Apoptotic vesicles derived from bone marrow mesenchymal stem cells increase angiogenesis in a hind limb ischemia model via the NAMPT/SIRT1/FOXO1 axis.

Background: Chronic limb-threatening ischemia (CLTI) is the most severe form of peripheral arterial disease (PAD). Mesenchymal stem cell (MSC) transplantation holds promise as a treatment for CLTI; however, the harsh local environment poses challenges to its effectiveness. Apoptotic vesicles (ApoVs) are extracellular vesicles produced by cells undergoing apoptosis, and they can carry various biomolecules from their parent cells, including proteins, RNA, DNA, lipids, ions, and gas neurotransmitters.

High-dimensional deconstruction of HNSC reveals clinically distinct cellular states and ecosystems that are associated with prognosis and therapy response.

Background: Characterizing the variety of cell types in the tumor microenvironment (TME) and their organization into cellular communities is vital for elucidating the biological diversity of cancer and informing therapeutic strategies.

Methods: Here, we employed a machine learning-based algorithm framework, EcoTyper, to analyze single-cell transcriptomes from 139 patients with head and neck squamous cell carcinoma (HNSC)and gene expression profiles from 983 additional HNSC patients, aiming to delineate the fundamental cell states and ecosystems integral to HNSC.

Results: A diverse landscape of 66 cell states and 9 ecosystems within the HNSC microenvironment was identified, revealing classical cell types while also expanding upon previous immune classifications.

Association between cancer-associated fibroblasts and prognosis of neoadjuvant chemoradiotherapy in esophageal squamous cell carcinoma: a bioinformatics analysis based on single-cell RNA sequencing.

Background: Esophageal squamous cell carcinoma (ESCC) is a prevalent and aggressive subtype of esophageal cancer, posing a significant mortality and economic burden, especially in East and Southeast Asia. Current therapeutic strategies have limitations in improving patient survival, particularly regarding disease progression and resistance. This study aimed to investigate the impact of neoadjuvant chemoradiotherapy (NCRT) on the ESCC microenvironment.

Epidemiological profile and antimicrobial resistance trends of Staphylococcus aureus in Chinese pediatric intensive care units from 2016 to 2022: a multi-center retrospective study.

Objective: This study aimed to analyze the profiles and evolution of Staphylococcus aureus in the pediatric intensive care units (PICUs) of 17 hospitals in China from 2016 to 2022.

Methods: Susceptibility testing was performed to bacterial strains with a uniform monitoring protocol, which was provided by the US Clinical and Laboratory Standards Institute (CLSI) and used by the China Antimicrobial Surveillance Network (CHINET). The results were interpreted in accordance with the performance standards for antimicrobial susceptibility testing issued by the US Clinical and Laboratory Standards Institute.

Genomic signatures of SnRKs highlighted conserved evolution within orchids and stress responses through ABA signaling in the Cymbidium ensifolium.

Sucrose non-fermenting 1-related protein kinases (SnRKs) are crucial for modulating plant responses to abiotic stresses, linking metabolism with stress signaling pathways. Investigating the roles and stress responses of SnRKs in plants paves the way for developing stress-tolerant strategies in orchid species. Here, 362 SnRK members were identified from nine current orchid genomes, highlighting the conservation of these genes in evolution.

Sociodemographic Disparities in Rectal Cancer Outcomes within Academic Cancer Centers.

Background: Sociodemographic disparities in cancer care outcomes are often related to delayed or limited care access. However, it is unknown whether outcome differences persist after establishing high-level care. This study evaluated the relationship between rectal cancer outcomes and sociodemographic status at academic cancer centers.

The autonomic response following taVNS predicts changes in level of consciousness in DoC patients.

Advancements in emergency medicine and critical care have significantly improved survival rates for patients with severe acquired brain injuries(sABI), subsequently increasing the prevalence of disorders of consciousness (DoC) such as Unresponsive Wakefulness Syndrome (UWS) and Minimally Conscious State (MCS). However, the assessment of conscious states relies on the observation of behavioral responses, the interpretation of which may vary from evaluator to evaluator, as well as the high rate of misdiagnosis, which together pose significant challenges for clinical diagnosis. The study investigates the utility of transcutaneous auricular vagus nerve stimulation (taVNS) in modulating autonomic responses, as evidenced through heart rate variability (HRV), for distinguishing between healthy individuals and DoC patients and for prognosticating patient outcomes.

Genomically defined hypervirulent Klebsiella pneumoniae contributed to early-onset increased mortality.

The presence of all five of the virulence-associated genes iucA, iroB, peg-344, rmpA, and rmpA2 is presently the most accurate genomic means for predicting hypervirulent Klebsiella pneumoniae (hvKp-p). With this longitudinal cohort study, we firstly provide novel insights into the clinical and genomic characteristics of hvKp-p in high-risk regions. Through propensity score matching, we show that hvKp-p is less likely to acquire antimicrobial resistance but develops more severe disease and result in increased mortality.

