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Abstract Background Longitudinal T1 relaxation time is a key imaging biomarker. In addition, T1 values are modulated by the administration of T1 contrast agents used in patients with tumors and metastases. However, in clinical practice, dedicated T1 mapping sequences are often not included in brain MRI protocols. The aim of this study is to address the absence of dedicated T1 mapping sequences in imaging protocol by deriving T1 maps from standard T1-weighted sequences. Methods A phantom, composed of 144 solutions of paramagnetic agents at different concentrations, was imaged with a three-dimensional (3D) T1-weighed turbo spin-echo (TSE) sequence designed for brain imaging. The relationship between the T1 values and the signal intensities was established using this phantom acquisition. T1 mapping derived from 3D T1-weighted TSE acquisitions in four healthy volunteers and one patient with brain metastases were established and compared to reference T1 mapping technique. The concentration of Gd-based contrast agents in brain metastases were assessed from the derived T1 maps. Results Based on the phantom acquisition, the relationship between T1 values and signal intensity (SI) was found equal to T1 = 0.35 × SI− 1.11 (R 2 = 0.97). TSE-derived T1 values measured in white matter and gray matter in healthy volunteers were equal to 0.997 ± 0.096 s and 1.358 ± 0.056 s (mean ± standard deviation), respectively. Mean Gd3+ concentration value in brain metastases was 94.7 ± 30.0 μM. Conclusion The in vivo results support the relevance of the phantom-based approach: brain T1 maps can be derived from T1-weighted acquisitions. Relevance statement High-resolution brain T1 maps can be generated, and contrast agent concentration can be quantified and imaged in brain metastases using routine 3D T1-weighted TSE acquisitions. Key Points Quantitative T1 mapping adds significant value to MRI diagnostics. T1 measurement sequences are rarely included in routine protocols. T1 mapping and concentration of contrast agents can be derived from routine standard scans. The diagnostic value of MRI can be improved without additional scan time. Graphical Abstract

The present work focused on examining the function of rumen-protected L-arginine (RP-Arg) or N-carbamylglutamate (NCG) in jejunal oxidative resistance, integrity and immune function in the ovine foetal model of intrauterine growth restriction (IUGR). Thirty-two twin-bearing Hu ewes at d 35 of gestation were randomised as 4 treatment groups (n = 8 each): Control (CON), received 100% of the recommended National Research Council (NRC) for pregnancy; Restricted (RES), received 50% of the recommended NRC for pregnancy; RES + ARG, RES ewes added with 20 g/d of RP-Arg; or RES + NCG treatment, RES ewes added with 5 g/d of NCG. Foetal jejunal samples were collected on d 110 of pregnancy and were assayed for biomarkers of oxidative damage, integrity and immune function. The villus height was elevated (p

【Objective】As one of the four major nutrients required by plants, sulfur is a crucial for plant growth and development, playing a pivotal role in enhancing plant resistance against both biotic and abiotic stresses. Sulfate transporters (SULTR) serve as primary regulators in the absorption and transport of sulfate in plants, playing an irreplaceable role in this process. The understanding of the fundamental characteristics and expression patterns of CaSULTR genes could help to provide theoretical support for advancing researches on SULTR in peppers.【Method】Based on the pepper genome, members of the epper CaSULTR gene family were identified at the whole-genome level. A comprehensive analysis of their physicochemical properties, conserved Motifs and gene structures was conducted. By utilizing publicly available transcriptome data and qPCR technology, the expression patterns of CaSULTR genes under various hormone stress conditions were analyzed. Additionally, differentially expressed genes were cloned for further investigation.【Result】A total of 13 CaSULTR genes were identified and designated as CaSULTR1;1~1;3, CaSULTR2;1~2;2, CaSULTR3;1~3;7 and CaSULTR4;1. These genes were distributed on seven chromosomes in pepper, with amino acid lengths ranging from 641 to 947 aa, molecular weights from 69.65 to 104.36 kD, and isoelectric points between 8.42 to 9.62. Characterized by the hydrophobicity, CaSULTR proteins were classified into four subgroups (Ⅰ-Ⅳ), with subgroup Ⅲ containing the highest number of members. Within the same subgroup, members exhibited relatively small differences in physicochemical properties, and Motifs and gene structures were relatively conserved. With the exception of CaSULTR2;1 and CaSULTR2;2, all members possessed Motif 5. Tissue expression analysis indicated that CaSULTR genes may be involved in the development of organs such as leaves, fruits and flowers, with CaSULTR4;1 exhibiting expression in leaves, roots and stems. Expression profile analysis under hormone stress, coupled with qPCR results, revealed significant up-regulation of CaSULTR1;1 and CaSULTR3;4 under hormone induction.【Conclusion】The expression patterns of CaSULTR genes under hormone stress are identified, suggesting that of CaSULTR1;1 and CaSULTR3;4 may be involved in the regulation of sulfur metabolism by exogenous hormones.

Abstract Objective Endometrial cancer (EC) is an oestrogen-dependent tumour, the occurrence of which is closely related to an imbalance of oestrogen homeostasis. Our previous studies explored the effects of Resveratrol(Res) on oestrogen metabolism. However, systematic research on the exact mechanism of action of Res is still lacking. Based on network pharmacology, molecular docking and animal experiments, the effects and molecular mechanisms of Res on endometrial cancer were investigated. Methods The target of Res was obtained from the high-throughput experiment and reference-guided database of TCM (HERB) and the Encyclopedia of Traditional Chinese Medicine (ETCM) databases, and the target of endometrial cancer was obtained by using the Genecards database. Venny map was used to obtain the intersection target of Res in the treatment of endometrial cancer, and the protein interaction network of the intersection target was constructed by importing the data into the STRING database. Then, the drug–disease–target interaction network was constructed based on Cytoscape 3.9.1 software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed for intersection targets using the OmicShare cloud platform. Res and core targets were analysed by molecular docking. EC model mice induced by MNNG were randomly divided into the control group, Res group, MNNG group, MNNG + Res group, and MNNG + Res + MAPK/ERKi group. The protein levels of ERK and p-ERK in the mouse uterus were detected by Western blot. The levels of E1, E2, E3, 16-epiE3, 17-epiE3, 2-MeOE1, 4-MeOE1, 2-MeOE2, 4-MeOE2, 3-MeOE1, 2-OHE1, 4-OHE1, 2-OHE2, 4-OHE2, and 16α-OHE1 in the serum and endometrial tissue of mice were measured by LC‒MS/MS. Results A total of 174 intersection targets of Res anti-endometrial cancer were obtained. The signalling pathways analysed by KEGG enrichment included the AGE-RAGE signalling pathway in diabetic complications, the PI3K-Akt signalling pathway and the MAPK signalling pathway. The top 10 core targets were MAPK3, JUN, TP53, CASP3, TNF, IL1B, AKT1, FOS, VEGFA and INS. Molecular docking showed that in addition to TNF, other targets had good affinity for Res, and the binding activity with MAPK3 was stable. Western blot results showed that Res increased the phosphorylation level of ERK and that MAPK/ERKi decreased ERK activation. In the LC-MS/MS analysis, the levels of 2-MeOE1, 2-MeOE2 and 4-MeOE1 in serum and uterine tissue showed a significantly decreasing trend in the MNNG group, while that of 4-OHE2 was increased (P

Introduction and Objectives: The increasing incidence of hepatocellular carcinoma (HCC) in China is an urgent issue, necessitating early diagnosis and treatment. This study aimed to develop personalized predictive models by combining machine learning (ML) technology with a demographic, medical history, and noninvasive biomarker data. These models can enhance the decision-making capabilities of physicians for HCC in hepatitis B virus (HBV)-related cirrhosis patients with low serum alpha-fetoprotein (AFP) levels. Patients and Methods: A total of 6,980 patients treated between January 2012 and December 2018 were included. Pre-treatment laboratory tests and clinical data were obtained. The significant risk factors for HCC were identified, and the relative risk of each variable affecting its diagnosis was calculated using ML and univariate regression analysis. The data set was then randomly partitioned into validation (20 %) and training sets (80 %) to develop the ML models. Results: Twelve independent risk factors for HCC were identified using Gaussian naïve Bayes, extreme gradient boosting (XGBoost), random forest, and least absolute shrinkage and selection operation regression models. Multivariate analysis revealed that male sex, age >60 years, alkaline phosphate >150 U/L, AFP >25 ng/mL, carcinoembryonic antigen >5 ng/mL, and fibrinogen >4 g/L were the risk factors, whereas hypertension, calcium 6.8 μmol/L, hemoglobin 40 U/L were the protective factors in HCC patients. Based on these factors, a nomogram was constructed, showing an area under the curve (AUC) of 0.746 (sensitivity = 0.710, specificity=0.646), which was significantly higher than AFP AUC of 0.658 (sensitivity = 0.462, specificity=0.766). Compared with several ML algorithms, the XGBoost model had an AUC of 0.832 (sensitivity = 0.745, specificity=0.766) and an independent validation AUC of 0.829 (sensitivity = 0.766, specificity = 0.737), making it the top-performing model in both sets. The external validation results have proven the accuracy of the XGBoost model. Conclusions: The proposed XGBoost demonstrated a promising ability for individualized prediction of HCC in HBV-related cirrhosis patients with low-level AFP.

