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AIM: To investigate the proliferation regulatory effect of cone-rod homeobox (CRX) in retinal pigment epithelium (RPE) and retinoblastoma (RB) cells to explore the potential application and side effect (oncogenic potential) of CRX-based gene therapy in RPE-based retinopathies. METHODS: Adult human retinal pigment epithelial (ARPE)-19 and human retinal pigment epithelial (RPE)-1 cells and Y79 RB cell were used in the study. Genetic manipulation was performed by lentivirus-based technology. The cell proliferation was determined by a CellTiter-Glo Reagent. The mRNA and protein levels were determined by quantitative real-time polymerase chain reaction (qPCR) and Western blot assay. The transcriptional activity of the promoter was determined by luciferase reporter gene assay. The bindings between CRX and transcription factor 7 (TCF7) promoter as well as TCF7 and the promoters of TCF7 target genes were examined by chromatin immunoprecipitation (ChIP) assay. The transcription of the TCF7 was determined by a modified nuclear run-on assay. RESULTS: CRX overexpression and knockdown significantly increased (n=3, P

High strength-ductility synergy is difficult to achieve in Nb alloys. Although high strength has been achieved through severe plastic deformation (SPD) technology, led to low ductility in alloys. In this work, FSP technology was applied to treat Nb–5W–2Mo–1Zr-0.1C (Nb521) alloys in preparation of fine-grained (FG)/ultrafine-grained (UFG) Nb521 with excellent strength and ductility. The microstructure evolution and mechanical property improvement mechanism were systematically studied for Nb521 alloy through various characterization pathways. The research results indicated that UFG Nb521 alloy with a grain size of 0.63 ± 0.41 μm can be prepared using low shoulder plunge depth FSP (LPD-FSP), which is the first report of UFG Nb521 alloy. The main reason for the formation of onion rings structure in SZ is the periodic wear of the stirring tool, and the onion rings structure does not cause mechanical damage. The texture formed by Nb521 alloy under different processing parameters is off-axis shear texture, which matches the ideal shear texture of D2 (112‾)[111] after rotation. In addition, this study also elaborated on the refinement mechanism of the second phase particles (Nb, Zr) C in Nb521 alloy during FSP. This study also indicated that the increase in yield strength of FSP samples at room temperature is mainly determined by grain refinement. These findings provided new ideas for the development of high-performance niobium alloys.

Abstract Background This study aimed at investigating the relationship between the weekend catch-up outdoor duration (WCOD) and prevalence of myopia among students in China. Methods This cross-sectional study recruited participants in 107 schools (six cities, 30 districts) from China from May to June 2021. Demographic characteristics (age, grade, sex, ethnicity, BMI, resident, and parents’ myopia), optically habits (bad writing habits, working/studying time per day, continuous working/studying time per day, and screen time per day) and outdoor duration (weekday and weekend) were obtained from questionnaire. WCOD was defined as outdoor time 1 h longer on weekends than on weekdays. Spherical equivalent (SE) of refractive error were measured with non-cycloplegic refraction. Adjusted multivariate logistic regression analysis was performed to evaluate the relationship between WCOD and prevalence of myopia. Results Students with myopia had shorter WCOD compared with those without myopia (P

Abstract Background Epstein-Barr virus (EBV) infection has been closely linked to the development of various types of cancer. EB nuclear antigen 1 binding protein 2 (EBNA1BP2) is a crucial molecule for stable isolation of EBV in latent infection. However, the role of EBNA1BP2 in multiple tumor types is remains unclear. In this study, we comprehensively analyzed the functional characteristics of EBNA1BP2 and investigate its potential as a prognostic biomarker in pan-cancer. Methods We utilized data from TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus) databases and employed various bioinformatics analysis tools, including TIMER2.0, HPA, GEPIA2.0, PrognoScan, cBioPortal, CancerSEA, and BioGRID to explore the expression pattern, prognostic value, immune infiltration, and methylation level of EBNA1BP2 in pan-cancer. Additionally, we conducted enrichment analysis of genes associated with EBNA1BP2 to identify potential biological functions and pathways. Results Our analysis revealed that EBNA1BP2 expression was significantly higher in tumor tissues compared to tumor-adjacent tissues. We observed that lower expression of EBNA1BP2 in adrenocortical carcinoma (ACC), brain lower grade glioma (LGG), sarcoma (SARC), and uterine carcinosarcoma (UCS) was significantly associated with improved overall survival (OS) and disease-free survival (DFS). Furthermore, the promoter methylation level of EBNA1BP2 was downregulated in the majority of cancer types. At the single-cell level, EBNA1BP2 was found to be positively correlated with cell cycle and DNA repair processes, while negatively correlated with hypoxia. Additionally, EBNA1BP2 was associated with the infiltration of immune cells such as B cells, cancer-associated fibroblast cells, and CD8+ T cells. Gene enrichment analysis indicated that EBNA1BP2 was mainly involved in nucleoplasm and RNA binding pathways. Conclusion Our findings suggest that EBNA1BP2 may serve as a potential prognostic biomarker for survival in pan-cancer. Further experimental studies are needed to validate these findings and explore the underlying mechanisms by which EBNA1BP2 contributes to tumorigenesis.

Objective Increasing breast meat production is one of the primary goals of the broiler industry. Over the past few decades, tremendous progress has been made in genetic selection and the identification of candidate genes for improving the breast muscle mass. However, the molecular network contributing to muscle production traits in chickens still needs to be further illuminated. Methods A total of 150 1-day-old male 817 broilers were reared in a floor litter system. At the market age of 50 d, eighteen healthy 817 broilers were slaughtered and the left pectoralis major muscle sample from each bird was collected for RNA-seq sequencing. The birds were then plucked and eviscerated and the whole breast muscle was removed and weighed. Breast muscle yield was calculated as the ratio of the breast muscle weight to the eviscerated weight. To identify the co-expression networks and hub genes contributing to breast muscle yield in chickens, we performed weighted gene co-expression network analysis (WGCNA) based on the 18 transcriptome datasets of pectoralis major muscle from eighteen 817 broilers. Results The WGCNA analysis classified all co-expressed genes in the pectoral muscle of 817 broilers into 44 modules. Among these modules, the turquoise and skyblue3 modules were found to be most significantly positively (r = 0.78, p = 1e–04) and negatively (r = −0.57, p = 0.01) associated with breast meat yield, respectively. Further analysis identified several hub genes (e.g., DLX3, SH3RF2, TPM1, CAV3, MYF6, and CFL2) that involved in muscle structure and muscle development were identified as potential regulators of breast meat production. Conclusion The present study has advanced our understanding of the molecular regulatory networks contributing to muscle growth and breast muscle production and will contribute to the molecular breeding of chickens in the future.

Abstract Background Research dissemination is essential to accelerate the translating of evidence into practice. Little is known about dissemination among Chinese public health researchers. This study aimed to explore the understanding and practices of disseminating research findings and to identify barriers and facilitators that influence dissemination activities to non-research audiences. Methods This study deployed an exploratory qualitative design with purposive and snowball sampling. One focus group with 5 participants and 12 in-depth interviews were conducted with participants working in diverse fields from universities (n = 10), the National Chinese Center for Disease Control and Prevention (n = 4), the Chinese National Cancer Center (n = 1), the Chinese National Center for Cardiovascular Disease (n = 1), and China office of a global research institute (n = 1) from May to December 2021 to reach saturation. Data were initially analyzed using inductive thematic analysis. The designing for dissemination (D4D) logic model was then used to organize themes and subthemes. Two coders independently coded all transcripts and discussed disparities to reach a consensus. Results Out of 17 participants, 12 misunderstood the concept of dissemination; 14 had disseminated to non-research audiences: 10 to the public, 10 to practitioners, and 9 to policymakers. We identified multiple barriers to dissemination to non-research audiences across four phases of the D4D logic model, including low priority of dissemination, limited application of D4D strategies, insufficient support from the research organizations, practice settings, and health systems, and overemphasis on academic publications. Conclusions There was a lack of understanding and experience of dissemination, indicating a lack of emphasis on active dissemination in China. We provide implications for raising awareness, building capacity, facilitating multidisciplinary collaboration, providing incentives and infrastructure, changing climate and culture, establishing communication and executive networks, and accelerating systematic shifts in impact focus.

