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Abstract Fractional flow reserve (FFR) has become the gold standard for evaluating coronary lesion-specific ischemia. However, FFR is an invasive method that may cause possible complications in the coronary artery and requires expensive equipment, which limits its use. Promising noninvasive diagnostic methods, such as computed tomography angiography–derived FFR (CT-FFR) and the quantitative flow ratio (QFR), have been proposed. In this study, we evaluated the diagnostic performance of the QFR and CT-FFR in predicting coronary lesion-specific ischemia, with the FFR serving as the reference standard. Patients with suspected or known coronary artery disease who underwent coronary CT angiography revealing 30–90% diameter stenosis in the main coronary artery (≥ 2.0 mm reference diameter) were enrolled. The FFR was measured during invasive coronary angiography (within 15 days after coronary CT angiography). An FFR ≤ 0.8 was the reference standard for coronary lesion-specific ischemia. A total of 103 vessels from 92 consecutive patients (aged 59.8 ± 9.2 years; 60.9% were men) were evaluated. The diagnostic performance of a QFR ≤ 0.80 for predicting coronary lesion-specific ischemia demonstrated good diagnostic accuracy, sensitivity, and specificity (92.2%, 87.2%, and 96.4%, respectively), with an area under the receiver operating characteristic curve (AUC) of 0.987 (P

Abstract Disruptions in energy homeostasis can lead to diseases like obesity and diabetes, affecting millions of people each year. Tanycytes, the adult stem cells in the hypothalamus, play crucial roles in assisting hypothalamic neurons in maintaining energy balance. Although tanycytes have been extensively studied in rodents, our understanding of human tanycytes remains limited. In this study, we utilized single-cell transcriptomics data to explore the heterogeneity of human embryonic tanycytes, investigate their gene regulatory networks, analyze their intercellular communication, and examine their developmental trajectory. Our analysis revealed the presence of two clusters of β tanycytes and three clusters of α tanycytes in our dataset. Surprisingly, human embryonic tanycytes displayed significant similarities to mouse tanycytes in terms of marker gene expression and transcription factor activities. Trajectory analysis indicated that α tanycytes were the first to be generated, giving rise to β tanycytes in a dorsal–ventral direction along the third ventricle. Furthermore, our CellChat analyses demonstrated that tanycytes generated earlier along the developmental lineages exhibited increased intercellular communication compared to those generated later. In summary, we have thoroughly characterized the heterogeneity of human embryonic tanycytes from various angles. We are confident that our findings will serve as a foundation for future research on human tanycytes.

Abstract The precise calculation and evaluation of the in-situ rock stress tensor is a crucial factor in addressing the major challenges related to subsurface engineering applications and earth science research. To improve the accuracy of in-situ stress measurement and prediction, an improved overcoring technique involving a measurement circuit, temperature compensation, and calculation method is presented for accurately measuring the in-situ rock stress tensor. Furthermore, an embedded grey BP neural network (GM–BPNN) model is established for predicting in-situ rock stress values. The results indicate that the improved overcoring technique has significantly improved the stress measurement accuracy, and a large number of valuable stress data obtained from many mines have proved the testing performance of this technique. Moreover, the mean relative errors of the prediction results of GM(0, 1) for the three principal stresses all reach 6–30%, and the accuracy of the model fails to meet the requirements. The average relative errors of the prediction results of the BPNN model are all less than 10%, and the model accuracy meets the requirements and has sufficient credibility. Compared with the GM and BPNN models, the embedded GM–BPNN model produces the best results, with mean relative errors of 0.0001–4.8338%. The embedded GM–BPNN model fully utilizes the characteristics of grey theory and BP neural network, which require a small sample size, weaken the randomness of the original data, and gradually approach the accuracy of the model, making it particularly suitable for situations with limited stress data.

Abstract Colorectal cancer (CRC) arises via the progressive accumulation of dysregulation in key genes including oncogenes and tumor-suppressor genes. Prostaglandin-endoperoxide synthase 2 (PTGS2, also called COX2) acts as an oncogenic driver in CRC. Here, we explored the upstream transcription factors (TFs) responsible for elevating PTGS2 expression in CRC cells. The results showed that PTGS2 silencing repressed cell growth, migration and invasion in HCT116 and SW480 CRC cells. The two fragments (499–981 bp) and (1053–1434 bp) were confirmed as the core TF binding profiles of the PTGS2 promoter. PTGS2 expression positively correlated with RUNX1 level in colon adenocarcinoma (COAD) samples using the TCGA-COAD dataset. Furthermore, RUNX1 acted as a positive regulator of PTGS2 expression by promoting transcriptional activation of the PTGS2 promoter via the 1086–1096 bp binding motif. In conclusion, our study demonstrates that PTGS2 upregulation induced by the TF RUNX1 promotes CRC cell growth, migration and invasion, providing an increased rationale for the use of PTGS2 inhibitors in CRC prevention and treatment.

Abstract Mounting data hints that the gut microbiota's role may be pivotal in understanding the emergence of psoriasis. However, discerning a direct causal link is yet elusive. In this exploration, we adopted a Mendelian randomization (MR) strategy to probe the prospective causal interplay between the gut's microbial landscape and the predisposition to psoriasis. Genetic markers acting as instrumental variables for gut microbiota were extrapolated from a genome-wide association study (GWAS) encompassing 18,340 individuals. A separate GWAS yielded summary data for psoriasis, which covered 337,159 patients and 433,201 control subjects. The primary analysis hinged on inverse variance weighting (IVW). Additional methods like the weighted median approach and MR-Egger regression were employed to validate the integrity of our findings. Intriguing correlations emerged between psoriasis risk and eight specific bacterial traits. To illustrate: Mollicutes presented an odds ratio (OR) of 1.003 with a 95% confidence interval (CI) spanning 1.001–1.005 (p = 0.016), while the family. Victivallaceae revealed an OR of 0.998 with CI values between 0.997 and 0.999 (p = 0.023). Eubacterium (coprostanoligenes group) revealed an OR of 0.997 with CI values between 0.994 and 0.999 (p = 0.027). Eubacterium (fissicatena group) revealed an OR of 0.997 with CI values between 0.996 and 0.999 (p = 0.005). Holdemania revealed an OR of 1.001 with CI values 1–1.003 (p = 0.034). Lachnospiraceae (NK4A136 group) revealed an OR of 0.997 with CI values between 0.995 and 0.999 (p = 0.046). Lactococcus revealed an OR of 0.998 with CI values between 0.996 and 0.999 (p = 0.008). Tenericutes revealed an OR of 1.003 with CI values between 1.001 and 1.006 (p = 0.016). Sensitivity analysis for these bacterial features yielded congruent outcomes, reinforcing statistically significant ties between the eight bacterial entities and psoriasis. This comprehensive probe underscores emerging evidence pointing towards a plausible causal nexus between diverse gut microbiota and the onset of psoriasis. It beckons further research to unravel the intricacies of how the gut's microbial constituents might sway psoriasis's pathogenesis.

