Co-Targeting BCL-xL with MCL-1 Induces Lethal Mitochondrial Dysfunction in Diffuse Mesothelioma.

Diffuse mesothelioma is a rare but highly aggressive and treatment-resistant neoplasm with low survival rates. Effective therapeutic strategies are limited, and resistance to treatment is a major obstacle. Myeloid cell leukemia (MCL)-1 and B-cell leukemia (BCL)-xL are antiapoptotic B-cell lymphoma 2 (Bcl-2) family proteins that block cell-intrinsic apoptosis through interactions on the mitochondrial outer membrane which contribute to therapeutic resistance.

In-situ induction of intramolecular hydrogen bonds to protect lignin during the geopolymer pretreatment process of biomass.

Traditional alkali pretreatment leads to excessive depolymerization of lignin due to the harsh delignification process, which cannot meet the requirements of biorefinery. In this study, an environmentally friendly process for highly selective delignification by geopolymer-enhanced NaOH pretreatment was proposed. Under the optimal conditions (m/m = 5, 120 min and 120 °C), the lignin yield was 60.

Co-Targeting Bcl-xL with Mcl-1 Induces Lethal Mitochondrial Dysfunction in Diffuse Mesothelioma.

Diffuse mesothelioma (DM) is a rare but highly aggressive and treatment resistant neoplasm with low survival rates. Effective therapeutic strategies are limited, and resistance to treatment is a major obstacle. Myeloid Cell Leukemia (MCL)-1 and B-cell leukemia (BCL)-xL are anti-apoptotic B-cell lymphoma 2 (Bcl-2) family proteins that block cell-intrinsic apoptosis through interactions on the mitochondrial outer membrane which contribute to therapeutic resistance.

Global evidence on the effectiveness of task-shifting and task-sharing strategies for managing individuals with multimorbidity: systematic review and meta-analysis.

Introduction: Task-shifting and task-sharing strategies show promise for managing chronic diseases especially in low-income and middle-income countries (LMICs), though their effectiveness in multimorbidity management remains unclear. This study synthesised evidence on task-shifting and task-sharing strategies globally and assessed the impact on core health outcomes in multimorbidity management.

Methods: We conducted a systematic review and meta-analysis of global studies evaluating task-shifting and sharing interventions for individuals with multimorbidity.

A rare combined injury of the cruciate ligament and occult tears of the medial and lateral heads of the gastrocnemius muscle: A case report.

Rationale: The diagnosis and treatment of high-energy knee trauma primarily focus on ligamentous and bony injuries, often overlooking potential concomitant gastrocnemius muscle injuries. Isolated closed tears of the medial and lateral heads of the gastrocnemius muscle (without associated fractures or dislocations) are exceptionally rare and clinically insidious, increasing the risk of missed diagnosis and compromised patient outcomes. This article presents a novel case of combined cruciate ligament injury and occult tears of both gastrocnemius heads, a condition not previously documented in the literature.

Focal Adhesion Kinase Drives Rho/ROCK and mTOR Signaling to Protect and Augment Aortic Dissections.

Dysfunctional mechanosensing via focal adhesions (FAs) significantly contributes to thoracic aortic dissection in the β-aminopropionitrile mouse model by triggering FA kinase activation and subsequent Rho/ROCK and mTOR signaling pathways. The present findings indicate that these signaling pathways play distinct roles in ascending vs descending dissections. Specifically, in the ascending aorta, smooth muscle cell FA kinase-Rho/ROCK signaling acts as a beneficial adaptive mechanism to prevent dissections, whereas mTOR signaling is pathogenic and contributes to dissections.

Long COVID in Elderly COPD Patients: Clinical Features, Pulmonary Function Decline, and Proteomic Insights.

Background: Elderly patients with chronic obstructive pulmonary disease (COPD) face a heightened risk of developing long coronavirus disease (COVID); however the exact clinical characteristics and underlying mechanisms remain unclear.

Methods: We enrolled 85 elderly COPD patients, of whom 43 reported newly onset persistent fatigue (the most dominant complaint of long COVID) within 1 year after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and they were allocated to the Long-COVID group. The remaining 42 patients were assigned to the Control group.

GLUL mediates FOXO3 O-GlcNAcylation to regulate the osteogenic differentiation of BMSCs and senile osteoporosis.

The abnormal osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) is an important cause of senile osteoporosis (SOP). Glutamine synthetase (GLUL) is a key enzyme in glutamine biosynthesis; however, its functional role in SOP remains unclear. Here, we found that GLUL expression was downregulated in the BMSCs of SOP patients.

