Structural insights into the activation mechanism of the human zinc-activated channel.

The zinc-activated channel (ZAC) is an atypical mammalian cys-loop receptor (CLR) that is activated by zinc ions and protons, allowing cations to pass through. The molecular mechanism that ligands use to activate ZAC remains elusive. Here, we present three cryo-electron microscopy reconstructions of human ZAC (hZAC) under different conditions.

Antibody Response to SARS-CoV-2 Vaccines in Transplant Recipients and Hemodialysis Patients: Data from the Dominican Republic.

: The global COVID-19 pandemic has resulted in approximately 7 million deaths and a historic vaccination effort, with over 13.6 billion doses administered. Despite this, understanding of immune responses in vulnerable populations, such as transplant recipients (TR) and hemodialysis patients (HD), remains limited, especially outside the US and Europe.

Clinical review and drug sensitivity test of complex isolates in non-lactating patients with severe mastitis.

Background: Previous microbiological investigations have demonstrated a significant correlation between complex (CKC) infection and mastitis. Recent studies have confirmed the existence of the CKC, with () identified as the primary infectious agent. Examining the incidence of CKC in cases of severe non-lactational mastitis, alongside the clinical characteristics of infected patients, as well as evaluating the drug sensitivity testing protocols for CKC, can provide a more robust foundation for the diagnosis and treatment of CKC infections.

Polarity-Sensitive fluorescent probes based on triphenylamine for fluorescence lifetime imaging of lipid droplets.

Non-alcoholic fatty liver disease (NAFLD) is a disease closely associated with metabolic abnormalities. Lipid droplets (LDs) serve as organelles that store intracellular neutral lipids and maintain cellular energy homeostasis. Their abnormalities can cause metabolic disorders and disease, which is also one of the distinctive characteristics of NAFLD patients.

Design and application of synthetic 17B-HSD13 substrates reveals preserved catalytic activity of protective human variants.

Several hydroxysteroid dehydrogenase 17-beta 13 variants have previously been identified as protective against metabolic dysfunction-associated steatohepatitis (MASH) fibrosis, ballooning and inflammation, and as such this target holds significant therapeutic potential. However, over 5 years later, the function of 17B-HSD13 remains unknown. Structure-aided design enables the development of potent and selective sulfonamide-based 17B-HSD13 inhibitors.

Studies of methylated CpG ODN from subsp. in a murine model: Implications for treatment of human allergic disease.

Allergen immunotherapy (AIT) is currently the most effective immunologic form of treatment for patients with atopic allergic diseases commonly used by allergist/immunologists to reduce allergic symptoms by gradually desensitizing the immune system to specific allergens. Currently, the primary mechanism of AIT emphasizes the crucial role of immune regulation, which involves a shift from a T-helper type 2 (Th2) cell response, which promotes allergy, to a T-regulatory (Treg) cell population, which inhibits the allergic inflammatory response through the production of immunosuppressive cytokines interleukin 10 and transforming growth factor β, which play pivotal roles in suppressing the allergic reaction. In a series of previous in vitro and in vivo experiments, we have demonstrated the capacity of synthetic methylated cytosine-phosphate-guanine (CpG) oligodeoxynucleotide (ODN) moieties as well as methylated genomic DNA ODN motifs from Bifidobacterium longum subspecies infantis to activate Treg cell differentiation in contrast to the unmethylated ODN moiety, which promotes proinflammatory responses driven by Th17-mediated responses.

Microcystin-LR Exposure Damages Neurons by Inducing α-Syn Aggregation via MAPK4/GATA2/SNCA and PP2A/GRKs Pathways.

Microcystin-LR (MC-LR) is a natural neurotoxin with strong toxicity, and studies have demonstrated that chronic MC-LR exposure generated Parkinson-like dyskinesia in mice. Parkinson's disease (PD) is a neurologic degenerative disease mostly occurring in elderly people, and the progressive loss of dopaminergic neurons and the formation of Lewy bodies are the hallmark pathological features. The main component of Lewy bodies is α-synuclein (α-syn) encoded by the SNCA gene, and the copy number mutation of SNCA gene can promote the overexpression of α-syn.

