Dual Role of Lysosome in Cancer Development and Progression.

Lysosomes are essential intracellular catabolic organelles that contain digestive enzymes involved in the degradation and recycle of damaged proteins, organelles, etc. Thus, they play an important role in various biological processes, including autophagy regulation, ion homeostasis, cell death, cell senescence. A myriad of studies has shown that the dysfunction of lysosome is implicated in human aging and various age-related diseases, including cancer.

Synthesis and evaluation of photoaffinity labeling reagents for identifying binding sites of sulfated neurosteroids on NMDA and GABA receptors.

The endogenous neurosteroids dehydroepiandrosterone sulfate (DHEAS) and pregnenolone sulfate (PS) are allosteric modulators of γ-aminobutyric acid type A (GABA) and -methyl-d-aspartate (NMDA) type glutamate receptors. Analogues of these endogenous steroid sulfates can be either positive or negative allosteric modulators (PAMs or NAMs, respectively) of these receptors, but there is limited information about the steroid-protein binding interactions that mediate these effects and photoaffinity labeling reagents (PALs) of sulfated steroids have not been reported previously. The synthesis of a panel of ten sulfated steroid analogues containing a diazirine group, five of which also contain an alkyne group for click chemistry reactions, for use in photoaffinity labeling studies to identify binding sites for steroid sulfates that are either positive or negative allosteric modulators is reported.

Eco-environmental responses of Eichhornia crassipes rhizobacteria community to co-stress of per(poly)fluoroalkyl substances and microplastics.

The stabilization of rhizobacteria communities plays a crucial role in sustaining healthy macrophyte growth. In light of increasing evidence of combined pollution from microplastics (MPs) and per- and polyfluoroalkyl substances (PFASs), Selecting typical floating macrophyte as a case, this study explored their impacts using hydroponic simulations and 16S rRNA high-throughput sequencing. A total of 31 phyla, 77 classes, 172 orders, 237 families, 332 genera, and 125 rhizobacteria species were identified.

Three classes of propofol binding sites on GABA receptors.

Propofol is a widely used anesthetic and sedative that acts as a positive allosteric modulator of gamma-aminobutyric acid type A (GABA) receptors. Several potential propofol binding sites that may mediate this effect have been identified using propofol-analogue photoaffinity labeling. Ortho-propofol diazirine (o-PD) labels β-H267, a pore-lining residue, whereas AziPm labels residues β-M286, β-M227, and α-I239 in the two membrane-facing interfaces [β(+)/α(-) and α(+)/β(-)] between α and β subunits.

Characteristics of organic matter driven by Eichhornia crassipes during co-contamination with per(poly)fluoroalkyl substances (PFASs) and microplastics (MPs).

Co-contamination with MPs and PFASs has been recorded, particularly in surface-water environments. Floating macrophyte microcosms are an important part of the surface water ecosystem, and dissolved organic matter (DOM) driven by floating macrophytes (FMDDOM) is critical for maintaining material circulation. However, knowledge gaps remain regarding the impact of MPs and PFASs co-pollution on FMDDOM.

Transformation of Metal-Organic Framework from Kinetic to Thermodynamic Product for Controlled Delivery of Vitamin C.

A biocompatible metal-organic framework (MOF), named HSTC-4, constructed using the flexible 4,4'-oxybis(benzoic acid) (OBA), was developed to enable efficient loading and controlled release of vitamin C (VC) through a combination of strategies involving ligand length, structure design, and metal selection. The kinetic product HSTC-4 demonstrates a propensity for transforming into the thermodynamically stable HSTC-5 under external stimuli, such as photoillumination and vacuum heating, as witnessed by single-crystal to single-crystal transformation. Density functional theory (DFT) calculations reveal that the VC guest molecules exhibit stronger binding affinity with HSTC-5 due to its narrower pores compared to HSTC-4, resulting in a slower release of VC from VC@HSTC-5.

Direct measurements of neurosteroid binding to specific sites on GABA receptors.

Background And Purpose: Neurosteroids are allosteric modulators of GABA currents, acting through several functional binding sites although their affinity and specificity for each site are unknown. The goal of this study was to measure steady-state binding affinities of various neurosteroids for specific sites on the GABA receptor.