Nasopharyngeal carcinoma (NPC) is a neoplasm related to inflammation; the expression of cytokines, such as CCL3, CCL4, CCL20, IL-1α, IL-1β, IL-6, IL-8, and IL-10, among others, is presumed to be associated with NPC occurrence and development. Therefore, the circulating levels of these cytokines may be potential biomarkers for assessing tumor aggressiveness, exploring cellular interactions, and monitoring tumor therapeutic responses. Numerous scholars have comprehensively explored the putative mechanisms through which these inflammatory factors affect NPC progression and therapeutic responses. Moreover, investigations have focused on elucidating the correlation between the systemic levels of these cytokines and the incidence and prognosis of NPC. This comprehensive review aims to delineate the advancements in research concerning the relationship between inflammatory factors and NPC while considering their prospective roles as novel prognostic and predictive biomarkers in the context of NPC.

Karst ecosystems, especially tropical karst forests, are crucial to the global carbon cycle. In mountainous and hilly areas, elevation-related changes in environment and vegetation often lead to shifts in the accumulation and decomposition of soil organic carbon (SOC). However, the elevational patterns and influencing variables of SOC and its fractions in tropical karst forest ecosystems remain largely unexplored. Here, we analyzed the elevational patterns of SOC and its fractions in the topsoil and subsoil in the tropical seasonal rainforests within typical peak-cluster depression region of Southwest China. Our results indicated that the SOC content was highest at 400 m asl, which was significantly higher than that at 200 m asl (p < 0.05). Overall, SOC content demonstrated an increasing trend with rising elevation. Additionally, SOC content was significantly higher in the topsoil compared to the subsoil (p < 0.05). The majority of SOC fractions exhibited an increase with elevation but decrease with soil depth. Notably, only water-soluble organic carbon (WSOC) displayed a decrease with elevation. Meanwhile, recalcitrant organic carbon (ROC, 54.27%), particulate organic carbon (POC, 30.19%), and easily oxidizable organic carbon (EOC, 16.95%) were the main SOC fractions. Labile organic carbon (LOC) in the karst forest soil was predominantly composed of EOC and POC. Correlation analysis unveiled significant positive correlations between SOC and certain fractions with elevation, soil total nitrogen, and exchangeable magnesium. Conversely, significant negative correlations were observed with soil bulk density (SBD), soil total phosphorus, and litter phosphorus (Litter P). Redundancy analysis indicated that elevation, SBD, and Litter P were the main environmental variables influencing shifts in SOC and its fractions. Structural equation models showed that SOC was primarily directly impacted by soil properties but indirectly impacted by elevation. ROC was mainly associated with the direct effects of soil properties and litterfall, although elevation exerted a substantial impact through indirect pathways. Moreover, LOC was predominantly influenced by the direct impact of soil properties. Therefore, this study demonstrates that SOC and its fractions are strongly influenced by elevation in karst peak-cluster depression regions and have important implications for forest management and sustainable ecosystem development in these regions.

Abstract Background Studies involving chronic rhinosinusitis with nasal polyps (CRSwNP) have mostly focused on bilateral cases, making unilateral CRSwNP inadequately recognized. This study examined the differences in clinical characteristics, outcomes, and risk factors for poor outcomes between unilateral and bilateral CRSwNP to facilitate a better assessment in the two groups. Methods Demographic information, tissue and blood cells, endoscopic scores, Lund‐Mackay scores, recurrence rates, and disease control conditions were compared between 310 unilateral and 596 bilateral CRSwNP patients. Furthermore, the stepwise regression multivariate Cox proportional hazard models were performed to generate risk factors for poor outcomes in the two groups. Results Bilateral cases exhibited higher rates of smoking, AR, and asthma comorbidities, along with higher numbers of tissue eosinophils and blood inflammatory cells when compared to unilateral patients. Endoscopic nasal polyp score, total computed tomography (CT) score (with scores for each sinus cavity), and adjusted CT scores were significantly higher in the bilateral group, except for a markedly higher adjusted maxillary score in the unilateral group. Furthermore, significantly higher proportions of bilateral patients experienced nasal polyp recurrence, uncontrolled status, and most disease control‐related symptoms at follow‐up. The primary risk factors for poor outcomes were asthma, tissue eosinophils, and total CT score in the bilateral group and blood basophils in the unilateral group. Conclusions Bilateral CRSwNP patients experience worse disease severity and outcomes than their unilateral counterparts. Primarily, asthma, tissue eosinophils, and total CT score were risk factors for poor outcomes in bilateral CRSwNP patients, with blood basophils in unilateral cases.

BackgroundDespite emerging evidence linking alterations in gut microbiota to childhood obesity, the metabolic mechanisms linking gut microbiota to the lipid profile during childhood obesity and weight loss remain poorly understood.MethodologyIn this study, children with obesity were treated with lifestyle weight loss therapy. Metagenomics association studies and serum untargeted lipidomics analyses were performed in children with obesity and healthy controls before and after weight loss.Main findingsWe identified alterations in gut microbiota associated with childhood obesity, as well as variations in circulating metabolite concentrations. Children with obesity showed significant decreases in the levels of s-Rothia_kristinae and s-Enterobacter_roggenkampii, alongsige elevated levels of s-Clostridiales_bacterium_Marseille-P5551. Following weight loss, the levels of s-Streptococcus_infantarius and s-Leuconostoc_citreum increased by factors of 3.354 and 1.505, respectively, in comparison to their pre-weight loss levels. Correlation analyses indicated a significant positive relationship between ChE(2:0) levels and both with s-Lachnospiraceae_bacterium_TF09-5 and fasting glucose levels. CoQ8 levels were significantly negatively correlated with s-Rothia_kristinae and HOMA-IR.ConclusionWe linked altered gut microbiota and serum lipid levels in children with obesity to clinical indicators, indicating a potential impact on glucose metabolism via lipids. This study contributes to understanding the mechanistic relationship between altered gut microbiota and childhood obesity and weight loss, suggesting gut microbiome as a promising target for intervention.Clinical trial registrationhttps://www.chictr.org.cn/showproj.html?proj=178971, ChiCTR2300072179.

Background: The limited understanding of the physiology and psychology of polar expedition explorers has prompted concern over the potential cognitive impairments caused by exposure to extreme environmental conditions. Prior research has demonstrated that such stressors can negatively impact cognitive function, sleep quality, and behavioral outcomes. Nevertheless, the impact of the polar environment on neuronal activity remains largely unknown. Methods: In this study, we aimed to investigate spatiotemporal alterations in brain oscillations of 13 individuals (age range: 22–48 years) who participated in an Arctic expedition. We utilized electroencephalography (EEG) to record cortical activity before and during the Arctic journey, and employed standardized low resolution brain electromagnetic tomography to localize changes in alpha, beta, theta, and gamma activity. Results: Our results reveal a significant increase in the power of theta oscillations in specific regions of the Arctic, which differed significantly from pre-expedition measurements. Furthermore, microstate analysis demonstrated a significant reduction in the duration of microstates (MS) D and alterations in the local synchrony of the frontoparietal network. Conclusion: Overall, these findings provide novel insights into the neural mechanisms underlying adaptation to extreme environments. These findings have implications for understanding the cognitive consequences of polar exploration and may inform strategies to mitigate potential neurological risks associated with such endeavors. Further research is warranted to elucidate the long-term effects of Arctic exposure on brain function.

