Integrative analysis based on CRISPR screen identifies apilimod as a potential therapeutic agent for cisplatin-induced acute kidney injury treatment.

Acute kidney injury (AKI), a life-threatening side effect of cisplatin therapy, significantly limits the drug's therapeutic potential. In this study, we conducted a genome-wide CRISPR/Cas9 knockout screen in human renal tubular epithelial cells, integrating the results with transcriptome analyses and the Connectivity Map (CMap) database. Apilimod and elacridar emerged as the top two candidates of mitigating cisplatin-induced nephrotoxicity, with apilimod demonstrating superior efficacy in drug matrix experiments.

Complex and severe infection in a 67-year-old liver transplant recipient due to Cunninghamella elegans, Bordetella bronchiseptica, and Pneumocystis jirovecii.

Introduction: Cunninghamella elegans infections cause rare and severe mucormycosis. Bordetella bronchiseptica and Pneumocystis jirovecii relate to pneumonia. They are all clinically uncommon pathogens and no reports of co-infections have been reported.

Yield of clinical metagenomics: insights from real-world practice for tissue infections.

Background: While metagenomic next-generation sequencing (mNGS) has been acknowledged as a valuable diagnostic tool for infections, its clinical validity and impact on patient management when using fresh tissue samples remains uncertain.

Methods: We conducted a retrospective cross-sectional study involving patients who underwent tissue mNGS at a tertiary hospital in China from February 2021 to February 2024, aiming to assess its ability to detect plausible pathogens and its clinical validity and impact.

Findings: A total of 520 mNGS results from 508 patients were analysed, detecting plausible pathogens in 302 (58.

Comparing the diagnostic value of targeted with metagenomic next-generation sequencing in immunocompromised patients with lower respiratory tract infection.

Background: Accurate identification of the etiology of lower respiratory tract infections (LRTI) is crucial, particularly for immunocompromised patients with more complex etiologies. The advent of next-generation sequencing (NGS) has enhanced the effectiveness of pathogen detection. However, assessments of the clinical diagnostic value of targeted NGS (tNGS) in immunocompromised patients with LRTI are limited.

Generation of hereditary spastic paraplegia patient-derived induced pluripotent stem cell line UJSi003-A.

Hereditary spastic paraplegia (HSP) is a rare neurodegenerative disorder with the predominant clinical manifestation of spasticity in the lower extremities. Patients with HSP experience spastic paralysis in both lower limbs, leading to progressive walking difficulties, increased reflexes, spasms, and extensor plantar responses. We successfully generated induced pluripotent stem cells (iPSCs) from peripheral blood mononuclear cells (PBMCs) obtained from a patient diagnosed with HSP.

Changing respiratory pathogens infection patterns after COVID-19 pandemic in Shanghai, China.

To assess the positive rate of 11 respiratory pathogens in 2023, providing a comprehensive summary and analysis of the respiratory infection patterns after COVID-19 pandemic. The study comprised 7544 inpatients suspected of respiratory infections who underwent respiratory pathogen multiplex polymerase chain reaction tests from July 2022 to December 31, 2023. We analyzed the positive rate of 11 pathogens over 18 months and the characterization of infection patterns among different age groups and immune states.

Post-pandemic trends: Epidemiological and etiological insights into acute respiratory infections in southern China.

Data on people suspected with acute respiratory infections (ARIs) from August 2022 to December 2023 in southern China were analyzed. Following the COVID-19 pandemic, the positive detection rates of respiratory pathogens increased to 56.9%.

An integrated analysis identifies six molecular subtypes of pancreatic ductal adenocarcinoma revealing cellular and molecular landscape.

Pancreatic ductal adenocarcinoma (PDA) has been found to have a high mortality rate. Despite continuous efforts, current histopathological classification is insufficient to guide individualized therapies of PDA. We first define the molecular subtypes of PDA (MSOP) based on a meta-cohort of 845 samples from 11 PDA datasets.

Cheilitis in an atopic dermatitis patient associated with co-infection of Staphylococcus pseudintermedius and Staphylococcus aureus.

