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Abstract Background While most research has focused on the association between intracytoplasmic sperm injection (ICSI) and neurodevelopmental disorders in children, relatively little attention has been given to its metabolic effects. Previous studies have reported that low serum lipid levels are associated with mental health problems. Our objective was to analyze the impact of ICSI on metabolic alterations compared to their in vitro fertilization (IVF) counterparts in male offspring, as well as its interaction with paternal overweight/obesity. Methods We recruited families between January 2006 and December 2017 at the Center for Reproductive Medicine, Shandong University, China. Prospective data of offspring were obtained for body mass index (BMI), blood pressure, glucose, and lipid profile in their 0–11 years old. Linear mixed models were utilized to compute the mean difference and 95% confidence intervals (CI). Results A total of 14,196 offspring visits were identified. In offspring aged 4–11 years, ICSI-conceived offspring exhibited significantly lower fasting glucose z-scores, total cholesterol z-scores, and low-density lipoprotein cholesterol (LDL-C) z-scores compared with their IVF counterparts (fasting glucose z-score: adjusted mean difference: − 0.13, 95% CI: − 0.23 to − 0.03; total cholesterol z-score: adjusted mean difference: − 0.13, 95% CI: − 0.23 to − 0.02; LDL-C z-score: adjusted mean difference: − 0.12, 95% CI: − 0.22 to − 0.01). Paternal overweight/obesity significantly influenced the relationship between ICSI and metabolic changes in offspring. In offspring born from fathers with overweight/obesity, ICSI-conceived offspring displayed significantly lower fasting glucose and total cholesterol z-scores than their IVF controls (fasting glucose z-score: adjusted mean difference: − 0.20, 95% CI: − 0.32 to − 0.08; total cholesterol z-score: adjusted mean difference: − 0.15, 95% CI: − 0.27 to − 0.02). In offspring born to fathers with normal weight, ICSI-conceived offspring showed significantly lower systolic blood pressure z-scores compared to those conceived via the IVF procedures (adjusted mean difference: − 0.21, 95% CI: − 0.37 to − 0.05). Conclusions The findings of this study suggested that ICSI was associated with altered glucose and lipid profiles compared to their IVF controls, characterized by lower fasting glucose z-scores, total cholesterol z-scores, and LDL-C z-scores. Encouraging fathers to reduce their body weight could potentially improve the metabolic health of their ICSI-conceived children.

Considerable research has been conducted into the efficacy of individual probiotics in broiler production, however information on the most effective combinations of synergistic Bacillus probiotic is lacking. This study investigated the impact of different Bacillus strain combinations in broiler chickens, as well as in vitro enzyme production. In experiment one, a total of 576 Ross 308 broilers at 1 d old were grown for 21 d across 6 treatments of maize-soybean diets (n = 12 pens per treatment) to compare three different strain combinations (formulation 1 [F1]: 3 strains Bacillus amyloliquefaciens; F2: Bacillus coagulans and 2 strains B. amyloliquefaciens; F3: B. coagulans, Bacillus licheniformis and 2 strains B. amyloliquefaciens; F5: Bacillus subtilis, B. licheniformis and 2 strains B. amyloliquefaciens), positive control (PC), and a negative control antibiotic treatment group (NC). In Exp. 2, a total of 360 one-day-old ROSS308 broilers were used to test five treatments (n = 9) including PC, NC, F1 and F5 (selected from Exp. 1), and F4 (Bacillus pumilis and 2 strains B. amyloliquefaciens) in a maize-soybean diet. B. amyloliquefaciens F1 demonstrated a significant improvement in feed conversion ratio (FCR) compared to F2 at d 14 (1.49 vs 2.10; P = 0.038) and the body weight (BW) at d 21 (847.0 g vs 787.4 g) compared to other combinations (P = 0.027). The FCR at d 21 tended to be lower in birds fed F1 (1.46 vs 1.66) compared to the control (P = 0.068). Probiotic treatments had significantly improved nutrient digestibility compared to the PC and NC. Also, probiotic treatments supported the growth of Streptococcus, a common commensal genus and reduced the abundance of genera that correlated with low weight gain such as Akkermansia. Experiment two revealed that F4 improved FCR (P

Oral ulcers can be managed using a variety of biomaterials that deliver drugs or cytokines. However, many patients experience minimal benefits from certain medical treatments because of poor compliance, short retention times in the oral cavity, and inadequate drug efficacy. Herein, we present a novel hydrogel patch (SCE2) composed of a biopolymer matrix (featuring ultraviolet-triggered adhesion properties) loaded with cuttlefish ink nanoparticles (possessing pro-healing functions). Applying a straightforward local method initiates the formation of a hydrogel barrier that adheres to mucosal injuries under the influence of ultraviolet light. SCE2 then demonstrates exceptional capabilities for near-infrared photothermal sterilization and neutralization of reactive oxygen species. These properties contribute to the elimination of bacteria and the management of the oxidation process, thus accelerating the healing phase's progression from inflammation to proliferation. In studies involving diabetic rats with oral ulcers, the SCE2 adhesive patch significantly quickens recovery by altering the inflamed state of the injured area, facilitating rapid re-epithelialization, and fostering angiogenesis. In conclusion, this light-sensitive hydrogel patch offers a promising path to expedited wound healing, potentially transforming treatment strategies for clinical oral ulcers.

Long non-coding RNA (lncRNA) H19 is an extensively studied lncRNA that is related to numerous pathological changes. Our previous findings have documented that serum lncRNA H19 levels are decreased in patients with chronic kidney disorder and lncRNA H19 reduction is closely correlated with renal tubulointerstitial fibrosis, an essential step in developing end-stage kidney disease. Nonetheless, the precise function and mechanism of lncRNA H19 in renal tubulointerstitial fibrosis are not fully comprehended. The present work utilized a mouse model of unilateral ureteral obstruction (UUO) and transforming growth factor-β1 (TGF-β1)-stimulated HK-2 cells to investigate the possible role and mechanism of lncRNA H19 in renal tubulointerstitial fibrosis were investigated. Levels of lncRNA H19 decreased in kidneys of mice with UUO and HK-2 cells stimulated with TGF-β1. Up-regulation of lncRNA H19 in mouse kidneys remarkably relieved kidney injury, fibrosis and inflammation triggered by UUO. Moreover, the increase of lncRNA H19 in HK-2 cells reduced epithelial-to-mesenchymal transition (EMT) induced by TGF-β1. Notably, up-regulation of lncRNA H19 reduced lipid accumulation and triacylglycerol content in kidneys of mice with UUO and TGF-β1-stimulated HK-2 cells, accompanied by the up-regulation of long-chain acyl-CoA synthetase 1 (ACSL1). lncRNA H19 was identified as a sponge of microRNA-130a-3p, through which lncRNA H19 modulates the expression of ACSL1. The overexpression of microRNA-130a-3p reversed the lncRNA H19-induced increases in the expression of ACSL1. The suppressive effects of lncRNA H19 overexpression on the EMT, inflammation and lipid accumulation in HK-2 cells were diminished by ACSL1 silencing or microRNA-130a-3p overexpression. Overall, the findings showed that lncRNA H19 ameliorated renal tubulointerstitial fibrosis by reducing lipid deposition via modulation of the microRNA-130a-3p/ACSL1 axis.

