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This study aims to investigate the relationship between carbon emissions ( CO 2 ) and economic policy uncertainty for East Asian countries. During recent decades, climate change has become a severe issue globally. To our understanding, the impact of economic policy uncertainty ( EPU ) on CO 2 emissions has not been thoroughly studied in the environment-energy literature. To overcome this research gap, this study explores the link between EPU , CO 2 emissions, foreign direct investment ( FDI ), and renewable energy for the panel of four East Asian economies, namely, China, Japan, South Korea, and Singapore, from 1997 to 2020. We used second-generation econometric estimations to confirm cross-sectional dependence, cointegration, and stationarity among the selected variables. This study finds that economic policy uncertanity ( EPU ), trade, and GDP have a positive correlation with carbon emissions. However, FDI and renewable energy consumption boost the quality of the environment of East Asian economies. The outcomes of the Dumitrescu–Hurlin panel causality estimation revealed two-way association between CO 2 and economic policy uncertainty, CO 2 and energy consumption, CO 2 and economic growth, and CO 2 and trade. Afterward, we use the FMOLS estimations for robustness check. Based on the inclusive outcomes, we draw substantial suggestions for decision-makers and urge them to consider the potential negative effects of EPU on CO 2 emissions policies. In addition to this, if policymakers seek to simultaneously control EPU and CO 2 emissions, they should work out for alternate ways such as the use of green technology related to energy, foreign capital investment, and renewable energy consumption to mitigate CO 2 emissions.

To sustain global warming below 2 °C, carbon dioxide emission mitigation has become an extensive worldwide priority. This paper proposes a comprehensive assessment by evaluating the effects of technology transfer, human capital, and renewable energy on carbon dioxide emissions among seven different regions along with the Belt and Road Initiatives from 2008 to 2018. Based on econometric estimations, it is found that human capital, renewable energy, and technology transfer show a negative but significant association with carbon dioxide emissions, indicating that an increase in human capital, renewable energy, and technology transfer can reduce carbon dioxide emissions in the Belt and Road countries. On the other hand, we found a positive and significant relationship between carbon dioxide emissions, economic growth, and foreign direct investment (FDI), indicating that economic growth and foreign direct investment increase carbon emissions. The findings of this study reveal that the adaptation of technology transfer, renewable energy consumption, and human capital are key factors in the reduction of carbon dioxide emissions in the Belt and Road counties. Our findings provide evidence of the social advantages of investing in advanced human capital, renewable energy, and technology transfer suggesting a promising route for devoting climate change without impeding economic growth.

Myocardial injury induced by ischemia-reperfusion or doxorubicin leads to cardiomyocyte necroptosis via RIP3-mediated phosphorylation of CaMKII and opening of the mitochondrial permeability transition pore. Regulated necrosis (necroptosis) and apoptosis are crucially involved in severe cardiac pathological conditions, including myocardial infarction, ischemia-reperfusion injury and heart failure. Whereas apoptotic signaling is well defined, the mechanisms that underlie cardiomyocyte necroptosis remain elusive. Here we show that receptor-interacting protein 3 (RIP3) triggers myocardial necroptosis, in addition to apoptosis and inflammation, through activation of Ca 2+ -calmodulin–dependent protein kinase (CaMKII) rather than through the well-established RIP3 partners RIP1 and MLKL. In mice, RIP3 deficiency or CaMKII inhibition ameliorates myocardial necroptosis and heart failure induced by ischemia-reperfusion or by doxorubicin treatment. RIP3-induced activation of CaMKII, via phosphorylation or oxidation or both, triggers opening of the mitochondrial permeability transition pore and myocardial necroptosis. These findings identify CaMKII as a new RIP3 substrate and delineate a RIP3-CaMKII-mPTP myocardial necroptosis pathway, a promising target for the treatment of ischemia- and oxidative stress–induced myocardial damage and heart failure.

Chronic obstructive pulmonary disease (COPD) combined with malnutrition results in decreased exercise capacity and a worse quality of life. We aimed to develop an observational case–control study to explore the effective and convenient method to identify potential individuals is lacking. This study included data from 251 patients with COPD and 85 participants in the control group. Parameters and body composition were compared between groups, and among patients with varied severity. The LASSO approach was employed to select the features for fitting a logistic model to predict the risk of malnutrition in patients with stable COPD. Patients with COPD exhibited significantly lower 6-min walk distance (6MWD), handgrip strength, fat-free mass index (FFMI), skeletal muscle mass (SMM) and protein. The significant predictors identified following LASSO selection included 6MWD, waist-to-hip ratio (WHR), GOLD grades, the COPD Assessment Test (CAT) score, and the prevalence of acute exacerbations. The risk score model yielded good accuracy (C-index, 0.866 [95% CI 0.824–0.909]) and calibration (Brier score = 0.150). After internal validation, the adjusted C-index and Brier score were 0.849, and 0.165, respectively. This model may provide primary physicians with a simple scoring system to identify malnourished patients with COPD and develop appropriate rehabilitation interventions.