Abstract Background Both copy number variant-sequencing (CNV-seq) and karyotype analysis have been used as powerful tools in the genetic aetiology of fetuses with congenital heart diseases (CHD). However, CNV-seq brings clinicians more confusions to interpret the detection results related to CHD with or without extracardiac abnormalities. Hence, we conducted this study to investigate the clinical value of CNV-seq in fetuses with CHD. Results A total of 167 patients with fetal CHD including 36 single CHD (sCHD), 41 compound CHD (cCHD) and 90 non-isolated CHD (niCHD) were recruited into the study. 28 cases (16.77%, 28/167) were revealed with chromosomal abnormalities at the level of karyotype. The pathogenic detection rate (DR) of CNV-seq (23.17%, 19/82) was higher than that of karyotyping (15.85%, 13/82) in 82 cases by CNV-seq and karyotyping simultaneously. The DR of pathogenic copy number variations (PCNVs) (31.43%) was higher in niCHD subgroup than that in sCHD and cCHD (9.52% and 23.08%). Conotruncal defect (CTD) was one of the most common heart malformations with the highest DR of PCNVs (50%) in 7 categories of CHD. In terms of all the pregnancy outcomes, 67 (40.12%) cases were terminated and 100 (59.88%) cases were live neonates. Only two among 34 cases with a pathogenic genetic result chose to continue the pregnancy. Conclusions CNV-seq combined with karyotyping is a reliable and accurate prenatal technique for identifying pathogenic chromosomal abnormalities associated with fetal CHD with or without extracardiac abnormalities, which can assist clinicians to perform detailed genetic counselling with regard to the etiology and related outcomes of CHD.

In order to expand the relevant theory of fractional differential equation systems, a class of coupled φ-Hilfer fractional differential systems with integral boundary conditions was studied. Firstly, the coupled φ-Hilfer fractional differential system with integral boundary conditions was transformed into an integral system. Secondly, the appropriate Banach product space and norm were defined, the appropriate integral operator was constructed, and the existence result of the solution of the coupled φ-Hilfer fractional differential system under the integral boundary condition was given by using the compressed image principle and Kransnoselskii's fixed point theorem, respectively. Finally, examples were given to illustrate the correctness of the conclusions obtained. The results show that the solutions of the coupled φ-Hilfer fractional differential system under the integral boundary condition exist. The existence of solutions of coupled φ-Hilfer fractional differential systems is studied for the first time by using the compressed image principle and Kransnoselskii's fixed point theorem, respectively, and some innovative new results are obtained. In addition, the research conclusion enriches the relevant theories of the theoretical solvability of coupled fractional differential systems, and provides certain theoretical reference value for the further study of fractional order differential equations.

Abstract Patients with advanced gastric cancer typically face a grim prognosis. This phase 1a (dose escalation) and phase 1b (dose expansion) study investigated safety and efficacy of first-line camrelizumab plus apatinib and chemotherapy for advanced gastric or gastroesophageal junction adenocarcinoma. The primary endpoints included maximum tolerated dose (MTD) in phase 1a and objective response rate (ORR) across phase 1a and 1b. Phase 1a tested three dose regimens of camrelizumab, apatinib, oxaliplatin, and S-1. Dose regimen 1: camrelizumab 200 mg on day 1, apatinib 250 mg every other day, oxaliplatin 100 mg/m² on day 1, and S-1 40 mg twice a day on days 1–14. Dose regimen 2: same as dose regimen 1, but oxaliplatin 130 mg/m². Dose regimen 3: same as dose regimen 2, but apatinib 250 mg daily. Thirty-four patients were included (9 in phase 1a, 25 in phase 1b). No dose-limiting toxicities occurred so no MTD was identified. Dose 3 was set for the recommended phase 2 doses and administered in phase 1b. The confirmed ORR was 76.5% (95% CI 58.8–89.3). The median progression-free survival was 8.4 months (95% CI 5.9-not evaluable [NE]), and the median overall survival (OS) was not mature (11.6-NE). Ten patients underwent surgery after treatment and the multidisciplinary team evaluation. Among 24 patients without surgery, the median OS was 19.6 months (7.8-NE). Eighteen patients (52.9%) developed grade ≥ 3 treatment-emergent adverse events. Camrelizumab plus apatinib and chemotherapy showed favorable clinical outcomes and manageable safety for untreated advanced gastric cancer (ChiCTR2000034109).

Abstract Background Aberrant DNA methylation is a vital molecular alteration commonly detected in type I endometrial cancers (EC), and tet methylcytosine dioxygenase 2 (TET2) and 5-hydroxymethylcytosine (5hmC) play significant roles in DNA demethylation. However, little is known about the function and correlation of TET2 and 5hmC co-expressed in EC. This study intended to investigate the clinical significance of TET2 and 5hmC in EC. Methods The levels of TET2 and 5hmC were detected in 326 endometrial tissues by immumohistochemistry, and the correlation of their level was detected by Pearson analysis. The association between the levels of TET2 and 5hmC and clinicopathologic characteristics was analyzed. Prognostic value of TET2 and 5hmC was explored by Kaplan–Meier analysis. The Cox proportional hazard regression model was used for univariate and multivariate analyses. Results Based on the analysis results, TET2 protein level was positively correlated with 5hmC level in EC tissues (r = 0.801, P

Silty-fine sand in the Yellow River floodplain is prone to geological hazards such as collapse, subsidence, gushing water, and sand routing triggered by groundwater seepage. As a new type of grouting material, permeable polymer is effective for solving silty-fine sand geologic hazards. With the rise and fall of the water table, capillary water, and transpiration, the reinforced silty-fine sand will be subjected to dry-wet cycles. Investigating the strength loss mechanism of specimens reinforced with permeable polymer during dry-wet cycles is essential for mitigating silty-fine sand geological hazards. The strength characteristics of permeable polymer grout-reinforced silty-fine sand specimens under dry-wet cycles and its extreme case (long-time immersion) were analyzed from macro and micro perspectives employing unconfined compressive strength (UCS) test and scanning electron microscope (SEM). The functional calculation model between the specimens and the initial grouting conditions under dry-wet cycles was constructed, and the main influencing factors of the UCS loss of the specimens were obtained. After permeable polymer grouting, the porosity of silty-fine sand is reduced effectively and the porous structure is changed. The grouted specimens maintain structural integrity and demonstrate excellent water stability even after dry-wet cycles.

To investigate the status quo and influencing factors of overall frailty and its 3 domains among rural community-dwelling older adults. This is a cross-sectional study. A convenience sample of 195 older adults from 6 villages in Bashang Area of Zhangjiakou City, Hebei Province, China, were recruited from August to September, 2022. The demographic characteristics, the Chinese version of Tilburg Frailty Indicator, Charlson Comorbidity Scale and Hospital Anxiety and Depression Scale were used to investigate frailty and its influencing factors. Univariate analysis and multiple linear regression analysis were employed. The prevalence of overall frailty among the older adults in Bashang Area was 85.13%. Multiple linear regression analysis showed that age, gender, marital status, regular exercise, comorbidity, and anxiety were the influencing factors of overall frailty. While anxiety was the only shared influencing factor for physical frailty, psychological frailty, and social frailty, age, gender, marital status, financial burden, the comorbidity, and regular exercise were factors which influenced 1 or 2 domains of frailty. The prevalence of overall frailty among the older adults in rural areas, Zhangjiakou City is high. It is influenced by many factors. Medical staff and policy makers should work hand in hand to improve frailty among rural community-dwelling older adults in China.

Water bamboo shoots (Zizania latifolia) is prone to quality deterioration during cold storage after harvest, which causes the decline of commodity value. Chlorophyll synthesis and lignin deposition are the major reasons for quality degradation. This paper studied the influence of exogenous melatonin (MT) on the cold storage quality of water bamboo shoots. MT treatment could delay the increase in skin browning, hardness and weight loss rate, inhibit chlorophyll synthesis and color change of water bamboo shoots, while maintain the content of total phenols and flavonoids, and inhibit lignin deposition by inhibiting the activity and gene expression of phenylpropanoid metabolism related enzymes as PAL, C4H, 4CL, CAD, and POD. The results indicate that exogenous MT treatment can effectively inhibit the quality degradation of cold stored water bamboo shoots.

