A Predictive Model for Initial Platinum-Based Chemotherapy Efficacy in Patients with Postoperative Epithelial Ovarian Cancer Using Tissue-Derived Small Extracellular Vesicles.

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.

Versatility of the supraclavicular artery island flap for head and neck reconstruction.

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.

Up-regulation of long non-coding RNA H19 ameliorates renal tubulointerstitial fibrosis by reducing lipid deposition and inflammatory response through regulation of the microRNA-130a-3p/long-chain acyl-CoA synthetase 1 axis.

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-ß1 (TGF-ß1)-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-ß1. 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-ß1. Notably, up-regulation of lncRNA H19 reduced lipid accumulation and triacylglycerol content in kidneys of mice with UUO and TGF-ß1-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.

Effect of different treatment protocols on in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) outcomes in adenomyosis women: a systematic review and meta-analysis.

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<0.00001), a 35% reduction in live birth rate (LBR; 30.72% vs 47.77%, OR: 0.65, 95% CI: 0.58 to 0.73, p<0.00001) and a 1.9-fold increase in miscarriage rate (MR; 27.82% vs 13.9%, OR: 1.90, 95% CI: 1.56 to 2.31, p<0.00001). Subgroup analysis suggested that, in fresh embryo transfer (ET) cycles, the CPR (34.4% vs 58.25%) in the long/short/antagonist protocol group was poorer than that in the ultralong protocol group. In frozen ET (FET) cycles, there were no statistical differences in CPR ((GnRHa+FET) AM(adenomyosis) vs non-AM: 51.32% vs 43.48%, p=0.31; (non-GnRHa+FET) AM vs non-AM: 50.25% vs 60.10%, p=0.82), MR ((GnRHa+FET) AM vs non-AM:12.82% vs 12.50%, p=0.97; (non-GnRHa+FET) AM vs non-AM: 30.5% vs 15.54%, p=0.15) and LBR ((GnRHa+FET) AM vs non-AM:44.74% vs 36.96%, p=0.31; (non-GnRHa+FET) AM vs non-AM: 34.42% vs 50.25%, p=0.28). The MR in the adenomyosis group was high in the fresh ET and FET cycles. CONCLUSIONS: FET might be a better choice for women with adenomyosis, especially those pretreated with GnRHa. In fresh ET cycles, pregnancy outcomes of the long/short/antagonist protocols were poorer than those of the ultralong protocol. TRIAL REGISTRATION NUMBER: CRD42022340743.

Identification of MAP1LC3A as a promising mitophagy-related gene in polycystic ovary syndrome.

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.

The combination of arginine and fluoride-containing bioactive glass acted synergistically in inhibiting enamel demineralization in permanent teeth.

OBJECTIVES: To evaluate the in-vitro efficacy of inhibiting enamel demineralization using arginine in combination with fluoride-containing bioactive glass (FBG). METHODS: In this study, the healthy enamel blocks were first demineralized in acetic acid for 24 h, then soaked in anti-demineralization treatment solutions containing either arginine or FBG or both for 96 h.The specimens treated in acetic acid were applied as the control group. The pH, calcium and phosphorus ion concentrations of the solutions were measured before and after treatment. Changes in enamel mineral weight, microhardness, and composition were also analyzed. RESULTS: The present of arginine facilitated fluorine release from treatment solutions with the presence of FBG. Both arginine and FBG significantly increased the pH of treatment solutions and prevented the further mineral weight loss compared to the control group. All anti-demineralization treatment groups showed significant increases in microhardness, but there was no statistical difference among the treatment groups. The SEM analysis showed enamel restoration in the arginine and FBG groups upon treatment, while the combined groups showing a superior anti-demineralization efficacy. 19F NMR showed the formation of fluorapatite in samples treated with solutions containing FBG. CONCLUSIONS: Both arginine and FBG could inhibit enamel demineralization to some extent, and their combination demonstrated an enhanced anti-demineralization efficacy. The low-concentration combination group exhibited anti-demineralization effects comparable to those of high-concentration ones. CLINICAL SIGNIFICANCE: This study introduces a new approach for caries prevention by combining the application of arginine and FBG. The release of fluorine promoted by the presented arginine along with calcium and phosphorus ions from FBG facilitated FAP formation. Additionally, the increment of pH resulting from arginine and FBG degradation further prevents enamel demineralization.

A cuttlefish ink nanoparticle-reinforced biopolymer hydrogel with robust adhesive and immunomodulatory features for treating oral ulcers in diabetes.

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.

Triphenyl phosphate (TPP) exposure promotes proliferation and migration capabilities of gastric cancer cells: Insights from gene expression and pathway analysis.

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.

1,6-Nucleophilic Di- and Trifluoromethylation of para-Quinone Methides with Me3SiCF2H/Me3SiCF3 Facilitated by CsF/18-Crown-6.

