Discrimination of isomeric dihydroflavone and chalcone by the boosting optimal collision energy-liquid chromatography-tandem mass spectrometry: A case study of pharmacokinetics in honey-fried licorice.

The occurrence of isomeric dihydroflavone and chalcone, two important subfamilies of flavonoid class, extensively happens in herbal medicines. However, identical MS/MS spectra make the identity confirmation a tough job, the complexity will be further boosted in biological samples. Inspired by that isomers possess distinct inherent physicochemical parameters, optimal collision energy (OCE), which is positively correlated with the bond dissociation energies (BDEs), was evaluated towards differentiating isomeric dihydroflavone and chalcone.

GASPS: A Multi-Omics Framework for Defining Genomic Aberration-Driven Signatures and Predicting Patient Outcomes in Lung Cancer.

Lung cancer is the most common cause of cancer-related death worldwide. Recent advancements in targeted therapies and immunotherapies have achieved remarkable success. However, patient responses to treatments with lung cancer vary substantially.

The association between adverse childhood experiences and chronic respiratory diseases in the Chinese middle-aged and elderly population.

Background: The relationship between adverse childhood experiences (ACEs) and respiratory diseases in the Chinese middle-aged and elderly population remains under explored. Furthermore, the potential moderating effects of social demographics factors and health-related behaviors on these associations have not been thoroughly investigated.

Methods: The association between ACEs and chronic respiratory diseases was evaluated using the validated China Health and Retirement Longitudinal Study(CHARLS)baseline questionnaire2, with data analyzed through a logistic regression model.

Adjuvant icotinib for resected EGFR-mutated stage II-IIIA non-small-cell lung cancer (ICTAN, GASTO1002): a randomized comparison study.

The efficacy, safety and ideal treatment duration of an adjuvant epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) for patients with resected EGFR-mutated non-small-cell lung cancer (NSCLC) were not known until 2014, when this study was initiated. In this phase 3 ICTAN trial (GASTO1002, NCT01996098), patients with completely resected, EGFR-mutated, stage II-IIIA NSCLC after adjuvant chemotherapy were assigned in a 1:1:1 ratio to receive icotinib (125 mg, three times daily) for 12 months, to receive icotinib for 6 months, or to undergo observation. The primary endpoint was disease-free survival (DFS).

Exposure-inducible genes may contribute to missingness in RNAseq-based gene expression analyses.

Missing gene expression values are a common issue in RNAseq-based analyses of gene expression. However, an analysis of genetic and environmental factors contributing to data missingness in RNAseq-based assessment of gene expression has never been conducted. In this study we tried to identify factors in RNAseq data missingness.

Prolonging lung cancer response to EGFR inhibition by targeting the selective advantage of resistant cells.

Non-small cell lung cancers (NSCLCs) treated with tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR) almost invariably relapse in the long term, due to the emergence of subpopulations of resistant cells. Through a DNA barcoding approach, we show that the clinically approved drug sorafenib specifically abolishes the selective advantage of EGFR-TKI-resistant cells, while preserving the response of EGFR-TKI-sensitive cells. Sorafenib is active against multiple mechanisms of resistance/tolerance to EGFR-TKIs and its effects depend on early inhibition of MAPK-interacting kinase (MKNK) activity and signal transducer and activator of transcription 3 (STAT3) phosphorylation, and later down-regulation of MCL1 and EGFR.

Multimodal Integration in Health Care: Development With Applications in Disease Management.

Multimodal data integration has emerged as a transformative approach in the health care sector, systematically combining complementary biological and clinical data sources such as genomics, medical imaging, electronic health records, and wearable device outputs. This approach provides a multidimensional perspective of patient health that enhances the diagnosis, treatment, and management of various medical conditions. This viewpoint presents an overview of the current state of multimodal integration in health care, spanning clinical applications, current challenges, and future directions.

Correcting for bias due to mismeasured exposure in mediation analysis with a survival outcome.