Doxorubicin (Dox) is an anti-tumor drug with a broad spectrum, whereas the cardiotoxicity limits its further application. In clinical settings, liposome delivery vehicles are used to reduce Dox cardiotoxicity. Here, we substitute extracellular vesicles (EVs) for liposomes and deeply investigate the mechanism for EV-encapsulated Dox delivery. The results demonstrate that EVs dramatically increase import efficiency and anti-tumor effects of Dox in vitro and in vivo, and the efficiency increase benefits from its unique entry pattern. Dox-loading EVs repeat a “kiss-and-run” motion before EVs internalization. Once EVs touch the cell membrane, Dox disassociates from EVs and directly enters the cytoplasm, leading to higher and faster Dox import than single Dox. This unique entry pattern makes the adhesion between EVs and cell membrane rather than the total amount of EV internalization the key factor for regulating the Dox import. Furthermore, we recognize ICAM1 as the molecule mediating the adhesion between EVs and cell membranes. Interestingly, EV-encapsulated Dox can induce ICAM1 expression by irritating IFN-γ and TNF-α secretion in TME, thereby increasing tumor targeting of Dox-loading EVs. Altogether, EVs and EV-encapsulated Dox synergize via ICAM1, which collectively enhances the curative effects for tumor treatment.

Background and objectiveHeavy metals, ubiquitous in the environment, pose a global public health concern. The correlation between these and diabetic kidney disease (DKD) remains unclear. Our objective was to explore the correlation between heavy metal exposures and the incidence of DKD.MethodsWe analyzed data from the NHANES (2005–2020), using machine learning, and cross-sectional survey. Our study also involved a bidirectional two-sample Mendelian randomization (MR) analysis.ResultsMachine learning reveals correlation coefficients of −0.5059 and − 0.6510 for urinary Ba and urinary Tl with DKD, respectively. Multifactorial logistic regression implicates urinary Ba, urinary Pb, blood Cd, and blood Pb as potential associates of DKD. When adjusted for all covariates, the odds ratios and 95% confidence intervals are 0.87 (0.78, 0.98) (p = 0.023), 0.70 (0.53, 0.92) (p = 0.012), 0.53 (0.34, 0.82) (p = 0.005), and 0.76 (0.64, 0.90) (p = 0.002) in order. Furthermore, multiplicative interactions between urinary Ba and urinary Sb, urinary Cd and urinary Co, urinary Cd and urinary Pb, and blood Cd and blood Hg might be present. Among the diabetic population, the OR of urinary Tl with DKD is a mere 0.10, with a 95%CI of (0.01, 0.74), urinary Co 0.73 (0.54, 0.98) in Model 3, and urinary Pb 0.72 (0.55, 0.95) in Model 2. Restricted Cubic Splines (RCS) indicate a linear linkage between blood Cd in the general population and urinary Co, urinary Pb, and urinary Tl with DKD among diabetics. An observable trend effect is present between urinary Pb and urinary Tl with DKD. MR analysis reveals odds ratios and 95% confidence intervals of 1.16 (1.03, 1.32) (p = 0.018) and 1.17 (1.00, 1.36) (p = 0.044) for blood Cd and blood Mn, respectively.ConclusionIn the general population, urinary Ba demonstrates a nonlinear inverse association with DKD, whereas in the diabetic population, urinary Tl displays a linear inverse relationship with DKD.

Changes in physio-biochemical metabolism, phenolics and antioxidant capacity during germination were studied in eight different wheat varieties. Results showed that germination enhanced sprout growth, and caused oxidative damage, but enhanced phenolics accumulation. Ferulic acid and p-coumaric acid were the main phenolic acids in wheat sprouts, and dihydroquercetin, quercetin and vitexin were the main flavonoids. The phenolic acid content of Jimai 44 was the highest on the 2th and 4th day of germination, and that of Bainong 307 was the highest on the 6th day. The flavonoid content of Hei jingang was the highest during whole germination. The enzymes activities of phenylalanine ammonia lyase (PAL), cinnamic acid 4-hydroxylase (C4H) and 4-coumarate coenzyme A ligase (4CL) were up-regulated. The activities of catalase, polyphenol oxidase and peroxidase were also activated. Antioxidant capacity of wheat sprouts was enhanced. The results provided new ideas for the production of naturally sourced phenolic rich foods.

Abstract Background Cervical cancer (CC) is a common malignancy of the female reproductive tract, and preoperative prediction of lymph node metastasis (LNM) is essential. This study aims to design and validate a magnetic resonance imaging (MRI) radiomics-based predictive model capable of detecting LNM in patients diagnosed with CC. Methods This retrospective analysis incorporated 86 and 38 CC patients into the training and testing groups, respectively. Radiomics features were extracted from MRI T2WI, T2WI-SPAIR, and axial apparent diffusion coefficient (ADC) sequences. Selected features identified in the training group were then used to construct a radiomics scoring model, with relevant LNM-related risk factors having been identified through univariate and multivariate logistic regression analyses. The resultant predictive model was then validated in the testing cohort. Results In total, 16 features were selected for the construction of a radiomics scoring model. LNM-related risk factors included worse differentiation (P < 0.001), more advanced International Federation of Gynecology and Obstetrics (FIGO) stages (P = 0.03), and a higher radiomics score from the combined MRI sequences (P = 0.01). The equation for the predictive model was as follows: −0.0493–2.1410 × differentiation level + 7.7203 × radiomics score of combined sequences + 1.6752 × FIGO stage. The respective area under the curve (AUC) values for the T2WI radiomics score, T2WI-SPAIR radiomics score, ADC radiomics score, combined sequence radiomics score, and predictive model were 0.656, 0.664, 0.658, 0.835, and 0.923 in the training cohort, while these corresponding AUC values were 0.643, 0.525, 0.513, 0.826, and 0.82 in the testing cohort. Conclusions This MRI radiomics-based model exhibited favorable accuracy when used to predict LNM in patients with CC. Relative to the use of any individual MRI sequence-based radiomics score, this predictive model yielded superior diagnostic accuracy.

Abstract Background Bisphenol A (BPA) is an environmental contaminant with endocrine-disrupting properties that induce fetal growth restriction (FGR). Previous studies on pregnant ewes revealed that BPA exposure causes placental apoptosis and oxidative stress (OS) and decreases placental efficiency, consequently leading to FGR. Nonetheless, the response of gut microbiota to BPA exposure and its role in aggravating BPA-mediated apoptosis, autophagy, mitochondrial dysfunction, endoplasmic reticulum stress (ERS), and OS of the maternal placenta and intestine are unclear in an ovine model of gestation. Results Two pregnant ewe groups (n = 8/group) were given either a subcutaneous (sc) injection of corn oil (CON group) or BPA (5 mg/kg/day) dissolved in corn oil (BPA group) once daily, from day 40 to day 110 of gestation. The maternal colonic digesta and the ileum and placental tissue samples were collected to measure the biomarkers of autophagy, apoptosis, mitochondrial dysfunction, ERS, and OS. To investigate the link between gut microbiota and the BPA-induced FGR in pregnant ewes, gut microbiota transplantation (GMT) was conducted in two pregnant mice groups (n = 10/group) from day 0 to day 18 of gestation after removing their intestinal microbiota by antibiotics. The results indicated that BPA aggravates apoptosis, ERS and autophagy, mitochondrial function injury of the placenta and ileum, and gut microbiota dysbiosis in pregnant ewes. GMT indicated that BPA-induced ERS, autophagy, and apoptosis in the ileum and placenta are attributed to gut microbiota dysbiosis resulting from BPA exposure. Conclusions Our findings indicate the underlying role of gut microbiota dysbiosis and gut-placental axis behind the BPA-mediated maternal intestinal and placental apoptosis, OS, and FGR. The findings further provide novel insights into modulating the balance of gut microbiota through medication or probiotics, functioning via the gut-placental axis, to alleviate gut-derived placental impairment or FGR. Video Abstract

Abstract Apatinib was the first anti-angiogenic agent approved for treatment of metastatic gastric cancer (GC). However, the emergence of resistance was inevitable. Thus investigating new and valuable off-target effect of apatinib directly against cancer cells is of great significance. Here, we identified extra spindle pole bodies-like 1 (ESPL1) was responsible for apatinib resistance in GC cells through CRISPR genome-wide gain-of-function screening. Loss of function studies further showed that ESPL1 inhibition suppressed cell proliferation, migration and promoted apoptosis in vitro, and accordingly ESPL1 knockdown sensitized GC cells to apatinib. In addition, we found ESPL1 interacted with mouse double minute 2 (MDM2), a E3 ubiquitin protein ligase, and the combination of MDM2 siRNA with apatinib synergistically ameliorated the resistance induced by ESPL1 overexpression. In summary, our study indicated that ESPL1 played a critical role in apatinib resistance in GC cells. Inhibition of MDM2 could rescue the sensitivity of GC cells to apatinib and reverse ESPL1-mediated resistance.

