simulation was conducted using DWSIM, an open-source platform. Following its validation, a sensitivity analysis was performed to identify the operational variables that influenced the molar fraction of DIB, DIM, and TBA in the outputs of the three columns. The input variables included the molar fraction of isobutylene (IB) and 2-butene (2-Bu) in the butane (C4) feed, the temperature of the C4 and TBA feeds, and the operating pressure of the CDC, ADC, and TDC columns. The network's design, training, validation, and testing were performed in MATLAB using the Neural FittinG app. The network structure was based on the Bayesian regularization (BR) algorithm, that consisted of 7 inputs and seven outputs with 30 neurons in the hidden layer. The designed, trained, and validated ANN demonstrated a high performance, with a mean squared error (MSE) of 0.0008 and a linear regression coefficient (R) of 0.9946. The statistical validation using an analysis of variance (ANOVA) (p-value > 0.05) supported the ANN's capability to reliably predict molar fractions. Future research will focus on the in-situ validation of the predictions and explore hybrid technologies for energy and environmental optimization in the process.

Background: Unexpected cardiovascular events are likely to occur within a short period following an acute myocardial infarction (AMI). The sodium-glucose co-transporter 2 inhibitor (SGLT2-I) is a recently recommended drug for the treatment of AMI. However, its role in the risk of the outcomes following an AMI, including all-cause death and heart failure readmission, remains controversial. Therefore, in this study, we explored the effect of SGLT2-Is on cardiovascular outcomes after an AMI. Methods: PubMed, Web of Science, and Embase were searched without language restrictions to retrieve case-control studies published before April 2024. Citations were independently screened by two authors, and the studies meeting the predefined inclusion criteria were retained. Data on author names, year of publication, location of the study group, gender and age of participants, outcome assessment, adjusted odds ratios (ORs) and 95% confidence intervals (CIs), and the follow-up period were extracted. Results: Eight studies were eligible for inclusion, and these studies showed that the use of SGLT2-Is after an AMI was significantly associated with a lower risk of hospitalization for heart failure (OR: 0.66, 95% CI 0.57–0.76, p < 0.01) and a lower incidence of major cardiovascular adverse events (OR: 0.79, 95% CI 0.70–0.89, p < 0.01), but was unrelated to a lower incidence of all-cause mortality (OR: 0.84, 95% CI 0.69–1.02, p = 0.07). Conclusions: Compared with placebo, SGLT2-I therapy following an AMI can reduce the risk of heart failure hospitalization and the incidence of major cardiovascular adverse events, but has no effect on all-cause mortality. The PROSPERO registration: CRD42024542335, https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024542335.

(1) Background: Endophytic fungi play an important role in plant growth and stress resistance. The presence of a special fungal taxon such as the dark septate endophytic (DSE) fungi in alpine environments is particularly important for plant resistance to environmental stresses. However, the composition of root endophytic fungi in different environments and between different host plants has not been well studied. (2) Results: A total of 408 culturable endophytic fungi were isolated from the roots of Saussurea involucrata and Rhodiola crenulata which were collected in 5 plots from the Tianshan and Karakoram Mountains of the Xinjiang region, belonging to 91 species, 54 genera, 31 families, and 3 phyla based on the morphological characteristics and molecular sequence. Among them, DSE fungi were the dominant group, accounting for 52.94%, and Leptodontidium orchidicola was the dominant species. In addition, we also compared the composition and diversity of root endophytic fungi from different plants and different sites, with emphasis on special fungal taxa such as DSE. (3) Conclusions: The composition and diversity of cultural endophytic fungi are significantly different in the two alpine medicinal plant species and across various locations. Some fungi showed the preferences of the host or environment. The endophytic fungal resources, especially DSE, were very rich in the two alpine medicinal plants, indicating that these fungi may play a crucial role in the ecological adaptation of host plants in harsh environments.

This study aimed to assess the impact of alcalase, trypsin, flavourzyme, and neutrase on the characteristics, antioxidant activity stability, and anti-fatigue activity of hydrolysates derived from Cucumaria frondosa tentacles (CFTHs). The results demonstrate that favourzyme hydrolysates exhibited the highest degree of hydrolysis (DH). Zeta potential and particle size measurements indicated that hydrolyzed peptides treated with favourzyme appeared aggregated and exhibited larger particle sizes. The antioxidant properties of CFTHs demonstrated good thermal stability, pH stability, and enhanced simulated gastrointestinal digestive stability. The anti-fatigue activity of CFTHs was examined using an acute exercise fatigue model. The results indicate that CFTHs extended the exhaustive swimming time of mice to 17.81 min. Additionally, CFTHs significantly elevated (p < 0.01) blood glucose (Glu) and liver glycogen (LG) levels, while also decreasing (p < 0.05) the concentrations of metabolites such as lactic acid (LA), urea nitrogen (BUN), creatine kinase (CK), lactate dehydrogenase (LDH), and ammonia (NH3). This reduction contributed to the alleviation of fatigue in the body. Furthermore, the levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were significantly increased (p < 0.05), which aided in mitigating oxidative damage induced by strenuous exercise. These findings strongly support the potential utilization of CFTHs in food products as natural antioxidant and anti-fatigue alternatives.

Iron (Fe) deficiency is a pervasive agricultural concern on a global scale. Intercropping plays a pivotal role in activating soil nutrient cycling and crop nutrient uptake and utilization. This study integrates plant physiology, soil physicochemical determination, high-throughput sequencing, and metabolomics techniques to conduct pot experiments using field-collected soils with soybean and maize plants. This study aims to investigate the mechanisms through which microorganisms in a soybean–maize intercropping system regulate Fe deficiency adaptation. The results revealed that intercropping enhances the resilience of soybean and maize in Fe-deficient environments, facilitates nutrient absorption by plants, and enriches soil nutrient content. Moreover, intercropping fostered more intricate microbial interactions in comparison to monocropping. The dominant microorganisms in the rhizosphere of intercropped soybean and maize included genera Microbacterium, Sphingomonas, Shinella, and Rhizobium. Microbacterium, Sphingomonas, Shinella, and Rhizobium have the potential to produce Fe chelators or enhance plant Fe absorption. Additionally, intercropping notably modified the composition of root exudates derived from soybean and maize. The soybean and maize rhizosphere exhibited significant enrichment with oleamide, coumestrol, glycitein, and daidzein. Coumestrol may have an effect of promoting Fe absorption, and it is significantly positively correlated with the genus Nakamurella in the maize rhizosphere and the genus Pirellula in the soybean rhizosphere. Consequently, these findings suggested that the rhizosphere of intercropped soybean and maize significantly enriches specific microbial communities and root exudates, thereby enhancing microecosystem stability and improving plant tolerance to Fe deficiency.