We investigate the impact of exposure measurement error on assessing mediation with a survival outcome modelled by Cox regression. We first derive the bias formulas of natural indirect and direct effects with a rare outcome and no exposure-mediator interaction. We then develop several calibration approaches to correct for the measurement error-induced bias, and generalize our methods to accommodate a common outcome and an exposure-mediator interaction.

Associations of multimorbidity with mortality, hospital stay, and hospitalization costs in Chinese surgical patients: a retrospective cohort study.

Background: Multimorbidity (≥ 2 chronic conditions) is rising in aging populations. China reports over 80 million surgeries annually. This study investigates health burdens of multimorbidity in Chinese surgical patients.

Gene signatures characterizing driver mutations in lung squamous carcinoma are predictive of the progression of pre-cancer lesions.

Unlabelled: Patients with lung squamous cell carcinoma (LUSC) are often diagnosed at advanced stages, limiting opportunities for early intervention. LUSC develops through a multistep progression from low-grade lesions to high-grade lesions, including carcinoma in situ (CIS), of which approximately half progress to invasive cancer while the other half regress. Although frequent mutations and copy number alterations have been documented in LUSC and observed in precursor lesions, their prognostic significance in precancerous stages remains largely unexplored.

Iridoids derived from Valeriana jatamansi Jones alleviates neuroinflammation and blood spinal cord barrier permeability after spinal cord injury by activating the Nrf2/HO-1 signaling pathway.

Background: Valeriana jatamansi Jones, a globally utilized medicinal plant, exhibits favorable pharmacological effects against depression and tumors. Iridoids derived from V. jatamansi (IRFV) promote recovery following spinal cord injury (SCI).

Promotion of HIV clearance by sensitization of HIV reservoirs to cell death.

Introduction: HIV integrates its proviral DNA into the host genome to establish persistent infection. To promote HIV clearance, we have designed an approach for selective elimination of host cells harboring replication-competent HIV (SECH), through inhibition of autophagy and anti-apoptotic molecules during viral reactivation. SECH approach can clear HIV-infected cells in approximately 50% humanized mice.

Spatial Proximity of Immune Cell Pairs to Cancer Cells in the Tumor Microenvironment as Biomarkers for Patient Stratification.

Background/objectives: The tumor microenvironment (TME) plays a critical role in cancer progression by shaping immune responses and influencing patient outcomes. We hypothesized that the relative proximity of specific immune cell pairs to cancer cells within the TME could help predict their pro- or anti-tumor functions and reflect clinically relevant immune dynamics.

Methods: We analyzed imaging mass cytometry (IMC) data from lung adenocarcinoma (LUAD) and triple-negative breast cancer (TNBC) cohorts.

Kisspeptin-10 protects against HIV-1 Tat-induced blood-brain barrier dysfunction and neuroinflammation via RhoA/ROCK pathway: Implications for HAND therapy.

This study investigated the effects of Kisspeptin-10 (Kp-10) on HIV-1 Tat-induced blood-brain barrier (BBB) permeability and oxidative stress using both in vivo and in vitro models. In vivo, one hour after intraperitoneal administration of 50 nmol/kg (DSS)*6-Kp-10, mice were intravenously injected with HIV-1 Tat (100 μg/kg). Markers of oxidative stress, inflammatory cytokines, and BBB integrity were then evaluated.

Integrative Analysis Reveals the Prognostic Effects of Epigenetic Regulators in Bladder Cancer.

Background: Epigenetic regulatory genes (epiRG) are pivotal in the epigenetic regulation of the human genome, primarily through DNA and histone modifications. These genes are frequently mutated in human cancers, particularly bladder cancer (BC). However, the functional impact of epiRG mutations on patient outcomes remains poorly understood.

A novel antimicrobial peptide NDYT-8 with broad-spectrum activity from Bacillus subtilis natto: Antibacterial mechanism and sequence simplification.