Abstract Objectives To establish a nomogram for differentiating malignant and benign focal liver lesions (FLLs) using ultrasomics features derived from contrast-enhanced ultrasound (CEUS). Methods 527 patients were retrospectively enrolled. On the training cohort, ultrasomics features were extracted from CEUS and b-mode ultrasound (BUS). Automatic feature selection and model development were performed using the Ultrasomics-Platform software, outputting the corresponding ultrasomics scores. A nomogram based on the ultrasomics scores from artery phase (AP), portal venous phase (PVP) and delayed phase (DP) of CEUS, and clinical factors were established. On the validation cohort, the diagnostic performance of the nomogram was assessed and compared with seniorexpert and resident radiologists. Results In the training cohort, the AP, PVP and DP scores exhibited better differential performance than BUS score, with area under the curve (AUC) of 84.1-85.1% compared with the BUS (74.6%, P

Abstract DHAV-1 is a highly infectious pathogen that can cause acute hepatitis in ducklings. MicroRNA (miRNA) plays an essential regulatory role in virus response. We characterized and compared miRNA and mRNA expression profiles in duck embryonic fibroblasts (DEF) and the liver of ducklings infected with DHAV-1. DHAV-1 infected DEF was divided into infection group (D group) and blank group (M group), and DHAV-1 infected duckling group was divided into infection group (H group) and blank group (N group). D vs. M have 130 differentially expressed (DE) miRNA (DEM) and 2204 differentially expressed (DE) mRNA (DEG), H vs. N have 72 DEM and 1976 DEG. By the intersection of D vs. M and H vs. N comparisons, 15 upregulated DEM, 5 downregulated DEM, 340 upregulated DEG and 50 downregulated DEG were found with both in vivo and in vitro DHAV-1 infection. In particular, we identified the same DE miRNA target genes and functional annotations of DE mRNA. We enriched with multiple gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, which may have important roles in viral virulence, host immunity, and metabolism. We selected miR-155, which is co-upregulated, and found that miR-155 targets SOCS1 to inhibit DHVA-1 replication.

Abstract Purpose To explore the effects of a single dose of uridine adenosine tetraphosphate (Up4A) administered through the tail vein, on the blood pressure of mice. Methods The mice were separated into three groups: the Up4A group, the norepinephrine (NA) group, and the α, β-methylene adenosine triphosphate (α, β-meATP) group. Each group of mice were injected drugs through the tail vein at 1, 3, 10, and 30 nmol/kg doses in an ascending order. Additionally, six mice were injected Up4A through the tail vein at 20, 40, 60, and 80 nmol/kg doses in an ascending order. The administration intervals for each dose were 20 min. Results Mice in these groups experienced a rapid increase in blood pressure, reaching its peak within 10 s after drug administration. It took approximately 120 s for the blood pressure to return to baseline levels after the administration of the drugs in both the NA and α, β-meATP groups. After higher doses of Up4A were administered to the mice, their blood pressure exhibited biphasic changes. Initially, blood pressure of the mice rapidly dropped to a minimum within 10 s, then rose rapidly to a peak within 30 s. Subsequently, it gradually declined, taking around 10 min to return to the levels before the drug administration. Conclusion Compared to NA and α, β-meATP, Up4A, which contains purine and pyrimidine components, displayed a weaker blood pressure-elevating potency. Through its corresponding structure, Up4A exerted vasodilatory and vasoconstrictive effects throughout the entire experiment resulting in biphasic changes in blood pressure.

Abstract Double-leg circles on pommel horse exercises require a high degree of dynamic balance. However, theoretical conditions for maintaining dynamic balance are unclear. The purpose of this paper is to propose a simple theoretical model of the dynamic balance of the circles, and to illustrate its qualitative properties. To this end, the body of a gymnast is simply modeled as one rigid body with one support point, and symmetric and constant-velocity circles are assumed in most analyses. The condition that the torques of wrist and shoulder joints are zero is assumed as a dynamic balance condition with minimum strength. A control law is proposed to demonstrate the motion. Various properties of the dynamic balance condition are analyzed as follows. In the symmetric circles, (1) as the period of a circle decrease, the heights and the radius of the toes increase, and (2) the rotation of the body around its longitudinal axis in the double-leg circle has the effect of lifting the toes. (3) The shoulder and wrist torques can change the pose around the dynamic balance condition. In asymmetric circles, (4) the radius of the center of mass (CoM) increases as the angular velocity of the CoM around the support point decreases, and (5) the body angle with respect to the horizontal plane increases as the upward acceleration of the CoM increases. Moreover, mechanical principles of the circles are discussed as follows. (6) The CoM motion during the symmetric circles of the simple model can be related to the conical pendulum. In the simple model, (7) the pommel reaction force should be parallel to the arm segment when the wrist torque and the shoulder torque are equal or zero, and (8) to change the vertical component of the angular momentum of the body around the support point, the wrist torque around the vertical axis is needed. These results provide theoretical and qualitative insights into understanding and improving pommel horse exercise.

Abstract Background Magnetic resonance-guided adaptive radiotherapy (MRgART) at MR-Linac allows for plan optimisation on the MR-based synthetic CT (sCT) images, adjusting the target and organs at risk according to the patient’s daily anatomy. Conversely, conventional linac image-guided radiotherapy (IGRT) involves rigid realignment of regions of interest to the daily anatomy, followed by the delivery of the reference computed tomography (CT) plan. This study aims to evaluate the effectiveness of MRgART versus IGRT for rectal cancer patients undergoing short-course radiotherapy, while also assessing the dose accumulation process to support the findings and determine its usefulness in enhancing treatment accuracy. Methods Nineteen rectal cancer patients treated with a 1.5 Tesla MR-Linac with a prescription dose of 25 Gy (5 Gy x 5) and undergoing daily adapted radiotherapy by plan optimization based on online MR-based sCT images, were included in this retrospective study. For each adapted plan ( $$\:{\text{T}\text{P}}_{\text{a}\text{d}\text{a}\text{p}}$$ ), a second plan ( $$\:{\text{T}\text{P}}_{\text{I}\text{G}\text{R}\text{T}}$$ ) was generated by recalculating the reference CT plan on the daily MR-based sCT images after rigid registration with the reference CT images to simulate the IGRT workflow. Dosimetry of $$\:{\text{T}\text{P}}_{\text{a}\text{d}\text{a}\text{p}}$$ and $$\:\:{\text{T}\text{P}}_{\text{I}\text{G}\text{R}\text{T}}$$ was compared for each fraction. Cumulative doses on the first and last fractions were evaluated for both workflows. The dosimetry per single fraction and the cumulative doses were compared using dose-volume histogram parameters. Results Ninety-five fractions delivered with MRgART were compared to corresponding simulated IGRT fractions. All MRgART fractions fulfilled the target clinical requirements. IGRT treatments did not meet the expected target coverage for 63 out of 94 fractions (67.0%), with 13 fractions showing a V95 median point percentage decrease of 2.78% (range, 1.65-4.16%), and 55 fractions exceeding the V107% threshold with a median value of 15.4 cc (range, 6.0-43.8 cc). For the bladder, the median $$\:{\text{D}}_{15\text{c}\text{c}}$$ values were 18.18 Gy for the adaptive fractions and 19.60 Gy for the IGRT fractions. Similarly the median $$\:{\text{D}}_{5\text{c}\text{c}}$$ values for the small bowel were 23.40 Gy and 25.69 Gy, respectively. No statistically significant differences were observed in the doses accumulated on the first or last fraction for the adaptive workflow, with results consistent with the single adaptive fractions. In contrast, accumulated doses in the IGRT workflow showed significant variations mitigating the high dose constraint, nevertheless, more than half of the patients still did not meet clinical requirements. Conclusions MRgART for short-course rectal cancer treatments ensures that the dose delivered matches each fraction of the planned dose and the results are confirmed by the dose accumulation process, which therefore seems redundant. In contrast, IGRT may lead to target dose discrepancies and non-compliance with organs at risk constraints and dose accumulation can still highlight notable dosimetric differences.

