A real-world pharmacovigilance analysis of potential ototoxicity associated with sacubitril/valsartan based on FDA Adverse Event Reporting System (FAERS).

Sacubitril/valsartan, a first-in-class angiotensin receptor neprilysin inhibitor, is widely used to treat heart failure. Despite its efficacy, sacubitril/valsartan inevitably causes adverse events such as hypotension, renal dysfunction, hyperkalemia, and angioedema. Sacubitril/valsartan-associated ototoxicity is often underreported in clinical studies and real-world settings.

Epidemiological characteristics of elderly osteoporosis fractures and their association with air pollutants: a multi-center study in Hebei Province.

To investigate the population distribution characteristics of elderly osteoporosis fracture patients in Hebei Province and analyze the effects of air pollutants on elderly osteoporosis fractures, We retrospectively collected 18,933 cases of elderly osteoporosis fractures from January 1, 2019, to December 31, 2022, from four hospitals in Hebei Province. The average age was 76.44 ± 7.

Footprint-C reveals transcription factor modes in local clusters and long-range chromatin interactions.

The proximity ligation-based Hi-C and derivative methods are the mainstream tools to study genome-wide chromatin interactions. These methods often fragment the genome using enzymes functionally irrelevant to the interactions per se, restraining the efficiency in identifying structural features and the underlying regulatory elements. Here we present Footprint-C, which yields high-resolution chromatin contact maps built upon intact and genuine footprints protected by transcription factor (TF) binding.

Substrate transport and drug interaction of human thiamine transporters SLC19A2/A3.

Thiamine and pyridoxine are essential B vitamins that serve as enzymatic cofactors in energy metabolism, protein and nucleic acid biosynthesis, and neurotransmitter production. In humans, thiamine transporters SLC19A2 and SLC19A3 primarily regulate cellular uptake of both vitamins. Genetic mutations in these transporters, which cause thiamine and pyridoxine deficiency, have been implicated in severe neurometabolic diseases.

Mammalian SLC39A13 promotes ER/Golgi iron transport and iron homeostasis in multiple compartments.

Iron is a potent biochemical, and accurate homeostatic control is orchestrated by a network of interacting players at multiple levels. Although our understanding of organismal iron homeostasis has advanced, intracellular iron homeostasis is poorly understood, including coordination between organelles and iron export into the ER/Golgi. Here, we show that SLC39A13 (ZIP13), previously identified as a zinc transporter, promotes intracellular iron transport and reduces intracellular iron levels.

Colon-targeted engineered postbiotics nanoparticles alleviate osteoporosis through the gut-bone axis.

The potential for mitigating intestinal inflammation through the gut-bone axis in the treatment of osteoporosis is significant. While various gut-derived postbiotics or bacterial metabolites have been created as dietary supplements to prevent or reverse bone loss, their efficacy and safety still need improvement. Herein, a colon-targeted drug delivery system is developed using surface engineering of polyvinyl butyrate nanoparticles by shellac resin to achieve sustained release of postbiotics butyric acid at the colorectal site.

DDX18 coordinates nucleolus phase separation and nuclear organization to control the pluripotency of human embryonic stem cells.

Pluripotent stem cells possess a unique nuclear architecture characterized by a larger nucleus and more open chromatin, which underpins their ability to self-renew and differentiate. Here, we show that the nucleolus-specific RNA helicase DDX18 is essential for maintaining the pluripotency of human embryonic stem cells. Using techniques such as Hi-C, DNA/RNA-FISH, and biomolecular condensate analysis, we demonstrate that DDX18 regulates nucleolus phase separation and nuclear organization by interacting with NPM1 in the granular nucleolar component, driven by specific nucleolar RNAs.

Oxidative potential and persistent free radicals in dust storm particles and their associations with hospitalization.

Sand and dust storms (SDS) can cause adverse health effects, with the oxidative potential (OP) and environmentally persistent free radicals (EPFRs) inducing oxidative stress. We mapped the OP and EPFRs concentrations at 1735 sites in China during SDS periods using experimental data for 2021-2023 and a random forest model. We examined 855,869 hospitalizations during SDS events for 2015-2022 in Beijing, China.

Human respiratory organoids sustained reproducible propagation of human rhinovirus C and elucidation of virus-host interaction.