In this paper, the low-cycle reciprocating load test was carried out on four-limb concrete-filled steel tubular (CFST) lattice columns with different slenderness ratios and axial compression ratios, and the seismic performance was studied. Two performance indicators, namely damage and hysteretic energy dissipation, were defined as the objective functions, and the axial compression ratio was used as an optimization variable to perform the multi-objective optimization analysis of four-limb CFST lattice columns. Optimization using the max–min problem approach aims to optimize the axial compression ratio to minimize damage and maximize the dissipation of hysteresis energy. The seismic performances before and after optimization were determined using a restoring force model and were evaluated by the finite element method under different axial compression ratios. The results show that, under low-cycle reciprocating loads, the load–displacement hysteresis curve is a bow shape (Members 1 and 2), inverse S-shape (Member 3), and approximate shuttle shape (Member 4). Through multi-objective optimization, the optimized axial compression ratio is 0.25 and the finite element analysis indicates that the optimal seismic performance is at an axial compression ratio of 0.25. Through the optimized design, the maximum horizontal load of lattice columns, the elastic stiffness, the dissipation capacity, and the seismic performance are all improved, under the premise of satisfying the structural safety.

Liquid metal is widely used as the primary coolant in many advanced nuclear energy systems. Prandtl number of liquid metal is much lower than that of the conventional coolant of water or gas. Based on the Reynolds analogy, the turbulent Prandtl number is assumed to be a constant around unity. For the turbulent convection of liquid metal, dissipations of half the temperature variance are larger than those of turbulent kinetic energies. The dissimilarity between the thermal and momentum fields increases as Pr decreases. The turbulent Prandtl number is larger than one for the liquid metal. In the current investigation, the turbulent convection of liquid metal in the channel is quasi-directly simulated with OpenFOAM-7. The turbulent statistics of the momentum and the thermal field are compared with the existing database to validate the numerical model. The power law for dimensionless temperature distribution with different Prandtl numbers is obtained by regression analysis of numerical results. A new Nusselt number correlation is derived based on the power law. The new Nusselt number correlation agrees well with the DNS results in the literature. The momentum mixing process between different layers in the cross section is compared with the thermal mixing process. The effects of the Prandtl number on the difference between the turbulence time scale and scalar time scale are analyzed. A new turbulent Prandtl number model with local parameters is obtained for turbulent convection with liquid metal. Combined with the k−ω model, the temperature distributions with the new turbulent Prandtl number model agree well with the DNS results in the literature. The new turbulent Prandtl number model can be used for turbulent convection with different Prandtl and different Reynolds numbers.

Background: Heart failure (HF) is a serious public health concern. Baicalin is one of the major active ingredients of a traditional Chinese herbal medicine, Huang Qin, which is used to treat patients with chest pain or cardiac discomfort. However, the underlying mechanism(s) of the cardioprotective effect of baicalin are still not fully understood. Methods: Isoprenaline injection or transverse aortic constriction-induced animal models and isoprenaline or angiotensin 2 administration-induced cell models of heart failure were established. Baicalin (15 mg/kg/day or 25 mg/kg/day) was administered in vivo, and 10 μM baicalin was administered in vitro. Potential pharmacological targets of baicalin and genes related to heart failure were identified via different databases, which suggested that PI3K–Akt may be involved in the effects of baicalin. Molecular docking was carried out to reveal the effect of baicalin on p85a. Results: We observed significant antihypertrophic and antifibrotic effects of baicalin both in vivo and in vitro. The mean cross-sectional area of cardiomyocytes recovered from 390 μm2 in the HF group to 195 μm2 in the baicalin-treated group. The area of fibrosis was reduced from 2.8-fold in the HF group to 1.62-fold in the baicalin-treated group. Baicalin displayed a significant cardioprotective effect via the inhibition of the PI3K signaling pathway by binding with five amino acid residues of the p85a regulatory subunit of PI3K. The combination treatment of baicalin and an inhibitor of PI3K p110 demonstrated a stronger cardioprotective effect. The mean ejection fraction increased from 54% in the baicalin-treated group to 67% in the combination treatment group. Conclusions: Our work identified baicalin as a new active herbal ingredient that is able to treat isoprenaline-induced heart dysfunction and suggests that p85a is a pharmacological target. These findings reveal the significant potential of baicalin combined with an inhibitor of PI3K p110 for the treatment of heart failure and support more clinical trials in the future.

Compound probiotics are capable of effectively breaking down mycotoxins, and glycyrrhizic acid (GA) exhibits hepatoprotective properties. However, the protective efficacy and the underlying mechanism of combined intervention of GA and probiotics (GAP) on ameliorating Deoxynivalenol (DON)-induced liver toxicity remains unclear. This experiment involved 120 weaned piglets, encompassing the control group, the DON group, and the GPD group (E. faecalis and S. cerevisiae + GA + DON). Results showed that GAP significantly mitigated DON-related liver damage and oxidative stress. Furthermore, GAP inhibited the Nrf2/MAPK/NF-κB pathway, ultimately decreasing liver inflammation and apoptosis. Additionally, GAP significantly enhanced the expressions of ZO-1, GLUT2, PePT1, ASCT2, Occludin and Claudin-1. Moreover, metabolomics analysis revealed that GAP modulated lipid metabolism and mitigated liver damage by elevating serum levels of metabolites, such as phosphatidylcholine, phosphatidylethanolamine, and 3-amino-4-hydroxybenzoic acid. The research provides a theoretically based framework for using GAP to combat DON-induced hepatotoxicity in piglets.

IntroductionThe causality between personality and psychiatric traits and lung cancer (LC) remains unclear. Therefore, we aimed to elucidate the causality between these traits and LC.MethodsBidirectional two-sample Mendelian randomization (MR) and bibliometric approaches were conducted to estimate the causality between personality (neuroticism, extraversion, agreeableness, conscientiousness, and openness) and psychiatric (schizophrenia, attention-deficit/hyperactivity disorder [ADHD], major depressive disorder, autism spectrum disorder, bipolar disorder, insomnia, and anxiety) traits and LC and its subtypes (lung squamous cell carcinoma, lung adenocarcinoma, and small cell LC). Summary data of these traits were extracted from large datasets (17,375–462,341 participants). Inverse variance weighting was used as the primary MR analysis, with supplementary models, including MR-Egger and weighted medians. Sensitivity analyses were conducted to detect pleiotropy. Bibliometric data were retrieved from the Web of Science Core Collection, Scopus, and PubMed. The main mapping techniques adopted were co-word, collaboration, and citation analyses.ResultsSchizophrenia was associated with an increased risk of LC (odds ratio [OR] = 1.077, 95% confidence interval [CI] = 1.030–1.126, P = 0.001). Moreover, LC increased the risk of ADHD (OR = 1.221, 95% CI = 1.096–1.362, P < 0.001). No significant bidirectional associations were observed between other mental traits and LC and its subtypes. Causality, psychiatry, and psychiatric comorbidity are emerging keywords. Research dynamics and landscapes were revealed.ConclusionThis study suggests that schizophrenia is a risk factor for LC and that LC is a risk factor for ADHD. Furthermore, causality, psychiatry, and psychiatric comorbidity have become emerging research trends in related fields.

