Development and validation of prognostic index based on purine metabolism genes in patients with bladder cancer

BackgroundBladder cancer (BLCA) is a prevalent malignancy affecting the urinary system and is associated with significant morbidity and mortality worldwide. Dysregulation of tumor metabolic pathways is closely linked to the initiation and proliferation of BLCA. Tumor cells exhibit distinct metabolic activities compared to normal cells, and the purine metabolism pathway, responsible for providing essential components for DNA and RNA synthesis, is believed to play a crucial role. However, the precise involvement of Purine Metabolism Genes (PMGs) in the defense mechanism against BLCA remains elusive.MethodsThe integration of BLCA samples from the TCGA and GEO datasets facilitated the quantitative evaluation of PMGs, offering potential insights into their predictive capabilities. Leveraging the wealth of information encompassing mRNAsi, gene mutations, CNV, TMB, and clinical features within these datasets further enriched the analysis, augmenting its robustness and reliability. Through the utilization of Lasso regression, a prediction model was developed, enabling accurate prognostic assessments within the context of BLCA. Additionally, co-expression analysis shed light on the complex relationship between gene expression patterns and PMGs, unraveling their functional relevance and potential implications in BLCA.ResultsPMGs exhibited increased expression levels in the high-risk cohort of BLCA patients, even in the absence of other clinical indicators, suggesting their potential as prognostic markers. GSEA revealed enrichment of immunological and tumor-related pathways specifically in the high-risk group. Furthermore, notable differences were observed in immune function and m6a gene expression between the low- and high-risk groups. Several genes, including CLDN6, CES1, SOST, SPRR2A, MYBPH, CGB5, and KRT1, were found to potentially participate in the oncogenic processes underlying BLCA. Additionally, CRTAC1 was identified as potential tumor suppressor genes. Significant discrepancies in immunological function and m6a gene expression were observed between the two risk groups, further highlighting the distinct molecular characteristics associated with different prognostic outcomes. Notably, strong correlations were observed among the prognostic model, CNVs, SNPs, and drug sensitivity profiles.ConclusionPMGs have been implicated in the etiology and progression of bladder cancer (BLCA). Prognostic models corresponding to this malignancy aid in the accurate prediction of patient outcomes. Notably, exploring the potential therapeutic targets within the tumor microenvironment (TME) such as PMGs and immune cell infiltration holds promise for effective BLCA management, albeit necessitating further research. Moreover, the identification of a gene signature associated with purine Metabolism presents a credible and alternative approach for predicting BLCA, signifying a burgeoning avenue for targeted therapeutic investigations in the field of BLCA

Hesperidin Protects against Acute Alcoholic Injury through Improving Lipid Metabolism and Cell Damage in Zebrafish Larvae

Alcoholic liver disease (ALD) is a series of abnormalities of liver function, including alcoholic steatosis, steatohepatitis, and cirrhosis. Hesperidin, the major constituent of flavanone in grapefruit, is proved to play a role in antioxidation, anti-inflammation, and reducing multiple organs damage in various animal experiments. However, the underlying mechanism of resistance to alcoholic liver injury is still unclear. Thus, we aimed to investigate the protective effects of hesperidin against ALD and its molecular mechanism in this study. We established an ALD zebrafish larvae model induced by 350 mM ethanol for 32 hours, using wild-type and transgenic line with liver-specific eGFP expression Tg (lfabp10α:eGFP) zebrafish larvae (4 dpf). The results revealed that hesperidin dramatically reduced the hepatic morphological damage and the expressions of alcohol and lipid metabolism related genes, including cyp2y3, cyp3a65, hmgcra, hmgcrb, fasn, and fads2 compared with ALD model. Moreover, the findings demonstrated that hesperidin alleviated hepatic damage as well, which is reflected by the expressions of endoplasmic reticulum stress and DNA damage related genes (chop, gadd45αa, and edem1). In conclusion, this study revealed that hesperidin can inhibit alcoholic damage to liver of zebrafish larvae by reducing endoplasmic reticulum stress and DNA damage, regulating alcohol and lipid metabolism