Abstract Objectives In this study, we aimed to validate the performance of the PAX1 and JAM3 methylation (PAX1 m /JAM3 m ) test as a triage tool for detecting cervical intraepithelial neoplasia grade 3 or worse (CIN3 +) in non-16/18 high-risk human papillomavirus-positive patients (non-16/18 hrHPV +). Methods The triage performance of liquid-based cytology (LBC) and the PAX1 m /JAM3 m test for detecting CIN3 + were compared. Results In total, 1851 participants had cervical histological outcomes and were included in the analysis. The sensitivity/specificity of the LBC test results with atypical squamous cells of undetermined significance or worse (LBC ≥ ASCUS) and the PAX1 m /JAM3 m test were 90.1%/26.7% and 84.8%/88.5%, respectively. PAX1 m /JAM3 m ( +) had the highest diagnostic AUC (0.866, 95% confidence interval (CI) 0.837–0.896) in the whole cohort. All cancers (n = 20) were detected by PAX1 m /JAM3 m (+). Compared with LBC ≥ ASCUS, PAX1 m /JAM3 m (+) reduced the number of patients who needed referral for colposcopy by 57.21% (74.66% vs. 17.45%). The odds ratios for detecting CIN3 + by LBC ≥ ASCUS and PAX1 m /JAM3 m (+) were 3.3 (95% CI 2.0–5.9) and 42.6 (27.1–69.6), respectively (p

Abstract With the penetration of the high proportion of power electronics interfaced energy resources, the frequency stability issue in power systems is becoming increasingly prominent. This paper proposes a coordinated control strategy of multiple voltage source converter based high voltage direct current transmission (VSC‐HVDC) to simultaneously improve the transient frequency and steady‐state frequency after a severe disturbance. Firstly, a modified average system frequency response (MASFR) model is constructed with reserve power limitation, which takes into account the frequency responses of different types of generators (thermal, hydro and new energy resources). Secondly, according to the frequency stability requirements, the corresponding constraints, which consider the overload capacity of VSC‐HVDC, the AC transmission capacity and the frequency of AC grids on both sides of VSC‐HVDC, are formulated. Thirdly, for the transient frequency control, the coordinated optimization control model of multiple VSC‐HVDC is established, which aims to minimize the control energy considering the transient frequency threshold. For the steady‐state frequency control, the coordinated optimization control model is fomulated, which aims to minimize the control cost while considering the steady‐state frequency threshold. The two control schemes achieve seamless and smooth switching. Finally, the correctness and effectiveness of the proposed control strategy are verified in the improved IEEE 39 bus system.

Abstract Increasing evidence suggests that mitophagy is crucially involved in the progression of polycystic ovary syndrome (PCOS). Exploration of PCOS-specific biomarkers related to mitophagy is expected to provide critical insights into disease pathogenesis. In this study, we employed bioinformatic analyses and machine learning algorithms to determine novel biomarkers for PCOS that may be tied with mitophagy. A grand total of 12 differential expressed mitophagy-related genes (DE‐MRGs) associated with PCOS were identified. TOMM5 and MAP1LC3A among the 12 DE‐MRGs were recognized as potential marker genes by LASSO, RF and SVM‐RFE algorithms. The area under the ROC curve (AUROC) of MAP1LC3A were all greater than 0.8 both in the training set and validation sets. The CIBERSORT analysis indicated a potential association between alterations in the immune microenvironment of PCOS individuals and MAP1LC3A expression. In addition, we found that MAP1LC3A was positively related to the testosterone levels of PCOS patients. Overall, MAP1LC3A was identified as optimal PCOS-specific biomarkers related to mitophagy. Our findings created a diagnostic strength and offered a perspective for investigating the mitophagy process in PCOS.

IntroductionOxidative stress plays a crucial role in the development and progression of hyperuricemia/gout. This study aims to explore the relationship between the Oxidative Balance Score (OBS) and hyperuricemia/gout.MethodsThe study utilized complete data from adult participants in the National Health and Nutrition Examination Survey (NHANES) spanning from 2009 to 2018. OBS, composed of scores for 20 dietary and lifestyle factors, served as the exposure variable. Multivariable linear regression model was applied to evaluate the association between OBS and uric acid (UA). Multivariable logistic regression, subgroup analyses, and restricted cubic spline (RCS) regression were conducted to explore the relationship between OBS and hyperuricemia/gout.ResultsA total of 18,998 participants were included. In the fully adjusted model, compared to the lowest quartile, the highest quartiles of OBS, dietary OBS, and lifestyle OBS were negatively correlated with UA (β=-0.31 (-0.36,-0.25), β=-0.18 (-0.24,-0.12), and β=-0.64 (-0.69,-0.59), respectively) and hyperuricemia (OR=0.63 (0.55,0.71), OR=0.76 (0.67,0.86), OR=0.37 (0.33,0.42), respectively). Moreover, the highest quartiles of OBS and lifestyle OBS exhibited a negative correlation with gout (OR=0.72(0.58,0.91), OR=0.54 (0.43,0.67), respectively). Subgroup analyses revealed differences in the negative association between OBS and hyperuricemia concerning hypertension (p for interaction =0.002) and diabetes (p for interaction= 0.004), while gender-related disparities were observed in the negative association between OBS and gout (p for interaction =0.008). RCS analysis demonstrated a linear negative association between hyperuricemia and OBS (p for non-linearity >0.05), while gout exhibited a non-linear negative association (p for non-linearity

Abstract Background 5-fluorouracil (5-FU) is conventionally used in chemotherapy for colon adenocarcinomas. Acquired resistance of 5-FU remains a clinical challenge in colon cancer, and efforts to develop targeted agents to reduce resistance have not yielded success. Protosappanin B (PSB), the main component of Lignum Sappan extract, is known to exhibit anti-tumor effects. However, whether and how PSB could improve 5-FU resistance in colon cancer have not yet been established. In this study, we aimed to explore the effects and underlying mechanisms of PSB in 5-FU-induced chemoresistance in colon adenocarcinoma. Methods Forty-seven paired colon cancer tissue samples from patients who received 5-FU chemotherapy were collected as clinical samples. Two 5-FU resistant colon cancer cell lines were established for in vitro experiments. Reverse transcription-quantitative PCR (RT-qPCR) was performed to determine the mRNA and microRNA (miRNA) expression levels in colon adenocarcinoma tissues and cell lines. Cell Counting Kit-8 (CCK-8) and flow cytometry assays were performed to evaluate cell proliferation and apoptosis, respectively. Results LINC00612 was highly expressed in colon adenocarcinoma samples and 5-FU resistant colon cancer cells. LINC00612 knockdown enhances 5-FU chemosensitivity in 5-FU resistant cells. Notably, PSB treatment attenuated LINC00612 expression in 5-FU resistant colon adenocarcinoma cells. Moreover, PSB treatment reversed the increase in LINC00612-induced 5-FU resistance. Mechanistically, LINC00612 specifically bound to miR-590-3p, which promoted 5-FU resistance in colon adenocarcinoma cells and attenuated the inhibitory effect of LINC00612 on GOLPH3 expression. Conclusion PSB attenuates 5-FU chemoresistance in colon adenocarcinoma by regulating the LINC00612/miRNA-590-3p/GOLPH3 axis. Graphical Abstract

Abstract Background To the best of our knowledge, no study has investigated the potential joint effect of large for gestational age (LGA) and assisted reproductive technology (ART) on the long-term health of children. Methods This was a prospective cohort study that recruited children whose parents had received ART treatment in the Center for Reproductive Medicine, Shandong Provincial Hospital, affiliated to Shandong University, between January 2006 and December 2017. Linear mixed model was used to compare the main outcomes. The mediation model was used to evaluate the intermediary effect of body mass index (BMI). Results 4138 (29.5%) children born LGA and 9910 (70.5%) children born appropriate for gestational age (AGA) were included in the present study. The offspring ranged from 0.4 to 9.9 years. LGAs conceived through ART were shown to have higher BMI, blood pressure, fasting blood glucose, fasting insulin, and homeostatic model assessment of insulin resistance values, even after controlling for all covariates. The odds of overweight and insulin resistance are also higher in LGA subjects. After adjusting for all covariates, LGAs conceived through ART had BMI and BMI z-scores that were 0.48 kg/m2 and 0.34 units greater than those of AGAs, respectively. The effect of LGA on BMI was identified as early as infancy and remained consistently significant throughout pre-puberty. Conclusions Compared to AGA, LGA children conceived from ART were associated with increased cardiovascular-metabolic events, which appeared as early as infancy and with no recovery by pre-puberty.

