SMAC-armed oncolytic virotherapy enhances the anticancer activity of PD1 blockade by modulating PANoptosis.

Background: Oncolytic viruses (OVs) are increasingly recognized as promising tools for cancer therapy, as they selectively infect and destroy tumor cells while leaving healthy cells unharmed. Despite considerable progress, the limited therapeutic efficacy of OV-based virotherapy continues to be a significant challenge in cancer treatment.

Methods: The SMAC/DIABLO gene was inserted into the genome of vesicular stomatitis virus (VSV) to generate VSV-S.

Iron Oxide Nanoparticles Induce Macrophage Secretion of ATP and HMGB1 to Enhance Irradiation-Led Immunogenic Cell Death.

ATP (adenosine triphosphate) and HMGB1 (high mobility group box 1 protein) are key players in treatments that induce immunogenic cell death (ICD). However, conventional therapies, including radiotherapy, are often insufficient to induce ICD. In this study, we explore a strategy using nanoparticle-loaded macrophages as a source of ATP and HMGB1 to complement radiation-induced intrinsic and adaptive immune responses.

Calcium nanoparticles target and activate T cells to enhance anti-tumor function.

Calcium signaling plays a crucial role in the activation of T lymphocytes. However, modulating calcium levels to control T cell activation in vivo remains a challenge. In this study, we investigate T cell activation using 12-myristate 13-acetate (PMA)-encapsulated CaCO nanoparticles.

Design, Synthesis, and Evaluation of Doxifluridine Derivatives as Nitroreductase-Responsive Anticancer Prodrugs.

Antimetabolite antitumor drugs interfere with nucleic acid and DNA synthesis, causing cancer cell death. However, they also affect rapidly dividing normal cells and cause serious side effects. Doxifluridine (5'-deoxy-5-fluorouridine [5'-DFUR]), a 5-fluorouracil (5-FU) prodrug converted to 5-FU by thymidine phosphorylase (TP), exerts antitumor effects.

Novel Phenoxyalkanoic Acid Derivatives as Free Fatty Acid Receptor 4 Agonists for Treating Type 2 Diabetes Mellitus.

Diabetes mellitus (DM) is a common metabolic disease that poses a severe threat to human health. Despite a range of therapeutic approaches, there remains a lack of effective and safe therapies with the existing drugs. Therefore, there is an urgent need to develop novel, effective, and safe therapeutic strategies for DM.

Machine learning prediction of stalk lignin content using Fourier transform infrared spectroscopy in large scale maize germplasm.

Lignin has been recognized as a major factor contributing to lignocellulosic recalcitrance in biofuel production and attracted attentions as a high-value product in the biorefinery field. As the traditional wet chemical methods for detecting lignin content are labor-intensive, time-consuming and environment-toxic, it is an urgent need to develop high-throughput and environment-friendly techniques for large-scale crop germplasms screening. In this study, we conducted a Fourier transform infrared (FTIR) assay on 150 maize germplasms with a diverse lignin composition to build predictive models for lignin content in maize stalk.

Exploring the impact of GSTM1 as a novel molecular determinant of survival in head and neck cancer patients of African descent.

Background: Blacks/African American (BAA) patients diagnosed with head and neck squamous cell carcinoma (HNSCC) have worse survival outcomes than White patients. However, the mechanisms underlying racial disparities in HNSCC have not been thoroughly characterized.

Methods: Data on gene expression, copy number variants (CNVs), gene mutations, and methylation were obtained from 6 head and neck cancer datasets.

Therapeutic Targeting of the GLS1-c-Myc Positive Feedback Loop Suppresses Glutaminolysis and Inhibits Progression of Head and Neck Cancer.

Head and neck squamous cell carcinoma (HNSCC) is addicted to glutaminolysis. Targeting this metabolic dependency has emerged as a potential therapeutic approach for HNSCC. In this study, we conducted a bioinformatic analysis of The Cancer Genome Atlas HNSCC cohort that revealed a robust correlation between expression of MYC (encoding the protein c-Myc) and glutaminase 1 (GLS1), which catalyzes the first step in glutaminolysis.

The protective effect of natural medicines in rheumatoid arthritis via inhibit angiogenesis.

Rheumatoid arthritis is a chronic immunological disease leading to the progressive bone and joint destruction. Angiogenesis, accompanied by synovial hyperplasia and inflammation underlies joint destruction. Delaying or even blocking synovial angiogenesis has emerged as an important target of RA treatment.