Abstract The stress measurements determined by both the overcoring (OC) and hydraulic fracturing (HF) methods in the Shuichang iron mine and Sanshandao gold mine were compared and evaluated, respectively. The results indicate that the independent OC and HF data in the two mines reveal the same dominant faulting stress regime. The σ H orientations derived from the OC and HF methods in the Shuichang iron mine are dominantly oriented in the N81.1°W–N89.4°W and N77.0°E–N88.0°E, respectively, and the σ H orientations yielded from the OC and HF techniques in the Sanshandao gold mine are predominantly in the N30°W–N90°W and N55.5°W–N60.4°W, respectively; hence, the σ H orientations obtained by the two different methods in the two mines are comparatively similar. In addition, the shapes of the probability density diagrams using an improved Bayesian regression approach of the three principal stresses measured by the OC and HF methods in the same mine are quite similar, and all the obtained Kolmogorov–Smirnov test p-values are larger than the selected significance level of 0.01, indicating that the stress data interpreted by the two methods approximately follow the same distribution law. Thus, the performance of the two techniques and the reliability of the measured data are satisfactory.

Abstract Observational studies have previously reported an association between depression and certain female reproductive disorders. However, the causal relationships between depression and different types of female reproductive disorders remain unclear in terms of direction and magnitude. We conducted a comprehensive investigation using a two-sample bi-directional Mendelian randomization analysis, incorporating publicly available GWAS summary statistics. Our aim was to establish a causal relationship between genetically predicted depression and the risk of various female reproductive pathological conditions, such as ovarian dysfunction, polycystic ovary syndrome(PCOS), ovarian cysts, abnormal uterine and vaginal bleeding(AUB), endometriosis, leiomyoma of the uterus, female infertility, spontaneous abortion, eclampsia, pregnancy hypertension, gestational diabetes, excessive vomiting in pregnancy, cervical cancer, and uterine/endometrial cancer. We analyzed a substantial sample size, ranging from 111,831 to 210,870 individuals, and employed robust statistical methods, including inverse variance weighted, MR-Egger, weighted median, and MR-PRESSO, to estimate causal effects. Sensitivity analyses, such as Cochran's Q test, MR-Egger intercept test, MR-PRESSO, leave-one-out analysis, and funnel plots, were also conducted to ensure the validity of our results. Furthermore, risk factor analyses were performed to investigate potential mediators associated with these observed relationships. Our results demonstrated that genetic predisposition to depression or dysthymia was associated with an increased risk of developing PCOS (OR = 1.43, 95% CI 1.28–1.59; P = 6.66 × 10–11), ovarian cysts (OR = 1.36, 95% CI 1.20–1.55; P = 1.57 × 10–6), AUB (OR = 1.41, 95% CI 1.20–1.66; P = 3.01 × 10–5), and endometriosis (OR = 1.43, 95% CI 1.27–1.70; P = 2.21 × 10–7) after Bonferroni correction, but no evidence for reverse causality. Our study did not find any evidence supporting a causal or reverse causal relationship between depression/dysthymia and other types of female reproductive disorders. In summary, our study provides evidence for a causal relationship between genetically predicted depression and specific types of female reproductive disorders. Our findings emphasize the importance of depression management in the prevention and treatment of female reproductive disorders, notably including PCOS, ovarian cysts, AUB, and endometriosis.

Abstract To evaluate whether single acetabular column can be reserved and the effect of reconstruction with femoral head plus total hip replacement (THR) for primary malignant peri-acetabulum tumors. From 2007 to 2015, nineteen patients with primary malignant peri-acetabulum tumors were enrolled. All cases underwent single column resection with clear surgical margins. Ten of the 19 tumor’s resections were assisted by computer navigation. Femoral heads were applied to reconstruct anterior or posterior column defects; THR was used for joint reconstruction. The surgical safety, oncologic outcome and prosthesis survivorship and function were evaluated by regular follow-up. The average follow-up period was 65.9 months. Surgical margins contained wide resection in 12 cases and marginal resection in 7 cases. One patient with Ewing's sarcoma died 14 months postoperative due to lung metastasis. One case with chondrosarcoma had recurrence. One prosthesis was removed due to infection. The average MusculoSkeletal Tumor Society (MSTS) function score was 83.7%. Due to the relative small number of cases, there was no significant difference in the recurrence rate and prosthesis failure rate between the navigation group and non-navigation group. Single column resection and reconstruction with femoral head autograft plus THR is an effective, safe method with less complication rate and better functional outcome for patients with peri-acetabular tumors.

Abstract Chinese sturgeon Dmrt gene family was identified and characterized for the first time. A total of 5 putative Dmrt genes were identified. The gene structure, conserved protein domain and the phylogenetic relationship of Dmrt gene family were systematically analyzed. The expressed profile of Chinese sturgeon Dmrt genes in gonad, pituitary and hypothalamus in the male and female were investigated. The results indicated that the accumulation of Dmrt genes was involved in different tissues, and the expression profile also differed among each Dmrt genes. ASDmrt1A, ASDmrt2, ASDmrt3, and ASDmrtA1 were highly expressed in the testis in comparison with other tissue. This result showed that ASDmrt1A, ASDmrt2, ASDmrt3, and ASDmrtA1 played an important role in the development of testicle, and may be useful tool in distinguishing between male and female of Chinese sturgeon. Our study will provide a basis for additional analyses of Chinese sturgeon Dmrt genes. This systematic analysis provided a foundation for further functional characterization of Dmrt genes with an aim of study of Chinese sturgeon Dmrt gene family.

Abstract Correction of leg length discrepancy (LLD) in skeletally mature patients with osteosarcoma was rarely reported and quite challenging. This study aimed to propose a treatment strategy of staged lengthening and reconstruction with a standard static prosthesis to address LLD and restore limb function. It also evaluated the effectiveness of the strategy in terms of leg lengthening, functional outcomes, and complications. The strategy for lengthening included three stages. In stage 1, the previous prosthesis was removed and an external fixator with a temporary rod-cement spacer was placed. In this stage, the external fixator was used to lengthen the limb to the appropriate length. In stage 2, the external fixator was removed and the old rod-cement spacer was replaced with a new one. In stage 3, the rod-cement spacer was removed and the standard static prosthesis was planted. Nine skeletally mature distal femoral osteosarcoma patients with unacceptable LLD were treated in our institution from 2019 to 2021. We performed a chart review on nine patients for the clinical and radiographic assessment of functional outcomes, LLD, and complications. The mean (range) leg lengthening was 7.3 cm (3.6–15.6). The mean (range) LLD of the lower limbs decreased from 7.6 cm (4.1–14.2) before the lengthening to 0.3 cm (− 0.3 to 2.1) at the final follow-up with statistical significance (P = 0.000). The mean (range) Musculoskeletal Tumor Society score improved from 30.3% (16.7%–53.3%) before the lengthening to 96.3% (86.7%–100%) at the final follow-up with statistical significance (P = 0.000). Three patients (33.3%) had a minor complication; none needed additional surgical intervention. In the short term, the current staged lengthening and reconstruction with standard static prosthesis provided satisfactory functional outcomes and LLD correction with few complications. The long-term effects of this method need further exploration.