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.

Upregulation of GOLPH3 mediated by Bisphenol a promotes colorectal cancer proliferation and migration: evidence based on integrated analysis.

Background: The 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. Methods: We 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. Results: Our 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. Conclusion: This 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.

The Association between Broiler Litter Microbiota and the Supplementation of Bacillus Probiotics in a Leaky Gut Model.

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.

Nomogram to predict the probability of clinical pregnancy in women with poor ovarian response undergoing in vitro fertilization/ intracytoplasmic sperm injection cycles.

BACKGROUND: Poor ovarian response (POR) is associated with decreased clinical pregnancy rates, emphasizing the need for developing clinical prediction models. Such models can improve prognostic accuracy, personalize medical interventions, and ultimately enhance live birth rates among patients with POR. OBJECTIVE: This study aims to develop and validate a prognostic model for predicting clinical pregnancy outcomes in individuals with POR undergoing in vitro fertilization/ intracytoplasmic sperm injection (IVF/ICSI) cycles. METHODS: A retrospective cohort of 969 patients with POR undergoing fresh embryo transfer cycles at the Reproductive Center of Fujian Maternal and Child Health Center from January 2018 to January 2022 was included. The cohort was randomly divided into model (n = 678) and validation (n = 291) groups in a 7:3 ratio. A single-factor analysis was performed on the model group to identify variables influencing clinical pregnancy. Optimal variables were selected using LASSO regression, and a clinical prediction model was constructed using multivariate logistic regression analysis. The model's calibration and discrimination were assessed using receiver operating characteristic (ROC) and calibration curves, while the clinical utility was evaluated using decision curve analysis. RESULTS: Multivariate logistic regression analysis revealed that the age of the women (odds ratio [OR] 0.936, 95% confidence interval [CI] 0.898-0.976, P = 0.002), body mass index (BMI) ≤ 24 (OR 2.748, 95% CI 1.724-4.492, P < 0.001), antral follicle count (AFC) (OR 1.232, 95% CI 1.073-1.416, P = 0.003), anti-Müllerian hormone (AMH) (OR 1.67, 95% CI 1.178-2.376, P = 0.004), number of mature oocytes (OR 1.227, 95% CI 1.075-1.403, P = 0.003), number of embryos transferred (OR 1.692, 95% CI 1.132-2.545, P = 0.011), and transfer of high-quality embryos (OR 3.452, 95% CI 1.548-8.842, P = 0.005) were independent predictors of clinical pregnancy in patients with POR. According to the receiver operating characteristic (ROC) analysis, the prediction model exhibited an area under the curve (AUC) of 0.752 (0.714, 0.789) in the model group and 0.765 (0.708, 0.821) in the validation group. The clinical decision curve demonstrated that the model held maximum clinical utility in both cohorts when the threshold probability of clinical pregnancy ranged from 6-81% to 12-82%, respectively. CONCLUSION: Clinical pregnancy outcomes in patients with POR who underwent IVF/ICSI treatment were influenced by several independent factors, including the age of the women, BMI, AFC, AMH, number of mature oocytes, number of embryos transferred, and transfer of high-quality embryos. A clinical prediction model based on these factors exhibited favorable clinical predictive and applicative value. Therefore, this model can serve as a valuable tool for clinical prognosis, intervention, and facilitating personalized medical treatment.

GOLPH3 inhibits erastin-induced ferroptosis in colorectal cancer cells.

Ferroptosis is a novel form of programmed cell death and is considered to be a druggable target for colorectal cancer (CRC) therapy. However, the role of ferroptosis in CRC and its underlying mechanism are not fully understood. In the present study we found that a protein enriched in the Golgi apparatus, Golgi phosphoprotein 3 (GOLPH3), was overexpressed in human CRC tissue and in several CRC cell lines. The expression of GOLPH3 was significantly correlated with the expression of ferroptosis-related genes in CRC. The overexpression of GOLPH3 in Erastin-induced Caco-2 CRC cells reduced ferroptotic phenotypes, whereas the knockdown of GOLPH3 potentiated ferroptosis in HT-29 CRC cells. GOLPH3 induced the expression of prohibitin-1 (PHB1) and prohibitin-2 (PHB2), which also inhibited ferroptosis in Erastin-treated CRC cells. Moreover, GOLPH3 interacted with PHB2 and nuclear factor erythroid 2-related factor 2 (NRF2) in Caco-2 cells. These observations indicate that GOLPH3 is a negative regulator of ferroptosis in CRC cells. GOLPH3 protects these cells from ferroptosis by inducing the expression of PHB1 and PHB2, and by interacting with PHB2 and NRF2.

Advances in research on spexin-mediated regulation of reproductive function in vertebrates.

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.