Chameleon-inspired molecular imprinted polymer with bicolored states for visual and stable detection of diethylstilbestrol in water and food samples.

A novel biomimetic molecular imprinted polymer chip with fluorescence (FL) and structural (STR) states, inspired by color patterns of chameleon skin, is fabricated for detecting diethylstilbestrol (DES). The chip features a regularly structured, non-closed-packed (NCP) colloidal photonic crystal (CPC) lattice made monodisperse MIP spheres containing fluorescence poly ionic liquid (FPIL) pigments. The FL color originates from FPIL pigments and is further enhanced by the Purcell effect, while the STR color results from the periodic arrangement of the NCP CPC structure.

Sulforaphane potentiates the efficacy of chemoradiotherapy in glioblastoma by selectively targeting thioredoxin reductase 1.

Chemoradiotherapy is a conventional treatment modality for patients with glioblastoma (GBM). However, the efficacy of this approach is significantly hindered by the development of therapeutic resistance. The thioredoxin system, which plays a crucial role in maintaining redox homeostasis, confers protection to cancer cells against apoptosis induced by chemoradiotherapy.

Comparative effectiveness of various orbital decompression techniques in treating thyroid-associated ophthalmopathy: a systematic review and meta-analysis.

Background: In thyroid-associated ophthalmopathy (TAO), orbital decompression is a critical surgical approach for functional and aesthetic reasons. Meanwhile, the presence of surgical complications, especially the new onset of primary gaze diplopia, also influences postoperative patient satisfaction. This research investigates the effectiveness and potential risks associated with different orbital decompression in patients with TAO.

Association between chronic pain and cognitive frailty among middle-aged and elderly individuals: evidence from the China Health and Retirement Longitudinal Study.

Background: Frailty, particularly cognitive frailty, is an escalating public health issue. Cognitive frailty is defined by the simultaneous presence of physical frailty and cognitive impairment, without a confirmed diagnosis of dementia, and has become a significant geriatric syndrome. This study aimed to explore the association between chronic pain and the risk of cognitive frailty.

Microneedle-Array-Mediated Transdermal Delivery of GCV-Functionalized Zeolitic Imidazolate Framework-8 Nanoparticles for KSHV Treatment.

Kaposi's sarcoma-associated herpesvirus (KSHV) is a variety of the human gamma-herpesvirus that often leads to the occurrence of malignant tumors. In addition, the occurrence of Kaposi's sarcoma is a major cause of death among AIDS patients. Ganciclovir (GCV) is the most widely used drug against KSHV infection in the clinic.

Optimizing load scheduling and data distribution in heterogeneous cloud environments using fuzzy-logic based two-level framework.

Cloud environment handles heterogeneous services, data, and users collaborating on different technologies and resource scheduling strategies. Despite its heterogeneity, the optimality in load scheduling and data distribution is paused due to unattended requests for a prolonged time. This article addresses the aforementioned issue using a Two-level Scheduling and Distribution Framework (TSDF) using Fuzzy Logic (FL).

Nails and skin co-infection by Fusarium verticillioides and Proteus vulgaris secondary to arterial occlusion of lower extremity.

Background: Post-traumatic Fusarium infection is rare. Arterial occlusive disease, a common vascular disorder in the elderly, often leads to ischemic necrosis of the lower extremities, which in turn increases the likelihood of secondary infections. Those secondary infections can be caused by bacteria, virus, or fungi.

Assessing the risk of high-grade squamous intraepithelial lesions (HSIL+) in women with LSIL biopsies: a machine learning-based study.

Objective: This study aims to analyze factors associated with the missed diagnosis of high-grade squamous intraepithelial lesions (HSIL+) in patients initially diagnosed with low-grade squamous intraepithelial lesions (LSIL) through colposcopic biopsy and to develop a predictive model for assessing the risk of missed HSIL+.

Methods: We conducted a retrospective analysis of 505 patients who underwent loop electrical excision procedure (LEEP) following an LSIL diagnosis by colposcopic biopsy. Logistic regression was used to identify demographic and pathological parameters associated with missed diagnoses of HSIL+.