This study aimed to investigate the effects of dietary supplementation of underfed Hu ewes from d 35 to 110 of gestation with either rumen-protected L-arginine (RP-Arg) or N-carbamylglutamate (NCG) on placental amino acid (AA) transport, angiogenic gene expression, and steroid anabolism. On d 35 of gestation, 32 Hu ewes carrying twin fetuses were randomly divided into four treatment groups, each consisting of eight ewes, and were fed the following diets: A diet providing 100% of NRC's nutrient requirements for pregnant ewes (CON); A diet providing 50% of NRC's nutrient requirements for pregnant ewes (RES); RES diet plus 5 g/d NCG (RES + NCG); or RES diet plus 20 g/d RP-Arg (RES + ARG). On the d 110 of pregnancy, blood samples were taken from the mother, and samples were collected from type A cotyledons (COT; the fetal portions of the placenta). The levels of 17β-estradiol and progesterone in the maternal serum and both the capillary area density (CAD) and capillary surface density (CSD) in type A COT were decreased in response to Arg or NCG supplementation when compared to the RES group. The concentrations of arginine, leucine, putrescine and spermidine in type A COT were higher (P

Abstract PARP inhibitors (PARPi)‐based synthetic lethal therapy demonstrates limited efficacy for most cancer types that are homologous recombination (HR) proficient. To potentiate the PARPi application, a nanocarrier based on 5‐azacytidine (AZA)‐conjugated polymer (PAZA) for the codelivery of AZA and a PARP inhibitor, BMN673 (BMN) is developed. AZA conjugation significantly decreased the nanoparticle (NP) size and increased BMN loading. Molecular dynamics simulation and experimental validations shed mechanistic insights into the self‐assembly of effective NPs. The small PAZA NPs demonstrated higher efficiency of tumor targeting and penetration than larger NPs, which is mediated by a new mechanism of active targeting that involves the recruitment of fibronectin from serum proteins following systemic administration of PAZA NPs. Furthermore, it is found that PAZA carrier sensitize the HR‐proficient nonsmall cell lung cancer (NSCLC) to BMN, a combination therapy that is more effective at a lower AZA/BMN dosage. To investigate the underlying mechanism, the tumor immune microenvironment and various gene expressions by RNAseq are explored. Moreover, the BMN/PAZA combination increased the immunogenicity and synergized with PD‐1 antibody in improving the overall therapeutic effect in an orthotopic model of lung cancer (LLC).

Objectives This qualitative study aimed to explore opportunities to strengthen tuberculosis (TB) health service delivery from the perspectives of health workers providing TB care in Shigatse prefecture of Tibet Autonomous Region, China.Design Qualitative research, semi-structured in-depth interviews.Setting The TB care ecosystem in Shigatse, including primary and community care.Participants Participants: 37 semi-structured interviews were conducted with village doctors (14), township doctors and nurses (14), county hospital doctors (7) and Shigatse Centre for Disease Control staff (2).Results The three main themes reported include (1) the importance of training primary and community health workers to identify people with symptoms of TB, ensure TB is diagnosed and link people with TB to further care; (2) the need to engage community health workers to ensure retention in care and adherence to TB medications; and (3) the opportunity for innovative technologies to support coordinated care, retention in care and adherence to medication in Shigatse.Conclusions The quality of TB care could be improved across the care cascade in Tibet and other high-burden, remote settings by strengthening primary care through ongoing training, greater support and inclusion of community health workers and by leveraging technology to create a circle of care. Future formative and implementation research should include the perspectives of health workers at all levels to improve care organisation and delivery.

ABSTRACTGrowing evidence indicates that gut microbiota is involved in the regulation of the host’s sex hormone levels, such as through interfering with the sex hormone metabolism in the intestine. However, if gut microbiota or its metabolites directly influence the sex hormone biosynthesis in the gonad remains largely unknown. Our previous study showed that colistin, as a narrow-spectrum antibiotic, can significantly downregulate the serum testosterone levels and thus enhance the antitumor efficiency of anti-PD-L1 in male mice; however, the underlying mechanism for the regulation of the host’s testosterone levels remains uninvestigated. In the present study, we analyzed the impact of colistin on the immune microenvironment of the testis as well as the composition and metabolism of gut microbiota in male mice. Our results showed that colistin has an impact on the immune microenvironment of the testis and can downregulate serum testosterone levels in male mice through inhibition of Akkermansia, leading to destroyed inosine metabolism. Supplement with inosine can restore testosterone secretion probably by prompting the recovery of the intestinal mucus barrier and the serum lipopolysaccharides levels. All these findings reveal a new pathway for the regulation of the host’s sex hormone levels by gut microbiota.IMPORTANCEThis study demonstrates that exposure to even narrow-spectrum antibiotics may affect the host’s testosterone levels by altering the gut microbiota and its metabolites. Our findings provide evidence that some specific gut bacteria have an impact on the sex hormone biosynthesis in the testis.

This work introduces the preparation of a novel type of crosslinked polymers support based on calcium lignosulfonate-chitosan (CLS-CS) hydrogel with capping/reducing ability to encapsulated gold nanoparticles (CLS-CS/Au NPs). The morphology, structure and physicochemical properties of the prepared nanoparticles were characterized by different analytical techniques such as FT-IR, FE-SEM, TEM, EDX-elemental mapping study. The obtained results shown that CLS-CS/Au NPs prepared as spherical particles with sizes of 20–30 nm. The CLS-CS/Au NPs was applied as well for reduction of nitroarenes. The reduction of nitroarenes was obtained with good to high yields within short times. The related nanocatalyst was recovered for eight runs without significant loss of its catalytic performance. The MTT examination was conducted to check the anti-pancreatic cancer, anti-gastric cancer, anti-colorectal carcinoma, and cytotoxicity efficacies of the treated cells with CLS-CS/Au NPs over a 48-hour period on normal (HUVEC) and cancer cells. The IC50 values of the CLS-CS/Au NPs were found to be 169 µg/mL for HT-29 (colorectal carcinoma cell), 196 µg/mL for MKN45 (Gastric cancer cell), and 112 µg/mL for PANC-1 (Pancreatic cancer cell). The growth of malignant colorectal, gastric and pancreatic cells was found to decrease in a dose-dependent manner when exposed to CLS-CS/Au NPs. Following clinical research, CLS-CS/Au NPs shows promise as an effective treatment for colorectal, gastric and pancreatic cancers.

Activating cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) holds great potential for cancer immunotherapy by eliciting type-I interferon (IFN-I) responses. Yet, current approaches to cGAS-STING activation rely on STING agonists, which suffer from difficult formulation, poor pharmacokinetics, and marginal clinical therapeutic efficacy. Here, we report nature-inspired oligonucleotide, Svg3, as a cGAS agonist for cGAS-STING activation in tumor combination immunotherapy. The hairpin-shaped Svg3 strongly binds to cGAS and enhances phase separation to form Svg3-cGAS liquid-like droplets. This results in cGAS-specific immunoactivation and robust IFN-I responses. Remarkably, Svg3 outperforms several state-of-the-art STING agonists in murine and human cells/tissues. Nanoparticle-delivered Svg3 reduces tumor immunosuppression and potentiates immune checkpoint blockade therapeutic efficacy of multiple syngeneic tumor models in wild-type mice, but in neither cGas−/− nor Sting−/− mice. Overall, these results demonstrate the great potential of Svg3 as a cGAS agonistic oligonucleotide for cancer combination immunotherapy.

Parkinson’s disease (PD) is a common movement disorder. In this study, we generated an induced pluripotent stem cell (iPSC) line from the dermal fibroblasts of a 68-year-old female patient, carrying LRRK2 and DNAJC6 mutations. This iPSC line will be a useful tool for investigating the pathogenesis and for developing treatment for PD.