Abstract Cracks are a common problem in concrete surfaces. With the continuous optimization of machine vision-based inspection systems, effective crack detection and recognition is the core of the entire system. In this study, support vector machine (SVM) was used to distinguish cracks from other regions. To complete the recognition system of the SVM, a framework consisting of an image processing and recognition model was proposed. An algorithm combining the Prewitt operator with the Otsu threshold was proposed for image segmentation. The binary image processed by the new algorithm combined with mathematical morphology can result in a more complete crack zone and fewer interference regions. After the initial parameter extraction, most of the impurity areas were screened by preliminary discrimination, removing 99% of the impurities. This processing step ensured the balance and effectiveness of the samples. To establish an automatic identification model based on SVM with a radial basis function, compactness, occupancy rate, and length–width ratio were selected as input parameters after comparing these three features with all six features of the crack. The recognition accuracy of this system reaches 97.14%, demonstrating that the proposed method is effective and satisfies practical requirements.

Abstract Background Spatiotemporal analysis is a vital method that plays an indispensable role in monitoring epidemiological changes in diseases and identifying high-risk clusters. However, there is still a blank space in the spatial and temporal distribution of tuberculosis (TB) incidence rate in Pudong New Area, Shanghai. Consequently, it is crucial to comprehend the spatiotemporal distribution of TB in this district, this will guide the prevention and control of TB in the district. Methods Our research used Geographic Information System (GIS) visualization, spatial autocorrelation analysis, and space-time scan analysis to analyze the TB incidence reported in the Pudong New Area of Shanghai from 2014 to 2023, and described the spatiotemporal clustering and seasonal hot spot distribution of TB incidence. Results From 2014 to 2023, the incidence of TB in the Pudong New Area decreased, and the mortality was at a low level. The incidence of TB in different towns/streets has declined. The spatial autocorrelation analysis revealed that the incidence of TB was spatially clustered in 2014, 2016–2018, and 2022, with the highest clusters in 2014 and 2022. The high clustering area was mainly concentrated in the northeast. The space-time scan analysis indicated that the most likely cluster was located in 12 towns/streets, with a period of 2014–2018 and a radiation radius of 15.74 km. The heat map showed that there was a correlation between TB incidence and seasonal variations. Conclusions From 2014 to 2023, the incidence of TB in the Pudong New Area of Shanghai declined, but there were spatiotemporal clusters and seasonal correlations in the incidence area. Local departments should formulate corresponding intervention measures, especially in high-clustering areas, to achieve accurate prevention and control of TB within the most effective time and scope.

Abstract Background The interplay between atrial fibrillation (AF) and obesity on mortality in critically ill patients warrants detailed exploration, given their individual impacts on patient prognosis. This study aimed to assess the associations between AF, obesity, and 1-year mortality in a critically ill population. Methods Utilizing data from the Medical Information Mart for Intensive Care (MIMIC)-IV database, we conducted a retrospective analysis of adult patients admitted to the intensive care unit. The primary endpoint was 1-year mortality, analyzed through Cox regression with hazard ratio (HR) and Kaplan-Meier survival methods. Results The study included 25,654 patients (median age 67.0 years, 40.6% female), with 39.0% having AF and 36.1% being obese. Multivariate COX regression analysis revealed that AF was associated with a 14.7% increase in the risk of 1-year mortality (p

Introduction: Lipid metabolism dysfunction is widely involved in the pathological process of acute ischemic stroke (AIS). The coordination of lipid metabolism between neurons and astrocytes is of great significance. However, the full scope of lipid dynamic changes and the function of key lipids during AIS remain unknown. Hence, identifying lipid alterations and characterizing their key roles in AIS is of great importance. Methods: Untargeted and targeted lipidomic analyses were applied to profile lipid changes in the ischemic penumbra and peripheral blood of transient middle cerebral artery occlusion (tMCAO) mice as well as the peripheral blood of AIS patients. Infarct volume and neurological deficits were assessed after tMCAO. The cell viability and dendritic complexity of primary neurons were evaluated by CCK8 assay and Sholl analysis. Seahorse, MitoTracker Green, tetramethyl rhodamine methyl ester (TMRM), 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA) and MitoSOX were used as markers of mitochondrial health. Fluorescent and isotopic free fatty acid (FFA) pulse-chase assays were used to track FFA flux in astrocytes. Results: Long-chain acylcarnitines (LCACs) were the lipids with the most dramatic changes in the ischemic penumbra and peripheral blood of tMCAO mice. LCACs were significantly elevated on admission in AIS patients and associated with poor outcomes in AIS patients. Increasing LCACs through a bolus administration of palmitoylcarnitine amplified stroke injury, while decreasing LCACs by overexpressing carnitine palmitoyltransferase 2 (CPT2) ameliorated stroke injury. Palmitoylcarnitine aggravated astrocytic mitochondrial damage after OGD/R, while CPT2 overexpression in astrocytes ameliorated cocultured neuron viability. Further study revealed that astrocytes stimulated by OGD/R liberated FFAs from lipid droplets into mitochondria to form LCACs, resulting in mitochondrial damage and lowered astrocytic metabolic support and thereby aggravated neuronal damage. Conclusion: LCACs could accumulate and damage neurons by inducing astrocytic mitochondrial dysfunction in AIS. LCACs play a crucial role in the pathology of AIS and are novel promising diagnostic and prognostic biomarkers for AIS.

Abstract Understanding the structures and reaction mechanisms of interfacial active sites in the Fisher-Tropsch synthesis reaction is highly desirable but challenging. Herein, we show that the ZrO2-Ru interface could be engineered by loading the ZrO2 promoter onto silica-supported Ru nanoparticles (ZrRu/SiO2), achieving 7.6 times higher intrinsic activity and ~45% reduction in the apparent activation energy compared with the unpromoted Ru/SiO2 catalyst. Various characterizations and theoretical calculations reveal that the highly dispersed ZrO2 promoter strongly binds the Ru nanoparticles to form the Zr-O-Ru interfacial structure, which strengthens the hydrogen spillover effect and serves as a reservoir for active H species by forming Zr-OH* species. In particular, the formation of the Zr-O-Ru interface and presence of the hydroxyl species alter the H-assisted CO dissociation route from the formyl (HCO*) pathway to the hydroxy-methylidyne (COH*) pathway, significantly lowering the energy barrier of rate-limiting CO dissociation step and greatly increasing the reactivity. This investigation deepens our understanding of the metal-promoter interaction, and provides an effective strategy to design efficient industrial Fisher-Tropsch synthesis catalysts.

Abstract Background/Objective Depression and infertility are major medical and social problems. The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) serves as an innovative and reliable lipid marker for cardiovascular disease risk assessment. Previous research has indicated a potential correlation among lipid metabolism, depression, and infertility. Nonetheless, the exact involvement of lipid metabolism in modulating the pathological mechanisms associated with depression-induced infertility remains to be fully elucidated. The aim of this study was to explore the connection between depression and infertility and to assess whether the NHHR mediates this association. Methods A cross-sectional analysis was performed utilizing data from there cycles (2013–2018) of the National Health and Nutrition Examination Survey (NHANES) database. Female infertility was assessed according to the responses to the RHQ074 question in the reproductive health questionnaire module. Depression states were evaluated using the Patient Health Questionnaire-9 and classified into three grades based on the total scores: no depression (0–4 points), minimal-to-mild depression (5–9 points) and moderate-to-severe depression (10 or more points). The NHHR was calculated from laboratory cholesterol test results. Baseline population characteristics were compared, and subgroup analyses were carried out based on the stratification of age and body mass index (BMI). Weighted multivariable logistic regression and linear regression models, with adjustments for various covariables, were employed to examine the associations among depression, infertility and the NHHR. Finally, mediation analysis was utilized to explore the NHHR's potential mediating role in depression states and female infertility. Results Within this cross-sectional study, 2,668 women aged 18 to 45 years residing in the United States were recruited, 305 (11.43%) of whom experienced infertility. The study revealed a markedly higher prevalence of depression (P = 0.040) and elevated NHHR (P

Abstract Variations in immune cell counts can trigger depressive symptoms, while physical activity effectively reduces the risk and severity of depressive symptoms. This study, based on the NHANES database, analyzes the relationship between neutrophil count and depressive symptoms and explores the moderating effect of physical activity on this relationship. Cross-sectional data from the NHANES database were extracted, including immune cell counts, PHQ-9 scores for self-assessment of depressive symptoms, and Global Physical Activity Questionnaire (GPAQ) scores (PA). The interrelations among physical activity, neutrophil count, and depressive symptoms were analyzed. After controlling for confounding factors, neutrophil count was found to have a significant role in identifying depressive symptoms with an odds ratio (OR) [95% Confidence Interval (CI)] = 1.13 [1.02, 1.251]; the moderating effect of physical activity on the impact of neutrophil count on depressive symptoms was statistically significant (coefficient = -0.0028, P