Transferrin-modified carboxymethyl chitosan-chitosan nanoparticles as an efficient delivery carrier for targeted therapy of depression.

Limitations of the blood-brain barrier (BBB) are responsible for the low efficacy and high toxicity of many antidepressants. However, strategies to enhance BBB targeting to improve the efficacy and safety of antidepressants remain challenging. In this study, we prepared transferrin (Tf)-functionalized chitosan (CS)-N,O-carboxymethy chitosan (NOCMS) nanosystems (NPs) (NOCMS-CS-Tf NPs), which can enhance BBB targeting in the depressive environment and allow more NPs to enter the brain.

Embryonic exposure to 6:2 fluorotelomer alcohol mediates autism spectrum disorder-like behavior by dysfunctional microbe-gut-brain axis in mice.

6:2 fluorotelomer alcohol (6:2 FTOH) is considered an emerging contaminant as a substitute for perfluoroalkyl and polyfluoroalkyl substances. Autism spectrum disorder (ASD) is a highly heterogeneous childhood neurodevelopmental disorder, the prevalence of which has been significantly increasing globally, possibly due to rising exposure to environmental pollutants. Additionally, the microbe-gut-brain axis plays a crucial role in the development of ASD.

Public Perceptions of Very Low Nicotine Content on Twitter: Observational Study.

Background: Nicotine is a highly addictive agent in tobacco products. On June 21, 2022, the US Food and Drug Administration (FDA) announced a plan to propose a rule to establish a maximum nicotine level in cigarettes and other combusted tobacco products.

Objective: This study aimed to understand public perception and discussion of very low nicotine content (VLNC) on Twitter (rebranded as X in July 2023).

Biofilm Formation in Clinical Isolates of .

Many microbial pathogens form biofilms, assemblages of polymeric compounds that play a crucial role in establishing infections. The biofilms of species also contribute to high antifungal resistance. Using our collection of 29 clinical isolates, we focused on characterizing differences in thermotolerance, anaerobic growth, and biofilm formation across four species complexes commonly found in clinical settings.

Efficacy of Tocilizumab in Refractory Graves Orbitopathy From Real-World Clinical Practice: An Observational Study.

Context: The efficacy of tocilizumab (TCZ) in treating Graves orbitopathy (GO) remains uncertain due to the small sample sizes of earlier studies, and there is a lack of research on the drug for juvenile GO.

Objective: To evaluate the effectiveness of TCZ in treating GO that is resistant to conventional therapy.

Design: This observational study at a tertiary care center included 79 Chinese GO patients, 15 of whom were pediatric patients, with 52 of these patients having moderate to severe active GO (all adult patients having steroid-resistant GO).

Fungal influence on immune cells and inflammatory responses in the tumor microenvironment (Review).

In recent years, a growing body of research has highlighted the significant influence of the microbiota on tumor immunity within the tumor microenvironment (TME). While much attention has been given to bacteria, emerging evidence suggests that fungi also play crucial roles in tumor development. The present review aimed to consolidate the latest findings on the mechanisms governing the interactions between fungi and the immune system or TME.

Effects of sterilization intensity on the flavor profile of canned Antarctic krill (Euphausia superba): Moderate vs. excessive.

Selecting the appropriate sterilization intensity is crucial for the canning of Antarctic krill (Euphausia superba). This study investigated the effects of different sterilization intensities on volatile organic compounds (VOCs) of canned krill. Using gas chromatography-ion mobility spectrometry (GC-IMS) and gas chromatography-mass spectrometry (GC-MS), which identified 45 and 36 VOCs, respectively.

SIRT3 Deficiency Promotes Lung Endothelial Pyroptosis Through Impairing Mitophagy to Activate NLRP3 Inflammasome During Sepsis-Induced Acute Lung Injury.

Acute lung injury (ALI) is a major cause of death in bacterial sepsis due to endothelial inflammation and endothelial permeability defects. Mitochondrial dysfunction is recognized as a key mediator in the pathogenesis of sepsis-induced ALI. Sirtuin 3 (SIRT3) is a histone protein deacetylase involved in preservation of mitochondrial function, which has been demonstrated in our previous study.