Targeting RPS6KC1 to overcome enzalutamide resistance in prostate cancer.

The androgen receptor signaling inhibitor enzalutamide (Enz) is one the primary therapeutic drugs for advanced prostate cancer (PCa). Nevertheless, most of patients ultimately develop resistance to Enz. Through an integrated analysis of CRISPR genome-wide and kinome-wide screens, coupled with observations of elevated expression levels in Enz-resistant cell lines and PCa tumor tissues, our study identified RPS6KC1 as a novel essential gene implicated in Enz resistance.

Experimental-simulation analysis on mechanical degradation and energy evolution characteristics of sandstone under water-rock coupling effects.

With increasing coal mining depths, water-rock interactions exacerbate the mechanical degradation of coal-rock masses and geological disaster risks. Investigating the mechanical properties and energy evolution mechanisms of water-bearing sandstone is crucial for ensuring safe mining operations. To address the existing research gap in analyzing energy evolution mechanisms of water-saturated rock masses from a macroscopic perspective and the lack of exploration into energy mechanisms at critical failure points at the mesoscale, this study employs the particle discrete element software PFC3D to establish numerical models of sandstone with varying water contents.

Experimental investigation of the acoustic emission and energy evolution of bedded coal under uniaxial compression.

Catastrophic events in underground coal mining usually originate from weak structures such as bedding and fractures. This study investigated the failure characteristics of coal samples with different bedding orientations by employing acoustic emission (AE) technology. Analysis of the AE time series, including ringing counts, amplitude, b-value, and the AF-RA relationship, was performed to characterize the failure behavior of the bedded coal.

Energy evolution and damage ontology modeling of coal destruction at different water contents.

The aim of this study was to investigate the energy evolution characteristics and an ontological model of the deformation of coal under different water contents. Uniaxial compression tests were conducted for coal with different water contents, and the analyses were based on the energy principle and the principle of minimum energy dissipation. The results showed that the physical properties of the coal specimens were different under different water contents, the peak strain was positively correlated with water content, and the compressive strength and elastic modulus were negatively correlated with water content.

Natural compounds in the management of polycystic ovary syndrome: a comprehensive review of hormonal regulation and therapeutic potential.

Polycystic ovary syndrome (PCOS) is a multifaceted endocrine disorder characterized by irregularities in gonadotropin secretion, hyperandrogenism, chronic anovulation, and polycystic ovarian morphology. In addition, it is often associated with metabolic dysfunctions, most notably insulin resistance (IR). This disorder affects approximately 6-20% of individuals, primarily emerging during early adolescence, and considerably increases the risk of conditions such as impaired glucose tolerance, type 2 diabetes, endometrial cancer, cardiovascular diseases, dyslipidemia, and postpartum complications.

Deformation mechanism and damage energy evolution of coal body under different gas pressures based on the energy principle.

With increasing mining depth, the coal pillars of a coal mine will be in a stressful environment characterized by high gas pressures and unidirectional loading. To investigate the damage evolution characteristics and energy evolution mechanism of coal pillars loaded in a gas pressure environment, a uniaxial compression test was performed on a coal body under different gas pressures using a load testing apparatus for gas-containing coal rocks. The obtained results showed that the mechanical properties of the coal body varied with the gas pressure.

Discovery of phloridzin as a new antagonist for Di(2-ethylhexyl) phthalate-induced male reproductive toxicity based on the adverse outcome pathway network and drug-target gene set enrichment analysis.

Di(2-ethylhexyl) phthalate (DEHP) is a widespread ubiquitous phthalate environmental contaminant. The male reproductive toxicity (MRT) from exposure to DEHP and its main metabolite, mono(2-ethylhexyl) phthalate (MEHP), has been well documented. Fully elucidating its toxic mechanism and discovering effective antagonists are desirable means to reduce the health risks of DEHP.

Genome-wide CRISPR-based screen identifies E2F transcription factor 1 as a regulator and therapeutic target of aristolochic acid-induced nephrotoxicity.