The improved prediction value of neutrophil to lymphocyte ratio to pneumonia severity scores for mortality in the older people with community-acquired pneumonia.

Objective: We aimed to evaluate whether there is a linear relationship between neutrophil to lymphocyte ratio (NLR) and adverse outcomes in the older hospitalised patients with community-acquired pneumonia (CAP). The performance of adding NLR to current pneumonia severity scores, including CURB-65, CRB-65, A-DROP and SMART-COP, in predicting 30-day mortality was also investigated.

Methods: This is a secondary analysis based on an existing dataset of an older cohort of CAP, including 812 patients.

Multi-functionalities of citric acid assisted thermal hydrolysis for sludge pretreatment: A novel method assisting in sludge treatment targeting multiple-objectives.

Pretreatment is essential for enhancing sludge treatment efficiency, including anaerobic digestion, phosphorus recovery, sludge dewatering, and heavy metal removal. However, few techniques simultaneously address multiple treatment objectives. In this study, a novel multifunctional sludge treatment method, citric acid-assisted thermal hydrolysis pretreatment (CA-assisted THP), was proposed to simultaneously achieve multiple treatment objectives.

Nosocomial transmission, adaption and clinical outcomes of carbapenem-resistant hypervirulent Klebsiella pneumoniae.

Background: Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-HvKp) poses a significant threat in healthcare settings. This study investigates the nosocomial transmission dynamics, adaptive phenotypes, and clinical outcomes of CR-HvKp with different evolutionary patterns.

Methods: A genomic analysis of 2,002 Klebsiella pneumoniae isolates collected from a major teaching hospital in China was performed to identify convergent isolates.

Patient and treatment characteristics that predict symptom resolution and limb amputation in patients with frostbite.

Purpose: To describe imaging and treatment received by frostbite patients and determine characteristics that predict symptom resolution and limb amputation.

Materials And Methods: This retrospective study included 174 adult patients with acute frostbite at a single institution from May 1, 2004, to August 31, 2019. Demographics, frostbite classification, symptoms present and imaging received at presentation, treatment received, and dates of symptom resolution, were collected.

The role of iron in Ni-Fe binary catalysts for electrochemical glycerol oxidation.

NiFe binary compounds have shown great potential in the electrocatalytic oxidation of biomass-derived glycerol towards valuable products. However, understanding the role of Fe on the glycerol oxidation process of Ni-based catalysts remains challenging due to the complex multi-alcohol-group oxidation. Herein, our systematic study identifies that Fe can improve both the dynamic process of Ni(OH) transformation into active NiOOH and the kinetic process of redox reaction between NiOOH and glycerol.

Smooth muscle cells and fibroblasts in the ascending aorta exhibit minor differences between embryonic origins in angiotensin II-driven transcriptional alterations.

Thoracic aortopathy is influenced by angiotensin II (AngII) and exhibits regional heterogeneity with the ascending aorta being particularly susceptible. In this region, smooth muscle cells (SMCs) and selected fibroblasts originate from the second heart field (SHF) and cardiac neural crest (CNC). While our previous study revealed a critical role of SHF-derived cells in AngII-mediated aortopathy, the contribution of CNC-derived cells remains unclear.

Comparing oxygenation assessment methods for the interventional management of hard-to-heal wounds.

Objective: To compare transcutaneous oxygen measurement (TCOM) and near infrared spectroscopy (NIRS) measurement of tissue oxygen levels in hard-to-heal (chronic) wounds.

Method: Patients aged 18-85 years presenting with hard-to-heal lower extremity wounds between 1 December 2019 and 31 July 2020 were included in this cross-sectional study. TCOM and NIRS measurements of tissue oxygenation were obtained.

Association of electrolytes and complete blood count in adolescent depression with and without psychotic symptoms.

Background: The aim of this study was to investigate physiological differences in electrolytes and complete blood counts in adolescent patients with depression with and without psychotic symptoms. By comparing baseline data in adolescent patients, it will provide more comprehensive information for individualised diagnosis and treatment of depression.

Methods: Clinical baseline data of adolescent patients were collected, including information on gender, age, smoking history, and alcohol consumption history.

Can a low b-value diffusion-weighted imaging sequence replace the standard T2-weighted fluid-sensitive sequence in breast MRI? A single-center prospective study.