Summary: Obstructive sleep apnea (OSA) leads to chronic intermittent hypoxia (CIH) and is not well addressed by current therapies. The genioglossus (GG) is the largest upper airway dilator controlling OSA pathology, making its repair a potential treatment. This study investigates dental pulp stem cells (DPSCs) in repairing GG injury in a CIH mouse model. We induced DPSCs to myogenic lineage cells (iDPSCs) and transplanted them into GG of CIH mice. DPSCs/iDPSCs grafts improved EMGGG and muscle type transitions while reducing tumor necrosis factor α (TNF-α), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and creatine kinase (CK) levels, improving body weight. Moreover, iDPSCs increased Pax7+/Ki67+ and human-derived STEM121 cells in the GG compared with DPSCs. DPSCs/iDPSCs enhanced Desmin+ myotube formation in myoblasts under hypoxia in vitro, with iDPSCs increased human-derived myogenic markers and nuclei in myotubes. These results indicate that iDPSCs, beyond their paracrine effects like DPSCs, directly participate in myogenic differentiation, supporting the potential use of DPSCs for OSA treatment.

BackgroundAlthough breakthroughs have been achieved in gastric cancer (GC) therapy with immune checkpoint inhibitors (ICIs) targeting programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1), the acquisition of high response rate remains a huge challenge for clinicians. It is imperative to identify novel biomarkers for predicting response to immunotherapy and explore alternative therapeutic strategy for GC.MethodsThe transcriptomic profiles and clinical information of GC patients from The Cancer Genome Atlas (TCGA)-stomach adenocarcinoma (STAD) database was used to screen differentially expressed lncRNAs between the tumor specimens and the paracancerous tissues. The TargetScan, miRDB and miRcode database were then utilized to construct competing endogenous RNA (ceRNA) networks and identify pivotal lncRNAs. An independent dataset from GEO (GSE70880) and 23 pairs of GC specimens of our cohort were subsequently performed for external validity. The relationship between clinical variables and gene expression were evaluated by Kruskal–wallis test and Wilcoxon signed-rank. The prognostic value of the candidate genes was assessed using Kaplan-Meier analysis and Cox regression models. CIBERSORT and Gene set enrichment analysis (GSEA) were used to determine immune cell infiltration. Gastric adenocarcinoma AGS cells and human embryonic kidney 293T (HEK293T) cells with knockdown of LINC01094 were generated by siRNA transfection, followed by detecting the alteration of the target miRNA and PD-L1/PD-L2 by RT-qPCR. Besides, the interaction between lncRNA and the miRNA–PD-L1/PD-L2 axis were verified by dual luciferase reporter assay.ResultsTwenty-two intersecting lncRNAs were identified to be PD-L1/PD-L2-related lncRNAs and LINC01094–miR-17-5p–PD-L1/PD-L2 was constructed as a potential ceRNA network. LINC01094 was increased in tumor specimens than adjacent normal samples and was positively associated with advanced tumor stages and EBV and MSI status. Furthermore, LINC01094 expression was an independent risk factor for poor overall survival (OS) in GC patients. CD8+ T cell exhaustion-related genes were enriched in high-LINC01094 tissues and high-PD-L2 group. A strong positive association of LINC01094 expression was established with M2 macrophages, IL-10+ TAM, as well as PD-L1 and PD-L2 levels, therefore a LINC01094–miR-17-5p–IL-10 network was proposed in macrophages. Using the exoRBase database, LINC01094 was assumed in blood exosomes of GC patients The results of knockdown experiments and luciferase reporter assays revealed that LINC01094 interacted with miR-17-5p and served as a miRNA sponge to regulate the expression of PD-L1 and PD-L2.ConclusionLINC01094 dually regulates the expression of PD-L1 and PD-L2 and shapes the immunosuppressive tumor microenvironment via sponging miR-17-5p. LINC01094 may serve as a potential prognostic predictor and therapeutic target in GC.

After successfully performing Agrobacterium-mediated CRISPR-Cas9-based gene editing in plants, isolation of the Cas9 T-DNA is essential for the stable inheritance of induced mutations. Here, we report a simple technique that allows the isolation of Cas9-free mutants, eliminating the need for outcrossing or other intricate methods. This method is based on the ability of Basta-sensitive Arabidopsis thaliana seedlings, which generally perish, to recover and grow once transplanted to Basta-free growth media. By growing gene-edited heterozygous populations of single-locus insertion Basta-resistant plants on Basta selection media, plants lacking the Cas9 T-DNA can be identified. These pale-looking plants lacking Cas9 are then rescued on media lacking the Basta to recover Cas9-free plants. The ability of seedlings to recover from Basta selection was also studied in camelina, canola, and wheat. All three crops showed different recovery rates, with wheat demonstrating the highest recovery once transplanted from Basta to normal growth media. In summary, our findings demonstrate that by harnessing the recovery capability of Basta-sensitive seedlings, we can effectively identify and rescue plants lacking the Cas9 T-DNA, enabling the isolation of Cas9-free mutants in Arabidopsis and potentially extending to other crops.

AimTo explore the risk factors for low-birth-weight infants born to pregnant women with GDM to develop a prediction model and to construct a prediction nomogram for the risk of low birth weight infants born to pregnant women with GDM.MethodsThe clinical data of singleton infants diagnosed with gestational diabetes mellitus in Southeast China in 2019 were retrospectively reviewed. Gestational conditions and neonatal weight were assessed.ResultsA total of 386 diabetic mothers and infants were enrolled, including 193 in the low birth weight group and 193 in the normal birth weight group. The statistically significant factors were age over 36 years (OR = 1.916, 95% CI 1.048–3.505), junior high school education (OR = 4.454, 95% CI 1.882–10.543), history of fetal distress (OR = 0.120, 95% CI 0.016–0.925), gestational hypertension (OR = 3.681, 95% CI 1.357–9.986), preeclampsia (OR = 24.652, 95% CI 5.956–102.036), threatened preterm birth (OR = 18.393, 95% CI 8.457–39.999), triglycerides (OR = 0.642, 95% CI 0.485–0.850), and inadequate gestational weight gain (OR = 1.997, 95% CI 1.162–3.432). The area under the receiver operating characteristic curve (AUC) was 0.834 (95% CI: 0.794–0.874, p

For the first time, we used laccase (LA) and hydrogen peroxide (H2O2) in supercritical fluid of carbon dioxide (SCF-CO2) to develop a method of bleaching cashmere fiber production in an ecofriendly way. The obtained results found that the whiteness of the cashmere was improved significantly involving a high bleaching efficient with this method, as well as influenced notably by the dosages of H2O2 and LA, bleaching temperature, pressure and duration. Various natural colorants on the cashmere sample were effectively decomposed and removed by the bleaching ingredients from the H2O2 and biologic catalyst of LA via an efficient transfer of those species onto cashmere surfaces from (H2O2 + LA+PEG1000 + H2O)/SCF-CO2 system. Particularly, this supercritical bleaching method with LA and H2O2 in SCF-CO2 reduced the number of damages to the cashmere fibers. Furthermore, we also successfully validated the supercritical removal of colorants by using X-ray energy spectroscopy (EDS) and scanning electron microscopy (SEM) analysis. Strength measurements and thermogravimetric (TG) and differential thermogravimetric (DTG) analysis demonstrate that supercritical bleaching had a reduced impact on the thermal and mechanical properties of the cashmere fiber. An optimized enzymatic-oxygen bleaching process in SCF-CO2 was further recommended by accompanying with a high whiteness value at 83.36 and an acceptable alkali solubility at 15.55 %. This developed supercritical bleaching method is prospective to be utilized for clear production of cashmere fibers by avoiding an extensive use of chemicals and the generation of heavy wastewater, as well as with less or non-effluent discharge.