In vitro cytocompatibility evaluation of poly(octamethylene citrate) monomers toward their use in orthopedic regenerative engineering

Citrate based polymer poly(octamethylene citrate) (POC) has shown promise when formulated into composite material containing up to 65 wt% hydroxylapatite (HA) for orthopedic applications. Despite significant research into POC, insufficient information about the biocompatibility of the monomers 1,8-Octanediol and Citrate used in its synthesis is available. Herein, we investigated the acute cytotoxicity, immune response, and long-term functionality of both monomers. Our results showed a cell-type dependent cytotoxicity of the two monomers: 1,8-Octanediol induced less acute toxicity to 3T3 fibroblasts than Citrate while presenting comparable cytotoxicity to MG63 osteoblast-like cells; however, Citrate demonstrated enhanced compatibility with hMSCs compared to 1,8-Octanediol. The critical cytotoxic concentration values EC30 and EC50, standard for comparing cytotoxicity of chemicals, were also provided. Additionally, Citrate showed slower and less inhibitory effects on long-term hMSC cell proliferation compared with 1,8-Octanediol. Furthermore, osteogenic differentiation of hMSCs exposure to Citrate resulted in less inhibitory effect on alkaline phosphatase (ALP) production. Neither monomer triggered undesired pro-inflammatory responses. In combination with diffusion model analysis of monomer release from cylindrical implants, based on which the maximum concentration of monomers in contact with bone tissue was estimated to be 2.2 × 10−4 mmol/L, far lower than the critical cytotoxic concentrations as well as the 1,8-Octanediol concentration (0.4 mg/mL or 2.7 mmol/L) affecting hMSCs differentiation, we provide strong evidence for the cytocompatibility of the two monomers degraded from citrate-based composites in the orthopedic setting

Risk-adapted locoregional radiotherapy strategies based on a prognostic nomogram for de novo metastatic nasopharyngeal carcinoma patients treated with chemoimmunotherapy

Abstract To develop a prognostic nomogram for individualized strategies on locoregional radiation therapy (LRRT) in patients with de novo metastatic nasopharyngeal carcinoma (dmNPC) treated with chemoimmunotherapy. Ninety patients with dmNPC treated with chemoimmunotherapy and diagnosed between 2019 and 2022 were included in our study. Cox regression analysis was performed to identify independent prognostic factors for overall survival (OS) and progression-free survival (PFS) to establish a nomogram. With a median follow-up of 17.5 months, the median PFS and OS were 24.9 months and 29.4 months, respectively. Sixty-nine patients and twenty-one patients were included in the LRRT group and without LRRT group, respectively. Multivariate analysis revealed that younger age, lower EBV DNA copy number before treatment, a single metastatic site, more cycles of chemotherapy and immunotherapy were significantly associated with better OS. A prognostic nomogram was constructed incorporating the above 5 independent factors, with a C-index of 0.894. Patients were divided into low- and high-risk cohorts based on nomogram scores. A significant improvement in OS was revealed in the LRRT group compared with the without-LRRT group for patients in the high-risk cohort (HR = 2.46, 95% CI 1.01–6.00, P = 0.049), while the OS was comparable between the two groups in the low-risk cohort. Our study indicates that LRRT may be associated with better prognosis in high-risk patients with dmNPC in the era of immunotherapy

Epithelium-derived SCUBE3 promotes polarized odontoblastic differentiation of dental mesenchymal stem cells and pulp regeneration