Abstract Objective This study aims to investigate the effect of diminished ovarian reserve (DOR) on the clinical outcomes and maternal and infant safety of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) procedures in young women aged ≤ 35 years. Methods A retrospective cohort study was performed to analyze the clinical data of 4,203 infertile women aged ≤ 35 years who underwent fresh embryo transfer (ET) in IVF/ICSI cycles. The data were collected from their initial visits to Fujian Maternity and Child Health Hospital between January 2015 and January 2022. Based on their ovarian reserve, the participants were categorized into two groups: DOR group (n = 1,027) and non-DOR group (n = 3,176). A propensity score matching (PSM) method was employed to ensure a relatively balanced distribution of covariates. The primary outcome assessed in this study was the live birth rate, while the secondary observation indicators included rates of high-quality embryo development, blastocyst formation, clinical pregnancy, and miscarriage, along with perinatal complications, neonatal birth weight, and the incidence of low birth weight (LBW). Results The DOR group showed notably lowered rates of blastocyst formation (59.8% vs. 64.1%), embryo implantation (29.8% vs.33.3%), clinical pregnancy (47.9% vs. 53.6%), and live birth (40.6% vs. 45.7%) compared to the non-DOR group (all P 0.05). Conclusion DOR has been found to reduce both clinical pregnancy and live birth rates in young females undergoing fresh ET in IVF/ICSI cycles. However, this reduction does not increase the risk of perinatal complications or LBW of infants through live birth cycles.

Abstract Objective To present our experience using the supraclavicular artery island flap (SCAIF) for head and neck reconstruction. Methods We performed a retrospective chart review to identify patients who underwent head and neck reconstruction with SCAIF at our institution. The following data were collected: age, sex, surgical indications, flap harvest time, flap dimensions, length of hospital stay, complications, and clinical outcomes. Results Thirty‐three patients underwent SCAIF reconstruction, of whom four underwent pectoralis major myocutaneous flap reconstruction simultaneously. Twenty flaps were used to repair pharyngeal or esophageal defects following resection for tonsillar, hypopharyngeal, laryngeal, and cervical esophageal cancers. Five flaps were used for tracheal reconstruction following resection for tracheal or thyroid gland cancer. Seven flaps were used for reconstruction of cervical skin defects or fistulas related to a previous treatment. One flap for tracheal stenosis following tracheotomy. The mean age of the patients was 60.69 ± 11.47 years. The mean flap harvest time was 32.00 ± 4.44 min. The mean flap size was 10.16 ± 3.91 × 5.78 ± 0.68 cm. The mean length of hospital stay is 24.84 ± 13.78 days. Three patients had partial necrosis of the distal portion of the flap, which resolved with anti‐infection therapy and local wound care. One patient developed a fistula that was resolved with wound care and further surgical intervention. Complete flap loss or major complications were not observed. No donor site complication or compromised shoulder function was observed. Conclusion The SCAIF can be successfully used to reconstruct head and neck defects with good outcomes and limited morbidity. Level of Evidence 4.

Abstract Epithelial ovarian cancer (EOC) is an often‐fatal malignancy marked by the development of resistance to platinum‐based chemotherapy. Thus, accurate prediction of platinum drug efficacy is crucial for strategically selecting postoperative interventions to mitigate the risks associated with suboptimal therapeutic outcomes and adverse effects. Tissue‐derived extracellular vesicles (tsEVs), in contrast to their plasma counterparts, have emerged as a powerful tool for examining distinctive attributes of EOC tissues. In this study, 4D data‐independent acquisition (DIA) proteomic sequencing was performed on tsEVs obtained from 58 platinum‐sensitive and 30 platinum‐resistant patients with EOC. The analysis revealed a notable enrichment of differentially expressed proteins that were predominantly associated with immune‐related pathways. Moreover, pivotal immune‐related proteins (IRPs) were identified by LASSO regression. These factors, combined with clinical parameters selected through univariate logistic regression, were used for the construction of a model employing multivariate logistic regression. This model integrated three tsEV IRPs, CCR1, IGHV_35 and CD72, with one clinical parameter, the presence of postoperative residual lesions. Thus, this model could predict the efficacy of initial platinum‐based chemotherapy in patients with EOC post‐surgery, providing prognostic insights even before the initiation of chemotherapy.

Background: Gastric cancer is a leading cause of cancer-related deaths influenced by both genetic and environmental factors. Triphenyl phosphate (TPP) is a prevalent flame retardant, but its health implications remain to be thoroughly understood. Objective: To explore the link between TPP exposure and gastric cancer by examining gene expression patterns and developing a predictive model. Methods: Gene expression data were sourced from The Cancer Genome Atlas (TCGA) and the Comparative Toxicogenomics Database (CTD). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were employed for analysis. Single-sample Gene Set Enrichment Analysis (ssGSEA) was used to obtain phosphate flame retardant-related scores. A predictive model was constructed through differential analysis, univariate COX regression, and LASSO regression. Molecular docking was performed to assess protein interactions with TPP. Results: ssGSEA identified scores related to phosphate flame retardants in gastric cancer, which had a strong association with immune-related traits. Several genes associated with TPP were identified and used to develop a prognostic model that has clinical significance. Molecular docking showed a high binding affinity of TPP with MTTP, a gene related to lipid metabolism. Pathway analysis indicated that TPP exposure contributes to gastric cancer through lipid metabolic processes. Conclusion: The study establishes a potential correlation between TPP exposure and gastric cancer onset, pinpointing key genes and pathways involved. This underscores the significance of environmental factors in gastric cancer research and presents a potential diagnostic tool for clinical application.

Objectives Pregnancy outcomes of different ovarian stimulation protocols for in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) in patients with adenomyosis are not explicit. This meta-analysis aimed to systematically evaluate the effects of different IVF/ICSI protocols on pregnancy outcomes.Design Meta-analysis.Data sources PubMed, Web of Science and Cochrane library were searched up to October 2023.Eligibility criteria Comparative studies on IVF/ICSI outcomes in the adenomyosis population were eligible. Studies on preimplantation genetic testing, reviews, case reports and animal experiments were excluded.Data extraction and synthesis Valid information was extracted by two independent authors according to a standard data format. All analyses were conducted using Review Manager (RevMan, V.5.3).Results Compared with the non-adenomyosis population, adenomyosis was responsible for a 26% reduction in clinical pregnancy rate (CPR; 42.47% vs 55.89%, OR: 0.74, 95% CI: 0.66 to 0.82, p

Spexin (SPX, NPQ) is a 14-amino acid neuroactive peptide identified using bioinformatics. This amino acid sequence of the mature spexin peptide has been highly conserved during species evolution and is widely distributed in the central nervous system and peripheral tissues and organs. Therefore, spexin may play a role in various biological functions. Spexin, the cognate ligand for GALR2/3, acting as a neuromodulator or endocrine signaling factor, can inhibit reproductive performance. However, controversies and gaps in knowledge persist regarding spexin-mediated regulation of animal reproductive functions. This review focuses on the hypothalamic-pituitary-gonadal axis and provides a comprehensive overview of the impact of spexin on reproduction. Through this review, we aim to enhance understanding and obtain in-depth insights into the regulation of reproduction by spexin peptides, thereby providing a scientific basis for future investigations into the molecular mechanisms underlying the influence of spexin on reproductive function. Such investigations hold potential benefits for optimizing farming practices in livestock, poultry, and fish industries.