The discovery of antimicrobial peptides (AMPs) holds critical significance in combating antibiotic resistance. In this study, a novel efficient antimicrobial peptide NDYT-8 with broad-spectrum activity was isolated and identified from Bacillus subtilis natto. Whole-genome sequencing revealed that NDYT-8 potentially derived from the minimal domain of 6-phosphogluconate dehydrogenase, exhibited broad-spectrum antibacterial activity against common foodborne pathogens, particularly Escherichia coli and Salmonella enterica, with a minimum inhibitory concentration (MIC) value of 16 μg/mL.

Gene expression in tumor and adjacent normal tissues in lung adenocarcinoma subtypes.

Background: Lung adenocarcinoma (LUAD) has several histologically distinct subtypes that differ by a number of clinical features including patient survival. Molecular mechanisms underlying histological and clinical differences between subtypes remain poorly understood.

Methods: We conducted a comparative analyses of gene expression in acinar, lepidic, papillary and solid subtypes, as well as mucinous adenocarcinoma.

Using machine learning algorithms to predict risk factors of heart failure after complete mesocolic excision in colorectal cancer patients.

Following complete mesocolic excision (CME), heart failure (HF) emerges as a significant complication, exerting substantial impacts on both short-term and long-term patient prognoses. The primary objective of our investigation was to develop a machine learning model capable of discerning preoperative and intraoperative high-risk factors, facilitating the prediction of HF occurrence subsequent to CME. A cohort comprising 1158 patients diagnosed with colon cancer was enrolled in our study, encompassing 172 individuals who developed postoperative HF.

TRIM29 promotes glioblastoma progression via ubiquitinating NEFL and activating the PI3K/AKT signaling pathway.

Tripartite motif-containing protein 29 (TRIM29) is a regulator of tumor progression across multiple cancer types. However, its functional significance in glioblastoma (GBM) remains poorly defined. In this study, we investigated the biological roles of TRIM29 in GBM and elucidated its underlying molecular mechanisms.

Predictive value of the systemic inflammation grade for overall survival in patients with colorectal cancer after surgery: outperforming NLR and mGPS.

Background: Accurate prognostic stratification remains challenging in colorectal cancer (CRC) patients after curative resection. The Systemic Inflammation Grade (SIG), integrating neutrophil-to-lymphocyte ratio (NLR) and modified Glasgow Prognostic Score (mGPS), was proposed as a composite marker to refine risk assessment.

Methods: This retrospective study analyzed 263 CRC patients undergoing R0 resection (2015-2019).

TRIM22 promotes glioblastoma development by ubiquitinating Bcl-2.

Glioblastoma (GBM) exhibits elevated TRIM22 expression correlated with tumor progression, as validated in TCGA/GEO databases. The effects of TRIM22 knockdown and overexpression on GBM proliferation were evaluated with cellular assays. TRIM22 was identified as a potential Bcl-2 activator via a ubiquitination microarray.

Advancing liver cancer treatment with dual-targeting CAR-T therapy.

Chimeric antigen receptor (CAR)-T cell therapy targeting glypican-3 (GPC3) has shown promise in the treatment of hepatocellular carcinoma (HCC). However, the efficacy of CAR-T cells that focus solely on cell surface tumor-associated antigens is often limited. To overcome this challenge, we developed a dual-targeting CAR-T cell strategy.

Dectin-1 facilitates lung fungal-mediated pulmonary fibrosis.

Dectin-1 (Clec7a), a C-type lectin receptor for β-glucans, is critical in host defense against fungal infections and has been implicated in allergic responses, yet its role in pulmonary fibrosis remains unclear. In this study, we reveal that bleomycin-induced pulmonary fibrosis was suppressed in Dectin-1-deficient mice, mediated by interactions with the commensal lung fungus Engyodontium. Dectin-1 was predominantly expressed on alveolar macrophages (AMs), correlating with fibrosis severity in both humans and mice.

Effects of Ag and melt undercooling on the microstructure of Sn-Ag solder balls.

Unlabelled: The microstructure of electronic solder joints is created by solidification in an undercooled melt. Here, we apply the framework of solidification microstructure selection maps (SMSMs) to Sn-Ag solder balls with compositions from 0.5 to 5.