Changing the order and ratio of substrate filling reduced CH and NO emissions from the aerated constructed wetlands.

Constructed wetlands (CWs) have been used to enhance pollutant removal by filling several types of material as substrates. However, research on substrate filling order remains still limited, particularly regarding the effects of greenhouse gas (GHG) emissions. In this study, six CWs were constructed using zeolite and ferric‑carbon micro-electrolysis (Fe-C) fillers to evaluate the effect of changing the filling order and ratio on pollutant removal, GHGs emissions, and associated microbial structure.

Evaluation of pharmacist-led medication reconciliation at county hospitals in China: A multicentre, open-label, assessor-blinded, nonrandomised controlled study.

Background: Due to a lack of related research, we aimed to determine the effectiveness of a pharmacist-led medication reconciliation intervention in China.

Methods: We conducted a multicentre, prospective, open-label, assessor-blinded, cluster, nonrandomised controlled study at six county-level hospitals, with hospital wards serving as the clusters. We included patients discharged from the sampled hospitals who were aged ≥60 years; had ≥1 studied diagnoses; and were prescribed with ≥3 medications at discharge.

Combined IL6 and CCR2 blockade potentiates antitumor activity of NK cells in HPV-negative head and neck cancer.

Background: While T cell-activating immunotherapies against recurrent head and neck squamous cell carcinoma (HNSCC) have shown impressive results in clinical trials, they are often ineffective in the majority of patients. NK cells are potential targets for immunotherapeutic intervention; however, the setback in monalizumab-based therapy in HNSCC highlights the need for an alternative treatment to enhance their antitumor activity.

Methods: Single-cell RNA sequencing (scRNA-seq) and TCGA HNSCC datasets were used to identify key molecular alterations in NK cells.

Modulation of Dendritic Cell Function via Nanoparticle-Induced Cytosolic Calcium Changes.

Calcium nanoparticles have been investigated for applications, such as drug and gene delivery. Additionally, Ca serves as a crucial second messenger in the activation of immune cells. However, few studies have systematically studied the effects of calcium nanoparticles on the calcium levels and functions within immune cells.

HSP90 inhibition suppresses tumor glycolytic flux to potentiate the therapeutic efficacy of radiotherapy for head and neck cancer.

Glycolytic metabolism may account for antitumor immunity failure. Pyruvate kinase M2 (PKM2) and platelet phosphofructokinase (PFKP), two key enzymes involved in the glycolytic pathway, are hyperactivated in head and neck squamous cell carcinoma (HNSCC). Using ganetespib as a drug model for heat shock protein 90 (HSP90) inhibition and combining results from clinical trials and animal treatment, we demonstrated that HSP90 inhibition leads to a blockade of glycolytic flux in HNSCC cells by simultaneously suppressing PKM2 and PFKP at both the transcriptional and posttranslational levels.

Occurrence and transport of novel and legacy poly- and perfluoroalkyl substances in coastal rivers along the Laizhou Bay, northern China.

The pollution profiles of 25 legacy and emerging poly- and perfluoroalkyl substances (PFASs) in the estuaries along the Laizhou Bay, northern China were investigated to better understand the new structure of PFASs under international regulations and to estimate the mass loadings of PFASs in coastal rivers. About 39.87 kg/d of PFASs were discharged into the Laizhou Bay by the Xiaoqing, Mi and Zhimai Rivers.

Biochemical and protein nutritional potential of mulberry (Morus alba L.) leaf: partial substitution improves the nutrition of conventional protein.

Background: With the requirements of environmental, cost and economic sustainability, new sources of alternative proteins in the livestock industry are receiving increasing attention. Mulberry (Morus alba L.) leaves are a unique feed resource because of their high protein content and large availability.

Application of alkali-heated corncobs enhanced nitrogen removal and microbial diversity in constructed wetlands for treating low C/N ratio wastewater.

Lack of carbon source is the main limiting factor in the denitrification of low C/N ratio wastewater in the constructed wetlands (CWs). Agricultural waste has been considered as a supplementary carbon source but research is still limited. To solve this problem, ferric carbon (Fe-C) + zeolite, Fe-C + gravel, and gravel were used as substrates to build CWs in this experiment, aiming to investigate the effects of different carbon sources (rice straw, corncobs, alkali-heated corncobs) on nitrogen removal performance and microbial community structure in CWs for low C/N wastewater.

