Protocol for identifying Dicer as dsRNA binding and cleaving reagent in response to transfected dsRNA.

Mammalian Dicer has been proved to be functional on double-stranded RNAs (dsRNAs) and involved in antiviral immunity or immune regulation. Here, we present a protocol for identifying Dicer as a dsRNA binding and cleaving factor to transfected dsRNA in cell lines, based on small RNA sequencing (RNA-seq) and dsRNA-immunoprecipitation (dsRNA-IP). We detail both experimental processes and analysis on small RNA-seq data.

Protocol for extraction of gut interstitial fluid in mice with two-front nutrient supply.

The intestine features a two-front nutrient supply environment, comprising an enteral side enriched with microbial and dietary metabolites and a serosal side supplied by systemic nutrients, collectively supporting intestinal and systemic homeostasis, but there is currently no optimal approach for extracting and assessing the local intestinal microenvironment. Here, we present a protocol for constructing a nutrient supply model in mice and extracting gut interstitial fluid (GIF) via centrifugation. This model and the extracted GIF are suitable for downstream analyses.

SLC39A10 is a key zinc transporter in T cells and its loss mitigates autoimmune disease.

Zinc homeostasis plays an essential role in maintaining immune function and is tightly regulated by zinc transporters. We previously reported that the zinc transporter SLC39A10, located in the cell membrane, critically regulates the susceptibility of macrophages to inflammatory stimuli; however, the functional role of SLC39A10 in T cells is currently unknown. Here, we identified two SNPs in SLC39A10 that are associated with inflammatory bowel disease (IBD).

Efficacy of General Magnetic Therapy and Motor-Evoked Potential-Guided Precision Magnetic Therapy in Patients with Overactive Bladder: A Randomized Controlled Trial.

Overactive bladder (OAB) is a prevalent chronic condition affecting approximately 12% of adults, with incidence increasing with age. While pharmacological and behavioural therapies are standard treatments, their efficacy is often limited by side effects and poor adherence. This study aimed to compare the therapeutic effects of precision magnetic stimulation guided by motor-evoked potential with general magnetic therapy in patients with OAB.

The Pentose Phosphate Pathway: From Mechanisms to Implications for Gastrointestinal Cancers.

The pentose phosphate pathway (PPP), traditionally recognized for its role in generating nicotinamide adenine dinucleotide phosphate (NADPH) and ribose-5-phosphate (R5P), has emerged as a critical metabolic hub with involvements in various gastrointestinal (GI) cancers. The PPP plays crucial roles in the initiation, development, and tumor microenvironment (TME) of GI cancers by modulating redox homeostasis and providing precursors for nucleotide biosynthesis. Targeting PPP enzymes and their regulatory axis has been a potential strategy in anti-GI cancer therapies.

Epigenetic Regulation of Stromal and Immune Cells and Therapeutic Targets in the Tumor Microenvironment.

The tumor microenvironment (TME) plays a pivotal role in neoplastic initiation and progression. Epigenetic machinery, governing the expression of core oncogenes and tumor suppressor genes in transformed cells, significantly contributes to tumor development at both primary and distant sites. Recent studies have illuminated how epigenetic mechanisms integrate external cues and downstream signals, altering the phenotype of stromal cells and immune cells.

SNP rs9364554 Modulates Androgen Receptor Binding and Drug Response in Prostate Cancer.

(1) Background: Prostate cancer treatment efficacy is significantly influenced by androgen receptor (AR) signaling pathways. SLC22A3, a membrane transporter, has been linked to SNP rs9364554 risk loci for drug efficacy in prostate cancer. (2) Methods: We examined the location of SNP rs9364554 in the genome and utilized TCGA and other publicly available datasets to analyze the association of this SNP with transcription levels.

Differentiation of Early Sacroiliitis Using Machine-Learning- Supported Texture Analysis.

We wished to compare the diagnostic performance of texture analysis (TA) against that of a visual qualitative assessment in identifying early sacroiliitis (nr-axSpA). A total of 92 participants were retrospectively included at our university hospital institution, comprising 30 controls and 62 patients with axSpA, including 32 with nr-axSpA and 30 with r-axSpA, who underwent MR examination of the sacroiliac joints. MRI at 3T of the lumbar spine and the sacroiliac joint was performed using oblique T1-weighted (W), fluid-sensitive, fat-saturated (Fs) T2WI images.