The lack of a robust system to reproducibly propagate HRV-C, a family of viruses refractory to cultivation in standard cell lines, has substantially hindered our understanding of this common respiratory pathogen. We sought to develop an organoid-based system to reproducibly propagate HRV-C, and characterize virus-host interaction using respiratory organoids. We demonstrate that airway organoids sustain serial virus passage with the aid of CYT387-mediated immunosuppression, whereas nasal organoids that more closely simulate the upper airway achieve this without any intervention.

Differential effects of fine particulate matter constituents on acute coronary syndrome onset.

Fine particulate matter has been linked with acute coronary syndrome. Nevertheless, the key constituents remain unclear. Here, we conduct a nationwide case-crossover study in China during 2015-2021 to quantify the associations between fine particulate matter constituents (organic matter, black carbon, nitrate, sulfate, and ammonium) and acute coronary syndrome, and to identify the critical contributors.

Bone Marrow Endothelial Progenitor Cells remodelling facilitates normal hematopoiesis during Acute Myeloid Leukemia Complete Remission.

Although acute myeloid leukemia (AML) affects hematopoietic stem cell (HSC)-supportive microenvironment, it is largely unknown whether leukemia-modified bone marrow (BM) microenvironment can be remodeled to support normal hematopoiesis after complete remission (CR). As a key element of BM microenvironment, endothelial progenitor cells (EPCs) provide a feasible way to investigate BM microenvironment remodeling. Here, we find reduced and dysfunctional BM EPCs in AML patients, characterized by impaired angiogenesis and high ROS levels, could be partially remodeled after CR and improved by N-acetyl-L-cysteine (NAC).

Immune checkpoint inhibitor-induced severe epidermal necrolysis mediated by macrophage-derived CXCL10 and abated by TNF blockade.

Immune checkpoint inhibitors (ICI) represent new anticancer agents and have been used worldwide. However, ICI can potentially induce life-threatening severe cutaneous adverse reaction (SCAR), such as Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), hindering continuous ICI therapy. We examine 6 cohorts including 25 ICI-induced SJS/TEN patients and conduct single-cell RNA sequencing (scRNA-seq) analysis, which shows overexpression of macrophage-derived CXCL10 that recruits CXCR3 cytotoxic T lymphocytes (CTL) in blister cells from ICI-SJS/TEN skin lesions.

An adenosine analog shows high antiviral potency against coronavirus and arenavirus mainly through an unusual base pairing mode.

By targeting the essential viral RNA-dependent RNA polymerase (RdRP), nucleoside analogs (NAs) have exhibited great potential in antiviral therapy for RNA virus-related diseases. However, most ribose-modified NAs do not present broad-spectrum features, likely due to differences in ribose-RdRP interactions across virus families. Here, we show that HNC-1664, an adenosine analog with modifications both in ribose and base, has broad-spectrum antiviral activity against positive-strand coronaviruses and negative-strand arenaviruses.

Mitophagy in ischemic heart disease: molecular mechanisms and clinical management.

The influence of the mitochondrial control system on ischemic heart disease has become a major focus of current research. Mitophagy, as a very crucial part of the mitochondrial control system, plays a special role in ischemic heart disease, unlike mitochondrial dynamics. The published reviews have not explored in detail the unique function of mitophagy in ischemic heart disease, therefore, the aim of this paper is to summarize how mitophagy regulates the progression of ischemic heart disease.

Aldehyde Dehydrogenase 2 Lactylation Aggravates Mitochondrial Dysfunction by Disrupting PHB2 Mediated Mitophagy in Acute Kidney Injury.

Mitochondrial dysfunction is a crucial event in acute kidney injury (AKI), leading to a metabolic shift toward glycolysis and increased lactate production. Lactylation, a posttranslational modification derived from lactate, plays a significant role in various cellular processes, yet its implications in AKI remain underexplored. Here, a marked increase in lactate levels and pan-Kla levels are observed in kidney tissue from AKI patients and mice, with pronounced lactylation activity in injured proximal tubular cells identified by single-cell RNA sequencing.

Hspa13 Deficiency Impaired Marginal Zone B Cells Regulatory Function and Contributed to Lupus Pathogenesis.

