Therapeutic restoration of mitochondria-endoplasmic reticulum cross talk for osteoarthritis.

Osteoarthritis is a prevalent joint disease in the aging population. The hallmark of osteoarthritis is the degeneration of the joint cartilage, characterized by changes in chondrocytes including mitochondrial dysfunction. However, the precise mechanisms of how this affects chondrocyte homeostasis and whether such processes can be explored as therapeutic targets for osteoarthritis remain unclear.

The westerlies-monsoon interaction shaped asymmetric lake expansions over the Tibetan Plateau in warming periods.

Modelling studies and recent observations suggest that the westerlies-monsoon interactions (WMI) have led to a spatial imbalance in lake expansions across the Tibetan Plateau (TP) during the past decades under anthropogenic warming. However, whether such imbalance reflects a short-term phenomenon or a long-term climatic trend remains unclear. Here, we present a 240,000-year lake level reconstruction from the inner TP to examine the extent to which WMI also operated for previous interglacials, natural warm regimes with large-scale climatic boundary changes.

Leveraging big data for environmental sustainability: Evidence from China's green transformation initiatives.

This study delves into the impact and underlying mechanisms of big data development on corporate green transformation. Leveraging balanced panel data of A-share listed firms spanning from 2009 to 2021, we employ China's national big data comprehensive pilot zone policy as an exogenous shock to identify the causal effect of big data development on corporate green transformation. The results confirm that firms situated within the pilot zones exhibit significantly higher levels of green transformation.

Trojan horse-inspired spatiotemporal strategy augments cartilage regeneration by enhancing mitochondrial energy production.

Treating osteoarthritis (OA) presents a significant challenge due to the fact that conventional intra-articular injections only achieve superficial penetration and uncontrolled drug release. Here, the amino-modified cationic mesoporous silica nanoparticles were covalently conjugated with cartilage-targeted peptides to form a Trojan horse-like architecture for enveloping the prochondrogenic fucoidan. The hydrogel microsphere, consisting of photocurable GelMA and ChSMA, were fabricated using a microfluidic platform for cargo delivery.

From PDMS-based exposure profiling to machine learning-predicted serum concentrations: SVOC exposure disparities across occupational and environmental scenarios.

Occupational exposure to semi-volatile organic compounds (SVOCs) among various population groups has garnered insufficient attention. We investigated the occupational exposures of waste disposal workers and daily exposure of university students to phthalates (PAEs), organophosphate esters (OPEs), and polycyclic aromatic hydrocarbons (PAHs) using polydimethylsiloxane (PDMS)-based passive sampling combined with machine learning-driven serum concentration predictions. The SVOC exposures of students varied depending on their professional activities, , experiments, but dormitories emerge as a significant source.

The effectiveness and safety of administering antiplatelet medications following reperfusion therapy in patients with ischemic stroke.

Background: Ischemic stroke is a major cause of morbidity and mortality worldwide. Although reperfusion therapy enhances patient outcomes, the ideal antiplatelet regimen post-treatment remains unclear. This study investigates the efficacy and safety of dual antiplatelet therapy (DAPT) versus triple antiplatelet therapy (TAT) in ischemic stroke patients after reperfusion.

SIRT3-PINK1-PKM2 axis prevents osteoarthritis via mitochondrial renewal and metabolic switch.

Maintaining mitochondrial homeostasis is critical for preserving chondrocyte physiological conditions and increasing resistance against osteoarthritis (OA). However, the underlying mechanisms governing mitochondrial self-renewal and energy production remain elusive. In this study, we demonstrated mitochondrial damage and aberrant mitophagy in OA chondrocytes.

Swimming exercise induces redox-lipid crosstalk to ameliorate osteoarthritis progression.

Conventional pharmacotherapy exhibits limited efficacy in halting cartilage degeneration, whereas exercise interventions have demonstrated promising protective effects against osteoarthritis (OA), albeit with unclear underlying mechanisms. This study investigated the beneficial effects of swimming in mitigating local joint damage through the enhancement of systemic antioxidant capacity. We found that overexpression of superoxide dismutase 3 (SOD3) could promote the elimination of extracellular reactive oxygen species (ROS) and preserve the cartilage extracellular matrix (C-ECM).

Exposure experiments and machine learning revealed that personal care products can significantly increase transdermal exposure of SVOCs from the environment.

