Intrinsic Opening of BK Channels Derives from Inherent Leakage in Hydrophobic Gating.

The big potassium (BK) channels remain open with a small limiting probability of ∼ 10 at minimal Ca and negative voltages < -100 mV. The molecular origin and functional significance of such "intrinsic opening" are not understood. Here we combine atomistic simulations and electrophysiological experiments to show that the intrinsic opening of BK channels is an inherent property of the vapor barrier, generated by hydrophobic dewetting of the BK inner pore in the deactivated state.

Functionalized biomimetic nanoparticles loaded with salvianolic acid B for synergistic targeted triple-negative breast cancer treatment.

The therapeutic effect of immune checkpoint inhibitors (ICIs) in triple-negative breast cancer (TNBC) is unsatisfactory. The immune "cold" microenvironment caused by tumor-associated fibroblasts (TAFs) has an adverse effect on the antitumor response. Therefore, in this study, mixed cell membrane-coated porous magnetic nanoparticles (PMNPs) were constructed to deliver salvianolic acid B (SAB) to induce an antitumor immune response, facilitating the transition from a "cold" to a "hot" tumor and ultimately enhancing the therapeutic efficacy of immune checkpoint inhibitors.

Overexpressing OsNF-YB12 elevated the content of jasmonic acid and impaired drought tolerance in rice.

Nuclear factor Y (NF-Y) is an evolutionarily conserved heterotrimeric transcription factor in eukaryotes. In a previous study, OsNF-YB12 was confirmed to be associated with drought tolerance using the Ecotilling method. In this study, real-time quantitative RT-PCR revealed that OsNF-YB12 was induced by various abiotic stresses and phytohormones, with expression levels differing between leaves and roots.

Brief Warm and Aldo-Keto Reductase Family Contribute to Cold Adaptation of .

not only damages plant leaves directly but also causes a sooty blotch due to the honeydew secreted by the nymphs and adults. This pest is widespread and seems to be spreading from low latitude to higher latitude areas where winters are typically colder, indicating an increase in its cold tolerance. Changes in temperature help insects to anticipate the arrival of winter, allowing them to take defensive measures in advance.

Photo-Crosslinking Hydrogel Based on Porcine Small Intestinal Submucosa Decellularized Matrix/Fish Collagen/GelMA for Culturing Small Intestinal Organoids and Repairing Intestinal Defects.

Organoid technology, as an innovative approach in biomedicine, exhibits promising prospects in disease modeling, pharmaceutical screening, regenerative medicine, and oncology research. However, the use of tumor-derived Matrigel as the primary method for culturing organoids has significantly impeded the clinical translation of organoid technology due to concerns about potential risks, batch-to-batch instability, and high costs. To address these challenges, this study innovatively introduced a photo-crosslinkable hydrogel made from a porcine small intestinal submucosa decellularized matrix (SIS), fish collagen (FC), and methacrylate gelatin (GelMA).

Risk assessment of chlorophenols (CPs) exposure in vitro:Inhibition of sulfotransferases (SULTs) activity.

Chlorophenols (CPs) are common organic pollutants widely used in many industries. The current study seeks to examine the inhibition of sulfotransferases (SULTs) by CPs. Four SULT isoforms were significantly inhibited by multiply CPs.

Identification of hypertension gene expression biomarkers based on the DeepGCFS algorithm.

Hypertension is a critical risk factor and cause of mortality in cardiovascular diseases, and it remains a global public health issue. Therefore, understanding its mechanisms is essential for treating and preventing hypertension. Gene expression data is an important source for obtaining hypertension biomarkers.

Enantioselective Trifluoromethylazidation of Styrenyl Olefins Catalyzed by an Engineered Nonheme Iron Enzyme.

Organofluorines, particularly those containing trifluoromethyl (CF3) groups, play a critical role in medicinal chemistry. While trifluoromethylation of alkenes provides a powerful synthetic route to construct CF3-containing compounds with broad structural and functional diversity, achieving enantioselective control in these reactions remains a formidable challenge. In this study, we engineered a nonheme iron enzyme, quercetin 2,3-dioxygenase from Bacillus subtilis (BsQueD), for the enantioselective trifluoromethylazidation of alkenes.

A Study of Volatile Organic Compounds in Patients with Obstructive Sleep Apnea.