ABSTRACT: After viral infection, the virus relies on the host cell's complex metabolic and biosynthetic machinery for replication. However, the impact of avian influenza virus (AIV) on metabolites and gene expression in poultry cells remains unclear. To investigate this, we infected chicken embryo fibroblasts DF1 cells with H9N2 AIV at an MOI of 3. Our aim was to explore how H9N2 AIV alters DF1 cells metabolic pathways to facilitate its replication. We employed metabolomics and transcriptomics techniques to analyze changes in metabolite content and gene expression. Metabolomics analysis revealed a significant increase in glutathione-related metabolites, including reduced glutathione (GSH), oxidized glutathione (GSSG) and total glutathione (T-GSH) upon H9N2 AIV infection in DF1 cells. Elisa results confirmed elevated levels of GSH, GSSG, and T-GSH consistent with metabolomics findings, noting a pronounced increase in GSSG compared to GSH. Transcriptomics showed significant alterations in genes involved in glutathione synthesis and metabolism post-H9N2 infection. However, adding the glutathione synthesis inhibitor BSO exogenously significantly promoted H9N2 replication in DF1 cells. This was accompanied by increased mRNA levels of pro-inflammatory cytokines (IL-1β, IFN-γ) and decreased mRNA levels of anti-inflammatory cytokines (TGF-β, IL-13). BSO also reduced catalase (CAT) gene expression and inhibited its activity, leading to higher reactive oxygen species (ROS) and malondialdehyde (MDA) level in DF1 cells. qPCR results indicated decreased mRNA levels of Nrf2, NQO1, and HO-1 with BSO, ultimately increasing oxidative stress in DF1 cells. Therefore, the above results indicated that H9N2 AIV infection in DF1 cells activated the glutathione metabolic pathway to enhance the cell's self-defense mechanism against H9N2 replication. However, when GSH synthesis is inhibited within the cells, it leads to an elevated oxidative stress level, thereby promoting H9N2 replication within the cells through Nrf2/HO-1 pathway. This study provides a theoretical basis for future rational utilization of the glutathione metabolic pathway to prevent viral replication.

Active phytochemicals with unique electron structures can adsorb on metal surfaces and effectively mitigate metal corrosion. Recently, plant extracts have garnered significant attention as green and renewable corrosion inhibitors. In this study, the abundant agricultural byproducts, namely Zea mays bracts, were used as the extract raw materials, and Zea mays bracts extract (ZMBE) was served as an eco-friendly corrosion inhibitor for mild steel (MS) in 1 M HCl pickling solution. The organic substances in ZMBE were analyzed via ultra-high performance liquid chromatography- quadrupole time-of-flight mass spectrometry (UPLC-QTFMS). The interaction between the active functional groups and MS was investigated using Fourier transform infrared (FT-IR) and ultraviolet–visible (UV–visible) spectroscopy and X-ray photoelectron spectroscopy (XPS). The corrosion inhibition behavior was scrutinized through potentiodynamic polarization (PDP) curves and electrochemical impedance spectroscopy (EIS). The results show that functional groups such as aromatic rings, double bonds, and hydroxyls successfully adsorb on the MS surface to form the protective films. ZMBE exhibits a mixed-type corrosion inhibition with a “geometric coverage” effect. The corrosion inhibition efficiency (η) increases with ZMBE concentration and solution temperature, the optimum η with 5.0 g·L−1 ZMBE at 318 K is 96.2 %. The adsorption of active ingredients follows the Langmuir and El-Awady isotherms. Density functional theory (DFT) and molecular dynamics (MD) simulations prove the synergistic effect of complex components in ZMBE and the corrosion inhibition mechanism. ZMBE is a promising acid pickling corrosion inhibitor with broad application prospects.

Grain of high yield and quality is needed worldwide due to the needs of a rapidly increasing human population. However, diseases caused by some stubborn types of phytopathogenic bacteria can limit the health and yields of crops. Even worse, conventional commercial bactericides have limited efficacy against such diseases. Therefore, exploring some efficacious bactericidal alternatives is urgently needed. In this work, a new type of 3-(piperazin-1-yl)propan-2-ol modified carbazole derivatives was synthesized and assessed for their bactericidal activity. Among them, compound B16 was the optimal active molecule, giving the EC50 values of 3.11 (Xanthomonas oryzae pv. oryzae), 3.20 (Xanthomonas axonopodis pv. citri) and 3.54 μg/mL (Pseudomonas syringae pv. actinidiae). Pot experiments revealed compound B16 to be able to control rice bacterial leaf blight. Some biochemical assays illustrated that our designed compounds could destroy the integrality of bacterial cell membranes and thereby leading to leaking the intracellular protein. These findings may be regard as a reference for the design of novel membrane-targeting antimicrobial agents for managing stubborn plant bacterial diseases.

C28H34FNO4, monoclinic, C2/c (no. 15), a = 21.7795(12) Å, b = 5.9103(4) Å, c = 39.830(2) Å, β = 100.866(3)°, V = 5035.1(5) Å3, Z = 8, R gt(F) = 0.0487, wR ref(F 2) = 0.1376, T = 170 K.

Abstract Purpose The aim of this study is to investigate the effect of double-tract reconstruction on short-term clinical outcome, quality of life and nutritional status of patients after proximal gastrectomy by comparing with esophagogastrostomy and total gastrectomy with Roux-en-Y reconstruction. Methods The clinical data of patients who underwent double tract reconstruction (DTR), esophagogastrostomy (EG), total gastrectomy with Roux-en-Y reconstruction (TG-RY) were retrospectively collected from May 2020 to May 2022. The clinical characteristics, short-term surgical outcomes, postoperative quality of life and nutritional status were compared among the three groups. Results Compared with the DTR group, the operation time in the TG group was significantly shorter (200(180,240) minutes vs. 230(210,255) minutes, p

Abstract Objective Based on resting-state electroencephalography (EEG) evidence, this study aimed to explore the relationship and pathways between EEG-mediated physical function and cognitive function in older adults with cognitive impairment. Methods A total of 140 older adults with cognitive impairment were recruited, and data on their physical function, cognitive function, and EEG were collected. Pearson correlation analysis, one-way analysis of variance, linear regression analysis, and structural equation modeling analysis were conducted to explore the relationships and pathways among variables. Results FP1 theta (effect size = 0.136, 95% CI: 0.025–0.251) and T4 alpha2 (effect size = 0.140, 95% CI: 0.057–0.249) were found to significantly mediate the relationship. The direct effect (effect size = 0.866, 95% CI: 0.574–1.158) and total effect (effect size = 1.142, 95% CI: 0.848–1.435) of SPPB on MoCA were both significant. Conclusion Higher physical function scores in older adults with cognitive impairment were associated with higher cognitive function scores. Left frontal theta and right temporal alpha2, as key observed indicators, may mediate the relationship between physical function and cognitive function. It is suggested to implement personalized exercise interventions based on the specific physical function of older adults, which may delay the occurrence and progression of cognitive impairment in older adults with cognitive impairment.

Abstract Background Cryoglobulinemia with pulmonary involvement is rare, and its characteristics, radiological findings, and outcomes are still poorly understood. Methods Ten patients with pulmonary involvement of 491 cryoglobulinemia patients at Peking Union Medical College Hospital were enrolled in this retrospective study. We analyzed the characteristics, radiological features and management of pulmonary involvement patients, and compared with those of non-pulmonary involvement with cryoglobulinemia. Results The 10 patients with pulmonary involvement (2 males; median age, 53 years) included three patients with type I cryoglobulinemia and seven patients with mixed cryoglobulinemia. All of 10 patients were IgM isotype cryoglobulinemia. All type I patients were secondary to B-cell non-Hodgkin lymphoma. Four mixed patients were essential, and the remaining patients were secondary to infections (n = 2) and systemic lupus erythematosus (n = 1), respectively. Six patients had additional affected organs, including skin (60%), kidney (50%), peripheral nerves (30%), joints (20%), and heart (20%). The pulmonary symptoms included dyspnea (50%), dry cough (30%), chest tightness (30%), and hemoptysis (10%). Chest computed tomography (CT) showed diffuse ground-glass opacity (80%), nodules (40%), pleural effusions (30%), and reticulation (20%). Two patients experienced life-threatening diffuse alveolar hemorrhage. Five patients received corticosteroid-based regimens, and four received rituximab-based regimens. All patients on rituximab-based regimens achieved clinical remission. The estimated two-year overall survival (OS) was 40%. Patients with pulmonary involvement had significantly worse OS and progression-free survival than non-pulmonary involvement patients of cryoglobulinemia (P

Mixtures of maltodextrin (MD), egg yolk protein (EYP), Manchurian walnut protein isolate (MWPI) and soybean protein isolate (SPI) in different proportions were used as wall materials to prepare Manchurian walnut oil microcapsules by spray drying. The micromorphology, thermal stability, storage stability and antioxidant stability of microcapsules were analyzed. The results showed that the encapsulation efficiency of microcapsules prepared with MWPI was 73.68%, with an intact and dense structure, indicating that Manchurian walnut oil was successfully encapsulated in and protected by the microcapsules. The microcapsule powder had good flowability and solubility. The MWPI microcapsules lost only 5.48% of its initial mass under programmed heating conditions (10 ℃/min, up to 150 ℃), which was much lower than that of SPI microcapsules (10.3%), thereby being more able to meet the requirements of most thermally processed products. Microencapsulation obviously slowed down the oxidation rate of Manchurian walnut oil and improved its storage stability. The antioxidant experiments demonstrated that microencapsulation could effectively improve the antioxidant stability of active ingredients in Manchurian walnut oil. Therefore, this study demonstrated MWPI to be an excellent microcapsule wall material by evaluating its performance, which will expand the range of selection of protein-based wall materials, and provide a new idea for the application of walnut protein isolate resources to improve the added value of Manchurian walnut.