We investigated the impacts of personal care products (PCPs) on dermal exposure to semi-volatile organic compounds (SVOCs), including phthalates, organophosphate esters, polycyclic aromatic hydrocarbons (PAHs), ultraviolet filters, and p-phenylenediamines, through an experiment from volunteers, explored the impact mechanisms of PCP ingredients on dermal exposure, and predicted the PCP effects on SVOC concentrations in human serum using machine learning. After applying PCPs, namely lotion, baby oil, sunscreen, and blemish balm, the dermal adsorption of SVOCs increased significantly by 1.63 ± 0.

Harnessing hydrogen sulfide in injectable hydrogels that guide the immune response and osteoclastogenesis balance for osteoporosis treatment.

Elevated levels of oxidative stress, inflammation, and a dysregulated osteoclastogenesis balance frequently characterize the microenvironment of osteoporosis, which impedes the processes of healing and repair. Existing treatment approaches are limited in scope and rely primarily on factors and drugs. An injectable hydrogel designed for the ROS-responsive release of HS gas is presented in this study.

Lactate supplementation after hypoglycemia alleviates cognitive dysfunction induced by recurrent non-severe hypoglycemia in diabetic mice.

Recurrent non-severe hypoglycemia (RH) in diabetes is an independent risk factor for cognitive dysfunction. However, the mechanisms and potential therapeutic strategies remain poorly understood. In this study, we aimed to elucidate the mechanisms underlying RH-induced diabetic cognitive impairment.

TCR-like bispecific antibodies toward eliminating infected hepatocytes in HBV mouse models.

Therapeutics for eradicating hepatitis B virus (HBV) infection are still limited and current nucleos(t)ide analogs (NAs) and interferon are effective in controlling viral replication and improving liver health, but they cannot completely eradicate the hepatitis B virus and only a very small number of patients are cured of it. The TCR-like antibodies recognizing viral peptides presented on human leukocyte antigens (HLA) provide possible tools for targeting and eliminating HBV-infected hepatocytes. Here, we generated three TCR-like antibodies targeting three different HLA-A2.

Krüppel-like factor 4 modulates the miR-101/COL10A1 axis to inhibit renal fibrosis after AKI by regulating epithelial-mesenchymal transition.

Acute kidney injury (AKI) can progress to renal fibrosis and chronic kidney disease (CKD), which reduces quality of life and increases the economic burden on patients. However, the molecular mechanisms underlying renal fibrosis following AKI remain unclear. This study tested the hypothesis that the Krüppel-like factor 4 (KLF4)/miR-101/Collagen alpha-1X (COL10A1) axis could inhibit epithelial-mesenchymal transition (EMT) and renal fibrosis after AKI in a mouse model of ischemia-reperfusion (I/R)-induced renal fibrosis and HK-2 cells by gene silencing, overexpression, immunofluorescence, immunohistochemistry, real-time quantitative PCR, Western blotting, dual-luciferase reporter assay, fluorescence hybridization (FISH) and ELISA.

Capturing cerium ions via hydrogel microspheres promotes vascularization for bone regeneration.

The rational design of multifunctional biomaterials with hierarchical porous structure and on-demand biological activity is of great consequence for bone tissue engineering (BTE) in the contemporary world. The advanced combination of trace element cerium ions (Ce) with bone repair materials makes the composite material capable of promoting angiogenesis and enhancing osteoblast activity. Herein, a living and phosphorylated injectable porous hydrogel microsphere (P-GelMA-Ce@BMSCs) is constructed by microfluidic technology and coordination reaction with metal ion ligands while loaded with exogenous BMSCs.

All-optical interrogation of brain-wide activity in freely swimming larval zebrafish.

We introduce an all-optical technique that enables volumetric imaging of brain-wide calcium activity and targeted optogenetic stimulation of specific brain regions in unrestrained larval zebrafish. The system consists of three main components: a 3D tracking module, a dual-color fluorescence imaging module, and a real-time activity manipulation module. Our approach uses a sensitive genetically encoded calcium indicator in combination with a long Stokes shift red fluorescence protein as a reference channel, allowing the extraction of Ca activity from signals contaminated by motion artifacts.

Activation of mitophagy improves cognitive dysfunction in diabetic mice with recurrent non-severe hypoglycemia.

Recurrent non-severe hypoglycemia (RH) in patients with diabetes might be associated with cognitive impairment. Previously, we found that mitochondrial dysfunction plays an important role in this pathological process; however, the mechanism remains unclear. The objective of this study was to determine the molecular mechanisms of mitochondrial damage associated with RH in diabetes mellitus (DM).