Abstract Background Polycystic ovarian syndrome (PCOS) is recognized as the most prevalent endocrine disorder among women of reproductive age. While the utilization of assisted reproductive technology (ART) has resulted in favorable outcomes for infertility treatment in PCOS patients, the inherent pathophysiological features of the condition give rise to complications and consequences during pregnancy and delivery for both the mother and offspring. This study was to assess the correlation between maternal PCOS and various pregnancy complications and neonatal outcomes undergone ART. Methods A systematic search was conducted on PubMed, EmBase, and the Cochrane Library to identify observational studies that investigated the association between PCOS and the risk of various pregnancy complications and neonatal outcomes, including gestational diabetes mellitus (GDM), hypertension in pregnancy (PIH), preeclampsia (PE), preterm birth, abortion, congenital malformations (CA), small for gestational age (SGA), large for gestational age (LGA), low birth weight (LBW), macrosomia, neonatal intensive care unit (NICU) admission and birth weight. Eligible studies were selected based on predetermined inclusion and exclusion criteria. The meta-analysis was conducted using Review Manager and Stata software, with odds ratios (ORs) or mean difference (MD), confidence intervals (CIs), and heterogeneity (I2) being calculated. The search was conducted up to March 2023. Results A total of 33 studies with a combined sample size of 92,810 participants were identified. The findings indicate that PCOS is significantly associated with an increased risk of GDM (OR 1.51, 95% CI:1.17–1.94), PIH (OR 1.72, 95% CI:1.25–2.39), PE (OR 2.12, 95% CI:1.49–3.02), preterm birth (OR 1.29, 95% CI:1.21–1.39), and LBW (OR 1.29, 95% CI:1.14–1.47). In subgroup analyses, the risks of GDM (OR 1.80, 95% CI:1.23–2.62) and abortion (OR 1.41, 95% CI:1.08–1.84) were elevated in fresh embryo transferred (ET) subgroup, whereas elevated risk of PE (OR 1.82, 95% CI:1.17–2.83) and preterm birth (OR 1.31, 95% CI:1.21–1.42) was identified in frozen ET subgroup. Whatever with or without hyperandrogenism, patients with PCOS had a higher risk in preterm birth (OR 1.69, 95% CI: 1.31–2.18; OR 1.24, 95% CI:1.02–1.50) and abortion (OR 1.38, 95% CI:1.12–1.71; OR 1.23, 95% CI:1.06–1.43). Conclusion Our findings suggest that individuals with PCOS undergone ART are at a notably elevated risk for experiencing pregnancy complications and unfavorable neonatal outcomes. Nevertheless, to establish a definitive association between PCOS and pregnancy-related outcomes, it is necessary to conduct extensive prospective, blinded cohort studies and effectively control for confounding variables.

Abstract Background Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease characterized by the presence of numerous autoantibodies. The interaction of infectious agents (viruses, bacteria and parasites) and a genetically susceptible host may be a key mechanism for SLE. Toxoplasma gondii is a widespread intracellular parasite that has been implicated in the pathogenesis of autoimmune diseases. However, the relationship between T. gondii infection and the increased risk of SLE in Chinese populations remains unclear. Methods The seroprevalence of T. gondii infection was assessed in 1771 serum samples collected from Chinese individuals (908 healthy controls and 863 SLE patients) from different regions of China using an enzyme-linked immunosorbent assay. Serum autoantibodies and clinical information were obtained and analysed. Results Our observations revealed a higher prevalence of anti-T. gondii antibodies (ATxA) immunoglobulin G (IgG) in serum samples from SLE patients (144/863, 16.7%) than in those from the healthy controls (53/917, 5.8%; P

Abstract Aims How different degrees of adherence to guideline‐directed medical therapy (GDMT) affect mortality risk in patients with heart failure (HF) in a real‐world clinical setting is poorly understood. This study sought to investigate how different levels of adherence to GDMT were associated with the risk of all‐cause mortality in patients with HF across a spectrum of left ventricular ejection fractions (LVEFs) in a real‐world clinical setting. Methods and results A total of 64 610 HF patients with no missing value of LVEF from the Swedish Heart Failure Registry were included in the study. Patients were divided according to different LVEFs (

BackgroundThe interaction between environmental endocrine-disrupting chemicals, such as Bisphenol A (BPA), and their influence on cancer progression, particularly regarding the GOLPH3 gene in colorectal cancer, remains unclear.MethodsWe performed an integrated analysis of transcriptional profiling, clinical data, and bioinformatics analyses utilizing data from the Comparative Toxicogenomics Database and The Cancer Genome Atlas. The study employed ClueGO, Gene Set Enrichment Analysis, and Gene Set Variation Analysis for functional enrichment analysis, alongside experimental assays to examine the effects of BPA exposure on colorectal cancer cell lines, focusing on GOLPH3 expression and its implications for cancer progression.ResultsOur findings demonstrated that BPA exposure significantly promoted the progression of colorectal cancer by upregulating GOLPH3, which in turn enhanced the malignant phenotype of colorectal cancer cells. Comparative analysis revealed elevated GOLPH3 protein levels in cancerous tissues versus normal tissues, with single-cell analysis indicating widespread GOLPH3 presence across various cell types in the cancer microenvironment. GOLPH3 was also associated with multiple carcinogenic pathways, including the G2M checkpoint. Furthermore, our investigation into the colorectal cancer microenvironment and genomic mutation signature underscored the oncogenic potential of GOLPH3, exacerbated by BPA exposure.ConclusionThis study provides novel insights into the complex interactions between BPA exposure and GOLPH3 in the context of colorectal cancer, emphasizing the need for heightened awareness and measures to mitigate BPA exposure risks. Our findings advocate for further research to validate these observations in clinical and epidemiological settings and explore potential therapeutic targets within these pathways.

IntroductionOvarian cancer (OV) is a highly lethal gynecological malignancy with a poor prognosis. Lactate metabolism is crucial for tumor cell survival, proliferation, and immune evasion. Our study aims to investigate the role of lactate metabolism-related genes (LMRGs) in OV and their potential as biomarkers for prognosis, immune microenvironment, and immunotherapy response.MethodsOvarian samples were collected from the TCGA cohort. And 12 lactate-related pathways were identified from the MsigDB database. Differentially expressed genes within these pathways were designated as LMRGs, which undergo unsupervised clustering to identify distinct clusters based on LMRGs. Subsequently, we assessed survival outcomes, immune cell infiltration levels, Hallmaker pathway activation patterns, and chemotaxis among different subtypes. After conducting additional unsupervised clustering based on differentially expressed genes (DEGs), significant differences in the expression of LMRGs between the two clusters were observed. The differentially expressed genes were subjected to subsequent functional enrichment analysis. Furthermore, we construct a model incorporating LMRGs. Subsequently, the lactate score for each tumor sample was calculated based on this model, facilitating the classification of samples into high and low groups according to their respective lactate scores. Distinct groups examined disparities in survival prognosis, copy number variation (CNV), single nucleotide variation (SNV), and immune infiltration. The lactate score served as a quantitative measure of OV's lactate metabolism pattern and an independent prognostic factor.ResultsThis study investigated the potential role of LMRGs in tumor microenvironment diversity and prognosis in OV, suggesting that LMRGs play a crucial role in OV progression and the tumor microenvironment, thus serving as novel indicators for prognosis, immune microenvironment status, and response to immunotherapy.

