Frailty and pre-frailty prevalence in community-dwelling elderly with multimorbidity: A systematic review and meta-analysis.

Background: The relationship between frailty/pre-frailty, and multimorbidity in the elderly is recognized, but specific prevalence among community-dwelling elderly with multimorbidity is unclear. This study aims to determine these rates, analyze subgroup, and identify sources of heterogeneity to bolster evidence-based interventions and health policies.

Methods: We searched nine databases from inception to November 16, 2023, for cross-sectional and cohort studies on community-dwelling elderly with multimorbidity.

Pathway analysis of the impact of family function and self-efficacy on depression and anxiety in patients undergoing in vitro fertilization-embryo transfer.

Background: Patients undergoing assisted reproductive technology (ART) experience significant psychological distress due to infertility, with depression and anxiety being the most common manifestations. This study investigates the influence of family support and self-efficacy on the mental health of patients undergoing in vitro fertilization-embryo transfer (IVF-ET). The aim is to assess the direct and indirect effects of family function and self-efficacy on depression and anxiety in IVF-ET patients through pathway analyses, thereby providing novel insights for improving patients' psychological well-being.

Monotherapy of PD-1 Inhibitor Camrelizumab Reverses Advanced Lung Squamous Cell Carcinoma with Low PD-1 Expression: A Case Report.

Introduction: Chemotherapy plus immunotherapy is the standard treatment worldwide for advanced lung squamous cell carcinoma with high programmed cell death protein-1 (PD-1) expression. The use of immunotherapy alone against advanced lung squamous cell carcinoma is rarely reported, and data on PD-1 inhibitor camrelizumab are missing. We report the first case of camrelizumab monotherapy, which can be a reference for the clinical applications of camrelizumab in a wider context.

N -N-Butyl Haloperidol Iodide Mitigates Myocardial Ischemia/Reperfusion Injury Through Activation of SIRT1-Nrf2 Signaling Loop.

N -n-butyl haloperidol iodide (F 2 ), a derivative of haloperidol developed by our group, exhibits potent antioxidative properties and confers protection against cardiac ischemia/reperfusion (I/R) injury. The protective mechanisms by which F 2 ameliorates I/R injury remain obscure. The activation of nuclear factor erythroid 2-related factor 2 (Nrf2), a key transcription factor transactivating many antioxidative genes, also attenuates I/R-induced myocardial damage.

N-n-butyl haloperidol iodide mediates cardioprotection via regulating AMPK/FoxO1 signalling.

Derangement of redox condition largely contributes to cardiac ischemia/reperfusion (I/R) injury. FoxO1 is a transcription factor which transcripts a series of antioxidants to antagonize I/R-induced oxidative myocardial damage. N-n-butyl haloperidol iodide (F ) is a derivative derived from haloperidol structural modification with potent capacity of inhibiting oxidative stress.

Resveratrol alleviates high glucose-induced oxidative stress and apoptosis in rat cardiac microvascular endothelial cell through AMPK/Sirt1 activation.

Diabetic cardiomyopathy (DCM) is a common complication of diabetes. DCM causes extensive lesions on cardiac microvasculature that is predominantly cardiac microvascular endothelial cells (CMECs). Reducing high glucose (HG)-induced damage such as oxidative damage and apoptosis could alleviate the development of DCM.

Approximating Nash equilibrium for anti-UAV jamming Markov game using a novel event-triggered multi-agent reinforcement learning.

In the downlink communication, it is currently challenging for ground users to cope with the uncertain interference from aerial intelligent jammers. The cooperation and competition between ground users and unmanned aerial vehicle (UAV) jammers leads to a Markov game problem of anti-UAV jamming. Therefore, a model-free method is adopted based on multi-agent reinforcement learning (MARL) to handle the Markov game.

T-Type Calcium Channel Inhibitors Induce Apoptosis in Medulloblastoma Cells Associated with Altered Metabolic Activity.

Medulloblastoma (MB) is the most common malignant paediatric brain tumour. In our previous studies, we developed a novel 3D assay for MB cells that was used to screen a panel of plasma membrane calcium channel modulators for their effect on the 3D growth of D341 MB cells. These studies identified T-type (CaV3) channel inhibitors, mibefradil and NNC-55-0396 (NNC) as selective inhibitors of MB cell growth.

Tomatidine provides mitophagy-independent neuroprotection after ischemic injury.

Cerebral ischemia is one of the leading causes of human mortality and disability worldwide. The treatment of cerebral ischemia is refractory due to its short therapeutic window and lack of effective clinical drugs. Mitophagy, the autophagic elimination of damaged mitochondria, attenuates neuronal injury in cerebral ischemia, indicating the potential of mitophagy inducers as therapies for cerebral ischemia.

Direct Amidation to Access 3-Amido-1,8-Naphthalimides Including Fluorescent Scriptaid Analogues as HDAC Inhibitors.