Abstract Background To investigate the effect of preoperative high-intensity strength training combined with balance training on the knee function of end-stage knee osteoarthritis (KOA) patients after total knee arthroplasty (TKA). Methods A prospective study was conducted on end-stage KOA patients awaiting TKA. The patients were divided into an experimental group and a control group according to whether they received a preoperative training intervention. The differences in knee flexor–extensor strength, knee range of motion (ROM), timed up and go (TUG) test result, stair ascend/descend test result, Knee Society score (KSS) and Berg balance scale (BBS) score were assessed in both groups at baseline (T1), before operation (T2), 3 months after operation (T3), and 1 year after operation (T4). Results After high-intensity strength training and balance training, the knee flexor–extensor strength, TUG test result, stair ascend/descend test result, and KSS were all significantly improved at T2 in the experimental group over the control group. At T3, the knee ROM, knee flexor–extensor strength, TUG test result, BBS score, and KSS clinical and functional scores were all significantly superior in the experimental group. The experimental group enjoyed a superiority in KSS clinical and functional scores until T4. Group × time and between-group interactions were found in all assessment indicators in both groups (p

In order to reduce the risk of early freezing damage to cement-based materials in winter construction, lime powder was used to improve the properties of the Portland cement–sulphoaluminate cement (PC–CSA) composite system at low temperatures. In this study, the effects of lime powder dosage on the properties of a PC–CSA blended system with two proportions (PC:CSA = 9:1 and 7:3) at −10 °C were investigated, and the mechanisms of improvement were revealed. The results showed that the compressive strength of the PC–CSA composite system was effectively improved, and the setting time was shortened by the addition of lime powder. Lime powder could effectively act as an early heating source in the PC–CSA composite system, as the maximum temperature of samples exposed to sub-zero temperatures was increased and the time before dropping to 0 °C was prolonged by the addition of lime powder. The extra CH generated by the hydration of lime powder provided an added hydration path for C4A3S¯, which accelerated the formation of AFt at each stage. Frozen water as well as the early frost damage were effectively decreased by lime powder because of the faster consumption of free water at an early stage. The modification of the hydration products also contributed to the denseness of the microstructure.

The utilization of baffle structures as a highly effective strategy for mitigating debris flow has attracted significant scholarly attention in recent years. Although the predominant focus of existing research has been on augmenting the energy dissipation capabilities of baffle structures, their deformation behavior under impact load has not been extensively investigated. Addressing this research gap, the current study systematically designs a series of physical model experiments, incorporating variables such as baffle height, shape, and various combinations of baffle types to comprehensively analyze the deformation characteristics of baffles subjected to debris flow impact. The experimental results reveal that the deformation of baffle group structures demonstrates a marked non-uniform spatial distribution and exhibits a latency effect. Additionally, distinct baffle configurations show considerable variations in peak strain, suggesting that combining different baffle shapes can not only optimize energy dissipation but also enhance resistance to deformation. Moreover, the relationship between baffle height and the development of deformation in relation to energy dissipation capacity is inconsistent, indicating that deformation must be a key consideration in the design of baffle structures. Consequently, this paper advocates for the formulation of a deformation-based design strategy for baffle structures, with the findings presented herein providing a foundational reference for future studies.

Micro-corona devices could be extensively utilized in gas sensing, switchgear, biomedicine, and other fields. As the influence mechanism of the cathode curvature radius on micro-corona discharge dynamical processes is very important for performance optimization and the promotion of these devices, a micro-scale corona discharge gas model in a mixture of N2-O2 is proposed based on the fluid–chemical mixing method, which describes the dynamic process of the discharge at atmosphere and normal temperatures. To reveal the influence mechanism of the nanowire curvature radius on the micro-corona discharge, the effect of the cathode nanowire radius on the discharge current, electric field, ionization reaction rate, and charged particle characteristics at different gaps and voltages were determined. The findings indicate that the effect of curvature radius on discharge intensity varies under different gap and voltage conditions. Further analysis indicates that an increase in curvature radius reduces the electric field near the tip while increasing the ionization area and secondary emission area as well as the number of positive ions in the space, consequently affecting the coupling process between the collision ionization and the secondary emission. Especially under the conditions of either small gap or low voltage, a suitable increase in the curvature radius could promote the coupling process and then increase the discharge current.

Natural soil and vegetation recovery following human disturbance is the primary means of restoring degraded ecosystems globally. However, it remains unclear how vegetation recovery in the tropical karst areas of China affects the soil physicochemical properties. Here, we investigated the impacts of natural vegetation recovery on soil physicochemical properties at different soil depths in tropical karst areas in southwestern China, using a space–time substitution method. We found that with the natural vegetation recovery, soil bulk density (SBD) decreased. Soil pH initially decreased and then increased, reaching its lowest value during the shrubland stage. There was a significant increase in other soil physicochemical factors. In the soil profiles, SBD tended to increase with depth. The pH, total potassium (TK), total phosphorus (TP), and exchangeable calcium remained relatively stable across the different soil layers. TK, TP, available phosphorus, SBD, total nitrogen, pH, exchangeable magnesium, and available potassium significantly contributed to the soil physicochemical properties. Soil physicochemical properties were predominantly directly affected by litter and biological factors, albeit indirectly influenced by topographic factors. Our study provides crucial insights into karst soils and their relationship with vegetation recovery, which are pivotal for steering vegetation restoration and soil amelioration in karst areas.

Rainfall-runoff nitrogen (N) pollution has emerged as the primary source of water contamination due to rapid urbanization. Green infrastructure (GI), as the representative measure, is widely used in controlling N pollution in runoff. However, there is limited research on the impact of woody plants on N reduction in GIs. Therefore, this study aimed to investigate the influence and relationship of Sophora japonica (with tap root) and Malus baccata (with fibrous root) on N removal in GIs. Utilizing the advanced root analysis software WinRHIZO (version 4.0b), a meticulous examination of the morphological traits of plant roots was conducted. The findings unveiled a striking contrast between the root systems of two species: S. japonica primarily boasts a vertically oriented root configuration, whereas M. baccata’s root system is characterized by an extensively lateral, or horizontal, growth pattern. Specifically, in comparison to S. japonica, the horizontal roots of M. baccata demonstrated a substantial superiority, with their total root length measuring 10.95 times longer, the surface area spanning 6.25 times wider, and the cumulative volume being 3.93 times greater. For comparing the load reduction rates on runoff NH3-N, NO3-N, and TN of the different root morphologies’ GIs, S. japonica GI had the highest purification effect on the three pollutants, and the average load reduction rates of three pollutants reached 67.74%, 33.83%, and 38.96%, respectively, which were 11.42%, 27.46%, and 6.16% higher than those of the control. The variance contribution rate of vertical root and horizontal root characteristics on runoff nitrogen load reduction accounted for 86.47% of the total root contribution rate. The volume of vertical roots emerged as the most crucial characteristic factor affecting the reduction of N load.

This subject took yak meat balls added with different kinds of edible fungus powder (shiitake mushrooms, hericium, porcini, tea tree mushroom) as the research objects, aiming to study the effects of edible fungi on the edible quality of yak meat balls during storage. Changes in quality indexes such as color, pH value, water retention, TBARS, texture properties, rheological properties, EAI and ESI of yak meat ball products of different treatment group during the storage were determined and analyzed. The results showed that in the storage period of 0 to 15 d, the addition of shiitake mushrooms could significantly improve the b* value of yak meat balls under refrigeration compared with the blank control group (b* value was 4.52 lower than blank group on 15 d), the pH value of yak meat balls was increased by adding porcini mushrooms and tea tree mushrooms (both were 6.64 on the 15 d), water retention was increased by adding shiitake mushrooms. Moreover, the elasticity and chewiness of yak meat balls were significantly improved by the addition of mushrooms and hericium, porcini (P

Abstract Introduction Colon cancer remains one of the most prevalent cancers worldwide. Unfortunately, there are no recognized and effective therapeutic strategies to prevent tumor recurrence after radical resection and chemotherapy, and the disease-free survival (DFS) in patients with stage IIIB or IIIC disease remains unsatisfactory. Xian-Lian-Jie-Du optimization decoction (XLJDOD) is a Chinese herbal medicine (CHM) empirical prescription, which has been validated experimentally and clinically that could inhibit the progression of colorectal cancer and ameliorate the symptoms. The purpose of this study is to evaluate the efficacy and safety of XLJDOD in prevention of recurrence of colon cancer. Methods This study is a multi-center, double-blind, randomized, placebo-controlled trial conducted at 13 hospitals of China. Following the completion of surgery and adjuvant 5- fluorouracil-based chemotherapy, a total of 730 subjects with stage IIIB or IIIC colon cancer will be randomized in a 1:1 ratio to an intervention group (n = 365; XLJDOD compound granule) and a control group (n = 365; Placebo). Patients will receive 6-month treatments and be followed up with 3 monthly assessments for 2 years. The primary outcome is 2-year DFS rate and the secondary outcomes are 1, 2-year relapse rate (RR), overall survival (OS) and quality of life (QoL). Safety outcomes such as adverse events will be also assessed. A small number of subgroup analysis will be carried out to explore the heterogeneity of effects of XLJDOD. Discussion The outcomes from this randomized controlled trial will provide objective evidences to evaluate XLJDOD’s role as an adjuvant treatment in colon cancer. Trial registration www.ClinicalTrials.gov , identifier: NCT05709249. Registered on 31 Jan 2023.