: Obstructive Sleep Apnea (OSA) is a prevalent sleep disorder characterized by intermittent upper airway obstruction, leading to significant health consequences. Traditional diagnostic methods, such as polysomnography, are time-consuming and resource-intensive. : This study explores the potential of proton-transfer-reaction mass spectrometry (PTR-MS) in identifying volatile organic compound (VOC) biomarkers for the non-invasive detection of OSA.

Integrative proteomic analysis reveals the potential diagnostic marker and drug target for the Type-2 diabetes mellitus.

Objective: The escalating prevalence of Type-2 diabetes mellitus (T2DM) poses a significant global health challenge. Utilizing integrative proteomic analysis, this study aimed to identify a panel of potential protein markers for T2DM, enhancing diagnostic accuracy and paving the way for personalized treatment strategies.

Methods: Proteome profiles from two independent cohorts were integrated: cohort 1 composed of 10 T2DM patients and 10 healthy controls (HC), and cohort 2 comprising 87 T2DM patients and 60 healthy controls.

Comparative response mechanisms of two cultivars of to f.sp. infection.

With the aim of enhancing plants' ability to respond to pathogenic fungi, this study focuses on disease resistance genes. We commenced a series of investigations by capitalizing on the pronounced differences in resistance to Fusarium wilt between resistant and susceptible varieties. Through an in-depth exploration of the metabolic pathways that bolster this defense, we identified genes associated with resistance to f.

[Guiding significance of intra-articular sagittal reduction in the treatment of tibial plateau fractures].

Tibial plateau fracture is a fracture involving the proximal articular surface of the tibia, and its injury mechanism is complex, the fracture morphology is different, and it is often accompanied by different degrees of soft tissue injury, which is difficult to diagnose and treat. In recent years, the research hotspot has focused on solving the reduction and fixation of the posterior lateral column of the tibial plateau, because it has been clinically found that the residual sagittal plane after tibial plateau fracture is insufficient reduction or loss of reduction leads to knee joint dysfunction. The posterior inclination angle of the tibial plateau is an important parameter to describe the sagittal alignment of the tibia.

Protocol for correlating the gut microbiome and metabolomics in patients with intracranial aneurysms.

Gut-microbiome-combined metabolomics studies in cerebrovascular disease highlight the microbiota-gut-brain axis in neurological disorders. Here, we present a protocol for correlating the gut microbiome and metabolomics in patients with intracranial aneurysms. We describe steps for sample collection, fecal genomic DNA extraction, rRNA PCR amplification, sequencing library construction, and rRNA sequencing.

Protective or limited? Maternal antibodies and RSV-associated lower respiratory tract infection in hospitalized infants aged 28-90 days.

Background: Respiratory syncytial virus (RSV) is a major cause of severe health problems in newborns and young children. The protective role and limitations of serum maternal RSV antibodies in infants under 3 months remain controversial.

Methods: A two-center prospective study from 2020 to 2023 recruited infants (n=286) admitted to the respiratory departments of two children's hospitals in southwestern and southeastern China during RSV epidemic.

Association analysis between forkhead box E1 gene and non-syndromic cleft lip with or without cleft palate in Han Chinese population.

Objectives: This study aims to explore the association between single nucleotide polymorphisms (SNPs) loci near the haplotype region hg19 chr9:100560865-100660865 of the forkhead box E1 (FOXE1) gene and the occurrence of non-syndromic cleft lip with or without cleft palate (NSCL/P) in western Han Chinese population.

Methods: In the first stage, our study recruited 159 NSCL/P patients and performed targeted region sequencing to screen SNPs loci near the haplotype region of the FOXE1 gene associated with NSCL/P. In the second stage, we selected 21 common SNPs and re-enrolled 1 000 non-syndromic cleft lip only (NSCLO) patients, 1 000 non-syndromic cleft palate only (NSCPO) patients, and 1 000 normal controls to verify the association.

Efficacy of Dexamethasone as an Adjuvant for Scalp Nerve Blocks to Prolong Analgesia: A Prospective, Double-Blind, Randomized Controlled Study.

Background: Scalp nerve blocks (SNB) may significantly reduce post-craniotomy pain (PCP) but only for a short period of time. Dexamethasone, as an adjuvant to local anesthetics, was reported to prolong the analgesia duration of never block; however, the addition of dexamethasone to SNB is rare. We therefore tested the hypothesis that dexamethasone as an adjuvant to bupivacaine in SNB is positive after craniotomy.