Abstract Wearable Internet of Things (WIoT) and Artificial Intelligence (AI) are rapidly emerging technologies for healthcare. These technologies enable seamless data collection and precise analysis toward fast, resource-abundant, and personalized patient care. However, conventional machine learning workflow requires data to be transferred to the remote cloud server, which leads to significant privacy concerns. To tackle this problem, researchers have proposed federated learning, where end-point users collaboratively learn a shared model without sharing local data. However, data heterogeneity, i.e., variations in data distributions within a client (intra-client) or across clients (inter-client), degrades the performance of federated learning. Existing state-of-the-art methods mainly consider inter-client data heterogeneity, whereas intra-client variations have not received much attention. To address intra-client variations in federated learning, we propose a federated clustered multi-domain learning algorithm based on ClusterGAN, multi-domain learning, and graph neural networks. We applied the proposed algorithm to a case study on stress-level prediction, and our proposed algorithm outperforms two state-of-the-art methods by 4.4% in accuracy and 0.06 in the F1 score. In addition, we demonstrate the effectiveness of the proposed algorithm by investigating variants of its different modules.

Abstract To investigate the biomechanical properties of posterior cruciate ligament avulsion fractures of the tibia fixed using four different methods, including triple tibial channel net suture fixation. In 40 porcine knees, a standardized bony avulsion of the posterior cruciate ligament was generated. Double tibial bone channel suture fixation was performed in group A, double-head hollow compression screw fixation was performed in group B, triple tibial bone channel net suture fixation was performed in group C, and cortical suspension EndoButton fixation was performed in group D. The constructs were cyclically loaded 500 times (10 to 100 N) to measure the initial displacement and stiffness values. Subsequently, loading to failure was performed, and the yield load and peak load were measured. The results were analysed by one-way ANOVA, with significance set at P

Abstract Group A streptococcal strains potentially acquire new M protein gene types through genetic recombination (emm switching). To detect such variants, we screened 12,596 invasive GAS genomes for strains of differing emm types that shared the same multilocus sequence type (ST). Through this screening we detected a variant consisting of 16 serum opacity factor (SOF)-positive, emm pattern E, emm82 isolates that were ST36, previously only associated with SOF-negative, emm pattern A, emm12. The 16 emm82/ST36 isolates were closely interrelated (pairwise SNP distance of 0–43), and shared the same emm82-containing recombinational fragment. emm82/ST36 isolates carried the sof12 structural gene, however the sof12 indel characteristic of emm12 strains was corrected to confer the SOF-positive phenotype. Five independent emm82/ST36 invasive case isolates comprised two sets of genetically indistinguishable strains. The emm82/ST36 isolates were primarily macrolide resistant (12/16 isolates), displayed at least 4 different core genomic arrangements, and carried 11 different combinations of virulence and resistance determinants. Phylogenetic analysis revealed that emm82/ST36 was within a minor (non-clade 1) portion of ST36 that featured almost all ST36 antibiotic resistance. This work documents emergence of a rapidly diversifying variant that is the first confirmed example of an emm pattern A strain switched to a pattern E strain.

Abstract Neutrophil extracellular traps (NETs) have been categorized as a form of inflammatory cell death mode of neutrophils (NETosis) involved in natural immunity and the regulation of adaptive immunity. More and more studies revealed the ability of NETs to reshape the tumor immune microenvironment (TIME) by limiting antitumor effector cells, which may impair the efficacy of immunotherapy. To explore whether NETs-related genes make vital impacts on Colon carcinoma (COAD), we have carried out a systematic analysis and showed several findings in the present work. First, we obtained the patient's data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) dataset, aiming to detect two NETs-associated subtypes by consensus clustering. For the purpose of annotating the roles of NETs-related pathways, gene ontology enrichment analyses were adopted. Next, we constructed a 6 novel NETs-related genes score using the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression model. We found that the NETs risk score was notably upregulated in COAD patient samples, and its levels were notably correlated with tumor clinicopathological and immune traits. Then, according to NETs-associated molecular subtypes and the risk signature, this study compared immune cell infiltration calculated through the estimate, CIBERSORT, TIMER, ssGSEA algorithms, tumor immune dysfunction, as well as exclusion (TIDE). Furthermore, we confirm that MPO(myeloperoxidase) was significantly upregulated in COAD patient samples, and its levels were significantly linked to tumor malignancy and clinic outcome. Moreover, multiplex immunohistochemistry (mIHC) spatial analysis confirmed that MPO was closely related to Treg and PD-1 + Treg in spatial location which suggested MPO may paly an important role in TIME formation. Altogether, the obtained results indicated that a six NETs-related genes prognostic signature was conducive to estimating the prognosis and response of chemo-/immuno-therapy of COAD patients.

Abstract Retinal ischemia‒reperfusion (I/R) injury can cause significant damage to human retinal neurons, greatly compromising their functions. Existing interventions have been proven to have little effect. Ferroptosis is a newly discovered type of programmed cell death that has been found to be involved in the process of ischemia‒reperfusion in multiple organs throughout the body. Studies have shown that it is also present in retinal ischemia‒reperfusion injury. A rat model of retinal ischemia‒reperfusion injury was constructed and treated with deferoxamine. In this study, we found the accumulation of Fe2+, reactive oxygen species (ROS), malondialdehyde (MDA), and the consumption of glutathione (GSH) via ELISA testing; increased expression of transferrin; and decreased expression of ferritin, SLC7A11, and GPX4 via Western blotting (WB) and real-time PCR testing. Structural signs of ferroptosis (mitochondrial shrinkage) were observed across multiple cell types, including retinal ganglion cells (RGCs), photoreceptor cells, and pigment epithelial cells. Changes in visual function were detected by F-VEP and ERG. The results showed that iron and oxidative stress were increased in the retinal ischemia‒reperfusion injury model, resulting in ferroptosis and tissue damage. Deferoxamine protects the structural and functional soundness of the retina by inhibiting ferroptosis through the simultaneous inhibition of hemochromatosis, the initiation of transferrin, and the degradation of ferritin and activating the antioxidant capacity of the System Xc-GSH-GPX4 pathway.

Abstract Phosphofructokinase, platelet (PFKP) is a rate-limiting enzyme of glycolysis that plays a decisive role in various human physio-pathological processes. PFKP has been reported to have multiple functions in different cancer types, including lung cancer and breast cancer. However, no systematic pancancer analysis of PFKP has been performed; this type of analysis could elucidate the clinical value of PFKP in terms of diagnosis, prognosis, drug sensitivity, and immunological correlation. Systematic bioinformation analysis of PFKP was performed based on several public datasets, including The Cancer Genome Atlas (TCGA), Cancer Cell Line Encyclopedia (CCLE), Genotype-Tissue Expression Project (GTEx), and Human Protein Atlas (HPA). Prospective carcinogenesis of PFKP across cancers was estimated by expression analysis, effect on patient prognosis, diagnosis significance evaluation, and immunity regulation estimation. Then, pancancer functional enrichment of PFKP was also assessed through its effect on the signaling score and gene expression profile. Finally, upstream expression regulation of PFKP was explored by promoter DNA methylation and transcription factor (TF) prediction. Our analysis revealed that high expression of PFKP was found in most cancer types. Additionally, a high level of PFKP displayed a significant correlation with poor prognosis in patients across cancers. The diagnostic value of PFKP was performed based on its positive correlation with programmed cell death-ligand 1 (PD-L1). We also found an obvious immune-regulating effect of PFKP in most cancer types. PFKP also had a strong negative correlation with several cancer drugs. Finally, ectopic expression of PFKP may depend on DNA methylation and several predicated transcription factors, including the KLF (KLF transcription factor) and Sp (Sp transcription factor) families. This pancancer analysis revealed that a high expression level of PFKP might be a useful biomarker and predictor in most cancer types. Additionally, the performance of PFKP across cancers also suggested its meaningful role in cancer immunity regulation, even in immunotherapy and drug resistance. Overall, PFKP might be explored as an auxiliary monitor for pancancer early prognosis and diagnosis.