LLT1 overexpression renders allogeneic-NK resistance and facilitates the generation of enhanced universal CAR-T cells.

Background: The benefit of universal CAR-T cells over autologous CAR-T cell therapy is that they are a treatment that is ready to use. However, the prevention of graft-versus-host disease (GVHD) and host-versus-graft reaction (HVGR) remains challenging. Deleting class I of human leukocyte antigen (HLA-I) and class II of human leukocyte antigen (HLA-II) can prevent rejection by allogeneic T cells; however, natural killer (NK) cell rejection due to the loss of self-recognition remains unresolved.

Development, implementation and evaluation of consultation case-based learning course to improve the interdisciplinary clinical reasoning ability-a pilot study from nephrology.

Background: In modern clinical settings, interdisciplinary clinical reasoning skills and associated education are pivotal and should be encouraged for residency training.

Methods: An interdisciplinary course on clinical reasoning was developed for residents based on ADDIE (Analysis, Design, Development, Implementation, and Evaluation) model. We collected frequently encountered consultation cases as our teaching resources with the methods of scenario case-based learning.

Severe fever with thrombocytopenia syndrome complicated with aspergillus endocarditis and multiple organ infarctions after glucocorticoid treatment in an immunocompetent man: a case report.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease characterized by leukopenia and thrombocytopenia, and aspergillosis is a common complication in severe cases. Previous studies have reported cases of SFTS complicated with invasive pulmonary aspergillosis (IPA) and central nervous system aspergillosis. Here, we present the first case of an immunocompetent patient with SFTS who progressed to IPA and Aspergillus endocarditis after glucocorticoid treatment, and embolism of the vegetations from the left ventricle led to multiple infarctions in the brain, kidney, and spleen.

Dynamic pathophysiological features of early primary blast lung injury: a novel functional incapacity pig model.

Introduction: While there is evidence supporting the use of ultrasound for real-time monitoring of primary blast lung injury (PBLI), uncertainties remain regarding the timely detection of early PBLI and the limited data correlating it with commonly used clinical parameters. Our objective is to develop a functional incapacity model for PBLI that better addresses practical needs and to verify the early diagnostic effectiveness of lung ultrasound in identifying PBLI.

Methods: We selected six healthy male pigs to develop an animal model using a bio-shock tube (BST-I).

Noninvasive diagnosis model for predicting significant liver inflammation in patients with chronic hepatitis B in the immune-tolerant phase.

The presence of significant liver inflammation is an important indication for antiviral therapy in immune-tolerant (IT)phase with chronic hepatitis B(CHB) patients. This study aims to establish a non-invasive model to assess significant liver inflammation in the IT-phase of CHB patients. This multicenter retrospective study included a total of 535 IT-phase CHB patients who underwent liver biopsy, and were randomly divided into a training and a validation set.

Lysosomes finely control macrophage inflammatory function via regulating the release of lysosomal Fe through TRPML1 channel.

Lysosomes are best known for their roles in inflammatory responses by engaging in autophagy to remove inflammasomes. Here, we describe an unrecognized role for the lysosome, showing that it finely controls macrophage inflammatory function by manipulating the lysosomal Fe-prolyl hydroxylase domain enzymes (PHDs)-NF-κB-interleukin 1 beta (IL1B) transcription pathway that directly links lysosomes with inflammatory responses. TRPML1, a lysosomal cationic channel, is activated secondarily to ROS elevation upon inflammatory stimuli, which in turn suppresses IL1B transcription, thus limiting the excessive production of IL-1β in macrophages.

Inhibition of P2X7 receptor mitigates atrial fibrillation susceptibility in isoproterenol-induced rats.