Abstract In this study, we aimed to investigate the risk factors associated with in-hospital mortality in patients with cirrhosis and sepsis, establish and validate the nomogram. This retrospective study included patients diagnosed with liver cirrhosis and sepsis in the Medical Information Mart for Intensive Care IV (MIMIC-IV). Models were compared by the area under the curve (AUC), integrated discriminant improvement (IDI), net reclassification index (NRI) and decision curve analysis (DCA). A total of 1,696 patients with cirrhosis and sepsis were included in the final cohort. Our final model included the following 9 variables: age, heartrate, total bilirubin (TBIL), glucose, sodium, anion gap (AG), fungal infections, mechanical ventilation, and vasopressin. The nomogram were constructed based on these variables. The AUC values of the nomograms were 0.805 (95% CI 0.776–0.833), which provided significantly higher discrimination compared to that of SOFA score [0.684 (95% CI 0.647–0.720)], MELD-Na [0.672 (95% CI 0.636–0.709)] and ABIC [0.674(95% CI 0.638–0.710)]. We established the first nomogram for predicting in-hospital mortality in patients with liver cirrhosis and sepsis based on these factors. This nomogram can performs well and facilitates clinicians to identify people at high risk of in-hospital mortality.

Abstract Objective This study aimed to construct a model based on 23 enrolled molecules to evaluate prognoses of pT2/3N0M0 esophageal squamous cell carcinoma (ESCC) patients with up to 20 years of follow-up. Methods The lasso-Cox model was used to identify the candidate molecule. A nomogram was conducted to develop the survival model (molecular score, MS) based on the molecular features. Cox regression and Kaplan-Meier analysis were used in this study. The concordance index (C-index) was measured to compare the predicted ability between different models. The primary endpoint was overall survival (OS). Results A total of 226 patients and 23 proteins were enrolled in this study. Patients were classified into high-risk (MS-H) and low-risk (MS-L) groups based on the MS score of 227. The survival curves showed that the MS-L cohort had better 5-year and 10-year survival rates than the MS-H group (5-year OS: 51.0% vs. 8.0%; 10-year OS: 45.0% vs. 5.0%, all p

Abstract 2,5-Dimethylpyrazine (2,5-DMP) is important pharmaceutical raw material and food flavoring agent. Recently, engineering microbes to produce 2,5-DMP has become an attractive alternative to chemical synthesis approach. In this study, metabolic engineering strategies were used to optimize the modified Escherichia coli BL21 (DE3) strain for efficient synthesis of 2,5-DMP using L-threonine dehydrogenase (EcTDH) from Escherichia coli BL21, NADH oxidase (EhNOX) from Enterococcus hirae, aminoacetone oxidase (ScAAO) from Streptococcus cristatus and L-threonine transporter protein (EcSstT) from Escherichia coli BL21, respectively. We further optimized the reaction conditions for synthesizing 2,5-DMP. In optimized conditions, the modified strain can convert L-threonine to obtain 2,5-DMP with a yield of 2897.30 mg/L. Therefore, the strategies used in this study contribute to the development of high-level cell factories for 2,5-DMP. Graphical Abstract

The zoonosis caused by Nocardia is increasing seriously. But commonly used antibiotic drugs often lead to resistance. N. seriolae dUTPase (NsdUTPase) plays a key role in the proliferation of Nocardia, and was regarded as a potent drug target. However, there was little report about the NsdUTPase inhibitors. In this study, we discovered a series of novel NsdUTPase inhibitors to fight against Nocardia. The first crystal structure of NsdUTPase was released, and a structure-based computational design was performed. Compounds 4b and 12b exhibited promising activities towards NsdUTPase (IC50 = 0.99 μM and 0.7 μM). In addition, they showed satisfied anti-Nocardia activity (MIC value ranges from 0.5 to 2 mg/L) and low cytotoxicity, which were better than approved drugs oxytetracycline and florfenicol. Molecular modelling study indicated that hydrophobic interaction might be the main contribution for ligand binding. Our results suggested that NsdUTPase inhibitors might be a useful way to repress Nocardia.

Purpose To investigate the dietary nutrient intake of Maintenance hemodialysis (MHD) patients, identify influencing factors, and explore the correlation between dietary nutrient intake and nutritional and disease control indicators.Methods This was a multicenter cross-sectional study. A dietary survey was conducted using a three-day dietary record method, and a self-designed diet management software was utilized to calculate the daily intake of dietary nutrients. The nutritional status and disease control indicators were assessed using subjective global assessment, handgrip strength, blood test indexes, and dialysis adequacy.Results A total of 382 MHD patients were included in this study. Among them, 225 (58.9%) and 233 (61.0%) patients’ protein and energy intake did not meet the recommendations outlined in the National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative Clinical Practice Guideline for Nutrition in Chronic Kidney Disease (2020 update). The average protein and energy intake for these patients were 0.99 ± 0.32 g/kg/d and 29.06 ± 7.79 kcal/kg/d, respectively. Multiple linear regression analysis showed that comorbidity-diabetes had a negative influence on normalized daily energy intake (nDEI = DEI / ideal body weight) (B = −2.880, p = 0.001) and normalized daily protein intake (nDPI = DPI / ideal body weight) (B = −0.109, p = 0.001). Pearson correlation analysis revealed that dietary DPI (r = −0.109, p

Objective To investigate the feasibility and efficacy of combining ultrasound-guided sharp needle technique with percutaneous transluminal angioplasty (PTA) for treating outflow stenosis or dysfunction in arteriovenous fistula (AVF) among hemodialysis patients.Methods From October 2021 to March 2023, patients with occluded or malfunctional fistula veins not amenable to regularly angioplasty were retrospectively enrolled in the study. They underwent ultrasound-guided sharp needle intervention followed by PTA. Data on the location and length between the two veins, technical success, clinical outcomes, and complications were collected. Patency rates post-angioplasty were calculated through Kaplan-Meier analysis.Results A total of 23 patients were included. The mean length of the reconstructed extraluminal segment was 3.18 cm. The sharp needle opening was performed on the basilic vein (60.9%), brachial vein (26.1%), or upper arm cephalic vein (13%) to create outflow channels. Postoperatively, all cases presented with mild subcutaneous hematomas around the tunneling site and minor diffuse bleeding. The immediate patency rate for the internal fistulas was 100%, with 3-month, 6-month, and 12-month patency rates at 91.3%, 78.3%, and 43.5%, respectively.Conclusion Sharp needle technology merged with PTA presents an effective and secure minimally invasive method for reconstructing the outflow tract, offering a new solution for recanalizing high-pressure or occluded fistulas.

