Mitochondria and the Repurposing of Diabetes Drugs for Off-Label Health Benefits.

This review describes our current understanding of the role of the mitochondria in the repurposing of the anti-diabetes drugs metformin, gliclazide, GLP-1 receptor agonists, and SGLT2 inhibitors for additional clinical benefits regarding unhealthy aging, long COVID, mental neurogenerative disorders, and obesity. Metformin, the most prominent of these diabetes drugs, has been called the "Drug of Miracles and Wonders," as clinical trials have found it to be beneficial for human patients suffering from these maladies. To promote viral replication in all infected human cells, SARS-CoV-2 stimulates the infected liver cells to produce glucose and to export it into the blood stream, which can cause diabetes in long COVID patients, and metformin, which reduces the levels of glucose in the blood, was shown to cut the incidence rate of long COVID in half for all patients recovering from SARS-CoV-2.

Scaffolding informed consent.

The principle of respecting patient autonomy underpins the concept and practice of informed consent. Yet current approaches to consent often ignore the ways in which the exercise of autonomy is deeply epistemically dependent.In this paper, we draw on philosophical descriptions of autonomy 'scaffolding' and apply them to informed consent in medicine.

Pangeneric genome analyses reveal the evolution and diversity of the orchid genus Dendrobium.

Orchids constitute one of the most diverse families of angiosperms, yet their genome evolution and diversity remain unclear. Here we construct and analyse chromosome-scale de novo assembled genomes of 17 representative accessions spanning 12 sections in Dendrobium, one of the largest orchid genera. These accessions represent a broad spectrum of phenotypes, lineages and geographical distributions.

Vaccine-induced T cell responses control Orthoflavivirus challenge infection without neutralizing antibodies in humans.

T cells have been identified as correlates of protection in viral infections. However, the level of vaccine-induced T cells needed and the extent to which they alone can control acute viral infection in humans remain uncertain. Here we conducted a double-blind, randomized controlled trial involving vaccination and challenge in 33 adult human volunteers, using the live-attenuated yellow fever (YF17D) and chimeric Japanese encephalitis-YF17D (JE/YF17D) vaccines.

Designer topological-single-atom catalysts with site-specific selectivity.

Designing catalysts with well-defined, identical sites that achieve site-specific selectivity, and activity remains a significant challenge. In this work, we introduce a design principle of topological-single-atom catalysts (T-SACs) guided by density functional theory (DFT) and Ab initio molecular dynamics (AIMD) calculations, where metal single atoms are arranged in asymmetric configurations that electronic shield topologically misorients d orbitals, minimizing unwanted interactions between reactants and the support surface. Mn/CeO catalysts, synthesized via a charge-transfer-driven approach, demonstrate superior catalytic activity and selectivity for NO removal.

Guidance on biomaterials for periodontal tissue regeneration: Fabrication methods, materials and biological considerations.

Regeneration of the multiple tissues and interfaces in the periodontal complex necessitates multidisciplinary evaluation to establish structure/function relationships. This article, an initiative of the Academy of Dental Materials, provides guidance for performing chemical, structural, and mechanical characterization of materials for periodontal tissue regeneration, and outlines important recommendations on methods of testing bioactivity, biocompatibility, and antimicrobial properties of biomaterials/scaffolds for periodontal tissue engineering. First, we briefly summarize periodontal tissue engineering fabrication methods.

Centering the body in agricultural development: Bridging conceptualizations of bodies-as-mechanism and bodies-as-affective.

There is resurgent interest in making agriculture more "nutrition sensitive" to address longstanding rural health disparities. Yet, the relations between agri-ecological systems and producer wellbeing and health are complex, and approaches to studying them are scattered across multiple disciplinary traditions. This paper forges a methodological framework to study how bodily and social wellbeing may be facilitated/hindered amongst individuals engaged in agriculture by centering the material body within agriculture-nutrition analyses.

Smart Imitator: Learning from Imperfect Clinical Decisions.