Abstract UQCRFS1 has been reported to be highly expressed in gastric and breast cancer, but the mechanism remains unclear. The prognosis and biological functions of UQCRFS1 in ovarian cancer (OC) have not been evaluated. The expression of UQCRFS1 in EOC was detected by GEPIA and HPA websites, and the prognosis value was investigated by Kaplan–Meier analysis. Then the correlation between the UQCRFS1 gene and tumor-related signature were analyzed by Spearman correlation analysis and rank sum test. Subsequently, the expression of the UQCRFS1 gene in four ovarian cancer cell lines was detected. A2780 and OVCAR8 with the highest expression of UQCRFS1 were selected in the following biological experiments. Cell proliferation was detected by CCK8 assay, cell cycle and apoptosis were determined by flow cytometry, reactive oxygen species (ROS) production was detected by DCFH-DA, DNA damage gene mRNA expression was analyzed by RT-PCR, and AKT/mTOR pathway protein expression were also examined by western blot after siRNA transfection. We found that UQCRFS1 was high-expression in EOC and associated with poor prognosis. Spearman correlation analysis revealed that the high expression of UQCRFS1 is associated with the cell cycle, apoptosis, oxidative phosphorylation, and DNA damage. Further studies found that knockdown of UQCRFS1 cells reduced cell proliferation, cell cycle arrest at the G1 phase, increased proportion of apoptosis, ROS production, and expression of DNA damage genes, inhibited ATK/mTOR pathway. The study suggested that UQCRFS1 may be a candidated target for diagnosis and treatments in OC.

Abstract Chronic inflammation and dyslipidemia are important risk factors in developing atherosclerotic cardiovascular disease, such as coronary heart disease. Acute coronary syndrome (ACS) is one of the most dangerous syndromes in coronary heart disease. Type 2 diabetes mellitus (T2DM) is considered equal to coronary heart disease owing to the high cardiac risk induced by chronic inflammation and dyslipidemia. The neutrophil to high-density lipoprotein cholesterol ratio (NHR) is a novel and straightforward marker that reflects inflammation and lipid metabolic disorder. However, few studies have been on the role of NHR in assessing the risk of ACS in T2DM patients. Here we analyzed NHR level in ACS patients with T2DM, exploring its predictive and diagnostic values. 211 hospitalized ACS patients with T2DM were recruited as the case group, and 168 hospitalized T2DM patients as the control group (all patients collected from 6/2020 to 12/2021 in Xiangya Hospital). Biochemical test results and echocardiograms, as well as demographic information such as age, BMI, diabetes mellitus, smoking, drinking, and history of hypertension, were recorded. Frequencies, percentages, means, and standard deviations were used to describe the data. The shapiro–Wilk test was used to assess the normality of the data. Normally distributed data were compared using the independent sample T-test, and non-normally distributed data were compared using Mann–Whitney U test. Correlation analysis was performed using the Spearman rank correlation test, and receiver operating characteristic (ROC) curve analysis and multivariable logistic regression analysis were performed by SPSS version 24.0 (SPSS Inc) and GraphPad Prism 9.0 (GraphPad Software Inc). p

Abstract In order to assess the effectiveness of the Special Antimicrobial Stewardship Campaign launched by Ministry of Health of China in 2011, this study focused on the effectiveness and trends in the clinical use of antimicrobial drugs in selected hospitals in Southern Sichuan, China. This study collected and analyzed antibiotic data from 9 hospitals in Southern Sichuanin 2010, 2015, and 2020, including the rate of antibiotic use, expense, the intensity of antibiotic use and antibiotic use during the type I incisions of perioperative period. After 10 years of continuous improvement, the utilization rate of antibiotics in outpatients of the 9 hospitals continued to decline and was controlled below 20% by 2020, while the utilization rate in inpatients also significantly decreased, most were controlled within 60%. The use intensity of antibiotics (DDD (defined daily doses) per 100 bed-days) decreased from an average of 79.95 in 2010 to 37.96 in 2020. The prophylactic use of antibiotics decreased significantly in type I incision. The proportion of use within 30 min–1 h before operation was significantly increased. After the special rectification and sustained development of the clinical application of antibiotics, the relevant indicators of antibiotics tend to be stable, indicating that this Administration of antimicrobial drugs is conducive to improving the level of rational clinical application of antibiotics.

Abstract End-stage renal disease (ESRD) results in hippocampal volume reduction, but the hippocampal subfields atrophy patterns cannot be identified. We explored the volumes and asymmetry of the hippocampal subfields and their relationships with memory function and biochemical changes. Hippocampal global and subfields volumes were derived from 33 ESRD patients and 46 healthy controls (HCs) from structural MRI. We compared the volume and asymmetric index of each subfield, with receiver operating characteristic curve analysis to evaluate the differentiation between ESRD and HCs. The relations of hippocampal subfield volumes with memory performance and biochemical data were investigated in ESRD group. ESRD patients had smaller hippocampal subfield volumes, mainly in the left CA1 body, left fimbria, right molecular layer head, right molecular layer body and right HATA. The right molecular layer body exhibited the highest accuracy for differentiating ESRD from HCs, with a sensitivity of 80.43% and specificity of 72.73%. Worse learning process (r = 0.414, p = 0.032), immediate recall (r = 0.396, p = 0.041) and delayed recall (r = 0.482, p = 0.011) was associated with left fimbria atrophy. The left fimbria volume was positively correlated with Hb (r = 0.388, p = 0.05); the left CA1 body volume was negatively correlated with Urea (r = − 0.469, p = 0.016). ESRD patients showed global and hippocampal subfields atrophy. Left fimbria atrophy was related to memory function. Anemia and Urea level may be associated with the atrophy of left fimbria and CA1 body, respectively.