Aristolochic Acid I (AAI) is widely present in traditional Chinese medicines derived from the Aristolochia genus and is known to cause significant damage to renal tubular epithelial cells. Genome-wide screening has proven to be a powerful tool in identifying critical genes associated with the toxicity of exogenous substances. To identify undiscovered key genes involved in AAI-induced renal toxicity, a genome-wide CRISPR library screen was conducted in the human kidney-2 (HK-2) cell line.

Development and validation of a clinical diagnostic model for surgical site infection after surgery in patients with gastric cancer.

Background: Surgical site infection (SSI) is a common and serious complication following gastric cancer surgery, often linked to patient age, surgery duration, and the surgical approach taken. Accurate prediction and personalized mitigation of SSI risk are crucial for improving surgical outcomes. While prior studies have focused on SSI rates after open and laparoscopic gastric cancer surgeries, it is important to also consider robot-assisted procedures.

Identification of sanguinarine as a novel antagonist for perfluorooctanoate/perfluorooctane sulfonate-induced senescence of hepatocytes: An integrated computational and experimental analysis.

Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS), two prominent per- and polyfluoroalkyl substances (PFASs), are potentially harmful to many human organs. However, there only exist limited methods to mitigate their health hazards. The aim of this study is to combine a bioinformatics analysis with in vitro experiments to discover small molecules that can alleviate liver damage caused by PFOA/PFOS.

SLC4A4 is a novel driver of enzalutamide resistance in prostate cancer.

The androgen receptor signaling inhibitor (ARSI) enzalutamide (Enz) has shown critical efficacy in the treatment of advanced prostate cancer (PCa). However, the development of drug resistance is a significant factor contributing to mortality in PCa patients. We aimed to explore the key mechanisms of Enz-resistance.

New insights into the interplay between autophagy, gut microbiota and insulin resistance in metabolic syndrome.

Metabolic syndrome (MetS) is a widespread and multifactorial disorder, and the study of its pathogenesis and treatment remains challenging. Autophagy, an intracellular degradation system that maintains cellular renewal and homeostasis, is essential for maintaining antimicrobial defense, preserving epithelial barrier integrity, promoting mucosal immune response, maintaining intestinal homeostasis, and regulating gut microbiota and microbial metabolites. Dysfunctional autophagy is implicated in the pathological mechanisms of MetS, involving insulin resistance (IR), chronic inflammation, oxidative stress, and endoplasmic reticulum (ER) stress, with IR being a predominant feature.

Multicomponent Polymerizations of Elemental Sulfur, CHCl, and Aromatic Amines toward Chemically Recyclable Functional Aromatic Polythioureas.

The exploration of new polymer materials required the development of efficient, economic, robust, and scalable synthetic routes, taking energy consumption, environmental benefit, and sustainability into overall consideration. Herein, through retro-polymerization analysis of functional aromatic polythioureas, a multicomponent reaction of elemental sulfur, CHCl, and aromatic amines was designed with the assistance of fluoride, and efficient, economic, and robust multicomponent polymerizations (MCPs) of these three abundantly available cheap monomers, elemental sulfur, CHCl, and aromatic diamines, were developed to realize scalable conversion directly from sulfur to a series of functional aromatic polythioureas with high molecular weights ( up to 50,800 g/mol) in excellent yields (up to 98%). The synergistic cooperation of the strong and selective coordination of thiourea with gold ions and the redox property of aromatic polythiourea enable in situ reduction of Au to elemental gold under a normal bench condition.

Preoperative neutrophil-to-lymphocyte ratio predicts symptomatic anastomotic leakage in elderly colon cancer patients: Multicenter propensity score-matched analysis.

Background: The neutrophil-to-lymphocyte ratio (NLR), a composite inflammatory biomarker, is associated with the prognosis in patients with colorectal tumors. However, whether the NLR can be used as a predictor of symptomatic postoperative anastomotic leakage (AL) in elderly patients with colon cancer is unclear.

Aim: To assess the role of the NLR in predicting the occurrence of symptomatic AL after surgery in elderly patients with colon cancer.