Objectives: To determine whether a low b-value (b0) diffusion-weighted imaging (DWI) sequence of a similar acquisition time can fulfill the role of a T2-weighted/fluid-sensitive short tau inversion recovery (STIR) sequence.

Materials And Methods: In this prospective, single-institutional study, participants underwent 3-T or 1.5-T breast MRI, which included a standard T2-weighted/fluid-sensitive short TI inversion recovery (STIR) sequence and an investigational DWI sequence (comprising readout segmented echo planar imaging (rs-EPI) and simultaneous multi-slice (SMS) imaging).

Brain outcomes with lifestyle change in adults with Down syndrome: Rationale and design for a 12-month randomized trial.

Most adults with Down syndrome (DS) will develop pathology associated with Alzheimer's disease (AD). By age 65, the cumulative incidence of dementia exceeds 90%. The available data from trials in typically developed adults suggest the potential for intentional weight loss and changes in dietary intake to prevent or delay the development of AD.

A Dual-Modal Wearable Pulse Detection System Integrated with Deep Learning for High-Accuracy and Low-Power Sleep Apnea Monitoring.

Despite being a serious health condition that significantly increases cardiovascular and metabolic disease risks, sleep apnea syndrome (SAS) remains largely underdiagnosed. While polysomnography (PSG) remains the gold standard for diagnosis, its clinical application is limited by high costs, complex setup requirements, and sleep quality interference. Although wearable devices using photoplethysmography (PPG) have shown promise in SAS detection, their continuous operation demands substantial power consumption, hindering long-term monitoring capabilities.

Intrinsic Capacity Deficits and 6-Month Outcomes in Older Adults with Acute LRTIs: A Multi-Center Study.

Objective: Intrinsic capacity (IC), representing an individual's physical and mental abilities, is associated with adverse outcomes. Acute lower respiratory tract infections (LRTIs) contribute to poor long-term prognosis, yet effective assessment and intervention strategies remain limited. Given the critical role of IC in the aging population, understanding its prevalence and impact in older adults with LRTIs is crucial for improving management strategies.

Development and validation of a clinical-friendly model for predicting 180-day mortality in the older with community-acquired pneumonia.

Objective: Currently, there is no effective way to identify older patients with community-acquired pneumonia (CAP) at high risk of long-term death. We aimed to develop and validate a pneumonia scoring system to predict 180-day mortality, and compare its performance with the commonly used CURB-65 score.

Methods: The prospective cohort study enrolled patients aged 65 years and older with CAP from 10 medical centers in China between April 2021 and December 2023.

Integrative approaches for predicting protein network perturbations through machine learning and structural characterization.

Chromatin remodeling complexes, such as the Saccharomyces cerevisiae INO80 complex, exemplify how dynamic protein interaction networks govern cellular function through a balance of conserved structural modules and context-dependent functional partnerships, as revealed by integrative machine learning and structural mapping approaches. In this study, we explored the INO80 complex using machine learning to predict network changes caused by genetic deletions. Tree-based models outperformed linear approaches, highlighting non-linear relationships within the interaction network.

pH-Sensitive Porphyrin Metal-Organic Frameworks for Controlled Delivery of Para-Toluenesulfonamide and Photodynamic Cancer Therapy.

Introduction: Photodynamic therapy (PDT) is a promising approach for tumor treatment. PDT for treating lung squamous cell carcinoma (LSCC) under the guidance of bronchoscopy has great potential for development. However, the use of high-intensity lasers in treatment may pose a risk of tissue damage.

A giant spinal schwannoma at the C1-C2 level: A case report.

Rationale: Giant spinal schwannomas located at the C1-C2 level pose significant surgical challenges because of their proximity to the brainstem, cervical spinal cord, and vertebral arteries. This case provides insight into the surgical management of giant spinal schwannomas at the C1-C2 level.

Patient Concerns: A 40-year-old female presented with a 2-year history of progressive limb numbness, weakness, and gait instability.

Endothelium- and Fibroblast-Derived C-Type Natriuretic Peptide Prevents the Development and Progression of Aortic Aneurysm.

Background: Thoracic (TAA) and abdominal (AAA) aortic aneurysm are life-threatening diseases characterized by dilation, inflammation, and structural weakness; development of pharmacological therapies is desperately needed. CNP (C-type natriuretic peptide) plays a key role in vascular homeostasis, mediating vasodilator, anti-inflammatory, and antiatherogenic actions. Since such processes drive AA, we determined the role of endogenous CNP in offsetting pathogenesis.