IntroductionLong-term care assistants are taking on more important roles in the healthcare system. The purpose of this study was to investigate what demographic factors influence the core competencies of nursing assistants, as well as to investigate the levels of organizational support, self-efficacy, and core competencies among nursing assistants in China, to explore the relationship between them.MethodsThis is a cross-sectional study with prospective data collection based on a self-report questionnaire. A total of 320 long-term care assistants from two healthcare institutions. We collected socio-demographic characteristics and measured their perceived organizational support, self-efficacy, and core competency levels of the participants. Pearson correlation tests were conducted to examine the relationships among three variables, and a structural equation model was developed to test the interrelationships among these variables.ResultsThe results indicated that age, employment type, licensing status, monthly income, pre-job training, and training methods were associated with core competency, with nursing knowledge identified as a weak area in core competencies. There were significant associations among each dimension of perceived organizational support, self-efficacy, and core competencies (p

BackgroundThere is limited research on cholesterol metabolism-related genes (CM-RGs) in non-alcoholic fatty liver disease (NAFLD), despite hypercholesterolemia being a recognized risk factor. The role of CM-RGs in NAFLD remains unclear.MethodsThe differentially expressed genes (DEGs) between NAFLD and control were acquired by differential expression analysis. The differentially expressed genes associated with cholesterol metabolism (DE-CM-RGs) were identified and functional enrichment analyses were performed. Protein-protein interaction network analysis and a two-sample Mendelian randomization study were utilized for identifying hub genes. Nomogram model, competing endogenous RNA and messenger RNA-drug networks were established. In addition, immunoinfiltration analysis was performed.ResultsWe identified four hub genes (MVK, HMGCS1, TM7SF2, and FDPS) linked to NAFLD risk. MVK and TM7SF2 were protective factors, HMGCS1 and FDPS were risk factors for NAFLD. The area under the curve values of nomograms in GSE135251 and GSE126848 were 0.79 and 0.848, respectively. The gene set enrichment analysis indicated that hub genes participated in calcium signaling pathways and biosynthesis of unsaturated fatty acids. NAFLD patients showed increased CD56dim NK cells and Th17. Tretinoin, alendronate, zoledronic acid, and quercetin are potential target agents in NAFLD.ConclusionOur study has linked cholesterol metabolism genes (MVK, HMGCS1, TM7SF2, and FDPS) to NAFLD, providing a promising diagnostic framework, identifying treatment targets, and offering novel perspectives into its mechanisms.

Background As a powerful tool, bioinformatics analysis is playing an increasingly important role in many fields. Osteogenic differentiation is a complex biological process involving the fine regulation of numerous genes and signaling pathways. Method Osteogenic differentiation-related genes are collected from the online databases. Then, we proposed two indexes Jaccard similarity and Sorensen-Dice similarity to measure the topological relevance of genes in the human PPI network. Furthermore, we selected three pathways involving osteoblast-related transcription factors, osteoblast differentiation, and RUNX2 regulation of osteoblast differentiation for investigation. Subsequently, we performed functional a enrichment analysis of these top-ranked genes to check whether these candidate genes identified by similarity-based metrics are enriched in some specific biological functions and states. we performed a permutation test to investigate the similarity score with four well-known osteogenic differentiation-related pathways including hedgehog signaling pathway, BMP signaling, ERK pathway, and Wnt signaling pathway to check whether these osteogenic differentiation-related pathways can be regulated by FOXA1. Lentiviral transfection was used to knockdown and overexpress gene FOXA1 in human bone mesenchymal stem cells (hBMSCs). Alkaline phosphatase (ALP) staining and Alizarin Red staining (ARS) were employed to investigate osteogenic differentiation of hBMSCs. Result After data collection, human PPI network involving 19,344 genes is included in our analysis. After simplifying, we used Jaccard and Sorensen-Dice similarity to identify osteogenic differentiation-related genes and integrated into a final similarity matrix. Furthermore, we calculated the sum of similarity scores with these osteogenic differentiation-related genes for each gene and found 337 osteogenic differentiation-related genes are involved in our analysis. We selected three pathways involving osteoblast-related transcription factors, osteoblast differentiation, and RUNX2 regulation of osteoblast differentiation for investigation and performed functional enrichment analysis of these top-ranked 50 genes. The results collectively demonstrate that these candidate genes can indeed capture osteogenic differentiation-related features of hBSMCs. According to the novel analyzing method, we found that these four pathways have significantly higher similarity with FOXA1 than random noise. Moreover, knockdown FOXA1 significantly increased the ALP activity and mineral deposits. Furthermore, overexpression of FOXA1 dramatically decreased the ALP activity and mineral deposits. Conclusion In summary, this study showed that FOXA1 is a novel significant osteogenic differentiation-related transcription factor. Moreover, our study has tightly integrated bioinformatics analysis with biological knowledge, and developed a novel method for analyzing the osteogenic differentiation regulatory network.

Direct land application of conventional compost may cause ecological risks due to the presence of heavy metals. To effectively reduce heavy metal bioavailability in compost, a multi-component passivator comprising Candida utilis, sodium humate, zeolite and attapulgite was developed, which showed passivation rates of 59.28%, 86.93% and 38.95% for zinc (Zn), copper (Cu), and ferrum (Fe), respectively, in compost. The addition of customized multi-component passivator in compost not only reduced the mobility of heavy metals, but also improved the quality of the compost and further increased the abundance of lignocellulose-degrading beneficial microorganisms in compost. Subsequent fertilization results showed that the compost product fermented with customized multi-component passivator greatly improved the growth of Chinese cabbage, with significant increases in height, weight, root length, and total chlorophyll contents of 97.63%, 210.13%, 20.42%, and 40.38%, respectively. It can be concluded that the custom-made multi-component passivator is expected to be a good additive for heavy metal passivation, high-quality compost, and plant growth.

Summary: Glioblastoma (GBM) is characterized by high morbidity, mortality, and low cure rates. Recent studies suggest that TSPAN4 is recognized as a marker protein for migrasomes, a vesicular organelle associated with cell migration. However, the intrinsic role of TSPAN4 in cancers has not been clarified, especially in GBM. Here, we report that TSPAN4 promotes GBM progression by interacting with epidermal growth factor receptor (EGFR) and regulating its stability. Clinically, TSPAN4 is highly expressed in GBM and is significantly correlated with poor prognosis. Functionally, TSPAN4 knockdown dramatically inhibits GBM cell proliferation and invasion in vitro, as well as tumorigenicity in vivo. Conversely, overexpression of TSPAN4 facilitates GBM progression. Mechanistically, TSPAN4 knockdown disrupts interaction with EGFR, destabilizing its expression and inactivating EGFR and downstream signaling pathways, such as MEK/ERK, STAT3, and AKT. Our study reveals that TSPAN4 drives GBM progression through regulating EGFR stability and could be a potential target for cancer therapy.