Background: Atopic dermatitis (AD) is an inflammatory skin condition distinguished by an activated Th2 immune response. The local skin microbial dysbiosis is a contributing factor to the development of AD. The pathogenic coagulase-positive Staphylococcus aureus is the primary species responsible for the progression of AD.

Clinical characteristics of the host DNA-removed metagenomic next-generation sequencing technology for detecting SARS-CoV-2, revealing host local immune signaling and assisting genomic epidemiology.

Background: Metagenomic next-generation sequencing (mNGS) technology has been central in detecting infectious diseases and helping to simultaneously reveal the complex interplay between invaders and their hosts immune response characteristics. However, it needs to be rigorously assessed for clinical utility. The present study is the first to evaluate the clinical characteristics of the host DNA-removed mNGS technology for detecting SARS-CoV-2, revealing host local immune signaling and assisting genomic epidemiology.

Multi-omics analysis identifies rare variation in leptin/PPAR gene sets and hypermethylation of ABCG1 contribute to antipsychotics-induced metabolic syndromes.

Antipsychotic-induced metabolic syndrome (APs-induced Mets) is the most common adverse drug reaction, which affects more than 60% of the psychiatric patients. Although the etiology of APs-induced Mets has been extensively investigated, there is a lack of integrated analysis of the genetic and epigenetic factors. In this study, we performed genome-wide, whole-exome sequencing (WES) and epigenome-wide association studies in schizophrenia (SCZ) patients with or without APs-induced Mets to find the underlying mechanisms, followed by in vitro and in vivo functional validations.

Identification of circular RNA biomarkers for Pien Tze Huang treatment of CCl4‑induced liver fibrosis using RNA‑sequencing.

Pien Tze Huang (PZH), a common hepatoprotective Traditional Chinese Medicine that has been found to be an effective treatment for carbon tetrachloride‑induced hepatic damage, including liver fibrosis. Circular RNAs (circRNAs) serve a crucial role in regulating gene expression levels via circRNA/micro (mi)RNA/mRNA networks in several human diseases and biological processes. However, whether circRNAs are involved in the underlying mechanism of the therapeutic effects of PZH on liver fibrosis remains unclear.

Drug response biomarkers of Pien Tze Huang treatment for hepatic fibrosis induced by carbon tetrachloride.

Objective: To explore biomarkers of Pien Tze Huang that ameliorated the symptoms of hepatic fibrosis.

Methods: Two groups of carbon tetrachloride-induced hepatic fibrosis (HF) mice model were constructed in our study: one group received PZH treatment and another group received no treatment. We performed this study to investigate the role of PZH in the regulation process of hepatic fibrosis.

Hypoxia-related LncRNAs signature predicts prognosis and is associated with immune infiltration and progress of head and neck squamous cell carcinoma.

Background: Disclosing prognostic information is necessary to enable good treatment selection and improve patient outcomes. Previous studies suggest that hypoxia is associated with an adverse prognosis in patients with HNSCC and that long non-coding RNAs (lncRNAs) show functions in hypoxia-associated cancer biology. Nevertheless, the understanding of lncRNAs in hypoxia related HNSCC progression remains confusing.

miR143-3p-Mediated NRG-1-Dependent Mitochondrial Dysfunction Contributes to Olanzapine Resistance in Refractory Schizophrenia.

Background: Olanzapine is an effective antipsychotic medication for treatment-resistant schizophrenia (TRS); however, the therapeutic effectiveness of olanzapine has been found to vary in individual patients. It is imperative to unravel its resistance mechanisms and find reliable targets to develop novel precise therapeutic strategies.

Methods: Unbiased RNA sequencing analysis was performed using homogeneous populations of neural stem cells derived from induced pluripotent stem cells in 3 olanzapine responder (reduction of Positive and Negative Syndrome Scale score ≥25%) and 4 nonresponder (reduction of Positive and Negative Syndrome Scale score <25%) inpatients with TRS.

FKBP51 promotes invasion and migration by increasing the autophagic degradation of TIMP3 in clear cell renal cell carcinoma.