Engineered mitochondria in diseases: mechanisms, strategies, and applications.

Mitochondrial diseases represent one of the most prevalent and debilitating categories of hereditary disorders, characterized by significant genetic, biological, and clinical heterogeneity, which has driven the development of the field of engineered mitochondria. With the growing recognition of the pathogenic role of damaged mitochondria in aging, oxidative disorders, inflammatory diseases, and cancer, the application of engineered mitochondria has expanded to those non-hereditary contexts (sometimes referred to as mitochondria-related diseases). Due to their unique non-eukaryotic origins and endosymbiotic relationship, mitochondria are considered highly suitable for gene editing and intercellular transplantation, and remarkable progress has been achieved in two promising therapeutic strategies-mitochondrial gene editing and artificial mitochondrial transfer (collectively referred to as engineered mitochondria in this review) over the past two decades.

Chenodeoxycholic acid modulates cholestatic niche through FXR/Myc/P-selectin axis in liver endothelial cells.

Cholestatic liver diseases are characterized by excessive bile acid accumulation in the liver. Endothelial cells (ECs) shape the local microenvironment in both normal conditions and liver injury, yet their role in cholestasis is unclear. Through a comparative analysis of single-cell RNA sequencing data from various murine models of liver injury, we identify distinctive Myc activation within ECs during obstructive cholestasis resulting from bile duct ligation (BDL).

Enhanced SIRT3 expression restores mitochondrial quality control mechanism to reverse osteogenic impairment in type 2 diabetes mellitus.

Osteoporosis represents a prevalent and debilitating comorbidity in patients diagnosed with type 2 diabetes mellitus (T2DM), which is characterized by suppressed osteoblast function and disrupted bone microarchitecture. In this study, we utilized male C57BL/6 J mice to investigate the role of SIRT3 in T2DM. Decreased SIRT3 expression and impaired mitochondrial quality control mechanism are observed in both in vitro and in vivo models of T2DM.

Bioactivities and Structure-Activity Relationships of Harmine and Its Derivatives: A Review.

Natural products and their derivatives play a crucial role in treating various diseases. Harmine, a tricyclic β-carboline alkaloid sourced from the seeds of Peganum harmala L., has been explored as a candidate molecule for a variety of diseases due to its diverse bioactivities.

Colon cancer-cell-specific drug delivery by gemcitabine conjugated with peptide chain targeting ENO1.

Gemcitabine, a chemotherapeutic agent widely approved for treating various cancers, faces significant clinical challenges, including drug resistance and poor tumor selectivity. To address the limitation of inadequate tumor targeting, a peptide chain was developed to specifically bind to colon cancer cells and conjugated to gemcitabine via aldehyde-amine condensation. This study aimed to exploit the oncogenic activity of the multifunctional protein α-Enolase (ENO1).

Microfibrillated cellulose reinforced polyethyleneimine cryogels fabricated via cryo-induced chemical crosslinking for enhanced removal of albumin-bound bilirubin.

Bilirubin exists as albumin-bound complexes in the bloodstream of patients with hyperbilirubinemia. Developing adsorbents with high removal efficiency for albumin-bound bilirubin and excellent hemocompatibility is essential for effective hemoperfusion therapy. Herein, microfibrillated cellulose-reinforced polyethyleneimine cryogels (PEI/MFC) with robust mechanical properties were fabricated through cryo-induced chemical crosslinking, using bis(vinylsulphonyl)methane (BVSM) as chemical cross-linker.

Characterization and Biocompatibility Assessment of 3D-Printed HA/PCL Porous Bionic Bone Scaffold: and Evaluation.

Objectives: This study aims to characterize a three-dimensional-printed hydroxyapatite (HA)/polycaprolactone (PCL) scaffold and assess its biocompatibility both and .

Methods: A bionic, porous HA/PCL scaffold was fabricated using 3D printing, and its microstructure, porosity, hydrophilicity, and mechanical properties were evaluated through scanning electron microscopy and various assays. Bone marrow mesenchymal stem cells (BMSCs) and vascular endothelial progenitor cells (VEPCs) were co-cultured with the scaffold, and their proliferation and osteogenic differentiation were assessed using the Cell Counting Kit-8, ALP assays, and alizarin red staining.

Polysocial risk score, lifestyle, genetic factors and risk of incident lung cancer.

Objectives: Lung cancer (LC) is the most frequently diagnosed cancer globally; however, the role of social risk factors in its development is not well understood. While previous studies have identified various lifestyle and genetic factors contributing to LC, the interplay between these elements and broader social determinants of health is still unclear. In this study, we aimed to construct a polysocial risk score (PsRS) that captures the multifaceted nature of social environment risk exposure and its relationship with incident LC, and to explore whether the effect of PsRS is influenced by lifestyle behaviours and heritable risk.

Asperuloside promotes innate immunity via IRE-1/XBP-1 mediated unfolded protein response.