Abstract Purpose To construct and validate a nomogram model for predicting clinical pregnancy in individuals with endometriosis undergoing fersh embryo transfer (ET). Methods A retrospective analysis was conducted on 1630 individuals with endometriosis who underwent in vitro fertilization (IVF) with fresh embryo transfer at the Reproductive Medicine Center of Fujian Maternity and Child Health Hospital from January 2018 to January 2022. The research population was sorted into two groups through random sampling, namely, the model group (n = 1141) and the validation group (n = 489), with a ratio of 7:3. Univariate analysis was utilized to determine the influencing factors for clinical pregnancy in the model group. The LASSO algorithm was utilized to select the optimal matching factors, which were then included in a multifactorial forward stepwise logistic regression to determine independent influencing factors and develop a nomogram. The discrimination, accuracy, and clinical efficacy of the prediction model were analyzed utilizing the receiver operating characteristic (ROC) curve, calibration curve, and clinical decision curve. Results Through multivariate-logistic-regression analysis, these factors were identified as independent influencing factors for the clinical pregnancy in endometriosis patients undergoing fresh embryo transfer: female age (OR = 0.933, 95% CI = 0.902–0.965, P 0.05). The clinical decision curve demonstrated that both the model and the validation groups achieved maximum net benefit at threshold probability values of 0.08–0.96 and 0.16–0.96, indicating good clinical efficacy within this range of threshold probabilities. Conclusion Female age, ASRM stage, postoperative to IVF duration, stimulation protocol, AFC, AMH, number of oocytes retrieved, number of high-quality cleavage embryos and number of transferred embryos are independent influencing factors for the clinical pregnancy rate in individuals with endometriosis receiving fresh embryo transfer. The nomogram model based on these factors demonstrates good clinical predictive value and efficacy, providing a basis for clinical prognosis, intervention, and individualized medical treatment planning.

Probiotics provided from hatch have a major influence on microbiota development, and together with environmental and bedding microbiota, shape the microbial community of the litter. We investigated the influence of probiotic supplementation and a leaky gut challenge induced using dexamethasone (DEX) on the litter microbial community and litter parameters. The probiotic product was a mix of three Bacillus amyloliquefaciens strains. The litter microbiota were compared to the microbial communities from other gut sections. The litter samples had higher microbial diversity compared to the caecum, gizzard, jejunum, and jejunal mucosa. The high similarity between the litter phylum-level microbiota and gizzard microbiota detected in our study could be a consequence of ingested feed and litter passing through the gizzard. Moreover, the litter microbial community is fundamentally distinct from the intestinal microbiota, as evidenced by the number of genera present in the litter but absent from all the intestinal sections and vice versa. Furthermore, LEfSe analysis identified distinct microbial taxa across different groups, with specific genera associated with different treatments. In terms of litter quality, the birds in the DEX groups had a significantly higher moisture content, indicating successful leaky gut challenge, while probiotic supplementation did not significantly affect the moisture levels. These findings provide comprehensive insights into the distinct microbiota characteristics of litter.

The direct 1,6-nucleophilic difluoromethylation, trifluoromethylation, and difluoroalkylation of para-quinone methides (p-QMs) with Me3SiRf (Rf = CF2H, CF3, CF2CF3, CF2COOEt, and CF2SPh) under mild conditions are described. Although Me3SiCF2H shows lower reactivity than Me3SiCF3, it can react with p-QMs promoted by CsF/18-Crown-6 to give structurally diverse difluoromethyl products in good yields. The products can then be further converted into fluoroalkylated para-quinone methides and α-fluoroalkylated diarylmethanes.

KASP marker technology has been used in molecular marker-assisted breeding because of its high efficiency and flexibility, and an intelligent evaluation model of KASP marker primer typing results is essential to improve the efficiency of marker development on a large scale. To this end, this paper proposes a gene population delineation method based on NTC identification module and data distribution judgment module to improve the accuracy of K-Means clustering, and introduces a decision tree to construct the KASP-IEva primer typing evaluation model. The model firstly designs the NTC identification module and data distribution judgment module to extract four types of data, grouping and categorizing to achieve the improvement of the distinguishability of amplification product signals; secondly, the K-Means algorithm is used to aggregate and classify the data, to visualize the five aggregated clusters and to obtain the morphology location eigenvalues; lastly, the evaluation criteria for the typing effect level are constructed, and the logical decision tree is used to make conditional discrimination on the eigenvalues in order to realize the score prediction. The performance of the model was tested by the KASP marker typing test results of 2519 groups of cotton varieties, and the following conclusions were obtained: the model is able to visualize the aggregation and classification effects of the amplification products of NTC, pure genotypes, heterozygous genotypes, and untyped genotypes, enabling rapid and accurate KASP marker typing evaluation. Comparing and analyzing the model evaluation results with the expert evaluation results, the average accuracy rate of the four grades evaluated by the model was 87%, and the overall evaluation results showed an uneven distribution of the grades with significant differential characteristics. When evaluating 2519 KASP fractal maps, the expert evaluation consumes 15 hours, and the model evaluation only uses 8min27.45s, which makes the model intelligent evaluation significantly better than the expert evaluation from the perspective of time. The establishment of the model will further enhance the application of KASP markers in molecular marker-assisted breeding and provide technical support for the large-scale screening and identification of excellent genotypes.

Abstract Zirconia implants have great application prospects due to their favorable biocompatibility and esthetic properties. However, the percentage of osseointegration of zirconia implants is lower than that of titanium implants. This study, structures bioactive surfaces on zirconia using a femtosecond laser combined with hydroxyapatite (HA) crystals and evaluates the surface morphology, functional groups, crystal phase, mechanical performance, and cell response. The results revealed that calcium phosphate deposition coincided with the establishment of micro‐grooves on the zirconia surface. The crystal composition and flexural strength of zirconia showed no significant changes after the surface treatment. Furthermore, the modified surface promoted cell adhesion and proliferation through adjustments in cell morphology. The findings suggest that the combination of femtosecond laser and HA crystals offers a clean, rapid, and controllable approach to preparing bioactive surfaces for zirconia implants.

Summary: Frozen embryo transfer (FET) is becoming popular in recent years. However, whether embryos freezing or other factors may affect intellectual performance in offspring is still unknown. We compared the Wechsler Intelligence Scale for Children Fourth Edition (WISC-IV) questionnaire scores between children born after fresh embryo transfer (fresh ET) and FET. They were matched in a 1:1 ratio on their sex and age (±1 month). 326 children were included in each group. We found children born after FET scored lower on the WISC-IV questionnaire (p = 0.002). In subgroup analysis, the full-scale scores are similar between fresh ET and FET in the cleavage-stage transfer group (p = 0.57). In the FET group, the blastocyst-stage transfer group had lower full-scale scores compared with the cleavage-stage transfer group (p = 0.004). Children born after FET scored lower on WISC-IV questionnaire might be linked to extended culture of embryos rather than the freezing process.

Abstract With the advancements in radiotherapy (RT) in recent years, several studies have shown that RT can significantly prolong the survival of patients with hepatocellular carcinoma (HCC). As a noninvasive treatment option, the application of RT for the treatment of HCC is garnering increasing attention. In this retrospective study, we included data from 13,878 patients with HCC from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2019 and 325 patients with HCC treated in three tertiary hospitals in China between 2015 and 2021. Patient data were divided into RT and non-RT groups based on whether the patients underwent RT. Propensity score matching analysis was performed to minimize the deviation between the RT and non-RT groups, and the Kaplan–Meier method, Cox proportional hazard model, and nomogram were used to assess the efficacy of undergoing RT. The median overall survival (mOS) of the RT group was significantly longer compared with that of the non-RT group for the SEER data (16 months versus 9 months, p

The investigation of bone defect repair has been a significant focus in clinical research. The gradual progress and utilization of different scaffolds for bone repair have been facilitated by advancements in material science and tissue engineering. In recent times, the attainment of precise regulation and targeted drug release has emerged as a crucial concern in bone tissue engineering. As a result, we present a comprehensive review of recent developments in responsive scaffolds pertaining to the field of bone defect repair. The objective of this review is to provide a comprehensive summary and forecast of prospects, thereby contributing novel insights to the field of bone defect repair.