Experimental Approach: Two methods were developed to measure neurosteroid binding affinity: (1) quenching of specific tryptophan residues in neurosteroid binding sites by the neurosteroid 17-methylketone group, and (2) FRET between MQ290 (an intrinsically fluorescent neurosteroid) and tryptophan residues in the binding sites.

The bioaccumulation and ecotoxicity of co-exposure of per(poly)fluoroalkyl substances and polystyrene microplastics to Eichhornia crassipes.

Gen X and F-53B have been popularized as alternatives to PFOA and PFOS, respectively. These per(poly)fluoroalkyl substances pervasively coexist with microplastics (MPs) in aquatic environments. However, there are knowledge gaps regarding their potential eco-environmental risks.

Fasudil alleviates alcohol-induced cognitive deficits and hippocampal morphology injury partly by altering the assembly of the actin cytoskeleton and microtubules.

Alcohol-Related Brain Damage (ARBD) manifests predominantly as cognitive impairment and brain atrophy with the hippocampus showing particular vulnerability. Fasudil, a Rho kinase (ROCK) inhibitor, has established neuroprotective properties; however, its impact on alcohol-induced cognitive dysfunction and hippocampal structural damage remains unelucidated. This study probes Fasudil's neuroprotective potential and identifies its mechanism of action in an in vivo context.

[Pathogenesis and Targeted Treatment Progress of Splenomegaly in Primary Myelofibrosis--Review].

Primary myelofibrosis (PMF) is a myeloproliferative neoplasm with splenomegaly as the major clinical manifestation, which is commonly considered to be linked to splenic extramedullary hematopoiesis. Alteration of CXCL12/CXCR4 pathway can lead to the migration of hematopoietic stem cells and hematopoietic progenitor cells from bone marrow to spleen which results in splenic extramedullary hematopoiesis. In addition, low GATA1 expression and the abnormal secretion of cytokines were found to be significantly associated with splenomegaly.

Multi-Omics Characteristics of Ferroptosis Associated with Colon Adenocarcinoma Typing and Survival.

Background: Ferroptosis, an iron-dependent form of cell death, plays a crucial role in the progression of various cancers, including colon adenocarcinoma (COAD). However, the multi-omics signatures relevant to ferroptosis regulation in COAD diagnosis remain to be elucidated.

Methods: The transcriptomic, miRNAomic, and methylomic profiles of COAD patients were acquired from the Cancer Genome Atlas (TCGA).

[Metabolic mechanism and intervention strategy of atrial fibrillation in the elderly].

Atrial fibrillation (AF) is a cardiovascular epidemic that occurs primarily in the elderly with primary cardiovascular diseases, leading to severe consequences such as stroke and heart failure. The heart is an energy-consuming organ, which requires a high degree of metabolic flexibility to ensure a quick switch of metabolic substrates to meet its energy needs in response to physiological and pathological stimulation. Metabolism is closely related to the occurrence of AF, and AF patients manifest metabolic inflexibility, such as insulin resistance and the metabolic shift from aerobic metabolism to anaerobic glycolysis.

The value of total tumor diameter in unilateral multifocal papillary thyroid carcinoma: a propensity score matching analysis.

Background: Tumor multifocality is frequently observed in papillary thyroid carcinoma (PTC). However, the maximum tumor diameter (MTD), currently utilized in various staging schemes, might not accurately indicate the level of aggressiveness exhibited by multifocal tumors. We aimed to investigate the relationship between total tumor diameter (TTD) and clinicopathological features of papillary thyroid carcinoma.

Global development and future trends of artificial sweetener research based on bibliometrics.

Artificial sweeteners have sparked a heated debate worldwide due to their ambiguous impacts on public and environmental health and food safety and quality. Many studies on artificial sweeteners have been conducted; however, none scientometric studies exist in the field. This study aimed to elaborate on the knowledge creation and development of the field of artificial sweeteners and predict the frontiers of knowledge based on bibliometrics.