BackgroundTo assess the bioequivalence between Gan & Lee (GL) glargine U300 and Toujeo® regarding pharmacokinetics (PK), pharmacodynamics (PD), and safety in Chinese healthy male participants.MethodsA single-center, randomized, double-blind, single-dose, two-preparation, two-sequence, four-cycle repeated crossover design study was performed to compare GL glargine U300 and Toujeo® in 40 healthy participants. The primary PK endpoints were the area under the curve of glargine metabolites, M1 concentration from 0 to 24 hours (AUC0-24h), and the maximum glargine concentration within 24 hours post-dose (Cmax). The primary PD endpoints were the area under the glucose infusion rate (GIR) curve from 0 to 24 hours (AUCGIR.0-24h) and the maximum GIR within 24 hours post-dose (GIRmax).ResultsGL Glargine U300 demonstrated comparable PK parameters (AUC0–24h, Cmax, AUC0–12h, and AUC12–24h of M1) and PD responses [AUCGIR.0–24h, GIRmax, AUCGIR.0–12h, and AUCGIR.12–24h] to those of Toujeo®, as indicated by 90% confidence intervals ranging from 80% to 125%. No significant disparities in safety profiles were observed between the two treatment groups, and there were no reported instances of serious adverse events.ConclusionThe PK, PD, and safety of GL glargine U300 were bioequivalent to that of Toujeo®.Clinical trial registrationhttps://www.chinadrugtrials.org.cn/, identifier CTR20212419.

Fermented total mixed ration (FTMR) is an effective method of preserving high-moisture byproducts with higher aerobic stability after fermentation. FTMR has the potential to fulfill the daily nutritional requirements of cattle and enhance their production performance. The objective of this research was to examine the influence of FTMR on lactation performance, total tract apparent digestibility, fecal microbiota communities, and fermentation profiles in lactating dairy cows. A total of 12 cows were randomly assigned into two groups: the TMR group and the FTMR group. The TMR group was fed a total mixed ration (TMR) diet, and the FTMR group was fed an FTMR diet. The FTMR did not impact milk yield in dairy cows despite a decrease in dry matter intake, which increased the efficiency of the feed. In contrast to that in the TMR group, the milk fat content in the FTMR group was greater. The FTMR group showed greater digestibility of neutral detergent fiber (NDF), organic matter (OM), dry matter (DM), crude protein (CP), and acid detergent fiber (ADF) in the total digestive tract than did the TMR group. The FTMR increased the concentration of butyrate in the fecal matter and reduced the pH of the feces. The Chao1, ACE, and Shannon indices of the archaeal community in dairy cow feces were significantly higher in cow fed the FTMR compared to those fed the TMR. LefSe analysis revealed higher levels of Oscillospira, Lactobacillus, Prevotella, and Dehalobacterium in the feces of dairy cows fed the FTMR than in those fed the TMR. However, the abundances of Roseburia, rc4-4, Bulleidia and Sharpea exhibited the opposite trend. The abundances of Halobacteria, Halobacteriales, and Halobacteriaceae, which are biomarkers for distinguishing fecal archaea in the TMR from the FTMR, were substantially greater in the feces of dairy cows that consumed the TMR than in those that consumed the FTMR. Therefore, FTMR can improve the milk fat content, total tract apparent feed digestibility efficiency, and diversity of archaea in the feces. Additionally, this work provides a theoretical basis for the feasibility of FTMR feeding for dairy cows.

In order to adjust and detect micro-nano periodic structure optical surface accurately and efficiently, the problem of composite scattering between micro-ellipsoidal periodic structure optical surface and pore defects is studied use the multi-resolution time domain (MRTD) approach. A calculation model is established for the intensity distribution of composite scattering, which is modulated by the micro-ellipsoidal periodic structure optical surface and microdefects. Results are in good agreement with those obtained using CST Microwave Studio software and the finite-different time-domain (FDTD) approach, which demonstrates the effectiveness of the calculation model and method. By combining the field distribution of the micro-ellipsoidal periodic structure optical surface containing microdefects with the optical response at different wavelengths, it is necessary to study the influence of various parameters of the micro-ellipsoidal structure and microdefects on the optical system of metamaterials. The effects of the parameters such as roughness, structure of micro-ellipsoidal unit, defect sizes and buried depths on the composite scattering characteristics are analyzed numerically. The results provide technical support for the fields of functional surface design, ultrasensitive detection, scattering peak orientation and frequency selection.

BackgroundNeuroblastoma (NB) primarily arises in children who are

BackgroundLung adenocarcinoma (LUAD) is the most common type of lung cancer, and its pathogenesis remains not fully elucidated. Inflammation and metabolic dysregulation are considered to play crucial roles in LUAD development, but their causal relationships and specific mechanisms remain unclear.MethodsThis study employed a two-sample Mendelian randomization (MR) approach to systematically evaluate the causal associations between 91 circulating inflammatory factors, 1,400 serum metabolites, and LUAD. We utilized LUAD genome-wide association studies (GWAS) data from the FinnGen biobank and GWAS data of metabolites and inflammatory factors from the GWAS catalog to conduct two-sample MR analyses. For the identified key metabolites, we further used mediator MR to investigate their mediating effects in the influence of IL-17A on LUAD and explored potential mechanisms through protein-protein interaction and functional enrichment analyses.ResultsThe MR analyses revealed that IL-17A (OR 0.78, 95%CI 0.62-0.99) was negatively associated with LUAD, while 71 metabolites were significantly associated with LUAD. Among them, ferulic acid 4-sulfate may play a crucial mediating role in the suppression of LUAD by IL-17A (OR 0.87, 95%CI 0.78-0.97). IL-17A may exert its anti-LUAD effects through extensive interactions with genes related to ferulic acid 4-sulfate metabolism (such as SULT1A1, CYP1A1, etc.), inhibiting oxidative stress and inflammatory responses, as well as downstream tumor-related pathways of ferulic acid 4-sulfate (such as MAPK, NF-κB, etc.).ConclusionThis study discovered causal associations between IL-17A, multiple serum metabolites, and LUAD occurrence, revealing the key role of inflammatory and metabolic dysregulation in LUAD pathogenesis. Our findings provide new evidence-based medical support for specific inflammatory factors and metabolites as early predictive and risk assessment biomarkers for LUAD, offering important clues for subsequent mechanistic studies and precision medicine applications.