The Transcription Factor CsgD Contributes to Engineered Resistance by Regulating Biofilm Formation and Stress Responses.

The high cell density, immobilization and stability of biofilms are ideal characteristics for bacteria in resisting antibiotic therapy. CsgD is a transcription activating factor that regulates the synthesis of curly fimbriae and cellulose in , thereby enhancing bacterial adhesion and promoting biofilm formation. To investigate the role of CsgD in biofilm formation and stress resistance in bacteria, the D deletion mutant ΔD was successfully constructed from the engineered strain BL21(DE3) using the CRISPR/Cas9 gene-editing system.

Construction and validation of prognostic models in critically Ill patients with sepsis-associated acute kidney injury: interpretable machine learning approach.

Background: Acute kidney injury (AKI) is a common complication in critically ill patients with sepsis and is often associated with a poor prognosis. We aimed to construct and validate an interpretable prognostic prediction model for patients with sepsis-associated AKI (S-AKI) using machine learning (ML) methods.

Methods: Data on the training cohort were collected from the Medical Information Mart for Intensive Care IV database version 2.

Elevated Serum NOX2 Levels Contribute to Delayed Cerebral Ischemia and a Poor Prognosis After Aneurysmal Subarachnoid Hemorrhage: A Prospective Cohort Study.

Background: NADPH oxidase 2 (NOX2) is highly expressed in injured brain tissues. We determined serum NOX2 levels of aneurysmal subarachnoid hemorrhage (aSAH) patients and further investigated correlation of serum NOX2 levels with disease severity, delayed cerebral ischemia (DCI) plus prognosis after aSAH.

Methods: Serum NOX2 levels were measured in 123 aSAH patients and 123 healthy controls.

Loss of Ufl1/Ufbp1 in hepatocytes promotes liver pathological damage and carcinogenesis through activating mTOR signaling.

Background: Ufm1-specific ligase 1 (Ufl1) and Ufm1-binding protein 1 (Ufbp1), as putative targets of ubiquitin-fold modifier 1 (Ufm1), have been implicated in several pathogenesis-related signaling pathways. However, little is known about their functional roles in liver disease.

Methods: Hepatocyte-specific Ufl1 and Ufbp1 mice were used to study their role in liver injury.

Adaptive c-Met-PLXDC2 Signaling Axis Mediates Cancer Stem Cell Plasticity to Confer Radioresistance-associated Aggressiveness in Head and Neck Cancer.

Unlabelled: Radiotherapy plays an essential role in the treatment of head and neck squamous cell carcinoma (HNSCC), yet radioresistance remains a major barrier to therapeutic efficacy. A better understanding of the predominant pathways determining radiotherapy response could help develop mechanism-informed therapies to improve cancer management. Here we report that radioresistant HNSCC cells exhibit increased tumor aggressiveness.

UFL1, a UFMylation E3 ligase, plays a crucial role in multiple cellular stress responses.

The UFM1 conjugation system(UFMylation)is a novel type of ubiquitin-like system that plays an indispensable role in maintaining cell homeostasis under various cellular stress. Similar to ubiquitination, UFMylation consists of a three-step enzymatic reaction with E1-like enzymes ubiquitin-like modifier activating enzyme5 (UBA5), E2-like enzymes ubiquitin-fold modifier-conjugating enzyme 1(UFC1), and E3-like ligase UFM1-specific ligase 1 (UFL1). As the only identified E3 ligase, UFL1 is responsible for specific binding and modification of the substrates to mediate numerous hormone signaling pathways and endocrine regulation under different physiological or pathological stress, such as ER stress, genotoxic stress, oncogenic stress, and inflammation.

A Novel TLR4-SYK Interaction Axis Plays an Essential Role in the Innate Immunity Response in Bovine Mammary Epithelial Cells.

Mammary gland epithelium, as the first line of defense for bovine mammary gland immunity, is crucial in the process of mammary glands’ innate immunity, especially that of bovine mammary epithelial cells (bMECs). Our previous studies successfully marked SYK as an important candidate gene for mastitis traits via GWAS and preliminarily confirmed that SYK expression is down-regulated in bMECs with LPS (E. coli) stimulation, but its work mechanism is still unclear.