The occurrence of metastasis is a serious risk for renal cell carcinoma (RCC) patients. In order to develop novel therapeutic approaches to control the progression of metastatic RCC, it is of urgent need to understand the molecular mechanisms underlying RCC metastasis and identify prognostic markers of metastatic risk. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) have been known to be closely associated with extracellular matrix (ECM) turnover, which plays a highly active role in tumor metastasis.

Target identification of hepatic fibrosis using Pien Tze Huang based on mRNA and lncRNA.

Hepatic fibrosis is a spontaneous wound-healing response triggered by chronic liver injury. Pien Tze Huang (PZH), a traditional Chinese herbal medicine, has been widely used to treat various hepatic diseases in Asia. We used a CCl-induced mouse model to establish a PZH group of hepatic fibrosis mice treated with PZH and a control group of hepatic fibrosis mice without any treatment.

Evaluating Distribution and Prognostic Value of New Tumor-Infiltrating Lymphocytes in HCC Based on a scRNA-Seq Study With CIBERSORTx.

Hepatocellular carcinoma (HCC) is a commonly diagnosed cancer with high mortality rates. The immune response plays an important role in the progression of HCC. Immunotherapies are becoming an increasingly promising tool for treating cancers.

Functional characterization of the chlorzoxazone 6-hydroxylation activity of human cytochrome P450 2E1 allelic variants in Han Chinese.

Backgrounds: Cytochrome P450 (P450) 2E1 is one of the primary enzymes responsible for the metabolism of xenobiotics, such as drugs and environmental carcinogens. The genetic polymorphisms of the gene in promoter and coding regions have been identified previously in the Han Chinese population from four different geographic areas of Mainland China.

Methods: To investigate whether genetic variants identified in the coding region affect enzyme function, the enzymes of four single nucleotide polymorphism (SNP) variants in the coding region (novel c.

TRIM22 inhibits endometrial cancer progression through the NOD2/NF‑κB signaling pathway and confers a favorable prognosis.

Endometrial cancer (EnC) is a malignant gynecological tumor commonly observed in developed countries, specifically among post‑menopausal women. Although numerous patients with EnC receive promising prognoses, those with advanced or metastatic disease often have a poor prognosis and an impaired quality of life. Tripartite motif‑containing 22 (TRIM22) has been confirmed to play many crucial roles in different biological processes, from inflammatory to tumorigenesis.

A methylation functional detection hepatic cell system validates correlation between DNA methylation and drug-induced liver injury.

Drug-induced liver injury (DILI) is a life-threatening, adverse reaction to certain drugs. The onset and extent of DILI can vary drastically in different patients using identical drugs. Association studies suggested that subtle differences in DNA methylation may help explain the individual differences in DILI.

Discovery of Novel Biomarkers of Therapeutic Responses in Han Chinese Pemetrexed-Based Treated Advanced NSCLC Patients.

Pemetrexed, one of the most commonly used drugs in advanced non-small cell lung cancer (NSCLC) therapies, often leads to various therapeutic responses in patients. These therapeutic responses to pemetrexed, including adverse drug reactions (ADRs) and its intended therapeutic effects, have been demonstrated to be highly individual-specific. Such difference in therapeutic responses across individuals may be caused by the unique genetic variations in each patient.

Hepatitis B Virus Inhibits Neutrophil Extracellular Trap Release by Modulating Reactive Oxygen Species Production and Autophagy.

Neutrophils, an important component of the innate immune system, release extracellular traps (NETs) to eliminate invading pathogens by trapping and killing microbes. Recent studies have shown that NETs play a multitude of additional roles in immunity and inflammatory diseases. Therefore, NETs may be involved in persistent hepatitis B virus (HBV) infection, and the objectives of the current study were to determine whether HBV influences NET release and to identify the underlying mechanisms.

FKBP51 promotes migration and invasion of papillary thyroid carcinoma through NF-κB-dependent epithelial-to-mesenchymal transition.

FK506-binding protein 51 (FKBP51) is a member of the immunophilin family, with relevant roles in multiple signaling pathways, tumorigenesis and chemoresistance. However, the function of FKBP51 in papillary thyroid carcinoma (PTC) remains largely unknown. In the present study, increased FKBP51 expression was detected in PTC tissues as compared with adjacent normal tissues, and the expression level was associated with clinical tumor, node and metastasis stage.