Background Metabolomics has the characteristics of terminal effects and reflects the physiological state of biological diseases more directly. Several current biomarkers of multiple omics were revealed to be associated with immune-related adverse events (irAEs) occurrence. However, there is a lack of reliable metabolic biomarkers to predict irAEs. This study aims to explore the potential metabolic biomarkers to predict risk of irAEs and to investigate the association of plasma metabolites level with survival in patients with lung cancer receiving PD-1/PD-L1 inhibitor treatment.Methods The study collected 170 plasmas of 85 patients with lung cancer who received immune checkpoint inhibitors (ICIs) treatment. 58 plasma samples of 29 patients with irAEs were collected before ICIs treatment and at the onset of irAEs. 112 plasma samples of 56 patients who did not develop irAEs were collected before ICIs treatment and plasma matched by treatment cycles to onset of irAEs patients. Untargeted metabolomics analysis was used to identify the differential metabolites before initiating ICIs treatment and during the process that development of irAEs. Kaplan-Meier curves analysis was used to detect the associations of plasma metabolites level with survival of patients with lung cancer.Results A total of 24 differential metabolites were identified to predict the occurrence of irAEs. Baseline acylcarnitines and steroids levels are significantly higher in patients with irAEs, and the model of eight acylcarnitine and six steroid metabolites baseline level predicts irAEs occurrence with area under the curve of 0.91. Patients with lower concentration of baseline decenoylcarnitine(AcCa(10:1) 2, decenoylcarnitine(AcCa(10:1) 3 and hexanoylcarnitine(AcCa(6:0) in plasma would have better overall survival (OS). Moreover, 52 differential metabolites were identified related to irAEs during ICIs treatment, dehydroepiandrosterone sulfate, corticoserone, cortisol, thyroxine and sphinganine 1-phaosphate were significantly decreased in irAEs group while oxoglutaric acid and taurocholic acid were significantly increased in irAEs group.Conclusions High levels of acylcarnitines and steroid hormone metabolites might be risk factor to development of irAEs, and levels of decenoylcarnitine (AcCa(10:1) 2, decenoylcarnitine (AcCa(10:1) 3 and hexanoylcarnitine (AcCa(6:0) could be used to predict OS for patients with lung cancer received ICIs treatment.

ABSTRACT Background Mitochondrial ribosomal protein L35 (MRPL35) has been reported to contribute to the growth of non–small cell lung cancer (NSCLC) cells. However, the functions and mechanisms of MRPL35 on glutamine metabolism in NSCLC remain unclear. Methods The detection of mRNA and protein of MRPL35, ubiquitin‐specific protease 39 (USP39), and solute carrier family 7 member 5 (SLC7A5) was conducted using qRT‐PCR and western blotting. Cell proliferation, apoptosis, and invasion were evaluated using the MTT assay, EdU assay, flow cytometry, and transwell assay, respectively. Glutamine metabolism was analyzed by detecting glutamine consumption, α‐ketoglutarate level, and glutamate production. Cellular ubiquitination analyzed the deubiquitination effect of USP39 on MRPL35. An animal experiment was conducted for in vivo analysis. Results MRPL35 was highly expressed in NSCLC tissues and cell lines, and high MRPL35 expression predicted poor outcome in NSCLC patients. In vitro analyses suggested that MRPL35 knockdown suppressed NSCLC cell proliferation, invasion, and glutamine metabolism. Moreover, MRPL35 silencing hindered tumor growth in vivo. Mechanistically, USP39 stabilized MRPL35 expression by deubiquitination and then promoted NSCLC cell proliferation, invasion, and glutamine metabolism. In addition, MRPL35 positively affected SLC7A5 expression in NSCLC cells in vitro and in vivo. Moreover, the anticancer effects of MRPL35 silencing could be rescued by SLC7A5 overexpression in NSCLC cells. Conclusion MRPL35 expression was stabilized by USP39‐induced deubiquitination in NSCLC cells, and knockdown of MRPL35 suppressed NSCLC cell proliferation, invasion, and glutamine metabolism in vitro and impeded tumor growth in vivo by upregulating SLC7A5, providing a promising therapeutic target for NSCLC.

Given the significant decline in vaccine efficacy against Omicron, the development of novel vaccines with specific or broad-spectrum effectiveness is paramount. In this study, we formulated four monovalent vaccines based on recombinant spike trimer proteins, along with three bivalent vaccines, and five monovalent vaccines based on recombinant spike proteins. We evaluated the efficacy of different vaccination regimens in eliciting neutralizing antibodies in mice through pseudovirus neutralization assays. Following two doses of primary immunization with D614G, mice received subsequent immunizations with Omicron (BA.1, BA.2, BA.4/5) boosters individually, which led to the generation of broader and more potent cross-neutralizing activity compared to D614G boosters. Notably, the BA.4/5 booster exhibited superior efficacy. Following two doses of primary immunization with Omicron (BA.1, BA.2, BA.4/5), mice were subsequently immunized with one dose of D614G booster which resulted in broader neutralizing activity compared to one dose of Omicron (BA.1, BA.2, or BA.4/5). In unvaccinated mice, full-course immunization with different bivalent vaccines induced broad neutralizing activity against Omicron and pre-Omicron variants, with D614G&BA.4/5 demonstrating superior efficacy. However, compared to other variants, the neutralizing activity against XBB.1.5/1.9.1 is notably reduced. This observation emphasizes the necessity of timely updates to the vaccine antigen composition. Based on these findings and existing studies, we propose a vaccination strategy aimed at preserving the epitope repertoire to its maximum potential: (1) Individuals previously vaccinated or infected with pre-Omicron variants should inoculate a monovalent vaccine containing Omicron components; (2) Individuals who have only been vaccinated or infected with Omicron should be inoculated a monovalent vaccine containing pre-Omicron variants components; (3) Individuals without SARS-CoV-2 infection and vaccination should inoculate a bivalent vaccine comprising both pre-Omicron and Omicron components for primary immunization. Additionally, through cross-inoculation of SARS-CoV-2 D614G spike trimer protein and SARS-CoV-1 spike protein in mice, we preliminarily demonstrated the possibility of cross-reaction between different coronavirus vaccines to produce resistance to the pan-coronavirus.

Developing an efficient photocatalytic system for hydrogen peroxide (H2O2) activation in Fenton-like processes holds significant promise for advancing water purification technologies. However, challenges such as high carrier recombination rates, limited active sites, and suboptimal H2O2 activation efficiency impede optimal performance. Here we show that single-iron-atom dispersed Bi2WO6 monolayers (SIAD-BWOM), designed through a facile hydrothermal approach, can offer abundant active sites for H2O2 activation. The SIAD-BWOM catalyst demonstrates superior photo-Fenton degradation capabilities, particularly for the persistent pesticide dinotefuran (DNF), showcasing its potential in addressing recalcitrant organic pollutants. We reveal that the incorporation of iron atoms in place of tungsten within the electron-rich [WO4]2− layers significantly facilitates electron transfer processes and boosts the Fe(II)/Fe(III) cycle efficiency. Complementary experimental investigations and theoretical analyses further elucidate how the atomically dispersed iron induces lattice strain in the Bi2WO6 monolayer, thereby modulating the d-band center of iron to improve H2O2 adsorption and activation. Our research provides a practical framework for developing advanced photo-Fenton catalysts, which can be used to treat emerging and refractory organic pollutants more effectively.