Abstract Background Signal peptide-CUB-EGF domain-containing protein 3 (SCUBE3), a secreted multifunctional glycoprotein whose transcript expression is restricted to the tooth germ epithelium during the development of embryonic mouse teeth, has been demonstrated to play a crucial role in the regulation of tooth development. Based on this, we hypothesized that epithelium-derived SCUBE3 contributes to bio-function in dental mesenchymal cells (Mes) via epithelium–mesenchyme interactions. Methods Immunohistochemical staining and a co-culture system were used to reveal the temporospatial expression of the SCUBE3 protein during mouse tooth germ development. In addition, human dental pulp stem cells (hDPSCs) were used as a Mes model to study the proliferation, migration, odontoblastic differentiation capacity, and mechanism of rhSCUBE3. Novel pulp–dentin-like organoid models were constructed to further confirm the odontoblast induction function of SCUBE3. Finally, semi-orthotopic animal experiments were performed to explore the clinical application of rhSCUBE3. Data were analysed using one-way analysis of variance and t-tests. Results The epithelium-derived SCUBE3 translocated to the mesenchyme via a paracrine pathway during mouse embryonic development, and the differentiating odontoblasts in postnatal tooth germ subsequently secreted the SCUBE3 protein via an autocrine mechanism. In hDPSCs, exogenous SCUBE3 promoted cell proliferation and migration via TGF-β signalling and accelerated odontoblastic differentiation via BMP2 signalling. In the semi-orthotopic animal experiments, we found that SCUBE3 pre-treatment-induced polarized odontoblast-like cells attached to the dental walls and had better angiogenesis performance. Conclusion SCUBE3 protein expression is transferred from the epithelium to mesenchyme during embryonic development. The function of epithelium-derived SCUBE3 in Mes, including proliferation, migration, and polarized odontoblastic differentiation, and their mechanisms are elaborated for the first time. These findings shed light on exogenous SCUBE3 application in clinic dental pulp regeneration

Variations in right colic vascular anatomy observed during laparoscopic right colectomy

Abstract Background This study aimed to analyze right colonic vascular variability. Methods The study included 60 consecutive patients who underwent laparoscopic radical right colectomy and D3 lymph node dissection for malignant colonic cancer on the ileocecal valve, ascending colon or hepatic flexure (March 2013 to October 2016). The videos of the 60 surgical procedures were collected. Variations of right colonic vascular anatomy were retrospectively analyzed based on 60 high-resolution surgical videos of laparoscopic surgery. Results The superior mesenteric artery and vein were present in all cases; 95.0% (57/60) had the superior mesenteric artery on the left side of the superior mesenteric vein. The ileocolic artery and vein occurred in 96.7% (58/60) and 100% (60/60) of cases, respectively; 50.0% (29/58) had the ileocolic artery passing the superior mesenteric vein anteriorly. Thirty-three (55.0%) cases had a right colic artery, and 2 (3.33%) had a double right colic artery; 90.9% (30/36) had the right colic vein passing anterior to the superior mesenteric artery. Fifty-six (93.3%) cases had a right colic vein; 7 (12.5%) had a right colic vein accompanied by a right colic artery, 66.1% (37/56) had the right colic vein draining into the gastrocolic trunk of Henle, 23.2% (13/56) had the right colic vein directly draining into superior mesenteric vein, and 10.7% (6/56) had one right colic vein draining into the superior mesenteric vein and the other into the gastrocolic trunk of Henle. Fifty-three (88.3%) cases had a gastrocolic trunk of Henle: a gastrocolic trunk in 35.8% (19/53), a gastropancreatic trunk in 9.4% (5/53), and a gastropancreaticocolic trunk in 54.7% (29/53). The frequencies of middle colic artery and vein were respectively 100% (60/60) and 93.3% (56/60). Conclusions Right colonic vascular variations were classified in Chinese patients. Notable findings included a superior mesenteric artery positioned to the right of the superior mesenteric vein and variation in middle colic artery length. This knowledge may be helpful to colorectal surgeons and could potentially help to improve safety by reducing vascular complications during minimally invasive procedures

The Effects of Bagging on Color Change and Chemical Composition in ‘Jinyan’ Kiwifruit (<i>Actinidia chinensis</i>)