Response to Brigatinib Targeted Therapy in Non-Small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor Exon 19 Deletion, T790M, and cis-C797S Triple Mutations: A Case Report.

Epidermal growth factor receptor () triple mutations with exon 19 deletion (del19), T790M, and cis-C797S (del19/T790M/cis-C797S mutations) frequently occur in patients with non-small cell lung cancer (NSCLC), while progression to frontline -tyrosine kinase inhibitors (TKIs) and osimertinib was resistant to all clinically available -TKIs. Brigatinib monotherapy may be a potential treatment for NSCLC harboring del19/T790M/cis-C797S mutations based on preclinical studies; however, no clinical report has evaluated its efficacy on del19/T790M/cis-C797S mutations. Herein, we present a case of a female patient with del19-mutated NSCLC treated with afatinib followed by osimertinib due to acquired T790M mutation.

Telestration with augmented reality improves surgical performance through gaze guidance.

Background: In minimally invasive surgery (MIS), trainees need to learn how to interpret the operative field displayed on the laparoscopic screen. Experts currently guide trainees mainly verbally during laparoscopic procedures. A newly developed telestration system with augmented reality (iSurgeon) allows the instructor to display hand gestures in real-time on the laparoscopic screen in augmented reality to provide visual expert guidance (telestration).

Advancing Prediction of Risk of Intraoperative Massive Blood Transfusion in Liver Transplantation With Machine Learning Models. A Multicenter Retrospective Study.

Background: Liver transplantation surgery is often accompanied by massive blood loss and massive transfusion (MT), while MT can cause many serious complications related to high mortality. Therefore, there is an urgent need for a model that can predict the demand for MT to reduce the waste of blood resources and improve the prognosis of patients.

Objective: To develop a model for predicting intraoperative massive blood transfusion in liver transplantation surgery based on machine learning algorithms.

The Effect of Trustor Age and Trustee Age on Trustworthiness Judgments: An Event-Related Potential Study.

Perceived trustworthiness based on facial appearance plays an important role in interpersonal trust and cooperative behavior. Interpersonal trust behaviors involve both trustors and trustees. However, there is no clear conclusion on how the age of the two individuals affects interpersonal trust behaviors.

Rapid Internal Control Reference Recombinase-Aided Amplification Assays for EBV and CMV Detection.

Epstein-Barr virus (EBV) and cytomegalovirus (CMV), two of the most prevalent human herpesviruses, cause a wide spectrum of diseases and symptoms and are associated with serious health problem. In this study, we developed an internal control reference recombinase-aided amplification (ICR-RAA) assay for the rapid detection of EBV and CMV within 30 min. The assay had a sensitivity of 5 and 1 copies/test for EBV and CMV, respectively, with no cross reaction with other pathogens.

Validation of Trifluoromethylphenyl Diazirine Cholesterol Analogues As Cholesterol Mimetics and Photolabeling Reagents.

Aliphatic diazirine analogues of cholesterol have been used previously to elaborate the cholesterol proteome and identify cholesterol binding sites on proteins. Cholesterol analogues containing the trifluoromethylphenyl diazirine (TPD) group have not been reported. Both classes of diazirines have been prepared for neurosteroid photolabeling studies and their combined use provided information that was not obtainable with either diazirine class alone.

A sex-linked SNP mutation in amhr2 is responsible for male differentiation in obscure puffer (Takifugu obscurus).

Background: Anti-Mullerian hormone receptor type II (Amhr2) is a key receptor of Amh signaling in regulating gonad development. The amhr2 gene has been identified in numerous species, including a few teleost fishes. However, the roles of Amhr2 in Amh signaling in fish are poorly studied.

Machine Learning for the Prediction of Red Blood Cell Transfusion in Patients During or After Liver Transplantation Surgery.

This study aimed to use machine learning algorithms to identify critical preoperative variables and predict the red blood cell (RBC) transfusion during or after liver transplantation surgery. A total of 1,193 patients undergoing liver transplantation in three large tertiary hospitals in China were examined. Twenty-four preoperative variables were collected, including essential population characteristics, diagnosis, symptoms, and laboratory parameters.