Rechargeable magnesium (Mg)-based energy storage has attracted extensive attention in electrochemical storage systems with high theoretical energy densities. The Mg metal is earth-abundant and dendrite-free for the anode. However, there is a strong Coulombic interaction between Mg2+ and host materials that often inhibits solid-state diffusion, resulting in a large polarization and poor electrochemical performances. Herein, we develop a Mg–Li hybrid battery using a Mg-metal anode, an FeSe2 powder with uniform size and a morphology utilizing a simple solution-phase method as the counter electrode and all-phenyl-complex/tetrahydrofuran (APC)-LiCl dual-ion electrolyte. In the Li+-containing electrolyte, at a current density of 15 mA g−1, the Mg–Li hybrid battery (MLIB) delivered a satisfying initial discharge capacity of 525 mAh g−1. Moreover, the capacity was absent in the FeSe2|APC|Mg cell. The working mechanism proposed is the “Li+-only intercalation” at the FeSe2 and the “Mg2+ dissolved or deposited” at the Mg foil in the FeSe2|Mg2+/Li+|Mg cell. Furthermore, ex situ XRD was used to investigate the structural evolution in different charging and discharging states.

Although conventional genetic modification approaches for protein knockdown work very successfully due to the increasing use of CRISPR/Cas9, effective techniques for achieving protein depletion in adult animals, especially in large animals such as non-human primates, are lacking. Here, we report a chemical approach based on PROTACs technology that efficiently and quickly knocks down FKBP12 (12-kDa FK506-binding) protein globally in vivo. Both intraperitoneal and oral administration led to rapid, robust, and reversible FKBP12 degradation in mice. The efficiency and practicality of this method were successfully demonstrated in both large and small animals (mice, rats, Bama pigs, and rhesus monkeys). Furthermore, we showed this approach can also be applied to effectively knockdown other target proteins such as Bruton's tyrosine kinase (BTK). This chemical protein knockdown strategy provides a powerful research tool for gene function studies in animals, particularly in large animals, for which gene-targeted knockout strategies may remain unfeasible.

MG53 acts as an E3 ligase that targets the insulin receptor and IRS1 for ubiquitin-dependent degradation; when MG53 is upregulated, metabolic syndrome ensues. Muscle enzyme MG53 as drug target This paper reports the surprising finding that dysregulation of the muscle-specific E3 ligase mitsugumin (MG53) causes insulin resistance and metabolic disorders in mice. When MG53 is upregulated metabolic syndrome ensues; removal of MG53 leaves insulin signalling intact, and prevents diet-induced metabolic syndrome. This work identifies MG53 as a promising therapeutic target for the treatment of metabolic diseases such as type 2 diabetes and associated cardiovascular complications. Insulin resistance is a fundamental pathogenic factor present in various metabolic disorders including obesity and type 2 diabetes 1 . Although skeletal muscle accounts for 70–90% of insulin-stimulated glucose disposal 2 , 3 , the mechanism underlying muscle insulin resistance is poorly understood. Here we show in mice that muscle-specific mitsugumin 53 (MG53; also called TRIM72) mediates the degradation of the insulin receptor and insulin receptor substrate 1 (IRS1), and when upregulated, causes metabolic syndrome featuring insulin resistance, obesity, hypertension and dyslipidaemia. MG53 expression is markedly elevated in models of insulin resistance, and MG53 overexpression suffices to trigger muscle insulin resistance and metabolic syndrome sequentially. Conversely, ablation of MG53 prevents diet-induced metabolic syndrome by preserving the insulin receptor, IRS1 and insulin signalling integrity. Mechanistically, MG53 acts as an E3 ligase targeting the insulin receptor and IRS1 for ubiquitin-dependent degradation, comprising a central mechanism controlling insulin signal strength in skeletal muscle. These findings define MG53 as a novel therapeutic target for treating metabolic disorders and associated cardiovascular complications.