Dysregulated IL-10 producing regulatory B cells (Bregs) are associated with the progression of systemic lupus erythematosus. An immunomodulatory role of heat shock proteins (HSPs) is implicated in autoimmune diseases. However, the molecular basis underlying the role of Hspa13 in regulating Bregs function and lupus pathogenesis remains unclear.

Ferritin-Based Supramolecular Assembly Drug Delivery System for Aminated Fullerene Derivatives to Enhance Tumor-Targeted Therapy.

Owing to their attractive antitumor effects, aminated fullerene derivatives are emerging as promising therapeutic drugs for cancer. However, their in vivo applications are severely limited due to cation toxicity. To address this problem, human heavy chain ferritin (HFn), possessing natural biocompatibility is utilized, to develop a novel supramolecular assembly drug delivery system.

Haplotype-Resolved Genotyping and Association Analysis of 1,020 β-Thalassemia Patients by Targeted Long-Read Sequencing.

Despite the well-documented mutation spectra of β-thalassemia, the genetic variants and haplotypes of globin gene clusters modulating its clinical heterogeneity remain incompletely illustrated. Here, a targeted long-read sequencing (T-LRS) is demonstrated to capture 20 genes/loci in 1,020 β-thalassemia patients. This panel permits not only identification of thalassemia mutations at 100% of sensitivity and specificity, but also detection of rare structural variants (SVs) and single nucleotide variants (SNVs) in modifier genes/loci.

Enhancing human ACE2 expression in mouse models to improve COVID-19 research.

Mice are one of the most common biological models for laboratory use. However, wild-type mice are not susceptible to COVID-19 infection due to the low affinity of mouse ACE2, the entry protein for SARS-CoV-2. Although mice with human ACE2 (hACE2) driven by Ace2 promoter reflect its tissue specificity, these animals exhibit low ACE2 expression, potentially limiting their fidelity in mimicking COVID-19 manifestations and their utility in viral studies.

Machine learning-enabled virtual screening indicates the anti-tuberculosis activity of aldoxorubicin and quarfloxin with verification by molecular docking, molecular dynamics simulations, and biological evaluations.

Drug resistance in Mycobacterium tuberculosis (Mtb) is a significant challenge in the control and treatment of tuberculosis, making efforts to combat the spread of this global health burden more difficult. To accelerate anti-tuberculosis drug discovery, repurposing clinically approved or investigational drugs for the treatment of tuberculosis by computational methods has become an attractive strategy. In this study, we developed a virtual screening workflow that combines multiple machine learning and deep learning models, and 11 576 compounds extracted from the DrugBank database were screened against Mtb.

Precise identification of somatic and germline variants in the absence of matched normal samples.

Somatic variants play a crucial role in the occurrence and progression of cancer. However, in the absence of matched normal controls, distinguishing between germline and somatic variants becomes challenging in tumor samples. The existing tumor-only genomic analysis methods either suffer from limited performance or insufficient interpretability due to an excess of features.

Robust Autism Spectrum Disorder-Related Spatial Covariance Gray Matter Pattern Revealed With a Large-Scale Multi-Center Dataset.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder and its underlying neuroanatomical mechanisms still remain unclear. The scaled subprofile model of principal component analysis (SSM-PCA) is a data-driven multivariate technique for capturing stable disease-related spatial covariance pattern. Here, SSM-PCA is innovatively applied to obtain robust ASD-related gray matter volume pattern associated with clinical symptoms.

Impact of COVID-19 vaccination on adolescent and youth students' mental health and bullying behaviors after the lifting of COVID-19 restrictions in China.

Background: Vaccination plays an important role in fighting against COVID-19. However, it is unclear about the association among vaccination, mental health, and bullying behaviors in China.

Method: This online survey was conducted to investigate the association among vaccination status, mental health problems and bullying behaviors in students from December 14, 2022 to February 28, 2023 in Sichuan, China.

Annao Pingchong decoction attenuates oxidative stress and neuronal apoptosis following intracerebral hemorrhage via RAGE-NOX2/4 axis.

Background: Intracerebral hemorrhage (ICH) is a severe condition associated with high mortality and disability rates. Oxidative stress plays a critical role in the development of secondary brain injury (SBI) following ICH. Previous research has demonstrated that Annao Pingchong decoction (ANPCD) treatment for ICH has antioxidant effects, but the exact mechanism is not yet fully understood.