Abstract Euryodendron excelsum H.T. Chang is a rare and endangered woody plant endemic to China. It is very important to conserve and propagate this species from extinction. In this study, leaves and petioles from the axillary shoots in vitro were used as explants to culture on the different plant growth regulator (PGR) woody plant medium (WPM) and establish an efficient shoot proliferation and plant regeneration system. WPM supplemented with 1.0 mg/L 2,4-D induced callus dedifferentiated into buds and somatic embryos on various media,including PGR-free WPM. However, only adventitious shoots formed on WPM with 1.0 mg/L of cytokinins such as 6-benzyladenine (BA), kinetin (KIN) or thidiazuron (TDZ). When another cytokinin, zeatin, was used, somatic embryos were induced directly from From cut surface of these explants. Adventitious roots could be induced from both explants on WPM with 1.0 mg/L α-naphthaleneacetic acid (NAA). Somatic embryos cultured in PGR-free WPM or WPM with 0.2 mg/L NAA developed roots. Plantlets derived from somatic embryos were transferred to a peat: sand (1:1, v/v) substrate, and showed survival rates of 64.3% at 30 days and 54.6% at 90 days. Callus clumps with adventitious shoot buds that were transferred to WPM containing 1.0 mg/L BA and 0.2 mg/L NAA generated a mean 3.3 multiple shoots. Callus-derived shoots regenerated and rooted successfully (100%) on agar-free vermiculite-based WPM with 0.5 μM NAA after 30 d. Plantlets transplanted to peat soil: vermiculite (1:1, v/v) displayed the highest survival (96.7%) after three months.

Abstract Reductions in the quality and yield of crops continuously produced in the same location for many years due to annual increases in soil-borne pathogens. Environmentally-friendly methods are needed to produce vegetables sustainably and cost effectively under protective cover. We investigated the impact of biofertilizers on cucumber growth and yield, and changes to populations of soil microorganisms in response to biofertilizer treatments applied to substrate or soil. We observed that some biofertilizers significantly increased cucumber growth and decreased soil-borne pathogens in soil and substrate. Rhizosphere microbial communities in soil and substrate responded differently to different biofertilizers, which also led to significant differences in microbial diversity and taxonomic structure at different times in the growing season. Biofertilizers increase the prospects of re-using substrate for continuously producing high-quality crops cost-effectively from the same soil each year while at the same time controlling soil-borne disease.

Abstract The Pacific saury (Cololabis saira) is one of the most commercially important pelagic fishes in Asia–Pacific countries. The oceanographic environment, especially the Oyashio Current, significantly affects the distribution of Pacific saury, and may lead to variations in their migration route and the formation of fishing grounds in Japanese coastal region and the high seas. In this study, six oceanographic factors, sea surface temperature (SST), sea surface chlorophyll-a concentration (SSC), sea surface salinity (SSS), sea surface height (SSH), mixed layer depth (MLD), and eddy kinetic energy (EKE), were associated with the monthly catch per unit effort 1 (monthly CPUE1, ton/vessel) and the monthly CPUE2 (ton/day) of Pacific saury from Chinese fishing vessels during the optimal fishing periods (September–November) in 2014–2017. The gradient forest analysis showed that the performance of monthly CPUE1 was higher than monthly CPUE2 and SST was the most important oceanographic factor influencing monthly CPUE1, followed by EKE. The generalized additive model indicated that SST, SSH, and EKE negatively affected monthly CPUE1, whereas SSC, SSS, and MLD induced dome-shaped increases in monthly CPUE1. The distributions of fishing locations are likely to form along Offshore Oyashio current and meanders, especially in October and November. Synchronous trends in the relationship between the intrusion area of the Oyashio and relative abundance variation index suggest that an increase in the intrusion area of the Oyashio causes more Pacific saury to migrate to the Japanese coastal region, and vice versa. These findings extend our understanding of the effects of the oceanographic environment on Pacific saury.

Abstract The purpose of this study was to compare the differences of V-pattern exotropia in craniosynostosis and normal children. 39 children were included in this study, 19 craniosynostosis and 20 children in control group. They underwent comprehensive ocular examinations and received strabismus surgery. The extraocular muscle samples were analysed. Compared with the control group, craniosynostosis group had larger deviation in primary and up gaze, larger V pattern, and more severe inferior oblique overaction. For 20–40, and 50–60 prism diopter exotropia, the lateral recession in the craniosynostosis group was larger than that in the control group, 7.13 ± 0.44 mm vs 6.71 ± 0.47 mm, 8.90 ± 0.21 mm vs 7.75 ± 0.46 mm (p = 0.025, 0.000). The anterior transposition of craniosynostosis group was more anterior than that of control group, posterior 1.03 ± 1.24 vs 2.68 ± 0.94 mm (p = 0.000). Compared with the control group, the extraocular muscle abnormality in craniosynostosis was significant, 32% vs 5% (p = 0.031). There were 40 proteins in craniosynostosis group, which were different from those in control group. A larger V pattern and larger deviation is common in craniosynostosis children. For the same PD of deviation, it usually needs more recession in craniosynostosis because of the thinner and weaker extraocular muscles. Collagen related proteins were increased in craniosynostosis, and decreased contraction related protein tropomodulin might play key role for the weakness of EOMs.

Abstract The comprehensive water quality index (CWQI) reflects the comprehensive pollution status of rivers through mathematical statistics of several water quality indicators. Using computational mathematical simulations, high-confidence CWQI predictions can be obtained based on limited water quality monitoring samples. At present, most of the CWQI reported in the literature are based on conventional indicators such as nitrogen and phosphorus levels, and do not include the petroleum hydrocarbons levels. This article takes a typical river in eastern China as an example, based on the 1-year monitoring at 20 sampling sets, a CWQI containing five factors, TN, NH4 +-N, TP, ∑n-Alks, and ∑PAHs was established, and further predicted by a Monte-Carlo model. The predicted CWQI for each monitoring section is above 0.7, indicating that most of the monitoring sections are moderately polluted, and some sections are seriously polluted. The Spearman rank correlation coefficient analysis results show that TN, ∑PAHs, and ∑n-Alks are the main factors influencing the water quality, especially the petroleum hydrocarbons have a significant impact on the middle and lower reaches due to shipping. In the future, more attention should be paid to petroleum hydrocarbon organic pollutants in the water quality evaluation of similar rivers.

Abstract To better implement the Strategy of Rural Revitalization, it is essential to characterize the rural settlements and understand their roles in the socio-environmental interactive system. This paper is hence aimed at achieving such a study using different spatial analysis such as kernel density and spatial autocorrelation (SA) and modeling approaches, e.g., simple and multiple linear regression analyses taking Jiangxi, a province in China as an example. Remote sensing, topographic and socioeconomic data were employed for this purpose. Through these analyses, it is found that the rural settlements in the study area appear to have a spatial distribution pattern of “dense north and sparse south” as an “F” type, and are quantitatively characterized as low elevations, flat terrain, high river and road densities, rich cultivated land resources and susceptible to the impact of urban radiation with a R2 of 0.520–0.748. Based on this understanding, a new inequality evaluation indicator of rural development, i.e., socio-environmental evaluation index (SEI), was developed. Areas with SEI lower than 0.40 should be given a priority to implement the revitalization strategy in the province. This index can also be extended to study of the imbalance of rural development in other regions and countries.