This review provides a comprehensive overview of recent advances in biodegradable materials for sustainable food packaging applications. Biodegradable polymers offer an alternative to conventional plastics by undergoing decomposition into water, carbon dioxide, and biomass. Synthetic biopolymers like PLA, PHAs, and bio-based polyesters as well as natural biopolymers such as polysaccharides and proteins have shown promise as substitutes for non-biodegradable packaging. These materials provide sustainability, waste reduction, and carbon neutrality benefits. However, inferior barrier properties, low heat resistance, poor mechanical strength, and high costs are limitations. Strategies like plasticization, blending, nanomaterial reinforcement, and multilayer composite structures have expanded biopolymer applicability for various foods. Biodegradation and life cycle assessment studies have demonstrated their environmental advantages over conventional plastics. Addressing remaining challenges in collection logistics, composting infrastructure, costs, and functional performance will be crucial for widespread commercial adoption. Recent advances make biopolymer packaging poised to make major contributions to sustainable development in the food industry.

In this study, headspace solid-phase microextraction/gas chromatography-mass spectrometry (HS-SPME/GC-MS) and other techniques were used to analyze the regular physical-chemical and microbiological properties, the content and aroma pattern of main volatile flavors, and the sensory evaluation of fermented sausages made with the inoculation of the mixed culture Lactobacillus plantarum L77 and Staphylococcus xylosus S120 (L77-S120) and the individual culture Lactobacillus plantarum 77 (L77), with the non-inoculated group as blank. The results showed that the TBARS value, nitrite content and Enterobacteriaceae count of the L77-S120 group were significantly lower than those of the blank and L77 group (P

In the present work, the diffusion behavior of the Ag–Cu–Ni alloys was comprehensively studied for the first time. Twelve solid-solid diffusion couples were prepared and annealed at 1023, 1123, and 1223K, respectively. Based on the measured composition-distance profiles, the interdiffusion coefficients in FCC Ag–Cu–Ni alloys at different temperatures were then calculated by both the Matano-Kirkaldy (MK) and numerical inversion (NI) methods. The atomic mobilities of the Ag–Cu–Ni alloys were also optimized. The results indicate that the model-predicted diffusion behavior shows reasonable agreement with the experimental data, validating the reliability of the two versions of atomic mobility obtained in this work and demonstrating the accuracy and efficiency of the NI method. Ag diffuses faster than Ni in the Cu matrix alloy. The pre-exponential factor D0Ag and the activation energy QAgAgCu show a slight change with the Ag, but significantly increase with the Ni. The variation of the pre-exponential factor D0Ni and the activation energy QNiNiCu with the concentration of Ag and Ni were presented with a 3-D planes and discussed in detail. The accurate diffusivities and atomic mobilities of FCC Ag–Cu–Ni alloys obtained in this work will provide crucial input for the development and design of multi-component low-Ag brazing filler metals.

Abstract Hyperuricemia (HUA) is a metabolic syndrome caused by abnormal purine metabolism. Although recent studies have noted a relationship between the gut microbiota and gout, whether the microbiota could ameliorate HUA-associated systemic purine metabolism remains unclear. In this study, we constructed a novel model of HUA in geese and investigated the mechanism by which Lactobacillus rhamnosus GG (LGG) could have beneficial effects on HUA. The administration of antibiotics and fecal microbiota transplantation (FMT) experiments were used in this HUA goose model. The effects of LGG and its metabolites on HUA were evaluated in vivo and in vitro. Heterogeneous expression and gene knockout of LGG revealed the mechanism of LGG. Multi-omics analysis revealed that the Lactobacillus genus is associated with changes in purine metabolism in HUA. This study showed that LGG and its metabolites could alleviate HUA through the gut-liver-kidney axis. Whole-genome analysis, heterogeneous expression, and gene knockout of LGG enzymes ABC-type multidrug transport system (ABCT), inosine-uridine nucleoside N-ribohydrolase (iunH), and xanthine permease (pbuX) demonstrated the function of nucleoside degradation in LGG. Multi-omics and a correlation analysis in HUA patients and this goose model revealed that a serum proline deficiency, as well as changes in Collinsella and Lactobacillus, may be associated with the occurrence of HUA. Our findings demonstrated the potential of a goose model of diet-induced HUA, and LGG and proline could be promising therapies for HUA.

Background: Coronary heart disease (CHD) is a common heart disease and a leading cause of death in developed countries and some developing countries such as China. It is recognized as a multifactorial disease, with dyslipidemia being closely associated with the progression of coronary atherosclerosis. Numerous studies have confirmed the relationship between a single indicator of low-density lipoprotein cholesterol (LDL-C) or high-density lipoprotein cholesterol (HDL-C) and CHD. However, the association between LDL-C to HDL-C ratio (LHR) and CHD remains unclear. This study aimed to comprehensively explore the association between LHR and CHD. Methods: This meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses. PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases were comprehensively searched up to June 15, 2023, to find the studies that indicated the connection between LHR and CHD. A total of 12 published studies were selected. The random-effects model was used to pool the data and mean difference (MD), and the 95% confidence intervals (CI) were taken as the overall outcome. No language restrictions existed in the study selection. The Review Manager 5.4 and Stata 12 were used to analyze the data. Results: Twelve high-quality clinical studies involving 5544 participants, including 3009 patients with CHD, were enrolled in the meta-analysis. The findings revealed that the LHR was higher by 0.65 in patients with CHD than in those without CHD (MD, 0.65; 95% CI, 0.50–0.80). Conclusion: The LHR was found to be positively correlated with CHD, suggesting that it may serve as a potential indicator of CHD.

We developed an artificial neural network (ANN) to predict mole fractions in the extractive distillation of an n-hexane and ethyl acetate mixture, which are common organic solvents in chemical and pharmaceutical manufacturing. The ANN was trained on 250 data pairs from simulations in DWSIM software. The training dataset consisted of four inputs: Feed flow inlet (T1-F), Feed Stream Mass Flow temperature pressure (FM1-F), Make-up stream mass flow (FM2-MU), and ERC tower reflux ratio (RR-ERC). The ANN demonstrated the ability to forecast four output variables (neurons): Mole fraction of n-hexane in the distillate of EDC (XHE-EDC), Mole fraction of N-methyl-2 pyrrolidone in the bottom of EDC (XNMP-EDC), Mole fraction of ethyl acetate in the distillate of ERC (XEA-ERC), and Mole fraction of N-methyl-2 pyrrolidone in the bottom of ERC (XNMP-ERC).The ANN architecture contained 80 hidden neurons. Bayesian regularization training yielded high prediction accuracy (MSE = 2.56 × 10–7, R = 0.9999). ANOVA statistical validation indicated that ANN could reliably forecast mole fractions. By integrating this ANN into process control systems, manufacturers could enhance product quality, decrease operating expenses, and mitigate composition variability risks. This data-driven modeling approach may also optimize energy consumption when combined with genetic algorithms. Further research will validate predictions onsite and explore hybrid energy optimization technologies.