Gold bimetallic nanostructures (AuBMNS) have exhibited superior Hg sensing activity as compared to their monometallic counterparts. Moreover, the Hg sensing performance of AuBMNS depends on their shape, size, composition, and surface chemistry. Thus, morphology-controlled preparation and application of these nanostructures in Hg detection is a hot area of research. Till now, no review paper in the literature accounts for the recent advances in the morphology-controlled synthesis of AuBMNS and their application in sensing Hg related to shape, size, optimum composition, morphology, and surface ligands. Taking this into consideration, we attempt to offer a clear understanding of the shape/size-controlled preparation, functionalization, and morphology-dependent application of AuBMNS in Hg detection. The chemical reduction approach for the morphology-controlled preparation of AuBMNS is critically discussed. The prospective role of different reaction parameters such as temperature, pH, time, reducing agents, nature/concentration of precursors, and capping/stabilizing agents in the morphology-controlled preparation of these nanostructures are reviewed. Moreover, morphology-dependent optical properties and performance of AuBMNS are discussed with recent (2020–2022) examples. In the later part, detection of Hg by using AuBMNS is reviewed and the effects of size, shape, surface chemistry/structure, optimum composition, and synergism are discussed. Finally, recent challenges in morphology-controlled preparation of AuBMNS, their shape/size-dependent performance, and prospects to resolve the related issues are discussed.

Abstract Aims To determine the incidence of hyperkalaemia in patients with heart failure with reduced ejection fraction (HFrEF) during up‐titration of guideline‐directed medical therapy (GDMT) in real‐world settings. Methods A retrospective review of medical records of all patients hospitalized for newly onset HFrEF at Sahlgrenska University Hospital, Sweden, between 1 January 2016 and 31 December 2019. Based on mineralocorticoid receptor antagonist (MRA) treatment within the first 6 months, patients were divided into four groups: (i) never received MRA, (ii) needed MRA dose reduction, (iii) needed discontinuation of MRA, and (iv) stable MRA treatment. Potassium levels were assessed at baseline and has the highest potassium level during the 6 months of up‐titration. Results Of 3456 patients hospitalized for heart failure, 630 (18%) were eligible (68.4% men, 66.8 years, mean EF of 29.4%). After up‐titration of GDMT 48.4% of patients received MRAs. Patients without MRA treatment were older (P

In view of the problems such as incomplete data collection and implementation layer, non embodiment of edge computing function, and unclear construction standards of integrated prevention and control platform during the construction of intelligent mine fire prevention and control subsystem, an architecture model based on “cloud-edge-end” collaboration was proposed in comparison with relevant provisions of national and local coal mine intelligent construction standards for fire prevention and control. Fire data sensing devices such as optical fiber temperature measurement, MEMS temperature sensors and inspection robot, as well as fire execution control devices such as grouting, nitrogen injection, automatic sprinkler and roadway rapid closure device were added to form the data sensing and execution control layer, which is responsible for sensing fire data information and executing control commands issued by cloud computing center or edge side; Edge computing devices were added to form the edge computing layer to realize the linkage control of on-site fire prevention and extinguishing devices; with the “Intelligent Mine Basic Information Platform” as the middle platform base, intelligent mine fire prevention and control business application was established to form a platform prevention and control layer, expert knowledge base was integrated, and professional analysis on key indicators of fire prevention and control were conducted. A comprehensive prevention and control system for intelligent analysis at the cloud platform layer, nearby analysis and control at the edge layer, and data collection and execution at the perception and execution layer were formed. The opposition and unity relationship among the three layers of “cloud-edge-end” fire prevention and control system were dialectically analyzed. Key devices and technologies such as wireless low-power fire sensor, patrol robot, monitoring point deployment optimization in fire hazard area, edge side supporting physical devices, edge side fire early warning algorithm, decision edge calculation algorithm, edge node deployment strategy, comprehensive prevention and control platform, fire data governance, fire early warning and decision model were discussed.

Objective: Accumulating evidence has demonstrated that lncRNA Taurine-upregulated gene 1 (TUG1) plays an important role in regulation of cell morphology, migration, proliferation and apoptosis. Our aim was to evaluate the oncogenic role of TUG1 in type I Endometrial Carcinoma (EC) and explore the precise mechanism of TUG1 involved in tumor progression. Materials and methods: The GSE17025 data set was used to analyze the correlation of TUG1 expression with type I EC patients’ prognosis. Furthermore, TUG1 expression profiles were measured by qRT-PCR from carcinoma tissues and adjacent nonneoplastic tissues (NNT) of 105 type I EC patients. The regulation of epithelial–mesenchymal transition (EMT) related molecules, p-AKT and AKT by TUG1 knockdown was investigated using Western blot analysis; meanwhile, the oncogenic roles of TUG1 were evaluated using cell viability and transwell migration/invasion assay in Hec-1-A and Ishikawa cell lines. Results: Firstly, we observed a significant association between higher TUG1 expression and lower survival rate in type I EC patients using the GSE17025 data set. A significant elevation of TUG1 levels was confirmed in type I EC tissues compared with NNT in the 105 type I EC patients, and high expression of TUG1 was associated with lymph vascular space invasion (LVSI) and lymph node metastasis (LNM). Subsequently, TUG1 knockdown could remarkably inhibit the Hec-1-A and Ishikawa cell invasion and migration in the functional experiment. Furthermore, our results showed that the protein levels of E-cadherin increased and N-cadherin decreased significantly, while β-catenin and Vimentin were not significantly altered upon TUG1 silencing in both Hec-1-A and Ishikawa cells. Finally, we found the p-AKT and AKT protein levels, and the rate of p-AKT/t-AKT has a tendency to be down-regulate in Hec-1-A cells, while the AKT pathway was not change significantly in Ishikawa cells after TUG1 knockdown. Conclusion: Collectively, our data reveal that TUG1 might be regarded as an oncogenic molecule that promotes type I EC cells metastasis leading to tumor progression, at least partially, by regulating E–N cadherin switch and the AKT pathway.

The supplementation of antimicrobial growth promoters (AGPs) has been banned in many countries because of the emergence of antimicrobial-resistant pathogens in poultry products and the environment. Probiotics have been broadly studied and demonstrated as a promising AGP substitute. Our study is centred on the effects of a multi-strain Bacillus-based probiotic product on broiler production performance and gut microbial profile in a dexamethasone-induced leaky gut challenge. Two hundred and fifty-six broiler chicks were hatched and randomly assigned into four groups (wheat-soybean meal basal diet (BD) = non-supplemented control (C), BD supplemented with dexamethasone in week 4 (CD), BD containing a probiotic from day one (P), and BD containing a probiotic from day one and supplemented with dexamethasone during challenge week 4 (PD)). The production performance and caecal, gizzard, jejunal lumen and jejunal mucosa swab microbiota were studied by 16S rRNA gene sequencing. The Bacillus probiotic product significantly improved production performance and altered caecal gut microbiota (p ≤ 0.05), but no significant impact on microbiota was observed in other gut sections.

Most research on immobilized microorganisms employs biomass charcoal as a carrier, but limited studies explore coal-based resources for microbial immobilization. Herein, lead-resistant functional strains were immobilized using weathered coal as a carrier, resulting in the development of a weathered coal-immobilized microbial material (JK-BW) exhibiting high efficiency in lead removal from solutions. A quadratic polynomial model for the adsorption capacity and adsorption rate of JK-BW on Pb2+ was developed using the Box-Behnken method to determine the optimal adsorption conditions. The Pb2+ adsorption mechanism of JK-BW was studied through batch adsorption and desorption experiments along with SEM-EDS, BET, FT-IR, and XPS analyses. Findings indicated that optimal conditions were identified at 306 K temperature, 0.36 g/L adsorbent dosage, and 300 mg/L initial solution concentration, achieving a peak adsorption performance of 338.9 mg/g (308 K) for the immobilized material, surpassing free cell adsorption by 3.8 times. Even after four cycles of repeated use, the material maintained its high adsorption capacity. Pb2+ adsorption by JK-BW involved monolayer chemisorption with ion exchange, complexation, precipitation, physical adsorption, and microbial intracellular phagocytosis. Ion exchange accounted for 22–42% and complexation accounted for 39–57% of the total adsorption mechanisms, notably involving exchanges with K, Ca, Na, and Mg ions as well as complexation with –OH, –COOH, CO–OH, –COOH, CO–, NH2, and the β-ring of pyridine for Pb2+ adsorption.