Reverse remodeling of mitral leaflets after medical treatment in recent-onset dilated cardiomyopathy.

BACKGROUND: The growth of mitral leaflets (MLs) adaptive to left ventricluar (LV) remodeling has been observed. However, the elasticity of MLs upon mechanical stimuli would be supposed if it shrinks with LV reverse remodeling (LVRR). MATERIAL AND METHODS: Patients with idiopathic recent-onset dilated cardiomyopathy (RODCM) (n = 82) and 50 matched normal controls (NC) were prospectively enrolled. Echocardiography was performed at baseline and 6 months of follow-up for the anterior and posterior mitral leaflet (AML and PML) length, mitral annular dimension (MAD), and tenting height (TH). LVRR was measured as a ≥ 15% reduction in LV end-diastolic volume (LVEDV). RESULTS: After 6 months, LVRR was achieved in 69.5% of patients. The AML (28 ± 3 vs. 26 ± 3 mm, p = 0.004) and PML (19 ± 4 vs. 17 ± 3 mm, p < 0.001) decreased in length, as well as the MAD (31 ± 5 vs. 28 ± 5 mm, p = 0.001) and TH (10 ± 3 vs. 8 ± 2 mm, p < 0.001). Compared with the NC group, the AML and PML of the RODCM group were 16.7% and 35.7% longer at baseline and remained 8.3% and 21.2% longer at follow-up, respectively. The change in AML or PML correlated moderately with that in LVEDV (r = 0.487, p < 0.001; r = 0.516, p < 0.001, respectively). The AML and PML length decreased in the LVRR (+) subgroup (AML, 28 ± 3 vs. 26 ± 3 mm, p = 0.001; PML, 20 ± 4 vs. 16 ± 3 mm, p < 0.001), but remained the same in the LVRR (-) subgroup (27 ± 4 vs. 28 ± 4 mm, p = 0.318; 17 ± 3 vs. 17 ± 3 mm, p = 0.790). CONCLUSIONS: Enlarged MLs could reverse accompanied by LV reverse remodeling. This study provided the other facet of ML plasticity adaptive to mechanical stretching.

Association between being large for gestational age and cardiovascular metabolic health in children conceived from assisted reproductive technology: a prospective cohort study.

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.

Protosappanin B enhances the chemosensitivity of 5-fluorouracil in colon adenocarcinoma by regulating the LINC00612/microRNA-590-3p/Golgi phosphoprotein 3 axis.

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.

PlantMine: A Machine-Learning Framework to Detect Core SNPs in Rice Genomics.

As a fundamental global staple crop, rice plays a pivotal role in human nutrition and agricultural production systems. However, its complex genetic architecture and extensive trait variability pose challenges for breeders and researchers in optimizing yield and quality. Particularly to expedite breeding methods like genomic selection, isolating core SNPs related to target traits from genome-wide data reduces irrelevant mutation noise, enhancing computational precision and efficiency. Thus, exploring efficient computational approaches to mine core SNPs is of great importance. This study introduces PlantMine, an innovative computational framework that integrates feature selection and machine learning techniques to effectively identify core SNPs critical for the improvement of rice traits. Utilizing the dataset from the 3000 Rice Genomes Project, we applied different algorithms for analysis. The findings underscore the effectiveness of combining feature selection with machine learning in accurately identifying core SNPs, offering a promising avenue to expedite rice breeding efforts and improve crop productivity and resilience to stress.

USP6 and circCYFIP2 target oncoprotein GOLPH3 for deubiquitination and induce platinum resistance in colon cancer.

GOLPH3 has been identified as an oncoprotein, playing a crucial role on progression and chemoresistancein of colon adenocarcinoma (COAD). However, it is still unclear the regulation of GOLPH3 expression at protein level. We discovered ubiquitin-specific proteases 6 (USP6) directly regulated the deubiquitination of the GOLPH3 protein and enhanced its stability in COAD. Overexpression of USP6 promoted COAD cell viability, inhibited apoptosis, and accelerated the growth of transplanted tumors growth in vitro and in vivo by deubiquitinating GOLPH3. Additionally, circCYFIP2 showed high expression levels in DDP-resistant colon cancer cells, promoting the cell proliferation. Mechanically, circCYFIP2 binds to both GOLPH3 protein and USP6, strengthening the interaction between GOLPH3 and USP6, and consequently induced DDP resistance in vitro and in vivo. In conclusion, USP6 operates as a deubiquitinase, targeting the GOLPH3 protein in COAD and enhancing its stability. Meanwhile, circCYFIP2 is crucial for the deubiquitination of GOLPH3 protein mediated by USP6 and acts as a scaffold to confer platinum resistance. The discovery of circCYFIP2/USP6/GOLPH3 pathway offers a potential target for overcoming chemoresistance in COAD.