Abstract Cellular senescence represents an irreversible state of cell-cycle arrest during which cells secrete senescence-associated secretory phenotypes, including inflammatory factors and chemokines. Additionally, these cells exhibit an apoptotic resistance phenotype. Cellular senescence serves a pivotal role not only in embryonic development, tissue regeneration, and tumor suppression but also in the pathogenesis of age-related degenerative diseases, malignancies, metabolic diseases, and kidney diseases. The senescence of renal tubular epithelial cells (RTEC) constitutes a critical cellular event in the progression of acute kidney injury (AKI). RTEC senescence inhibits renal regeneration and repair processes and, concurrently, promotes the transition of AKI to chronic kidney disease via the senescence-associated secretory phenotype. The mechanisms underlying cellular senescence are multifaceted and include telomere shortening or damage, DNA damage, mitochondrial autophagy deficiency, cellular metabolic disorders, endoplasmic reticulum stress, and epigenetic regulation. Strategies aimed at inhibiting RTEC senescence, targeting the clearance of senescent RTEC, or promoting the apoptosis of senescent RTEC hold promise for enhancing the renal prognosis of AKI. This review primarily focuses on the characteristics and mechanisms of RTEC senescence, and the impact of intervening RTEC senescence on the prognosis of AKI, aiming to provide a foundation for understanding the pathogenesis and providing potentially effective approaches for AKI treatment.

Abstract Background Acute respiratory distress syndrome (ARDS) is a severe respiratory condition characterized by a high mortality rate, the management of which relies on supportive care and a profound understanding of its pathophysiology. Heparin, with its anticoagulant and potential anti-inflammatory properties, offers a new therapeutic opportunity for the treatment of ARDS. Methods In this retrospective cohort study, we examined the MIMIC-IV database for ARDS patients who received prophylactic heparin within the first 72 h of ICU admission. Employing propensity score matching and inverse probability weighting (IPW) analysis, we evaluated the impact of early heparin use on patient outcomes, focusing on mortality rates. Results Patients who received prophylactic heparin had a significantly lower in-hospital mortality rate compared to those who did not (13.55% vs 17.93%, HR = 0.71, 95% CI: 0.54–0.93, P = 0.012). This result remained significant after propensity score matching (12.75% vs 17.93%, HR = 0.65, 95% CI 0.47–0.90, P = 0.010). Analysis using five different statistical models indicated that early use of heparin significantly reduced the in-hospital mortality rate, with HR = 0.669 (95% CI 0.487–0.919, P = 0.013) in the doubly robust model without balanced covariates; HR = 0.705 (95% CI 0.515–0.965, P = 0.029) with all covariates considered; HR = 0.660 (95% CI 0.491–0.888, P = 0.006) in the propensity score (IPW) model; HR = 0.650 (95% CI 0.470–0.900, P = 0.010) in the propensity score matching model; and HR = 0.706 (95% CI 0.536–0.930, P = 0.013) in the multivariate Cox regression model. Secondary outcomes indicated that heparin use was also associated with reduced mortality rates at 60 days, and 90 days. Conclusion This research highlights that early prophylactic administration of heparin may substantially lower mortality in ARDS patients. These findings underscore the potential of heparin as a key component in the management of ARDS, offering a new perspective and novel strategies for clinical treatment.

Abstract Cysteine protease inhibitor 1 (CST1) is a cystatin superfamily protein that inhibits cysteine protease activity and is reported to be involved in the development of many malignancies. Mitochondrial oxidative phosphorylation (OXPHOS) also plays an important role in cancer cell growth regulation. However, the relationship and roles of CST1 and OXPHOS in esophageal squamous cell carcinoma (ESCC) remains unclear. In our pilot study, CST1 was shown the potential of promoting ESCC migration and invasion by the activation of MEK/ERK pathway. Transcriptome sequencing analysis revealed that CST1 is closely associated with OXPHOS. Based on a real-time ATP rate assay, mitochondrial complex I enzyme activity assay, immunofluorescence, co-immunoprecipitation, and addition of the OXPHOS inhibitor Rotenone and MEK/ERK inhibitor PD98059, we determined that CST1 affects mitochondrial complex I enzyme activity by interacting with the GRIM19 protein to elevate OXPHOS levels, and a reciprocal regulatory relationship exists between OXPHOS and the MEK/ERK pathway in ESCC cells. Finally, an in vivo study demonstrated the potential of CST1 in ESCC metastasis through regulation of the OXPHOS and MEK/ERK pathways. This study is the first to reveal the oncogenic role of CST1 in ESCC development by enhancing mitochondrial respiratory chain complex I activity to activate the OXPHOS/MEK/ERK axis, and then promote ESCC metastasis, suggesting that CST1/OXPHOS is a promising target for ESCC treatment.

Abstract Recent advances in surface-patterning techniques of liquid crystals have enabled the precise creation of topological defects, which promise a variety of emergent applications. However, the manipulation and application of these defects remain limited. Here, we harness the moiré effect to engineer topological defects in patterned nematic liquid crystal cells. Specifically, we combine simulation and experiment to examine a nematic cell confined between two substrates of periodic surface anchoring patterns; by rotating one surface against the other, we observe a rich variety of highly tunable, novel topological defects. These defects are shown to guide the three-dimensional self-assembly of colloids, which can conversely impact defects by preventing the self-annihilation of loop-defects through jamming. Finally, we demonstrate that certain nematic moiré cells can engender arbitrary shapes represented by defect regions. As such, the proposed simple twist method enables the design and tuning of mesoscopic structures in liquid crystals, facilitating applications including defect-directed self-assembly, material transport, micro-reactors, photonic devices, and anti-counterfeiting materials.

Abstract Background Metastasis is one of the leading cause contributes to treatment failure and poor prognosis of hepatocellular carcinoma (HCC) patients. The underlying mechanism of HCC metastasis remains to be determined. Although several RNA binding proteins (RBPs) have been found to participate in tumorigenesis and progression of liver cancer, the role of RBPs in HCC patients with extrahepatic metastases is poorly understood. Methods By performing RNA-seq of primary HCC tissues (including HCC with extrahepatic metastasis and those did not develop metastasis), we identified a set of HCC metastasis-associated RBPs candidates. Among which, ribosomal protein S7 (RPS7) was found to be remarkably increased in HCC tissues and be strongly related to HCC poor survival. Overexpression or CRISPR-Cas9–mediated knockout were applied to investigate the role of RPS7 on the metastasis-associated phenotypes of HCC cells. RNA sequencing, RIP, RNA-pull down, dual luciferase reporter assay, nascent RNA capture assay, and RNA decay and so on, were applied to reveal the underlying mechanism of RPS7 induced HCC metastasis. Results Gain- and loss- of function analyses revealed that RPS7 promoted HCC cells adhesion, migration and invasion capabilities, as well as lung metastasis. Mechanistically, we uncovered that lysyl oxidase-like 2 (LOXL2) was a critical downstream target of RPS7. RPS7 could stabilize LOXL2 mRNA by binding to AUUUA motifs in the 3155–3375 region of the 3’UTR of LOXL2 mRNA, thus increased LOXL2 expression via elevating LOXL2 mRNA abundance. Further research revealed that LOXL2 could accelerate focal adhesion formation through maintaining the protein stability of ITGB1 and activating ITGB1-mediated FAK/SRC signaling pathway, and thereby contribute to the pro-metastasis effect of RPS7. Conclusions Taken together, our data reveal a novel function of RPS7 in HCC metastasis, also reveal the critical roles of the RPS7/LOXL2/ITGB1 axis in HCC metastasis and shed new light on the exploration of molecular drugs against HCC.