To explore the effect of bagging on the nutritional quality and color of kiwifruit (Actinidia spp.), the fruits of yellow-fleshed kiwifruit cultivars were analyzed after bagging treatment. Bagging treatment promoted the degreening of mesocarp and increased brightness. Bagging significantly reduced the accumulation of dry matter, titratable acids, starch, sucrose, fructose, and glucose during kiwifruit development. Additionally, bagging significantly reduced the accumulation of chlorophyll and carotenoids during development, whereas after debagging, the chlorophyll and carotenoid contents were significantly increased. Gene expression analysis showed that during most of the fruit development periods, the chlorophyll biosynthesis genes AcRCBS, AcGLUTR, and AcCHLG, and degradation genes AcCBR, AcPAO, AcPPH, AcCLH, and AcSGR had significantly lower expression levels in bagged fruit. Bagging also inhibited the expression of carotenoid metabolism genes, especially AcSGR and AcLCYB, which may play a key role in the process of fruit development during bagging by decreasing the accumulation of chlorophyll and carotenoids in kiwifruit. Additionally, bagging significantly reduced the content of AsA. The expression of the AsA biosynthesis genes AcPMI2, AcGPP2, and AcGalDH in bagged fruit was significantly lower than in the control, indicating that these may be the key genes responsible for the difference in the accumulation of AsA after bagging

Improving the Interfacial Stability between Lithium and Solid-State Electrolyte via Dipole-Structured Lithium Layer Deposited on Graphene Oxide

Utilization of lithium (Li) metal anode in solid-state batteries (SSBs) with sulfide solid-state electrolyte (SSE) is hindered by the instable Li/SSE interface. A general solution to solve this problem is to place an expensive indium (In) foil between the SSE and Li, while it decreases the output voltage and thus the energy density of the battery. In this work, an alternative strategy is demonstrated to boost the cycling performances of SSB by wrapping a graphene oxide (GO) layer on the anode. According to density functional theory results, initial deposition of a thin Li layer on the defective GO sheets leads to the formation of a dipole structure, due to the electron-withdrawing ability of GO acting on Li. By incorporating GO sheets in a nanocomposite of copper-cuprous oxide-GO (Cu-Cu2O-GO, CCG), a composite Li anode enables a high coulombic efficiency above 99.5% over 120 cycles for an SSB using Li10GeP2S12 SSE and LiCoO2 cathode, and the sulfide SSE is not chemically decomposed after cycling. The highest occupied molecule orbital/lowest unoccupied molecular orbital energy gap of this Li/GO dipole structure likely stretches over those of Li and sulfide SSE, enabling stabilized Li/SSE interface that can replace the expensive In layer as Li protective structure in SSBs

Amelioration of Chilling Injury by Fucoidan in Cold-Stored Cucumber via Membrane Lipid Metabolism Regulation

Cucumber fruit is very sensitive to chilling injury, which rapidly depreciates their commodity value. Herein, the effect of fucoidan treatment on cucumber under cold stress were investigated. Fucoidan treatment of cold-stored cucumber alleviated the occurrence of chilling injury, delayed weight loss, lowered electrolyte leakage and respiration rate, and retarded malondialdehyde accumulation. Different from the control fruit, fucoidan treated fruit showed a high level of fatty acid unsaturated content, fatty acid unsaturation, and unsaturation index and increased ω-FDAS activity, along with upregulated expression levels of CsSAD and CsFAD genes. Fucoidan reduced the phosphatidic acid content and membrane lipid peroxidation, lowered the phospholipase D (PLD) and lipoxygenase (LOX) activity, and downregulated the expression levels of CsPLD and CsLOX genes. Collectively, fucoidan treatment maintained the integrity of cell membrane in cold-stress cucumbers. The results provide a new prospect for the development of fucoidan as a preservative agent in the low-temperature postharvest storage of cucumbers