Objectives: This study introduces Smart Imitator (SI), a 2-phase reinforcement learning (RL) solution enhancing personalized treatment policies in healthcare, addressing challenges from imperfect clinician data and complex environments.

Materials And Methods: Smart Imitator's first phase uses adversarial cooperative imitation learning with a novel sample selection schema to categorize clinician policies from optimal to nonoptimal. The second phase creates a parameterized reward function to guide the learning of superior treatment policies through RL.

Treatment of very high risk membranous nephropathy complicated by pulmonary embolism with glucocorticoids and rituximab: Case report.

Rationale: We report the efficacy of combination prednisolone and intravenous (IV) rituximab as an immunosuppressive regimen for a young male presenting with extensive venous thromboembolism including a submassive pulmonary embolism secondary to life-threatening nephrotic syndrome from very high risk anti-phospholipase-A2 receptor (PLA2R) positive membranous nephropathy. Initial treatment was with mechanical thrombectomy and anticoagulation. Thereafter, oral prednisolone was initiated to induce remission, during a period of uninterrupted anticoagulation.

Sequential Targeting Chondroitin Sulfate-Bilirubin Nanomedicine Attenuates Osteoarthritis via Reprogramming Lipid Metabolism in M1 Macrophages.

The infiltration and excessive polarization of M1 macrophages contribute to the induction and persistence of low-grade inflammation in joint-related degenerative diseases such as osteoarthritis (OA). The lipid metabolism dysregulation promotes M1 macrophage polarization by coordinating the compensatory pathways of the inflammatory and oxidative stress responses. Here, a self-assembling, licofelone-loaded nanoparticle (termed LCF-CSBN), comprising chondroitin sulfate and bilirubin joined by an ethylenediamine linker, is developed to selectively reprogram lipid metabolism in macrophage activation.

Reprogrammable Flexible Piezoelectric Actuator Arrays with a High Degree of Freedom for Shape Morphing and Locomotion.

The high degree of freedom (DoF) shape morphing widely exists in biology for mimicry, camouflage, and locomotion. Currently, a lot of bionic soft/flexible actuators and robots with shape-morphing functions have been developed to realize conformity, grasp, and movement. Among these solutions, two-dimensional responsive materials and structures that can shape morph into different three-dimensional configurations are valuable for creating reversible high DoF shape morphing.

Whole-genome phylogenetic analysis of complex from clinical respiratory samples.

Unlabelled: The complex (MAC) is a common causative agent causing nontuberculous mycobacterial (NTM) pulmonary disease worldwide. Whole-genome sequencing was performed on a total of 203 retrospective MAC isolates from respiratory specimens. Phylogenomic analysis identified eight subspecies and species.

Country-specific key lifestyle factors and health outcomes for resource allocation in the general population: a network analysis across 29 countries.

Background: We aimed to identify the central lifestyle, the most impactful among lifestyle factor clusters; the central health outcome, the most impactful among health outcome clusters; and the bridge lifestyle, the most strongly connected to health outcome clusters, across 29 countries to optimise resource allocation for local holistic health improvements.

Methods: From July 2020 to August 2021, we surveyed 16 461 adults across 29 countries who self-reported changes in 18 lifestyle factors and 13 health outcomes due to the pandemic. Three networks were generated by network analysis for each country: lifestyle, health outcome, and bridge networks.

Remission of persistent hypertension and hypokalaemia following redo adrenalectomy for primary aldosteronism - case report.

We report on a case of a 67-year-old male who was referred to our care with persistent aldosteronism post adrenalectomy. Biochemical failure after surgery is rare after surgery for primary aldosteronism (PA). Persistent hypokalaemia and raised aldosteronism is an indication of treatment failure after surgery.

Highly Selective AIEgen-Based "Turn On" Fluorescent Imaging for Inflammation Detection.

Hypochlorous acid (HClO) is released by immune cells in the immune system, and it helps the body fight off infections and inflammation by killing bacteria, viruses, and other pathogens. However, tissue damage or apoptosis may also be induced by excess HClO. On this basis, we designed the probe TPE-NS by choosing tetraphenylethylene (TPE) as the luminescent unit and dimethylthiocarbamoyl chloride as the recognition site.