Numerous studies have reported that asperuloside (ASP), a monomeric compound extracted from the traditional Chinese medicine Spreading Hedyotis Herb, possesses a variety of medicinal properties, including the treatment of obesity, cancer, inflammatory diseases, and bacterial infections. However, its role in innate immunity and the underlying mechanisms of action remain largely unexplored. Protein homeostasis and the health of the endoplasmic reticulum (ER) are crucial for organismal function, as a well-balanced ER is essential not only for maintaining cellular integrity but also for ensuring immune homeostasis.

Design, synthesis and anticancer evaluation of novel 1,3-imidazole-type phenylhistin derivatives: Dual mechanism via P53 induction and microtubulin inhibition.

To enhance biological activity and deepen the understanding of the structure-activity relationship, a systematic study was conducted on the 5-position of the 1,3-imidazol-4-yl group in phenylahistin. The interaction between phenylahistin derivative 16j and the colchicine-binding site was first analyzed in detail, leading to the development of a fragment library to replace the tert-butyl group. A series of 20 novel phenylhistin derivatives were designed, synthesized, and characterized.

Design, synthesis and biological evaluation of pyrrolopyrimidine urea derivatives as novel KRAS inhibitors for the treatment of cancer.

The KRAS mutation, which occurs in approximately 14 % of lung adenocarcinomas, has recently become a crucial target for therapy via small molecules that covalently bind to the mutated cysteine. In this study, a novel series of pyrrolopyrimidine derivatives was rationally designed and synthesized, employing a structure-based drug design strategy. Through structure-activity relationship (SAR) analysis, compound SK-17 emerged as a direct and highly potent inhibitor of KRAS.

Suppression of the LKB1-AMPK-SLC7A11-GSH signaling pathway sensitizes NSCLC to albumin-bound paclitaxel via oxidative stress.

Albumin-bound paclitaxel (nab-PTX) is an important chemotherapeutic drug used for the treatment of advanced and metastatic non-small cell lung cancer (NSCLC). One critical issue in its clinical application is the development of resistance; thus, a deeper understanding of the mechanisms underlying the primary resistance to nab-PTX is expected to help to develop effective therapeutic strategies to overcome resistance. In this study, we made an unexpected discovery that NSCLC with wild-type (WT) Liver kinase B1 (LKB1), an important tumor suppressor and upstream kinase of AMP-activated protein kinase (AMPK), is more resistant to nab-PTX than NSCLC with mutant LKB1.

Identification of 13 natural antioxidants in green calyx plum using AAPH, ABTS, and FRAP-coupled HPLC-DAD via QTOF-MS/MS.

The novel application of a combined screening method, utilizing AAPH, ABTS, and FRAP assays with HPLC, is first used for screening natural antioxidants in Green Calyx plums (GCP). This method was assumed that the peak areas of compounds with antioxidant activity in HPLC chromatograms would be significantly reduced or disappeared after incubating with the AAPH, ABTS, and FRAP. The thirteen screened antioxidants can be identified by Q-TOF-MS/MS.

Circadian Rhythm Defects in Prader-Willi Syndrome Neurons.

Prader-Willi syndrome (PWS) is a neurodevelopmental disorder characterized by a spectrum of symptoms, including developmental delay, intellectual disability, and increased risk of autism. PWS is an imprinting disorder caused by the loss of paternal expression of critical genes in the 15q11.2-q13 region, including MAGEL2, SNRPN/SNURF, and SNORD116.

Two Emerging Providencia Species from Clinical Samples: Providencia zhejiangensis and Providencia xihuensis sp. nov.

Members of the genus Providencia are typically opportunistic pathogens that can cause severe infections in immunocompromised hosts. This study identified two Providencia strains, SKLX146130 and SKLX074055, representing novel species designated as Providencia zhejiangensis sp. nov.

Treatment Outcomes And Key Factors Contributing to Unfavorable Outcomes Among Isoniazid-Resistant Pulmonary Tuberculosis Patients in Shanghai, China.

Objectives: Given that more than 1 million people annually develop isoniazid-resistant tuberculosis (Hr-TB), the issue of Hr-TB may go unnoticed. However, limited studies have focused on the clinical treatment of Hr-TB in China, particularly regarding treatment outcomes and influencing factors. This study aimed to evaluate the treatment outcomes of Hr-TB patients in Shanghai from 2018 to 2021 and analyze the influencing factors, including demographic characteristics, clinical features, and treatment-related factors.

Dynamic ALBI score and FIB-4 index trends to predict complications after resection of hepatocellular carcinoma: A K-means clustering approach.

Background: Severe postoperative complications still occur following hepatectomy among patients with hepatocellular carcinoma (HCC). There is a need to identify high-risk patients for severe complications to enhance patient safety. We sought to evaluate the combined impact of pre- and postoperative albumin-bilirubin (ALBI) score and Fibrosis-4 (FIB-4) index trends to predict severe complications after HCC resection.