Methodology to access fluorescent 3-amido-1,8-naphthalimides using direct Buchwald-Hartwig amidation is described. The protocol was successfully used to couple a number of substrates (including an alkylamide, an arylamide, a lactam and a carbamate) to 3-bromo-1,8-naphthalimide in good yield. To further exemplify the approach, a set of scriptaid analogues with amide substituents at the 3-position were prepared.

Bioactivity Profiles of Cytoprotective Short-Chain Quinones.

Short-chain quinones (SCQs) have been investigated as potential therapeutic candidates against mitochondrial dysfunction, which was largely thought to be associated with the reversible redox characteristics of their active quinone core. We recently reported a library of SCQs, some of which showed potent cytoprotective activity against the mitochondrial complex I inhibitor rotenone in the human hepatocarcinoma cell line HepG2. To better characterize the cytoprotection of SCQs at a molecular level, a bioactivity profile for 103 SCQs with different compound chemistries was generated that included metabolism related markers, redox activity, expression of cytoprotective proteins and oxidative damage.

Novel Short-Chain Quinones to Treat Vision Loss in a Rat Model of Diabetic Retinopathy.

Diabetic retinopathy (DR), one of the leading causes of blindness, is mainly diagnosed based on the vascular pathology of the disease. Current treatment options largely focus on this aspect with mostly insufficient therapeutic long-term efficacy. Mounting evidence implicates mitochondrial dysfunction and oxidative stress in the central etiology of DR.

Comparative In Vitro Toxicology of Novel Cytoprotective Short-Chain Naphthoquinones.

Short-chain quinones (SCQs) have been identified as potential drug candidates against mitochondrial dysfunction, which largely depends on the reversible redox characteristics of the active quinone core. We recently identified 11 naphthoquinone derivatives, - from a library of SCQs that demonstrated enhanced cytoprotection and improved metabolic stability compared to the clinically used benzoquinone idebenone. Since the toxicity properties of our promising SCQs were unknown, this study developed multiplex methods and generated detailed toxicity profiles from 11 endpoint measurements using the human hepatocarcinoma cell line HepG2.

Mixed alkoxy/hydroxy 1,8-naphthalimides: expanded fluorescence colour palette and in vitro bioactivity.

An efficient and functional group tolerant route to access hydroxy 1,8-naphthalimides has been used to synthesise a range of mono- and disubstituted hydroxy-1,8-naphthalimides with fluorescence emissions covering the visible spectrum. The dialkoxy substituted compounds prepared possess high quantum yields (up to 0.95) and long fluorescent lifetimes (up to 14 ns).

Advanced Resistance Studies Identify Two Discrete Mechanisms in to Overcome Antibacterial Compounds that Target Biotin Protein Ligase.

Biotin protein ligase (BPL) inhibitors are a novel class of antibacterial that target clinically important methicillin-resistant () In BPL is a bifunctional protein responsible for enzymatic biotinylation of two biotin-dependent enzymes, as well as serving as a transcriptional repressor that controls biotin synthesis and import. In this report, we investigate the mechanisms of action and resistance for a potent anti-BPL, an antibacterial compound, biotinyl-acylsulfamide adenosine (BASA). We show that BASA acts by both inhibiting the enzymatic activity of BPL in vitro as well as functioning as a transcription co-repressor.

Metabolic Stability of New Mito-Protective Short-Chain Naphthoquinones.

Short-chain quinones (SCQs) have been identified as potential drug candidates against mitochondrial dysfunction, which is largely dependent on their reversible redox characteristics of the active quinone core. We recently synthesized a SCQ library of > 148 naphthoquinone derivatives and identified 16 compounds with enhanced cytoprotection compared to the clinically used benzoquinone idebenone. One of the major drawbacks of idebenone is its high metabolic conversion in the liver, which significantly restricts is therapeutic activity.

Enrichment and Separation of Cationic, Neutral, and Chiral Analytes by Micelle to Cyclodextrin Stacking-Micellar Electrokinetic Chromatography.

Analyte focusing by micelle to cyclodextrin stacking (MCDS) in micellar electrokinetic chromatography (MEKC) using sodium dodecyl sulfate (SDS) and fused silica capillaries is demonstrated for neutral, cationic, and chiral analytes. The stacking was at a dynamic boundary formed between the injected charged SDS micelles and neutral γ-cyclodextrin (γ-CD) zones, where the analytes bound inside micelles were released due to the formation of stable SDS-CD inclusion complexes. The complex formation reduced or eliminated the affinity of the analytes to the micellar phase.

Halogenation of Biotin Protein Ligase Inhibitors Improves Whole Cell Activity against Staphylococcus aureus.

We report the synthesis and evaluation of 5-halogenated-1,2,3-triazoles as inhibitors of biotin protein ligase from Staphylococcus aureus. The halogenated compounds exhibit significantly improved antibacterial activity over their nonhalogenated counterparts. Importantly, the 5-fluoro-1,2,3-triazole compound 4c displays antibacterial activity against S.