To ensure the performance of C/C composites, a surface-modified C/C composite was prepared with a C/C composite as the substrate, one-dimensional SiC as the intermediate, and vertically oriented graphene as the modification material without changing the microstructure or composition of the C/C composites. C/C composite surface modifications were prepared in two steps. Its specific surface area is improved from 0.25 m2/g to 10.44 m2/g, and the electromagnetic interference shielding efficiency is enhanced from 13.08 dB to 23.86 dB. Different from the C/C composites without surface modification, the electromagnetic interference shielding mechanism of surface-modified C/C composites changed from electromagnetic reflection to the interaction of electromagnetic absorption and reflection. The reason is that the increased specific surface area elongates the transmission paths of the electromagnetic waves by multiple reflections, leading to significantly improved electromagnetic interference shielding efficiency.

Abstract This paper uses the bibliometric method to analyze the basic characteristics and disciplinary knowledge structure of family-friendly policy research, as well as research hotspots and trends. The basic data source is the literature in the Web of Science Core Collection from 1985 to 2022. The following findings were obtained. First, the number of publications and citations in this field have increased exponentially, with scholars and research institutions from the US dominating the field of family-friendly policy research. Second, family-friendly policy research has been concentrated in the fields of management, sociology, and psychology, with a gradual trend toward cross-disciplinary integration, but a core group of authors has yet to be formed. Third, most of the family-friendly policy research has been conducted at the organizational level to explore the impact of family-friendly policies, with married women as the main research object. Finally, current family-friendly policy research focuses on policy fairness, childcare services, employee satisfaction, and work flexibility. Future research should focus on the dynamics of family-friendly policies and the empirical analysis of cross-level integration to improve the matching of policies with employee orientation. This study fills an analytical gap in the integration of family-friendly policies and scientometrics, proposes an expandable field of family-friendly policy research and research methods, and provides references and insights for future family-friendly policy research and practice.

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) and CRISPR-associated (Cas) proteins serve as an adaptive immune system that safeguards prokaryotes and some of the viruses that infect prokaryotes from foreign nucleic acids (such as viruses and plasmids). The genomes of the majority of archaea and about half of all bacteria contain various CRISPR-Cas systems. CRISPR-Cas systems depend on CRISPR RNAs (crRNAs). They act as a navigation system to specifically cut and destroy foreign nucleic acids by recognizing invading foreign nucleic acids and binding Cas proteins. In this review, we provide a brief overview of the evolution and classification of the CRISPR-Cas system, focusing on the functions and applications of the CRISPR-Cas13a system. We describe the CRISPR-Cas13a system and discuss its RNA-directed ribonuclease function. Meanwhile, we briefly introduce the mechanism of action of the CRISPR-Cas13a system and summarize the applications of the CRISPR-Cas13a system in pathogen detection, eukaryotes, agriculture, biosensors, and human gene therapy. We are right understanding of CRISPR-Cas13a has been broadened, and the CRISPR-Cas13a system will be useful for developing new RNA targeting tools. Therefore, understanding the basic details of the structure, function, and biological characterization of CRISPR-Cas13a effector proteins is critical for optimizing RNA targeting tools.

Two new nitrates Rb3ZnNO3Cl4 and Rb5Na(NO3)4Cl2 have been synthesized by hydrothermal method, and they are crystallized in orthorhombic space group Pnma (no. 62) and tetragonal space group P4/mnc (no. 128), respectively. ZnCl4 and RbO3Cl6 polyhedron, NaO4Cl2 and RbO8Cl2 polyhedron are connected by sharing O or Cl atoms to construct three-dimensional (3D) frameworks with trigonal plane NO3 units as pseudo-layers, in which different types of channels are presented. In addition, Rb5Na(NO3)4Cl2 exhibits a perovskite-related framework, and Rb3ZnNO3Cl4 crystals is grown with dimensions up to 5×4.5×1 mm3. Notably, these two compounds have short UV cut-off edge (below 222 nm and 238 nm, respectively). Theoretical calculations indicate that the birefringence enhancement is mainly derived from π-conjugated NO3 units.

Multiple Sclerosis (MS) is an immune-related disease and the relationship between MS and cancer has raised attention. Previous studies of the relationship between MS and cancer have reached conflicting conclusions. In this study, the two-sample MR method is used to investigate whether MS has a causal correlation with cancers and offer scientific evidence for cancer prevention. Single nucleotide polymorphisms (SNPs) related to MS were obtained from the genome-wide association study (GWAS) based on International Multiple Sclerosis Genetics Consortium (IMSGC) and SNPs related to 15 types of cancers were obtained from the GWASs based on UK Biobank. Inverse variance weighted (IVW) method was mainly used to assess causal effects. Sensitivity analyses were conducted with Cochran's Q-test, MR Egger intercept, leave-one-out test, and MR Steiger method. IVW analysis showed that MS was only associated with a marginal increased risk of cervical cancer (OR 1.0004, 95% CI 1.0002-1.0007, p = 0.0003). Sensitivity analyses showed that the results of MR analysis were robust and found no heterogeneity, no pleiotropy, and no reverse causation. In conclusion, this study finds no causal relationship between MS and 15 types of cancers except cervical cancer.

Introduction Frailty is one of the most common comorbidities in kidney transplant recipients (KTRs). Physical, psychological and social frailty could be improved by exercise intervention. Baduanjin, also known as Eight-section Brocades, is a type of traditional Chinese medicine exercise characterised by the interplay between physical postures and movements, breathing and mind. It can help frail patients strengthen their upper and lower body muscles, improve their mood, quality of life and frailty. However, the effectiveness of Baduanjin on frail KTRs remains unknown. Therefore, we will conduct a randomised controlled trial (RCT) to evaluate the effectiveness of Baduanjin on frail KTRs.Methods and analysis This protocol describes an assessor and analyst blinded, parallel RCT for frail KTRs comparing Baduanjin group (n=72) with care-as-usual group (n=72). The primary outcomes are frailty assessed by Frailty Phenotype scale and Tilburg Frailty Indicator scale, and muscle strength assessed by a grip strength metre. The secondary outcomes are quality of life assessed by Medical Outcomes Study 36-Item Short-Form Health Survey (MOS SF-36) and depression assessed by the Hospital Anxiety and Depression Scale. All these data will be collected at the baseline, after 3, 6, 9 and 12 months, respectively. Two-way mixed analysis of variance (ANOVA) will be used to test the effectiveness of Baduanjin exercise. Qualitative interviews with participants in the intervention group will also be performed after 6 months. Themes will be extracted from interview transcripts using NVivo software.Ethics and dissemination The Ethics Committees of Beijing University of Chinese Medicine (2022BZYLL1018) and China-Japan Friendship Hospital (2022-KY-250) had approved the study. The organ donors were all from China-Japan Friendship Hospital. They provided informed consent and they were not executed prisoners. We have provided BMJ Open with documentation from the hospital that indicates that the organs will be harvested ethically. The findings of this study will be disseminated through peer-reviewed journals, international conferences, media reports and briefings.Trial registration number ChiCTR2100041730

Abstract Background The presence of high fibrinogen and low albumin levels in serum is associated with a negative prognosis in acute ischemic stroke (AIS). Fibrinogen‐to‐albumin ratio (FAR), a new inflammatory biomarker, may provide better prognostic insights in patients with AIS than separate evaluation of fibrinogen or albumin. The objective of this investigation is to examine the correlation between FAR and 3‐month functional prognosis after intravenous thrombolysis (IVT) in AIS patients. Methods The retrospective study recruited AIS patients who received IVT from June 2014 to December 2021. The 3‐month functional prognosis was assessed using the Modified Rankin Scale (mRS). A mRS score of ≤2 indicated a good outcome, whereas a mRS score of >2 suggested a poor outcome. Results A total of 591 AIS patients who underwent IVT were included and 147 patients (24.9 %) had a poor outcome. Among the 102 pairs of patients after propensity score matching, there was a significant association between FAR and 3‐month prognosis (adjusted OR, 1.19; 95% CI, 1.03–1.38; p = .020). The optimal FAR cutoff value was found to be 7.57, and even after stratifying patients based on this value, we still observed a significant correlation between high FAR level and poor outcome (adjusted OR, 2.08; 95% CI, 1.28–3.40; p = .003). Conclusions FAR may serve as a prospective biomarker of predicting 3‐month prognosis in AIS patients after IVT.