Let H denote the quaternion algebra. This paper investigates the generalized complementary covariance, which is the ϕ-Hermitian quaternion matrix. We give the properties of the generalized complementary covariance matrices. In addition, we explore the unitary diagonalization of the covariance and generalized complementary covariance. Moreover, we give the generalized quaternion unitary transform algorithm and test the performance by numerical simulation.

Theaflavins (TFs) are benzopropenoids containing multiple phenolic hydroxyl groups with broad-spectrum pharmacological activities, which can control and regulate the expression of tumour-initiating enzymes or related factors or promote apoptosis, inhibit tumour cell proliferation and metastasis, thus efficiently participating in both pre-cancer prevention and post-cancer treatment. This review summarizes the available in vitro and in vivo evidence, using various tumour cell lines and animal models, to demonstrate that theophyllin inhibits tumour cell proliferation, growth and metastasis mainly by inducing cell cycle arrest and apoptosis, and identifies the targets of action of theophyllin in some tumours, with far-reaching implications for the prevention and treatment of some tumours.

Selenium (Se)-based cathode materials have garnered considerable interest for lithium-ion batteries due to their numerous advantages, including low cost, high volumetric capacity (3268 mAh cm−3), high density (4.82 g cm−3), ability to be cycled to high voltage (4.2 V) without failure, and environmental friendliness. However, they have low electrical conductivity, low coulombic efficiency, and polyselenide solubility in electrolytes (shuttle effect). These factors have an adverse effect on the electrochemical performance of Li-Se batteries, rendering them unsuitable for real-world use. In this study, we briefly examined numerous approaches to overcoming these obstacles, including selecting an adequate electrolyte, the composition of Se with carbonaceous materials, and the usage of metal selenide base electrodes. Furthermore, we examined the effect of introducing interlayers between the cathode and the separator. Finally, the remaining hurdles and potential study prospects in this expanding field are proposed to inspire further insightful work.

Abstract To support communication channels with non‐stationary properties, the pilots are usually configured for the channel worst case in order to ensure the accuracy of tracking the channel, which inevitably causes a waste of resources. To solve this issue, first, a flexible two‐dimensional pilot muting mechanism is proposed by exploiting the time and frequency diversity of the pilot sequence of the resource grid for non‐stationary channel fading environment. Then a super‐resolution based non‐stationary channel recovery scheme for data channel recovery is further proposed for two‐dimensional pilot muting, and the energy efficiency of a resource block is also maximized. Numerical results show that the proposed mechanism can bring about as much as 8 dB performance gain in system energy efficiency.

Polymethoxyflavonoids (PMFs), the main bioactive compounds naturally occurring in the pericarp of Citrus reticulata ‘Chachi’ (CRCP), possess significant antitumor action. However, the action of PMFs in nasopharyngeal carcinoma (NPC) is currently unknown. The present research study was conducted to investigate the inhibitory mechanisms of PMFs from CRCP on NPC growth in vivo and in vitro. In our research, we used high-speed counter-current chromatography (HSCCC) to separate four PMFs (nobiletin (NOB), 3,5,6,7,8,3′,4′-heptamethoxyflavone (HMF), tangeretin (TGN), and 5-hydroxy-6,7,8,3′,4′-pentamethoxyflavone (5-HPMF)) from CRCP. CCK-8 assay was used to preliminarily screen cell viability following exposure to the four PMFs. Colony formation, Hoechst-33258 staining, transwell, and wound scratch assays were performed to assess the anti-proliferation, invasion, migration, and apoptosis-inducing effects of HMF on NPC cells. NPC tumors in xenograft tumor transplantation experiments were also established to explore the effect of HMF (100 and 150 mg/kg/day) on NPC. The histopathological changes in the treated rats were observed by H&E staining and Ki-67 detection by immunohistochemical techniques. The expressions of P70S6K, p-P70S6K, S6, p-S6, COX-2, p53, and p-p53 were measured by Western blot. The four PMFs were obtained with high purity (>95.0%). The results of the preliminary screening by CCK-8 assay suggested that HMF had the strongest inhibitory effect on NPC cell growth. The results of the colony formation, Hoechst-33258 staining, transwell, and wound scratch assays indicated that HMF had significant anti-proliferation, invasion, migration, and apoptosis-inducing ability in NPC cells. Moreover, HMF suppressed NPC tumor growth in xenograft tumor transplantation experiments. Further investigation suggested that HMF regulated NPC cells proliferation, apoptosis, migration, and invasion by activating AMPK-dependent signaling pathways. In conclusion, HMF-induced AMPK activation inhibited NPC cell growth, invasion, and metastatic potency by downregulating the activation of the mTOR signaling pathway and COX-2 protein levels, as well as enhancing the p53 phosphorylation level. Our study provides a crucial experimental basis for the clinical treatment of NPC, as well as the development and utilization of PMFs from CRCP.

Endometrial decidualization is a decidual tissue formed by the proliferation and re-differentiation of endometrial stroma stimulated by decidualization inducing factors. It is very important for the proper maintenance of pregnancy. Previous studies speculated that Golgi phosphoprotein 3 (GOLPH3) may have a regulatory role in the process of endometrial decidualization, while the specific molecular mechanisms of GOLPH3 is unclear. In this part, GOLPH3 was silenced in human endometrial stromal cells (hESCs), and the transcriptome data (RNA-seq) by GOLPH3 knockdown (siGOLPH3) was obtained by high-throughput sequencing technology so as to analyze the potential targets of GOLPH3 at expression and alternative splicing levels in hESCs. Through bioinformatics analysis, we found that siGOLPH3 can significantly affect the overall transcriptional level of hESCs. A total of 6,025 differentially expressed genes (DEGs) and 4,131 differentially alternative splicing events (DASEs) were identified. Through functional cluster analysis of these DEGs and genes where differential alternative splicing events are located, it is found that they are enriched in the PI3K/Akt signaling pathway, RNA splicing and processing, transcription factors and other pathways related to endometrial decidualization and important biological processes, indicating the important biological function of GOLPH3. At the same time, we focused on the analysis of the transcription factors regulated by GOLPH3, including gene expression regulation and the regulation of variable splicing. We found that GOLPH3can regulate the expression of transcription factors such as LD1, FOSL2, GATA2, CSDC2 and CREB3L1. At the same time, it affects the variable splicing mode of FOXM1 and TCF3. The function of these transcription factors is directly related to decidualization of endometrium. Therefore, we infer that GOLPH3 may participate in endometrial de membrane by regulating expression and alternative splicing levels of transcription factors. We further identified the role of GOLPH3 in the transcriptional mechanism. At the same time, it also expands the function mode of GOLPH3 protein molecule, and provides a theoretical basis for downstream targeted drug research and development and clinical application.