Abstract This paper evaluates the potential usage of graphene/crosslinked polyethylene (graphene/XLPE) as the insulating material for high voltage direct current (HVDC) cables. Thermal, mechanical and electrical properties of blends with/without graphene were evaluated by differential scanning calorimetry (DSC), tensile strength, DC conductivity, space charge measurements and water tree aging test. The results indicate that 0.007–0.008% weight amount of graphene can improve the mechanical and electrical insulation properties of XLPE blends, namely higher tensile/yield strength, improved space charge distribution, and shorter/fewer water tree branches. The improvements mainly attribute to the high stiffness of graphene, deep traps introduced by the interaction zones of graphene and XLPE, and the blockage effect of graphene within XLPE. For thermal performance of XLPE blends, graphene nano-fillers have but limited improvement. The crystallinity of the blends barely changes with the addition of graphene. However, the crosslinking degree increases as the additive-like amounts of graphene doped. The above findings provide a guide for tailoring lightweight XLPE materials with excellent mechanical and electrical performances by doping them with a small amount of graphene.

Abstract Programmed cell death ligend-1 (PD-L1) expression by immunohistochemistry (IHC) assays is a predictive marker of anti-PD-1/PD-L1 therapy response. With the popularity of anti-PD-1/PD-L1 inhibitor drugs, quantitative assessment of PD-L1 expression becomes a new labor for pathologists. Manually counting the PD-L1 positive stained tumor cells is an obviously subjective and time-consuming process. In this paper, we developed a new computer aided Automated Tumor Proportion Scoring System (ATPSS) to determine the comparability of image analysis with pathologist scores. A three-stage process was performed using both image processing and deep learning techniques to mimic the actual diagnostic flow of the pathologists. We conducted a multi-reader multi-case study to evaluate the agreement between pathologists and ATPSS. Fifty-one surgically resected lung squamous cell carcinoma were prepared and stained using the Dako PD-L1 (22C3) assay, and six pathologists with different experience levels were involved in this study. The TPS predicted by the proposed model had high and statistically significant correlation with sub-specialty pathologists’ scores with Mean Absolute Error (MAE) of 8.65 (95% confidence interval (CI): 6.42–10.90) and Pearson Correlation Coefficient (PCC) of 0.9436 ( $$p < 0.001$$ p < 0.001 ), and the performance on PD-L1 positive cases achieved by our method surpassed that of non-subspecialty and trainee pathologists. Those experimental results indicate that the proposed automated system can be a powerful tool to improve the PD-L1 TPS assessment of pathologists.

Abstract To contribute to the understanding of the aetiology and pathogenesis of Meige syndrome, the metabolic networks of patients with Meige syndrome were investigated using 18F-fluoro-D-glucose positron emission tomography (18F-FDG-PET) imaging of cerebral glucose metabolism. Fifty right-handed and unmedicated primary Meige syndrome patients enrolled between September 2017 and September 2020 at the Department of Neurosurgery, Peking University People’s Hospital, and 50 age- and sex-matched healthy control subjects participated in the study. Metabolic connectivity and graph theory analysis were used to investigate metabolic network differences based on 18F-FDG-PET images. Glucose hypometabolism was detected in the left internal globus pallidus and parietal lobe, right frontal lobe and postcentral gyrus, and bilateral thalamus and cerebellum of patients with Meige syndrome. Clustering coefficients (Cps) (density threshold: 16–28%; P

Abstract Sandalwood (Santalum album L.) is highly valued for its fragrant heartwood and extracted oil. Santalols, which are the main components of that oil, are terpenoids, and these are biosynthesized via the mevalonic acid (MVA) pathway. Mevalonate kinase (MK) and phosphomevalonate kinase (PMK) are key enzymes in the MVA pathway. Little is known about the genes that encode MK and PMK in S. album or the mechanism that regulates their expression. To isolate and identify the functional genes involved in santalol biosynthesis in S. album, an MK gene designated as SaMK, and a PMK gene designated as SaPMK, were cloned from S. album. The sequences of these genes were analyzed. A bioinformatics analysis was conducted to assess the homology of SaMK and SaPMK with MK and PMK genes from other plants. The subcellular localization of SaMK and SaPMK proteins was also investigated, as was the functional complementation of SaMK and SaPMK in yeast. Our results show that the full-length cDNA sequences of SaMK and SaPMK were 1409 bp and 1679 bp long, respectively. SaMK contained a 1381 bp open reading frame (ORF) encoding a polypeptide of 460 amino acids and SaPMK contained a 1527 bp ORF encoding a polypeptide of 508 amino acids. SaMK and SaPMK showed high homology with MK and PMK genes of other plant species. Functional complementation of SaMK in a MK-deficient mutant yeast strain YMR208W and SaPMK in a PMK-deficient mutant yeast strain YMR220W confirmed that cloned SaMK and SaPMK cDNA encode a functional MK and PMK, respectively, mediating MVA biosynthesis in yeast. An analysis of tissue expression patterns revealed that SaMK and SaPMK were constitutively expressed in all the tested tissues. SaMK was highly expressed in young leaves but weakly expressed in sapwood. SaPMK was highly expressed in roots and mature leaves, but weakly expressed in young leaves. Induction experiments with several elicitors showed that SaMK and SaPMK expression was upregulated by methyl jasmonate. These results will help to further study the role of MK and PMK genes during santalol biosynthesis in S. album.

Abstract The purpose of this study was to evaluate genome-wide DNA methylation changes in intestinal mucosa tissue of adult patients with Crohn's disease comprehensively. DNA methylation chip was used to analyze abnormal methylation sites among penetrating and non-penetrating intestinal mucosa tissue of Crohn's disease and normal intestinal mucosa tissue of healthy controls. Methylation abnormalities of different locus were verified by pyrosequencing and quantitative polymerase chain reaction. Differential DNA methylation sites were participated in the positive regulation of apoptosis and the positive regulation of IL-8 production and were enriched in signaling pathways related to inflammatory bowel disease and extracellular matrix receptor interaction signaling pathways. Correlation analysis showed that the methylation abnormalities of HLA-DRB1 (r = − 0.62, P

Abstract Site-directed mutagenesis for large plasmids is a difficult task that cannot easily be solved by the conventional methods used in many laboratories. In this study, we developed an effective method for Site-directed Mutagenesis for Large Plasmids (SMLP) based on a PCR technique. The SMLP method combines several effective approaches, including a high-efficiency DNA polymerase for the large DNA amplification, two independent PCR reactions and a fast recombinational ligation. Using this method, we have achieved a variety of mutants for the filamin A gene (7.9 kb) cloned in the pcDNA (5.4 kb) or the pLV-U6-CMV-EGFP (9.4 kb) plasmids, indicating that this method can be applied to site-directed mutagenesis for the plasmids up to 17.3 kb. We show that the SMLP method has a greater advantage than the conventional methods tested in this study, and this method can be applied to substitution, deletion, and insertion mutations for both large and small plasmids as well as the assembly of three fragments from PCR reactions. Altogether, the SMLP method is simple, effective, and beneficial to the laboratories that require completing the mutagenesis of large plasmids.