High paracrine activity of hADSCs cartilage microtissues inhibits extracellular matrix degradation and promotes cartilage regeneration.

Due to its unique structure, articular cartilage has limited self-repair capacity. Microtissues are tiny tissue clusters that can mimic the function of target organs or tissues. Using cells alone for microtissue construction often results in the formation of necrotic cores.

Identifying New Susceptibility Genes of Non-Syndromic Orofacial Cleft Based on Syndromes Accompanied With Craniosynostosis.

Objectives: Orofacial cleft (OC) can be classified into syndromic orofacial cleft (SOC) and non-syndromic orofacial cleft (NSOC), depending on whether there are other congenital deformities. Craniosynostosis, the premature closure of cranial sutures, is a common phenotype of SOC resulting in abnormal ossification of skull and brain development disorders. Its correlation with OC offers a promising approach to identify susceptibility genes for NSOC by examining causative genes of SOCs with craniosynostosis.

Impact of sodium alginate hydrogel containing bacteriophage peptides that specifically bind to the EtCab protein on the inhibition of Eimeria tenella infection.

Avian coccidiosis, caused by the protozoan Eimeria, leads to significant economic losses for the poultry industry. In this study, bacteriophages that specifically bind to the calcium-binding protein (EtCab) of Eimeria tenella were selected using a biopanning process with a pIII phage display library. The recombinant EtCab protein served as the ligand in this selection process.

Association between deep gray matter iron deposition and clinical symptoms in Parkinson's disease: a quantitative susceptibility mapping study.

Purpose: This study aimed to assess the association between motor and non-motor symptoms of Parkinson's disease (PD) and iron accumulation within the deep gray matter of the brain by Quantitative Susceptibility Mapping (QSM).

Methods: Fifty-six PD patients and twenty-nine healthy controls were recruited in this study. According to the Hoehn and Yahr (H-Y) stage score, PD patients were divided into early stage (H-Y ≤ 2) and advanced stage (H-Y > 2) groups.

Sacubitril/valsartan attenuates inflammation and myocardial fibrosis in Takotsubo-like cardiomyopathy.

Background: Takotsubo syndrome (TTS) primarily manifests as a cardiomyopathy induced by physical or emotional stress, remains a poorly understood condition with no established treatments. In this study, we investigated the potential of sacubitril/valsartan (sac/val) to increase the survival of TTS patients and reduce inflammation and myocardial fibrosis in experimental models.

Aim: This study aimed to evaluate whether sac/val could improve survival rates in TTS patients, mitigate cardiac remodeling in vivo, and explore its anti-inflammatory and antifibrotic mechanisms in vitro.

Macro/Microgel-Encapsulated, Biofilm-Armored Living Probiotic Platform for Regenerating Bacteria-Infected Diabetic Wounds.

Infectious diabetic wounds pose an arduous threat to contemporary healthcare. The combination of refractory biofilms, persistent inflammation, and retarded angiogenesis can procure non-unions and life-threatening complications, calling for advanced therapeutics potent to orchestrate anti-infective effectiveness, benign biocompatibility, pro-reparative immunomodulation, and angiogenic regeneration. Herein, embracing the emergent "living bacterial therapy" paradigm, a designer probiotic-in-hydrogel wound dressing platform is demonstrated.

Interferon regulatory factor 5 attenuates kidney fibrosis through transcriptional suppression of Tgfbr1.

Tubulointerstitial fibrosis is a common pathway of the progressive development of chronic kidney diseases (CKD) with different etiologies. The transcription factor interferon regulatory factor 5 (IRF5) can induce anti-type I interferons and proinflammatory cytokine genes and has been implicated as a therapeutic target for various inflammatory and autoimmune diseases. Currently, no experimental evidence has confirmed the role of IRF5 in CKD.

Secrets revealed by the skin: initial success of tislelizumab and targeted therapy in advanced renal cell carcinoma-a case report and literature review.

Background: In renal cell carcinoma (RCC), skin metastases (SMs) occur in only 3.3% of cases and are even rarer as an initial manifestation of the disease. Although combination therapy with immune checkpoint inhibitors (ICIs) and targeted agents is the current standard of care, access to these treatments may be limited in certain regions due to cost constraints.