The lack of early renal function recovery among geriatric patients with acute kidney injury (AKI) in the intensive care unit (ICU) is a commonly observed and acknowledged poor prognostic factor, especially for older adults. However, no reliable prognostic biomarker is available for identifying individuals at risk of renal non-recovery or mortality in older adults. In this prospective observational cohort study, we enrolled critically ill older adults (aged ≥ 60 years) with AKI from the ICU and followed their disease progression. The primary endpoint was renal non-recovery within seven days of follow-up, while the secondary endpoint was the determinants of 30-day mortality after AKI. We assessed the predictive accuracy using receiver operating characteristic curves and performed between-group comparisons using the log-rank test. Among 209 older adults, 117 (56.0%) experienced renal recovery. Multiple regression analysis revealed that urine levels of tissue inhibitor of metalloproteinase-2 (TIMP-2) multiplied by insulin-like growth factor-binding protein 7 (IGFBP7) ([TIMP-2]*[IGFBP7]), AKI stages 2–3, and the Acute Physiology and Chronic Health Evaluation (APACHE II) score were independently associated with renal non-recovery. The regression model incorporating [TIMP-2]*[IGFBP7] demonstrated a fair predictive value (AUC 0.774, p

Background: Even with significant advancements, treating multiple myeloma (MM) remains difficult. At present, the main treatment methods include combined treatment of stem cell transplantation, drug treatment, etc. With the clarification of the molecular biological mechanism of MM, as well as the in-depth study of the internal signal of myeloma cells and the microenvironment of MM patients, more and more new drugs targeting myeloma and microenvironment are gradually used in clinical maintenance treatment, such as inhibit the proteosome: ixazomib, bortezomib and carfilzomib, immune - modulators: thalidomide and lenalidomide, monoclonal antibodies, etc. have made great progress in MM maintenance treatment. With the continuous development of proteasome inhibitor maintenance treatment in MM, the prognosis of the disease has been significantly improved. Our aim is to evaluate the effectiveness and adverse reactions of proteasome inhibitors in maintenance therapy for multiple myeloma, providing new ideas for clinical medication. Methods: Four databases containing randomized controlled studies on the effectiveness and safety of proteasome inhibitors in the maintenance therapy of multiple myeloma are retrieved by the computer. Once the quality of the literature has been thoroughly evaluated, run the data via the RevMan 5.3 software. Results: Eventually 8 studies were added in this systematic review. Compared with the placebo group, proteasome inhibitor in maintenance treatment of multiple myeloma patients with prolonged the survival without progression and overall existence. 5 studies reported the peripheral neuropathy of multiple myeloma in the treatment group compared to placebo group, which was remarkably greater (OR: 1.98; 95 % Cl: 1.35, 2.92; P

BackgroundCryptococcosis is an invasive infection that commonly affects immunosuppressed individuals, especially patients with HIV infection. Cryptococcal infection in HIV-infected patients should be considered a major health concern because it is associated with high morbidity and mortality rates. In this study, we aimed to evaluate the clinical characteristics and prognostic factors of cryptococcal infections in human immunodeficiency virus (HIV)-infected patients to facilitate effective clinical management and improve patient outcomes.MethodsWe reviewed and analyzed the clinical data and relevant laboratory test results of HIV-infected patients with positive cryptococcal cultures and reserved strains between 2013 and 2023 from Beijing Youan Hospital affiliated to Capital Medical University. The clinical characteristics and laboratory test results of the patients were compared, and the correlation between parameters and the prognoses of the patients at different observation timepoints (3, 6, 9, and 12 months) was analyzed.ResultsA total of 76 patients (70 males and six females; median age, 37 years) were included in this study. The results indicated that the later the initiation of antiretroviral therapy (ART) after the diagnosis of HIV infection (> 6 months), the higher the probability of death. Analysis of the correlation between the time of ART initiation and the timing of treatment for cryptococcal infections showed that the time of ART initiation was strongly related to survival at different timepoints. Initiation of ART time within 0-4 weeks, 4-6 weeks and more than 6weeks of starting treatment for Cryptococcus infection was associated with a lower mortality rate at 12-month, the 3-month, 6- and 9-month follow-up timepoint separately.ConclusionsAlthough cryptococcal infection in HIV-infected patients continues to be a challenging and intricate issue, ART is a key factor that affects its prognosis. The later ART is started, the worse the prognosis of the infection. The time of ART initiation and the timing of treatment for cryptococcal infections should be further refined and balanced based on different clinical courses. Thus, clinicians should pay closer attention to cryptococcal infections in patients with HIV infection and initiate ART based on the patient’s clinical condition.

BackgroundHypoalbuminemia and cognitive impairment (CI) each independently increase the mortality risk in older adults. However, these two geriatric syndromes can occur simultaneously. In community-dwelling older adults, is the combination of hypoalbuminemia and CI linked to a higher mortality risk than either condition alone?ObjectiveWe aimed to investigate the association between plasma albumin, cognitive function, and their synergistic effect on mortality in Chinese community-dwelling older adults.MethodsData from the Chinese Longitudinal Healthy Longevity Survey (2012) included 1,858 participants aged ≥65. Baseline assessments comprised albumin levels and cognitive status. All-cause mortality was confirmed through 2014–2018 surveys. Cox proportional hazards models assessed associations, and restricted cubic splines explored albumin-mortality relationship.ResultsDuring a median follow-up of 48.85 months, 921 deaths. Albumin≥35 g/L vs

IntroductionIntroduction: The influenza virus primarily targets the respiratory tract, yet both the respiratory and intestinal systems suffer damage during infection. The connection between lung and intestinal damage remains unclear.MethodsOur experiment employs 16S rRNA technology and Liquid Chromatography-Mass Spectrometry (LC-MS) to detect the impact of influenza virus infection on the fecal content and metabolites in mice. Additionally, it investigates the effect of influenza virus infection on intestinal damage and its underlying mechanisms through HE staining, Western blot, Q-PCR, and flow cytometry.ResultsOur study found that influenza virus infection caused significant damage to both the lungs and intestines, with the virus detected exclusively in the lungs. Antibiotic treatment worsened the severity of lung and intestinal damage. Moreover, mRNA levels of Toll-like receptor 7 (TLR7) and Interferon-b (IFN-b) significantly increased in the lungs post-infection. Analysis of intestinal microbiota revealed notable shifts in composition after influenza infection, including increased Enterobacteriaceae and decreased Lactobacillaceae. Conversely, antibiotic treatment reduced microbial diversity, notably affecting Firmicutes, Proteobacteria, and Bacteroidetes. Metabolomics showed altered amino acid metabolism pathways due to influenza infection and antibiotics. Abnormal expression of indoleamine 2,3-dioxygenase 1 (IDO1) in the colon disrupted the balance between helper T17 cells (Th17) and regulatory T cells (Treg cells) in the intestine. Mice infected with the influenza virus and supplemented with tryptophan and Lactobacillus showed reduced lung and intestinal damage, decreased Enterobacteriaceae levels in the intestine, and decreased IDO1 activity.DiscussionOverall, influenza infection caused damage to lung and intestinal tissues, disrupted intestinal microbiota and metabolites, and affected Th17/Treg balance. Antibiotic treatment exacerbated these effects. Supplementation with tryptophan and Lactobacillus improved lung and intestinal health, highlighting a new understanding of the lung-intestine connection in influenza-induced intestinal disease.

Background: Non-alcoholic steatohepatitis (NASH), an escalating global health concern, is a primary factor behind cirrhosis, liver transplantation, and hepatocellular carcinoma. Effective treatments remain elusive. Danggui-Shaoyao-San (DGSY), a classic famous prescription employed in treating NASH, could hold promise, although its molecular underpinnings are still under investigation. This study undertakes an exploration of the impacts of DGSY on NASH and seeks to illuminate the mechanisms at play. Methods: UHPLC-Q-Orbitrap HRMS was employed to identify compounds within DGSY. Mice underwent a 25-week regimen of HFHC diet and high-sugar water, with 4 weeks of DGSY treatment for efficacy and pathogenic mechanism exploration in vivo. L02 cells were cultured with 0.2 mM FFA for 24 h, exposed to DGSY at 1 mg/ml and 2 mg/ml for efficacy and pathogenic mechanism exploration in vitro. Using online databases, we sought potential targets for NASH treatment, and through PPI networks, identified key targets. Expression levels of genes and proteins were examined by western blotting, RT-PCR, and immunofluorescence staining. Results: Thirty-four compounds were identified within DGSY. DGSY brought about marked reductions in biochemical indicators and yielded significant improvements in NASH mice histological features. Additionally, it mitigated hepatic steatosis and inflammation both in vivo and in vitro. The top 10 targets from two network pharmacology analyses, one focusing on structural prediction and the other on literature mining, identified APOE and APP as potential therapeutic targets for DGSY in NASH treatment. PCR validation confirmed that DGSY reduced APP expression after treatment, and further investigation revealed that DGSY significantly suppressed hepatic APP and Aβ expression, indicating its effectiveness in treating NASH. Furthermore, it inhibited Aβ-induced Cathepsin B lysosomal release, reducing hepatic inflammation. Conclusion: Danggui-Shaoyao-San has anti-steatohepatitis effects in ameliorating hepatic APP protein expression, reducing hepatic lysosomal CTSB release, and suppressing hepatic NF-κB activation. The study provided a more theoretical basis for the future clinical application of DGSY.