A Self-Adaptive Biomimetic Periosteum Employing Nitric Oxide Release for Augmenting Angiogenesis in Bone Defect Regeneration.

The periosteum plays a vital role in the regeneration of critical-size bone defects and highly comminuted fractures, promoting the differentiation of osteoblasts, accelerating the reconstruction of the vascular network, and guiding bone tissue regeneration. However, the materials loaded with exogenous growth factors are limited by the release and activity of the elements. Therefore, the material structure must be carefully designed for the periosteal function.

COPA syndrome caused by a novel p.Arg227Cys COPA gene variant.

Background: COPA syndrome is a recently described and rare monogenic autosomal dominant disease caused by heterozygous missense mutations in the Coatomer Protein Subunit alpha (COPA) gene that encodes the alpha subunit of coat protein complex I (COPI). Its main clinical manifestations are inflammatory lung disease, arthritis, and renal disease. The development of inflammation in COPA syndrome maybe due to abnormal autophagic response and abnormal activation of type I interferon pathway.

Retuning Mitochondrial Apoptosis/Mitophagy Balance via SIRT3-Energized and Microenvironment-Modulated Hydrogel Microspheres to Impede Osteoarthritis.

Full-range therapeutic regimens for osteoarthritis (OA) should consider organs (joints)-tissues (cartilage)-cells (chondrocytes)-organelles cascade, of which the subcellular mitochondria dominate eukaryotic cells' fate, and thus causally influence OA progression. However, the dynamic regulation of mitochondrial rise and demise in impaired chondrocytes and the exact role of mitochondrial metronome sirtuins 3 (SIRT3) is not clarified. Herein, chondrocytes are treated with SIRT3 natural agonist dihydromyricetin (DMY) or chemical antagonist 3-TYP, respectively, to demonstrate the positive action of SIRT3 on preserving cartilage extracellular matrix (ECM).

Mitophagy disorder mediates cardiac deterioration induced by severe hypoglycemia in diabetic mice.

Severe hypoglycemia is closely related to adverse cardiovascular outcomes in patients with diabetes; however, the specific mechanism remains unclear. We previously found that severe hypoglycemia aggravated myocardial injury and cardiac dysfunction in diabetic mice, and that the mechanism of damage was related to mitochondrial oxidative stress and dysfunction. Based on the key regulatory role of mitophagy in mitochondrial quality control, this study aimed to further explore whether the myocardial damage caused by severe hypoglycemia is related to insufficient mitophagy and to clarify their underlying regulatory relationship.

Eccentricity-paced geomagnetic field and monsoon rainfall variations over the last 870 kyr.

Whether there are links between geomagnetic field and Earth's orbital parameters remains unclear. Synchronous reconstructions of parallel long-term quantitative geomagnetic field and climate change records are rare. Here, we present Be-derived changes of both geomagnetic field and Asian monsoon (AM) rainfall over the last 870 kyr from the Xifeng loess-paleosol sequence on the central Chinese Loess Plateau.

Study on the correlation between maternal serum uric acid and foetal birth weight in Naqu, Tibet.

In high-altitude regions, low birth weight is mainly caused by hypoxia. We aimed to determine whether maternal serum uric acid (SUC) level was associated with decreased foetal birth weight. The relevant data of individual pregnant women who delivered between 37 and 40 weeks in the People's Hospital of Naqu City, Tibet were retrospectively collected.

Analysis of anti-M antibody status and blood transfusion strategy in Hunan, China.

Background: By analyzing the detection rate of anti-M antibody in patients with the MNS blood group system in the Hunan area, we aimed to explore its clinical significance and blood transfusion strategy.

Methods: We retrospectively analyzed the clinical data of patients who had been confirmed to contain anti-M antibodies through serological methods such as the saline tube method and cassette anti-human globulin method.

Results: Irregular antibody screening tests had been applied to 94,452 patients, from which 652 results were positive.

Low FT3/FT4 Ratio Is Linked to Poor Prognosis of Acute Myocardial Infarction in Euthyroid Patients with Type 2 Diabetes Mellitus.

This is an observational, retrospective, single-center study aimed to determine whether the free triiodothyronine (FT3) to free thyroxine (FT4) ratio was related to acute myocardial infarction (AMI) prognosis in individuals with type 2 diabetes mellitus (T2DM). A total of 294 euthyroid T2DM patients with new-onset AMI were enrolled. FT3/FT4 ratio tertiles were used to categorize patients into Group 1 (FT3/FT4 ≥ 4.