Background: Atrial fibrillation (AF) is a common cardiac arrhythmia that is characterized by atrial electrical remodeling. The P2X7 receptor (P2X7R), an ATP-gated ion channel, has been implicated in cardiovascular pathologies; however, its role in atrial electrical remodeling remains unclear. This study investigated whether inhibition of P2X7R could mitigate isoproterenol (ISO)-induced atrial electrical remodeling in rats and explored the underlying mechanisms.

Establishment of critical values for AMH screening with PCOS based on restricted cubic spline plots.

Background: The aim is to develop age-specific anti-Müllerian hormone screening criteria for polycystic ovary syndrome to facilitate the early detection and diagnosis of the condition, and to subsequently evaluate the screening criteria.

Methods: A retrospective analysis was performed on patient data from Hangzhou Women's Hospital between July 2021 and August 2024. The use of restricted cubic spline analysis helped identify age-related inflection points, which were crucial for segmenting the patient population.

The corneal biomechanical changes of phacoemulsification in cataract patients: A systematic review and meta-analysis.

Purpose: To evaluate the corneal biomechanical properties of phacoemulsification in the treatment of cataract patients.

Methods: Pertinent studies were searched in PubMed, EMBASE, Web of Science and clinicaltrials.gov.

ERBB4 selectively amplifies TGF-β pro-metastatic responses.

Transforming growth factor β (TGF-β) is well known to play paradoxical roles in tumorigenesis as it has both growth-inhibitory and pro-metastatic effects. However, the underlying mechanisms of how TGF-β drives the opposing responses remain largely unknown. Here, we report that ERBB4, a member of the ERBB receptor tyrosine kinase family, specifically promotes TGF-β's metastatic response but not its anti-growth response.

Endoplasmic Reticulum-Targeted Polymer-Manganese Nanocomplexes for Tumor Immunotherapy.

Manganese ions (Mn) are an immune activator that enhances the activation of both cGAS and STING proteins. The STING signaling activation and subsequential immune responses are predominantly associated with endoplasmic reticulum (ER). Therefore, ER targeting of Mn in the subcellular compartments would promote the activation of STING signaling pathways.

Indole-3-Lactic Acid Inhibits Doxorubicin-Induced Ferroptosis Through Activating Aryl Hydrocarbon Receptor/Nrf2 Signalling Pathway.

The clinical application of doxorubicin (DOX) is limited due to its cardiotoxicity, which is primarily attributed to its interaction with iron in mitochondria, leading to lipid peroxidation and myocardial ferroptosis. This study aimed to investigate the role of the gut microbiota-derived metabolite, indole-3-lactic acid (ILA), in mitigating DOX-induced cardiotoxicity (DIC). Cardiac function, pathological changes, and myocardial ferroptosis were assessed in vivo.

A CRISPR-Cas and Argonaute-Driven Two-Factor Authentication Strategy for Information Security.

The escalating growth in computing power and the advent of quantum computing present a critical threat to the security of modern cryptography. Two-factor authentication strategies can effectively resist brute-force attacks to improve the security of access control. Herein, we proposed a two-factor and two-authentication entity strategy based on the trans-cleavage activity of CRISPR-Cas and the "dual-step" sequence-specific cleavage of Argonaute.

3D Mechanical Response Stem Cell Complex Repairs Spinal Cord Injury by Promoting Neurogenesis and Regulating Tissue Homeostasis.

Spinal cord injury (SCI) leads to acute tissue damage that disrupts the microenvironmental homeostasis of the spinal cord, inhibiting cell survival and function, and thereby undermining treatment efficacy. Traditional stem cell therapies have limited success in SCI, due to the difficulties in maintaining cell survival and inducing sustained differentiation into neural lineages. A new solution may arise from controlling the fate of stem cells by creating an appropriate mechanical microenvironment.

Galectin-1-Induced Tumor Associated Macrophages Repress Antitumor Immunity in Hepatocellular Carcinoma Through Recruitment of Tregs.

Tumor-associated macrophages (TAMs) are commonly considered accomplices in tumorigenesis and tumor development. However, the precise mechanism by which tumor cells prompt TAMs to aid in evading immune surveillance remains to be further investigated. Here, it is elucidated that tumor-secreted galectin-1 (Gal1) conferred immunosuppressive properties to TAMs.