[The mediational role of cognitive function on occupational outcomes in persons with major depressive and bipolar disorder].

Background: Improving functioning in adults with major depressive disorder (MDD) and bipolar disorder (BD) is a priority therapeutic objective.

Methods: This retrospective post hoc secondary analysis evaluated 108 patients with MDD or BD receiving the antidepressants vortioxetine, ketamine, or infliximab. The analysis aimed to determine if changes in objective or subjective cognitive function mediated the relationship between depression symptom severity and workplace outcomes.

Wireless microwave-to-optical conversion via programmable metasurface without DC supply.

Microwave-optical interaction and its effective utilization are vital technologies at the frontier of classical and quantum sciences for communication, sensing, and imaging. Typically, state-of-the-art microwave-to-optical converters are realized by fiber and circuit approaches with multiple processing steps, and external powers are necessary, which leads to many limitations. Here, we propose a programmable metasurface that can achieve direct and high-speed free-space microwave-to-laser conversion.

Divergent roles of mA in orchestrating brown and white adipocyte transcriptomes and systemic metabolism.

N-methyladenosine (mA) is among the most abundant mRNA modifications, yet its cell-type-specific regulatory roles remain unclear. Here we show that mA methyltransferase-like 14 (METTL14) differentially regulates transcriptome in brown versus white adipose tissue (BAT and WAT), leading to divergent metabolic outcomes. In humans and mice with insulin resistance, METTL14 expression differs significantly from BAT and WAT in the context of its correlation with insulin sensitivity.

Factors Associated With Mental Health Literacy, Depression, and Anxiety Amongst Indonesian Adolescents.

Aims: This study aims to identify factors associated with mental health literacy (mental health knowledge and attitudes towards mental health and help-seeking behaviours), depression and anxiety amongst adolescents, and test the hypothesised model by examining the interrelationships between these outcomes.

Design: Cross-sectional descriptive quantitative research.

Methods: Using convenient sampling, 615 adolescents from four public schools completed online questionnaires measuring mental health literacy, depression, and anxiety.

Formation of I+III supercomplex rescues respiratory chain defects.

Mitochondrial electron transport chain (ETC) complexes partition between free complexes and quaternary assemblies known as supercomplexes (SCs). However, the physiological requirement for SCs and the mechanisms regulating their formation remain controversial. Here, we show that genetic perturbations in mammalian ETC complex III (CIII) biogenesis stimulate the formation of a specialized extra-large SC (SC-XL) with a structure of I+III, resolved at 3.

Impact of local government environmental attention on corporate total factor productivity: Evidence from 288 Chinese cities.

To improve the effectiveness of government environmental attention on resource allocation, this study proposes a measurement framework using text analysis and an unsupervised Word2vec model to quantify local government environmental attention of 288 Chinese cities. We further examine its impact on total factor productivity (TFP) of China's listed firms from 2010 to 2021 using the high-dimensional fixed-effects and panel quantile regression models. The findings show that: (1) Local government environmental attention contributes positively to TFP, with each unit increase raising TFP by approximately 1.

Preliminaries to artificial consciousness: A multidimensional heuristic approach.

The pursuit of artificial consciousness requires conceptual clarity to navigate its theoretical and empirical challenges. This paper introduces a composite, multilevel, and multidimensional model of consciousness as a heuristic framework to guide research in this field. Consciousness is treated as a complex phenomenon, with distinct constituents and dimensions that can be operationalized for study and for evaluating their replication.

Right Ventricular Injury Definition and Management in Veno-Venous Extracorporeal Membrane Oxygenation.

Right ventricular injury (RVI) in respiratory failure receiving veno-venous extracorporeal membrane oxygenation (VV ECMO) is associated with significant mortality. A scoping review is necessary to map the current literature and guide future research regarding the definition and management of RVI in patients receiving VV ECMO. We searched for relevant publications on RVI in patients receiving VV ECMO in Medline, EMBASE, and Web of Science.