Summary: Background: Rosai-Dorfman disease (RDD) is a rare heterogeneous histiocytic disorder lacking standardized first-line treatment. Methods: This single-center, phase 2 prospective study enrolled 13 newly diagnosed and 10 recurrent RDD patients from June 2021 to March 2023 at Peking Union Medical College Hospital (Beijing, China). Lenalidomide 25 mg days 1–21 plus dexamethasone 40 mg days 1, 8, 15, 22 was administered in 28-day cycles, totaling 12 cycles. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall response rate (ORR) to lenalidomide and dexamethasone (RD) regimen, toxicity, and overall survival (OS) measured from RD start to death or last follow-up. OS and PFS were estimated according to Kaplan–Meier survival analysis and compared with the log-rank test. For OS and OR rate, 95% confidence limits were obtained using the Clopper-Pearson method, with standard methods used for PFS. p

The widespread utilization of polyethylene terephthalate (PET) has caused a variety of environmental and health problems. Compared with traditional thermomechanical or chemical PET cycling, the biodegradation of PET may offer a more feasible solution. Though the PETase from Ideonalla sakaiensis (IsPETase) displays interesting PET degrading performance under mild conditions; the relatively low thermal stability of IsPETase limits its practical application. In this study, enzyme-catalysed PET degradation was investigated with the promising IsPETase mutant HotPETase (HP). On this basis, a carbohydrate-binding module from Bacillus anthracis (BaCBM) was fused to the C-terminus of HP to construct the PETase mutant (HLCB) for increased PET degradation. Furthermore, to effectively improve PET accessibility and PET-degrading activity, the truncated outer membrane hybrid protein (FadL) was used to expose PETase and BaCBM on the surface of E. coli (BL21with) to develop regenerable whole-cell biocatalysts (D-HLCB). Results showed that, among the tested small-molecular weight ester compounds (p-nitrophenyl phosphate (pNPP), p-Nitrophenyl acetate (pNPA), 4-Nitrophenyl butyrate (pNPB)), PETase displayed the highest hydrolysing activity against pNPP. HP displayed the highest catalytic activity (1.94 μM(p-NP)/min) at 50 °C and increased longevity at 40 °C. The fused BaCBM could clearly improve the catalytic performance of PETase by increasing the optimal reaction temperature and improving the thermostability. When HLCB was used for PET degradation, the yield of monomeric products (255.7 μM) was ∼25.5 % greater than that obtained after 50 h of HP-catalysed PET degradation. Moreover, the highest yield of monomeric products from the D-HLCB-mediated system reached 1.03 mM. The whole-cell catalyst D-HLCB displayed good reusability and stability and could maintain more than 54.6 % of its initial activity for nine cycles. Finally, molecular docking simulations were utilized to investigate the binding mechanism and the reaction mechanism of HLCB, which may provide theoretical evidence to further increase the PET-degrading activities of PETases through rational design. The proposed strategy and developed variants show potential for achieving complete biodegradation of PET under mild conditions.

Human activities have increased nitrogen (N) and phosphorus (P) inputs to the Yellow River Delta and the supply level of N and P affects plant growth as well as ecosystem structure and function directly. However, the root growth, stoichiometry, and antioxidant system of plants in response to N and P additions, especially for herbaceous halophyte in the Yellow River Delta (YRD), remain unknown. A field experiment with N addition (0, 5, 15, and 45 g N m-2 yr-1, respectively) as the main plot, and P addition (0 and 1 g N m-2 yr-1, respectively) as the subplot, was carried out with a split-plot design to investigate the effects on the root morphology, stoichiometry, and antioxidant system of Suaeda salsa. The results showed that N addition significantly increased the above-ground and root biomass as well as shoot-root ratio of S. salsa, which had a significant interaction with P addition. The highest biomass was found in the treatment with 45 g N m-2 yr-1 combined with P addition. N addition significantly increased TN content and decreased C:N ratio of root, while P addition significantly increased TP content and decreased C:P ratio. The main root length (MRL), total root length (TRL), specific root length (SRL), and root tissue density (RTD) of S. salsa root were significantly affected by N addition and P addition, as well as their interaction. The treatments with or without P addition at the 45 g N m-2 yr-1 of N addition significantly increased the superoxide dismutase (SOD), peroxidase (POD), catalase (CAT) activities and soluble protein content of roots, decreased malondialdehyde (MDA) content. And there was a significant interaction between the N and P addition on SOD activity. Therefore, N and P additions could improve the growth of S. salsa by altering the root morphology, increasing the root nutrient content, and stimulating antioxidant system.

Summary: This study examines the relationship between gastrointestinal symptoms in patients with functional gastrointestinal disorders (FGIDs) and type D personality traits, as well as emotion regulation strategies. Analyzing a diverse group of FGID patients, we uncover significant effects of gender and age on gastrointestinal symptoms. Negative Affectivity emerges as a key predictor, positively associated with symptom severity, whereas Social Inhibition correlates negatively with Abdominal Pain. Additionally, our findings suggest that the expressive suppression strategy predicts heightened gastrointestinal symptoms, whereas cognitive reappraisal predicts lower levels of certain symptoms. These findings provide valuable insights for precise diagnosis and tailored treatments of FGIDs. Further research is warranted to explore underlying mechanisms and inform evidence-based interventions.

Background: Despite regional brain structural changes having been reported in patients with chronic low back pain (CLBP), the topological properties of structural covariance networks (SCNs), which refer to the organization of the SCNs, remain unclear. This study applied graph theoretical analysis to explore the alterations of the topological properties of SCNs, aiming to comprehend the integration and separation of SCNs in patients with CLBP. Methods: A total of 38 patients with CLBP and 38 healthy controls (HCs), balanced for age and sex, were scanned using three-dimensional T1-weighted magnetic resonance imaging. The cortical thickness was extracted from 68 brain regions, according to the Desikan–Killiany atlas, and used to reconstruct the SCNs. Subsequently, graph theoretical analysis was employed to evaluate the alterations of the topological properties in the SCNs of patients with CLBP. Results: In comparison to HCs, patients with CLBP had less cortical thickness in the left superior frontal cortex. Additionally, the cortical thickness of the left superior frontal cortex was negatively correlated with the Visual Analogue Scale scores of patients with CLBP. Furthermore, patients with CLBP, relative to HCs, exhibited lower global efficiency and small-worldness, as well as a longer characteristic path length. This indicates a decline in the brain's capacity to transmit and process information, potentially impacting the processing of pain signals in patients with CLBP and contributing to the development of CLBP. In contrast, there were no significant differences in the clustering coefficient, local efficiency, nodal efficiency, nodal betweenness centrality, or nodal degree between the two groups. Conclusions: From the regional cortical thickness to the complex brain network level, our study demonstrated changes in the cortical thickness and topological properties of the SCNs in patients with CLBP, thus aiding in a better understanding of the pathophysiological mechanisms of CLBP.

A novel p–n heterojunctions composite of BiBaO3 and Ag3PO4 were synthesized to significantly enhance the degradation efficiency of antibiotic wastewater. Through compositional analysis, micron-sized BiBaO3 particles were combined with nano-sized Ag3PO4 particles, resulting in a composite (Ag/0.75Bi) with excellent visible light absorption properties. Moreover, the photocatalytic efficiency was evaluated for Tetracycline and Oxytetracycline degradation, demonstrating remarkable degradation efficiencies. Under visible light irradiation, pollutants were degraded almost completely within 40 min, while the composite photocatalysts exhibited acceptable stability. The photocatalyst mechanism was investigated by conducting photoelectric effect, free radical capturing, and detection experiments. The p-type BiBaO3 and n-type Ag3PO4 compound facilitated the transfer of photogenerated electrons and holes, reducing their recombination probability and improving photocatalytic efficiencies. Furthermore, hydroxyl and superoxide radicals played a crucial role in the photodegradation of pollutants. Overall, this study provides novel insights into the development of composite catalyst for the photocatalytic degradation of antibiotic wastewater.