Abstract Self-reported skin discomfort is a common problem during pregnancy, but it is not clear whether skin barrier function is altered in the process. Few studies have described the skin barrier function during pregnancy. In this work, we used highly sensitive and high-resolution ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) to distinguish skin surface lipid (SSL) combined with multivariate analysis of lipids and metabolic changes to determine the relationship between SSL changes and skin physiology during pregnancy in order to better understand the skin condition of pregnant women. The results showed a significant reduction in the total lipid content in pregnant women. A total of 2270 lipids were detected, and the relative abundances of fatty acyls and glycerolipids were significantly reduced, while glycerophospholipids (GPs), sphingolipids, and saccharolipids was significantly increased in the pregnancy group. Multivariate data analysis indicated that 23 entities constituted the most important individual species responsible for the discrimination and phosphatidylcholine was the most abundant lipid in pregnancy group. In addition, compared to SSL profile of control group, it was observed that the average chain length of ceramides and fatty acids both decreased in SSL profile of pregnancy group. The main and most commonly affected pathway was that of GP pathways. These findings indicate that skin lipids are significantly altered in mid-pregnancy compared to the control group. Changes in ostrogen during pregnancy also make the skin more susceptible to inflammatory factors and lead to more fragile and susceptible skin, weakening the skin barrier along with the lipid alterations.

Abstract The purpose of this study was to evaluate the functional results, complications and related factors of prosthesis reconstruction after malignant tumor resection of primary proximal humeral, and also evaluate whether soft tissue reconstruction with mesh patch and anchors can improve clinical results. From 2002 to 2016, forty-one patients were enrolled in this study. The pathological diagnosis contained 27 cases of osteosarcoma, 7 cases of chondrosarcoma and other primary malignant bone tumors. Both mesh patch and anchors were used in the reconstruction of joint capsule and the surrounding soft tissues in 27 cases. The mean postoperative follow-up was 60.6 months. The average active abduction angle and passive abduction angle was 33.5 (5–71) degrees and 72.4 (52–104) degrees. The prosthetic humeral head displacement was over 2 cm in 5 cases (12.2%). The average MSTS score was 23.1. The overall 5-year survival rate of prosthesis was 88.2%. The length of osteotomy, whether preserving deltoid muscle, whether applying mesh patch and anchors had significant effects on the abduction angle of shoulder joint; the length of osteotomy, whether applying mesh patch and anchors had significant effects on the degree of upward displacement of prosthesis. The application of both mesh patch and anchors in prosthesis reconstruction achieved more stable result and better function of shoulder joint. To ensure the stability of shoulder joint and the firm wrapping of surrounding soft tissue are key factors affecting the postoperative function.

Abstract Sandalwood (Santalum album L.) is famous for its unique fragrance derived from the essential oil of heartwood, whose major components are santalols. To understand the mechanism underlying the biosynthesis of santalols, in this study, we cloned two related genes involved in the mevalonate pathway in S. album coding for acetyl-CoA C-acetyl transferase (AACT) and 3-hydroxy-3-methyglutary-CoA synthase (HMGS). These genes were characterized and functionally analyzed, and their expression profiles were also assessed. An AACT gene designated as SaAACT (GenBank accession No. MH018694) and a HMGS gene designated as SaHMGS (GenBank accession No. MH018695) were successfully cloned from S. album. The deduced SaAACT and SaHMGS proteins contain 415 and 470 amino acids, and the corresponding size of their open-reading frames is 1538 bp and 1807 bp, respectively. Phylogenetic trees showed that the SaAACT protein had the closest relationship with AACT from Hevea brasiliensis and the SaHMGS proteins had the highest homology with HMGS from Siraitia grosvenorii. Functional complementation of SaAACT and SaHMGS in a mutant yeast strain deficient in these proteins confirmed that SaAACT and SaHMGS cDNA encodes functional SaAACT and SaHMGS that mediate mevalonate biosynthesis in yeast. Tissue-specific expression analysis revealed that both genes were constitutively expressed in all examined tissues (roots, sapwood, heartwood, young leaves, mature leaves and shoots) of S. album, both genes showing highest expression in roots. After S. album seedlings were treated with 100 μM methyl jasmonate, the expression levels of SaAACT and SaHMGS genes increased, suggesting that these genes were responsive to this elicitor. These studies provide insight that would allow further analysis of the role of genes related to the sandalwood mevalonate pathway in the regulation of biosynthesis of sandalwood terpenoids and a deeper understanding of the molecular mechanism of santalol biosynthesis.

Abstract An efficient regeneration system via shoot organogenesis and somatic embryogenesis from in vitro leaf and root explants was established for Scaevola sericea for the first time. The highest axillary shoot proliferation coefficient (4.8) was obtained on Murashige and Skoog (MS) medium supplemented with 1.0 mg/L 6-benzyladenine (BA) and 0.1 mg/L α-naphthaleneacetic acid (NAA) every 45 days. Young in vitro leaves and roots, which were used as explants, were cultured onto medium supplemented with different plant growth regulators. Our results showed that only cytokinins BA and thidiazuron (TDZ), could induce adventitious shoots and somatic embryos from leaf and root explants. The optimal medium to achieve this was MS medium supplemented with 2.5 mg/L BA and which induced most adventitious shoots (2.7) and somatic embryos (17.3) from leaf explants within 30 days. From root explants, 1.1 adventitious shoots and 7.6 somatic embryos could be induced on MS medium supplemented with 2.5 mg/L TDZ. Histological observation showed that both somatic embryos and adventitious shoots were originated from homogeneous parenchyma and the development of somatic embryos was visible. Maximum rooting percentage (99.0%) was achieved on half-strength MS medium supplemented with 2.5 mg/L NAA. Well-rooted plantlets, which were transplanted into a substrate of pure river sand, displayed a high survival percentage of 91.7% after transplanting for 45 days while the best substrate for plantlet growth was river sand: coral sand (1:1).

Abstract A major challenge in maize (Zea mays) production is to achieve high grain yield (yield hereafter) by improving resource use efficiency. Using a dataset synthesized from 83 peer-reviewed articles, this study mainly investigated the effects of water and/or nitrogen (N) input on maize yield, water productivity (WP), and N use efficiency (NUE); and evaluated the effects caused by planting density, environmental (temperature, soil texture), and managerial factors (water and/or N input). The input of water increased maize yield, WP, and NUE only when the input was less than 314, 709, and 311 mm, respectively; input of N increased maize yield, WP, and NUE until input was greater than 250, 128, and 196 kg ha−1, respectively. Additionally, results of the mixed-effects model and random forest analysis suggested that mean annual temperature (MAT) was the most critical factor for narrowing gaps (between the actual and attainable variable, which was indicated as response ratio of the treatment relative to the control) of yield (RR Y), WP (RR WP), and NUE (RR NUE), respectively. Specifically, RR Y, RR WP, or RR NUE were negatively correlated to MAT when MAT was higher than 15 °C. Additionally, the structural equation model showed that water input and RR WP with the higher coefficient were more important than N input and RR NUE in improving RR Y. These findings provide new insights into the causes and limitations of global maize production and offer some guidances for water and/or N managements.