Abstract RNA-binding proteins (RBPs) have been related to cancer development. Their functions in cervical cancer, however, are virtually unknown. One of these proteins, Mex-3 RNA-binding family member D (MEX3D), has been recently found to exhibit oncogenic properties in a variety of cancer types. In this present study, the functional roles and the regulatory mechanisms underlying MEX3D were examined in cervical cancer. The detection of MEX3D mRNA expression levels in cervical tissues was performed using reverse transcription-quantitative PCR. For functional analysis, for detecting apoptosis and cell proliferation in cervical cancer cells, the Cell Counting Kit-8, colony formation, and flow cytometry were utilized (SiHa and CaSki). The potential mechanisms of MEX3D were assessed and elucidated utilizing western blot analysis, RNA pull-down, RNA immunoprecipitation, and mRNA stability assays. For verification of MEX3D role in vivo, mouse xenograft models were established. When compared to normal cervical tissues, MEX3D expression was observed to be higher in cervical cancer tissues. MEX3D expression was increased in human papillomavirus (HPV) 16 positive cervical cancer tissues and positively regulated by HPV16 E7. When MEX3D expression was knocked down in cervical cancer cells, cell proliferation was decreased, colony formation was inhibited, and apoptosis was promoted. Furthermore, in a mouse xenograft model, knocking down MEX3D expression reduced cervical cancer tumor growth. In addition, MEX3D acted as an RBP to reduce TSC22 domain family protein 1 (TSC22D1) mRNA stability by directly binding to TSC22D1 mRNA. The findings revealed that MEX3D is upregulated by HPV16 E7 and has a crucial oncogenic in cervical cancer development via sponging TSC22D1 for destabilizing its mRNA levels. According to the findings of this study, MEX3D may be a potential therapeutic target for treating cervical cancer patients.

Abstract Background Clinical phenotype and prognosis of heart failure (HF) may be variable among different racial populations. Therefore, a patient-level comparison of hospitalized HF patients in two university hospitals from China and Sweden was performed. Methods and results This study was a pooled data analysis of the patients prospectively enrolled in two single-center studies in China (n = 949) and Sweden (n = 1639) from 2011 to 2015. Clinical characteristics and 6-month all-cause mortality were collected. Higher systolic blood pressure (126.1 ± 20.3 vs. 114.2 ± 15.4 mmHg, p

In the original publication [...]

In order to better identify the faults of gearbox under varying working conditions caused by noise and time-varying speed conditions， a fault identification method of gearbox under varying conditions is developed by combining DWAE and GRUNN， which could extract robust fault characteristics from noisy samples. The Adam and Dropout methods are used for training， and the softmax classifier is used to accurately identify the operating state of the gearbox under different working conditions. The results show that the six fault states of gears can be separated effectively when the model is used to identify gear faults， so as to meet the optimization function of gear state clustering. This model can extract the robust characteristic parameters of DWAE， and it can also use GRUNN to eliminate the gradient. When the number of training samples increased， the accuracy of waiting samples also improved significantly. When the number of samples is more than 200， stable accuracy could be obtained by testing the waiting samples， and the accuracy is the highest by dWAe-Grunn method. The model can maintain good accuracy under variable speed working conditions.

Cancer is a major threat to human health today. Although the existing anticancer treatments have effectively improved the prognosis of some patients, there are still other patients who cannot benefit from these well-established strategies. Reprogramming of lipid metabolism is one of the typical features of cancers. Recent studies have revealed that key enzymes involved in lipid metabolism may be effective anticancer therapeutic targets, but the development of therapeutic lipid metabolism targets is still insufficient. ECHS1 (enoyl-CoA hydratase, short chain 1) is a key enzyme mediating the hydration process of mitochondrial fatty acid β-oxidation and has been observed to be abnormally expressed in a variety of cancers. Therefore, with ECHS1 and cancer as the main keywords, we searched the relevant studies of ECHS1 in the field of cancer in Pubmed, summarized the research status and functions of ECHS1 in different cancer contexts, and explored its potential regulatory mechanisms, with a view to finding new therapeutic targets for anti-metabolic therapy. By reviewing and summarizing the retrieved literatures, we found that ECHS1 regulates malignant biological behaviors such as cell proliferation, metastasis, apoptosis, autophagy, and drug resistance by remodeling lipid metabolism and regulating intercellular oncogenic signaling pathways. Not only that, ECHS1 exhibits early diagnostic and prognostic value in clear cell renal cell carcinoma, and small-molecule inhibitors that regulate ECHS1 also show therapeutic significance in preclinical studies. Taken together, we propose that ECHS1 has the potential to serve as a therapeutic target of lipid metabolism.

ObjectiveTo explore the relative factors for best ovarian response in patients undergoing assisted reproductive technology with the gonadotropin-releasing hormone antagonist protocol and to establish a nomogram prediction model of ovarian response.MethodsA retrospective cohort analysis of the clinical data of 1,944 patients who received assisted reproductive treatment in the Center for Reproductive Medicine of Fujian Maternity and Child Health Hospital from April 1, 2018, to June 30, 2020. According to the number of oocytes obtained, there were 659 cases in the low ovarian response group (no more than five oocytes were retrieved), 920 cases in the normal ovarian response group (the number of retrieved oocytes was >5 but ≤18), and 365 cases in the high ovarian response group (>18 oocytes retrieved). Independent factors affecting ovarian responsiveness were screened by logistic regression, which were the model entry variables, and a nomogram prediction model was established based on the regression coefficients.ResultsThere were statistically significant differences in age, anti-Mullerian hormone, antral follicle count, the diagnosis of endometriosis, decreased ovarian reserve, polycystic ovary syndrome, basal follicle-stimulating hormone and basal luteinizing hormone among the three groups (P < 0.001). Multifactorial stepwise regression analysis showed that female age (0.95 [0.92–0.97], P = 0.000), decreased ovarian reserve (0.27 [0.19-0.38]), P = 0.000), endometriosis (0.81 [0.56-0.86], P = 0.000), antral follicle count (1.09 [1.06-1.12], P = 0.000), basal follicle-stimulating hormone (0.90 [0.85-0.96], P = 0.001), Anti-Mullerian hormone (1.19 [1.13–1.26], P= 0.000) and luteinizing hormone on trigger day (0.73 [0.66–0.80], P= 0.000), were independent factors for the occurrence of different ovarian responses during ovarian hyperstimulation. The predictive model of ovarian responsiveness was constructed based on the above factors, and the model was verified with 589 patients’ data from July 1, 2020, to December 31, 2020, at this center. The predicted ovarian response (number of eggs obtained) of a total of 450 patients was consistent with the actual results, with a coincidence degree of 76.4%, and the consistency index of the model is 0.77.ConclusionThe nomogram model was successfully developed to effectively, intuitively, and visually predict the ovary reactivity in the gonadotropin-releasing hormone antagonist protocol and provide guidance for clinical practice.

Background: Premna Puberula Pamp. Pectin (PP) was a Wudang functional food in China. It has the effect of dispelling fire, clearing heat and detoxification in folk medicine. However, little studies have been reported for their preparation, quality control, effects and toxicity. Methods: The P. Puberula leaves were collected from different pharms and seasons. The compounds in PP were identified using UPLC-Q-TOF-MS/MS. UV-VIS spectrophotometry with phenol-sulfuric acid and sodium nitrite aluminum nitrate were conducted for analyzing the water-soluble sugars and total flavonoids, respectively. L9(34) orthogonal experimental method was used to optimize the preparation process of PP. For the pharmacological effects of PP, the swelling right hind paw of ICR mice was modeled using subcutaneous injection of carrageenan gum solution, and the local tissue inflammatory reactions of the model mice were investigated using vernier calipers and HE staining. The serum inflammatory factor expression was detected using ELISA. The acute toxicity experiments were carried out for safety assessment of PP in ICR mice. Results: Fifty-three compounds were initially identified in PP among which flavonoids were dominant (19 out of 53). The average values of water-soluble sugar content and total flavonoid content of PP were 13.366 and 4.970 mg/g, respectively. The best preparation process of PP was powder-liquid ratio 1: 20, temperature 90 °C, and stirring time 3 min. Data showed that PP reduced paw edema and decrease the serum level of IL-6, TNF-α and IL-1β in the model mice. There was no toxic effect of PP on mice at a total dose of 6000 mg/kg/24h. Conclusion: In summary, by optimizing the preparation process, PP with stable quality can be obtained. PP has anti-inflammatory effects without toxicity.