ABSTRACTParkinson’s disease (PD) is recognized as a multisystem disease concerning gastrointestinal (GI) dysfunction and microbiota dysbiosis. However, the mechanism by which microbial dysbiosis contributes to pathogenesis of PD and the relationship between gut microbes and metabolites remain to be deeply elucidated. This study aims to explore the altered microflora and serum metabolites in PD mice and their role in PD etiology. Herein, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 30 mg/kg) was injected intraperitoneally to establish the PD mice model. 16S rRNA sequencing and ultrahigh-performance liquid chromatography coupled with Q Exactive HF-X mass spectrometry were used to depict the profile of gut bacteria and metabolites. Phylogenetic investigation of communities by reconstruction of unobserved states 2 analysis was performed to elucidate the functional link between the microbe-metabolite axis and PD. We confirmed the MPTP-induced dopaminergic (DA) neuron loss accompanied by the GI dysfunction. Higher abundances of Aerococcus, Staphylococcus, and Ruminococcaceae, and lower abundances of Lactobacillus, Lachnospiraceae, and Adlercreutzia were identified in PD mice. Meanwhile, the differential metabolites concerning “taurine and hypotaurine metabolism” were markedly downregulated in PD mice. Furthermore, Lactobacillus, Adlercreutzia, and taurine-related metabolites showed the most significant correlation with pathological and GI performance of PD mice. The abundances of microbial transporter and enzymes participating in the degeneration of taurine were disturbed in PD mice. More importantly, taurine supplement is protected from MPTP-induced motor deficits and DA neuron loss. The detection of disturbed taurine metabolism in PD mice suggests a mechanism whereby dysregulation of the microbiota-metabolism axis contributes to the etiology of MPTP-treated mice.IMPORTANCEPD is recognized as a multisystem disease concerning GI dysfunction and microbiota dysbiosis but still lacks ideal therapies. Recently, aberrant microbiota-derived metabolites are emerging as important participants in PD etiology. However, the alterations of gut microbiota community and serum untargeted metabolite profile have not been fully investigated in a PD mice model. Here, we discover sharply reduced levels of Lactobacillus and taurine in MPTP-treated mice. Moreover, Lactobacillus, Adlercreutzia, and taurine-related metabolites showed the most significant correlation with pathological and GI performance of PD mice. The abundances of microbial transporter and enzymes participating in the degeneration of taurine were disturbed in PD mice. Most importantly, taurine supplement ameliorates MPTP-induced motor deficits, DA neuron loss, and microglial activation. Our data highlight the impaired taurine-based microbiome-metabolism axis during the progression of PD and reveal a novel and previously unrecognized role of genera in modulating taurine metabolism.

Objective To investigate the role of segmental bioelectrical impedance technique (SBIA) in the assessment of intraperitoneal ultrafiltration volume with peritoneal dialysis patients.Method We selected the patients at the Department of Nephrology of the First Affiliated Hospital of Zhengzhou University and measured the segmental bioelectrical impedance by a German Fresenius body composition analyzer (the Fresenius whole body composition measurement (BCM) machine was used as a segmental machine in this study). An alternating current (5 kHz, 0.05–0.7 mA) was continuously released during the measurement. The released current penetrated the peritoneal cavity on both sides of the body, from which the segmental resistance at a frequency of 5 kHz was obtained from the multifrequency data (R5/Ω). Baseline BIA measurements were initiated after the patient entered the supine position for 5–10 min, then dialysate was instilled into the peritoneal cavity. BIA measurements were performed at 10-min intervals during the retention of dialysate in the abdomen and finally ended when dialysate drainage was complete. Real-time intraperitoneal volume estimated by SBIA (IPVSBIA)and ultrafiltration volume estimated by SBIA(UFVSBIA) was calculated. At the same time, the actual ultrafiltration volume at the end of peritoneal dialysis was weighed and measured (UFVMEA).Results A total of 30 patients were included in the study, 9 patients withdrew from the study due to subjective factors during the measurement process, and 21 patients completed the study. The correlation coefficient R2 of UFVSBIA and UFVMEA was 0.21 (p

Background: Childhood maltreatment (CM) is a common psychological stressor associated with multiple mental disorders. While CM is associated with vulnerability to depression and anxiety, little is known about the specific mechanism underlying this relationship. Objective: This study aimed to investigate the white matter (WM) of healthy adults with CM and their relationships with depression and anxiety to provide biological evidence for the development of mental disorders in subjects with childhood trauma. Methods: The CM group included 40 healthy adults with CM. The non-CM group included 40 healthy adults without CM. Diffusion tensor imaging (DTI) data were collected, and tract-based spatial statistics (TBSS) were applied to the whole brain to assess WM differences between the two groups; post-hoc fibre tractography was used to characterise the developmental differences; and mediation analysis was used to assess the relationships among the Child Trauma Questionnaire (CTQ) results, DTI indices, and depression and anxiety scores. Results: Relative to the non-CM group, the CM group revealed significantly lower fractional anisotropy (FA) in the right posterior corona radiata (PCR-R), right anterior corona radiata (ACR-R), left super corona radiata (SCR-L), anterior thalamic radiation (ATR), and right posterior limb of the internal capsule (PLIC-R). Additionally, shorter fibre bundles passed through the PCR-R, ACR-R, and ATR in the CM group compared with the non-CM group. Besides, the length of the ACR-R mediated the relationship between CM and trait anxiety. Conclusions: The alteration of white matter microstructure associated with childhood trauma in healthy adults may reflect biomarkers of childhood trauma. Besides, an alteration of WM microstructure in healthy adults with CM mediates the association between CM and trait anxiety, which may represent the vulnerability to developing mental disorders after childhood trauma experiences.

ABSTRACTAccumulating evidence suggested that both gut microbiome and sex play a critical role in the efficacy of immune checkpoint blockade therapy. Considering the reciprocal relationship between sex hormones and gut microbiome, the sex hormone-gut microbiome axis may participate in the regulation of the response to immune checkpoint inhibitors (ICIs). In this review, it was attempted to summarize the current knowledge about the influences of both sex and gut microbiome on the antitumor efficacy of ICIs and describe the interaction between sex hormones and gut microbiome. Accordingly, this review discussed the potential of enhancing the antitumor efficacy of ICIs through regulating the levels of sex hormones through manipulation of gut microbiome. Collectively, this review provided reliable evidence concerning the role of the sex hormone-gut microbiome axis in tumor immunotherapy.

AbstractPurpose Bioelectrical impedance analysis (BIA) is simple, noninvasive, inexpensive and frequently used for estimating fat free mass (FFM). The aims of this study were to evaluate the applicability of different BIA equations on FFM in Chinese subjects, and to compare the difference in hemodialysis and peritoneal dialysis patients with healthy controls respectively.Methods Dialysis patients and healthy adults were enrolled in this study, and the subjects were matched by age, gender, and the minimum sample size in each group was calculated using PASS. FFM estimated by BIA was calculated using equations of Kyle, Sun SS and Segal, and TBW/0.73. Dual-energy X-ray absorptiometry (DXA) method was set as reference method. Pearson’s correlation and Bland-Altman analysis were used to test the validity of the BIA equations.Results 50 hemodialysis (HD) patients, 52 peritoneal dialysis (PD) patients and 30 healthy adults aged 22–67 y were included in this study. Age, height, weight, BMI and gender did not differ significantly among HD, PD patients, and healthy controls (p > 0.05), but BIA parameters were quite different (p＜0.01). Bland-Altman analysis showed that in healthy volunteers, all equations showed good agreement with DXA measured. For dialysis patients, the FFM predictions of different equations showed differences between HD and PD patients, and the equations seemed more applicable for HD patients.Conclusion The equations developed by healthy subjects might be not appropriate for dialysis patients, especially peritoneal dialysis patients. It is recommended to develop a specific BIA equation from dialysis population.