Abstract Estrus expression by gilts and sows is hereditable and important for heat detection. To better understand the molecular biological mechanisms of estrus expression in gilts, the mRNA expression profiles of follicular tissue from Large White gilts in diestrus (LD, n = 3) and estrus (LE, n = 3), and Chinese indigenous Mi gilts in diestrus (MD, n = 2) and estrus (ME, n = 3) were investigated using RNA sequencing. We detected 122,804-335,295 SNPs, 6,140-14,947 InDel and 12 types of AS events (39.57% TSS, 34.90% TTS) in 11 samples. A total of 2,838 differentially expressed genes (DEGs) were found in LD vs MD, LE vs ME, LE vs LD, or ME vs MD comparisons. Two DEGs (ACP5 and PIGS) were observed in all comparisons. Two new genes (ENSSSCG00000028235 and ENSSSCG00000021903) were exclusively expressed in Mi and Large White gilts, respectively. Bioinformatics analyses indicate that these DEGs are involved in single-organism process, catalytic activity, cell adhesion and enriched in ECM-receptor interaction, olfactory transduction, ovarian steroidogenesis, steroid biosynthesis and CAMs signaling pathways. These results of RNA-Seq have provided important information for screening the key functional genes or molecular markers of estrus expression in gilts.

Abstract Taxanes are chemotherapeutic agents commonly used to treat several cancers. However, the effects of taxanes on advanced gastric cancer (AGC) are still not clear, especially when used as a first-line treatment. This systematic review and meta-analysis aims to investigate the efficacy and safety of taxanes as a first-line treatment of AGC. The quality of our included studies was assessed using the Cochrane risk of bias tool for RCTs and NOS scale for nRCTs, and the data of the included studies was of satisfactory quality to analyze. The outcomes included overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and toxicity. Taxanes significantly improved OS (HR = 0.84, 95% CI 0.76–0.92, P = 0.0004) and had a slight effect on ORR (RR = 1.23, 95% CI 1.00–1.51, P = 0.05). However, taxanes may also increase the risks of neutropenia and leucopenia, similar to effects observed in other conventional chemotherapeutic treatments such as oxaliplatin and epirubicin. Therefore, patient characteristics including concomitant diseases, physical condition, and prior therapies should be considered before selecting taxane-based treatments for AGC.

Abstract Surface nanopatterning of metals has been an effective technique for improved performance and functionalization. However, it is of great challenge to fabricate nanostructure on carbon steels despite their extensive use and urgent needs to maintain the performance reliability and durability. Here, we report a one-step anodization technique to nanopattern a carbon steel in 50 wt.% NaOH solution for highly effective anti-adhesion by sulphate reducing bacteria (SRB), i.e., Desulfovibrio desulfuricans subsp. desulfuricans (Beijerinck) Kluyver and van Niel. We characterize the morphology, structure, composition, and surface roughness of the nanostructured film formed on the steel as a function of anodizing potential. We quantify the surface hydrophobicity by contact angle measurements, and the SRB adhesion by fluorescent analysis. The optimal anodization potential of 2.0 V is determined for the best performance of anti-adhesion of SRB to the steel, resulting in a 23.5 times of reduction of SRB adhesion compared to bare steel. We discuss the mechanisms for the film formation on the steel during anodization, and the high-performance anti-adhesion of bacteria to nanopatterned steels. Our technique is simple, cost-effective and environment-friendly, providing a promising alternative for industry-scale surface nanopatterning of carbon steels for effective controlling of bacterial adhesion.

Abstract Mycoplasma mycoides subsp.mycoides (Mmm) is a pathogen that causes pneumonia, otitis media, and arthritis in young calves. Its pathogenesis is attributed in part to excessive immune responses. Mmm-derived lipid-associated membrane proteins (LAMPs) are potent inducers of the host innate immune system; however, interactions between Mmm-derived LAMPs as pathogenic agents, toll-like receptors (TLRs), and the signaling pathways responsible for activating inflammation and nuclear factor (NF)-κB have not been fully elucidated. Here, we analyzed the expression kinetics of interleukin (IL)-1β in Mmm-derived LAMP-stimulated embryonic bovine lung (EBL) cells and found that Mmm-derived LAMPs induced IL-1β expression. Subcellular localization analysis revealed the nuclear translocation of the NF-κB p65 subunit after EBL cells were stimulated with Mmm-derived LAMPs. Furthermore, a specific inhibitor assay demonstrated that NF-κB is required for Mmm-derived LAMP-induced IL-1β expression. Additionally, overexpression of TLR2, myeloid differentiation primary response gene 88 (MyD88), and IL-1 receptor-associated kinase 4 (IRAK4) increased IL-1β expression during LAMP stimulation, and TLR2-neutralizing antibodies reduced IL-1β expression in EBL cells during LAMP stimulation. Furthermore, LAMPs inhibited IL-1β expression following transfection with dominant-negative MyD88 and IRAK4 variants. These results suggested that Mmm-derived LAMPs activate IL-1β production through the NF-κB pathway via TLR2, MyD88, and IRAK4.

Abstract Enhancer of zeste homolog 2 (EZH2) is often increased in malignant tumors and is involved in metastasis. EZH2 silences gene expression by tri-methylating the lysine 27 residue of histone H3 (H3K27me3). However, the mechanism underlying EZH2 promotion of ovarian cancer metastasis remains elusive. Here, we showed that EZH2 is up-regulated in ovarian cancer and is associated with tumor metastasis and poor survival by mRNA sequencing and microarray results from databases. Tissue microarray and immunohistochemistry results revealed that EZH2 was negatively correlated with the expression of tissue inhibitor of metalloproteinases 2 (TIMP2). EZH2 overexpression inhibited TIMP2 expression and promoted proteolytic activities of matrix metalloproteinases 2 and 9 and vice versa. EZH2 promoted ovarian cancer invasion and migration, which could be largely reversed by TIMP2 down-regulation in vitro and in vivo. Both H3K27me3 inhibition and demethylation could reduce methylation of the TIMP2 promoter and finally reactivate TIMP2 transcription. The presence of EZH2 and H3K27me3 at the TIMP2 promoter was confirmed by chromatin immunoprecipitation. H3K27me3 and DNA methyltransferases at the promoter were significantly increased by EZH2 overexpression. These results suggest that EZH2 inhibits TIMP2 expression via H3K27me3 and DNA methylation, which relieve the repression of MMP and facilitate ovarian cancer invasion and migration.

Abstract Dietary micronutrients are integral to the development and progression of constipation; however, the specific relationship between dietary copper intake and constipation has not been thoroughly investigated. This study aims to examine the correlation between dietary copper intake and constipation among U.S. adults, thereby offering novel insights and recommendations for the clinical management and prevention of constipation. Bowel health data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2005 and 2010 were analyzed. Subjects’ dietary information was collected through questionnaire records. Multivariate logistic regression analysis, subgroup analysis, and curve fitting analysis were used to assess the correlation between dietary copper intake and chronic constipation. After adjusting for all possible confounders, each unit increase in dietary copper intake (converted to natural logarithms) was associated with a 20% reduction in the prevalence of constipation (OR = 0.80; 95% CI 0.65–0.98; P = 0.037). The interaction P-values for all subgroups were greater than 0.05, indicating that the findings were stable and consistent across subgroups. The present study showed a significant negative association between dietary copper intake and chronic constipation in adults. This finding raises clinical and healthcare professionals’ awareness of the impact of dietary trace elements on intestinal health and has important implications for the development of personalized meal plans and rational supplementation of trace copper in patients with constipation.