CRISPR genome-wide screening identifies PAK1 as a critical driver of ARSI cross-resistance in prostate cancer progression.

Next-generation androgen receptor signaling inhibitors (ARSIs), such as enzalutamide (Enza) and darolutamide (Daro), are initially effective for the treatment of advanced prostate cancer (PCa) and castration-resistant prostate cancer (CRPC). However, patients often relapse and develop cross-resistance, which consequently makes drug resistance an inevitable cause of CRPC-related mortality. By conducting a comprehensive analysis of GEO datasets, CRISPR genome-wide screening results, ATAC-seq data, and RNA-seq data, we systemically identified PAK1 as a significant contributor to ARSI cross-resistance due to the activation of the PAK1/RELA/hnRNPA1/AR-V7 axis.

PVA/PAA/DMTD electrospun nanofibrous membrane for the selective adsorption of Pb(II) ions in liquid foods.

Lead (Pb(II)) contamination is common in liquid foods and can result from Pb(II) being present in the raw materials or during handling processes. However, due to the complexity of food matrices, there is limited data available concerning Pb(II) ion removal from food sources. This study focused on fabricating a PVA/PAA/DMTD electrospun nanofibrous membrane (ENFM) to efficiently and selectively remove Pb(II) ions from liquid foods.

A nomogram for the prediction of survival for colorectal signet ring cell carcinoma after surgery: A population-based study.

The aim was to construct and verify a nomogram-based assessment of cancer-specific survival (CSS) in patients with colorectal signet ring cell carcinoma after surgery. Patients were collected from Surveillance, Epidemiology, and End Results program between 2004 and 2015. Independent prognostic indicators were determined in the training cohort by Cox regression model.

Development and validation of a nomogram to predict overall survival for cervical adenocarcinoma: A population-based study.

This study aimed to develop and validate a nomogram for predicting the overall survival of cervical adenocarcinoma (CAC) patients using a large database comprising patients with different ethnicities. We enrolled primary CAC cases with complete clinicopathological and survival data from the Surveillance, Epidemiology, and End Results program during 2004 to 2015. For training set samples, this work applied the Cox regression model to obtain factors independently associated with patient prognosis, which could be incorporated in constructing the nomogram.

The transcription activity of on expression is significantly blocked by methylation of CpG shore in non-promoter of lung cancer cell lines.

Background: The aberrant expression of the classical tumor suppressor gene is a frequent event in lung cancer mainly due to the hypermethylation of its 5'-cytosine-phosphate-guanine-3' island (Cgi). However, whether methylation happens in other regions and how expression and function are affected are largely unknown.

Methods: Clustered Regularly Interspaced Short Palindromic Repeats/dCas9 (CRISPR/dCas9) technology was used for methylation editing at specific site of .

Mechanical characteristics and energy evolution in a rock mass with a weak structural plane.

The present aims to investigate the mechanical characteristics and energy evolution in rock masses containing weak structural planes under conventional triaxial loading conditions. Using a fluid-solid coupling test system of coal rock, numerous conventional triaxial compression tests were performed on rock masses at various dip angles of the structural plane. The obtained empirical outcomes revealed that the deviatoric stress-strain curve of the weak structural plane rock mass with an inclination angle greater than 20° rises step-by-step.

Effect of intraoperative anastomotic reinforcement suture on the prevention of anastomotic leakage of double-stapling anastomosis for laparoscopic rectal cancer: a systematic review and meta-analysis.

Background And Aims: The use of sutures to strengthen the anastomosis after rectal cancer surgery to reduce the possibility of anastomotic leakage has been debated. The aim of this systematic review and meta-analysis was to investigate the influence of intraoperative anastomotic reinforcing sutures on anastomotic leakage of double-stapling anastomosis for laparoscopic rectal cancer surgery.

Methods: A systematic search of PubMed, Embase, Web of Science, and Cochrane databases was performed to identify literature examining anastomotic leak as the primary outcome to compare studies of laparoscopic surgery for rectal cancer using the double-stapling anastomosis technique with or without intraoperative anastomotic reinforcement with sutures.