Intensive care unit-acquired weakness (ICU-AW) is a common complication in critically ill patients and is associated with a variety of adverse outcomes. These include the need for prolonged mechanical ventilation and ICU stay; higher ICU, in-hospital, and 1-year mortality; and increased in-hospital costs. ICU-AW is associated with multiple risk factors including age, underlying disease, severity of illness, organ failure, sepsis, immobilization, receipt of mechanical ventilation, and other factors related to critical care. The pathological mechanism of ICU-AW remains unclear and may be considerably varied. This review aimed to evaluate recent insights into ICU-AW from several aspects including risk factors, pathophysiology, diagnosis, and treatment strategies; this provides new perspectives for future research.

Abstract Background The triglyceride glucose-body mass index (TyG-BMI index) has been suggested as a novel predictor of insulin resistance. However, its predictive value for slow coronary flow phenomenon (SCFP) in patients with ischemia and nonobstructive coronary arteries (INOCA) remains unclear. Methods We consecutively recruited 1625 patients with INOCA from February 2019 to February 2023 and divided them into two groups based on thrombolysis in myocardial infarction (TIMI) frame counts (TFCs): the SCFP group (n = 79) and the control group. A 1:2 age-matched case–control study was then performed. The TyG-BMI index was calculated as ln [plasma triglyceride (mg/dL) × fasting blood glucose (mg/dL)/2] × BMI. Results TyG-BMI index in the SCFP group (218.3 ± 25.2 vs 201.0 ± 26.5, P

Abstract. Background:. The Global Leadership Initiative on Malnutrition (GLIM) criteria were published to build a global consensus on nutritional diagnosis. Reduced muscle mass is a phenotypic criterion with strong evidence to support its inclusion in the GLIM consensus criteria. However, there is no consensus regarding how to accurately measure and define reduced muscle mass in clinical settings. This study aimed to investigate the optimal reference values of skeletal muscle mass index for diagnosing sarcopenia and GLIM-defined malnutrition, as well as the prevalence of GLIM-defined malnutrition in hospitalized cirrhotic patients. Methods:. This retrospective study was conducted on 1002 adult patients with liver cirrhosis between January 1, 2018, and February 28, 2022, at Beijing You-An Hospital, Capital Medical University. Adult patients with a clinical diagnosis of liver cirrhosis and who underwent an abdominal computed tomography (CT) examination during hospitalization were included in the study. These patients were randomly divided into a modeling group (cohort 1, 667 patients) and a validation group (cohort 2, 335 patients). In cohort 1, optimal cut-off values of skeletal muscle index at the third lumbar skeletal muscle index (L3-SMI) were determined using receiver operating characteristic analyses against in-hospital mortality in different gender groups. Next, patients in cohort 2 were screened for nutritional risk using the Nutritional Risk Screening 2002 (NRS-2002), and malnutrition was diagnosed by GLIM criteria. Additionally, the reference values of reduced muscle mass in GLIM criteria were derived from the L3-SMI values from cohort 1. Multivariate logistic regression analysis was used to analyze the association between GLIM-defined malnutrition and clinical outcomes. Results:. The optimal cut-off values of L3-SMI were 39.50 cm2/m2 for male patients and 33.06 cm2/m2 for female patients. Based on the cut-off values, 31.63% (68/215) of the male patients and 23.3% (28/120) of the female patients had CT-determined sarcopenia in cohort 2. The prevalence of GLIM-defined malnutrition in cirrhotic patients was 34.3% (115/335) and GLIM-defined malnutrition was an independent risk factor for in-hospital mortality in patients with liver cirrhosis (Wald = 6.347, P = 0.012). Conclusions:. This study provided reference values for skeletal muscle mass index and the prevalence of GLIM-defined malnutrition in hospitalized patients with liver cirrhosis. These reference values will contribute to applying the GLIM criteria in cirrhotic patients.

Immunoglobulin heavy chain variable (IGHV) region mutations, TP53 mutation, fluorescence in situ hybridization (FISH), and cytogenetic analysis are the most important prognostic biomarkers used in chronic lymphocytic leukemia (CLL) patients in our daily practice. In real-life environment, there are scarce studies that analyze the correlation of these factors with outcome, mainly referred to time to first treatment (TTFT) and overall survival (OS). This study aimed to typify IGHV mutation status, family usage, FISH aberrations, and complex karyotype (CK) and to analyze the prognostic impact in TTFT and OS in retrospective study of 375 CLL patients from a Spanish cohort. We found unmutated CLL (U-CLL) was associated with more aggressive disease, shorter TTFT (48 vs. 133 months, p

Fenneropenaeus merguiensis is one of the largest species of penaeid shrimp. It has a wide distribution of germplasm resources in the South China Sea and the southeastern coastal regions of China, yet its germplasm characteristics remain insufficiently understood. Therefore, we conducted analyses of basic nutritional components, amino acids, fatty acids, antioxidant indices, and genetic diversity in three F. merguiensis populations (FmRP, FmSZ, FmSY). The results showed a significant difference in ash content, with FmSZ having the highest ash content (1.77 g/100 g) (p < 0.05). A total of 17 amino acids were detected, and FmSZ exhibited higher concentrations of most amino acids, especially essential amino acids (p < 0.05). The analysis of fatty acid composition revealed significant differences between the populations, with FmSY potentially having a nutritional advantage overall (p < 0.05). In terms of antioxidant capacity and genetic diversity, there were no significant differences in total antioxidant capacity (T-AOC), catalase (CAT), or superoxide dismutase (SOD) among the populations (p > 0.05). However, genetic analysis indicated that FmSZ had the lowest inbreeding coefficient and relatively higher genetic diversity. In conclusion, among the three F. merguiensis populations, FmSZ has relatively higher nutritional quality and genetic diversity, and F. merguiensis is a high-quality aquatic product worth promoting. The analysis and characterization of various aspects of F. merguiensis from the three locations provide important information and data support for germplasm resources and genetic breeding efforts.