Type 2 asthma is characterized by airway inflammation, mucus hypersecretion, and remodeling, and circadian rhythm dysregulation is implicated in its pathogenesis. Melatonin, a key circadian hormone, modulates inflammatory signaling, but its role in type 2 airway inflammation remains unclear. This study investigated whether melatonin alleviates airway inflammation and epithelial-mesenchymal transition (EMT) through the melatonin receptor 1 (MT1)-Sirtuin 1 (Sirt1) signaling pathway and circadian clock regulation. An ovalbumin (OVA)-induced mouse model of type 2 airway inflammation and cultured airway epithelial cells were used. Lung structural remodeling and mucus production were evaluated using hematoxylin and eosin, Masson's trichrome, and periodic acid-Schiff staining. Airway inflammation was assessed by differential inflammatory cell counts in bronchoalveolar lavage fluid. The mRNA and protein expression of circadian clock genes (CRY1 and PER1) and key components of the MT1-Sirt1 pathway were assessed by quantitative real-time PCR, Western blotting, and immunohistochemistry. EMT-related markers were further examined to explore downstream mechanisms. Melatonin treatment activated MT1-Sirt1 signaling and reduced the expression of circadian clock genes CRY1 and PER1. These effects were accompanied by decreased airway inflammation, reduced mucus production, and attenuation of epithelial-mesenchymal transition (EMT) in airway epithelial cells, all of which reached statistical significance. Our findings identify a novel MT1-Sirt1-circadian gene regulatory axis through which melatonin mitigates type 2 airway inflammation and airway remodeling. These results highlight the therapeutic potential of melatonin for type 2 asthma. Limitations include the use of a single animal model and analysis at a single time point.

Objective: Human endogenous retrovirus-H long terminal repeat associating 2 (HHLA2) is a new immune checkpoint in the B7 family, and the value of HHLA2 in small cell lung cancer (SCLC) is unknown. Methods: We retrospectively detected HHLA2 expression by immunohistochemistry in SCLC patients. Moreover, plasma biomarkers of SCLC were detected retrospectively. Results: Seventy-four percent of SCLC patients exhibited HHLA2 expression. HHLA2 staining was localised within the nucleus of SCLC cells, while no staining was detected in normal lung tissue specimens. The correlation between HHLA2 expression and clinical factors was also analysed. Limited stage (LS) SCLC was more common than extensive stage (ES) SCLC among patients with HHLA2 staining. SCLC patients without metastasis had higher HHLA2 expression than SCLC patients with metastasis. HHLA2 expression was more frequently detected in the group with a tumour size greater than 5 cm than in the group with a tumour size less than 5 cm. The proportion of patients with HHLA2-positive staining was greater in the stage III and IV SCLC groups than in the stage I and II SCLC groups. A high proportion of SCLC patients with HHLA2-positive staining had a survival time <2 years. Neuron-specific enolase (NSE), CEA and Ki-67 levels were measured. The NSE level in the HHLA2-positive group was significantly greater than that in the HHLA2-negative group. The CEA and Ki-67 levels did not significantly differ between the HHLA2-positive and HHLA2-negative patients, nor were age, sex, smoking status, nodal metastasis status, Karnofsky Performance Scale (KPS) score, or Ki-67 expression score. HHLA2-positive SCLC patients had higher tumour stages and shorter 2-year survival times than HHLA2-negative patients did. Conclusion: The new immune molecule HHLA2 may be an ideal clinical biomarker for predicting SCLC progression and could serve as a new immunotherapy target in SCLC.

It is crucial to comprehend the interplay between air pollution and meteorological conditions in relation to population health within the framework of \"dual-carbon\" targets. The purpose of this study was to investigate the impact of intricate environmental factors, encompassing both meteorological conditions and atmospheric pollutants, on respiratory disease (RD) mortality in Qingdao, a representative coastal city in China. The RD mortality cases were collected from the Chronic Disease Surveillance Monitoring System in Qingdao during Jan 1st, 2014 and Dec 31st, 2020. The distributed-lag nonlinear model and generalized additivity model were used to assess the association between daily mean temperature (DMT), air pollutant exposure and RD mortality. To ascertain the robustness of the model and further investigate this relationship, a stratified analysis and sensitivity analysis were conducted to mitigate potential confounding factors. A total of 19,905 mortalities from RD were recorded. The minimum mortality temperature (MMT) was determined to be 23.5°C, and DMT and RD mortality showed an N-shaped relationship. At the MMT of 23.5°C, the cumulative relative risk (cumRR) for mortality within a lag period of 0-14 days from the highest temperature (31°C) was estimated at 2.114 (95% confidence interval [CI]: 1.475 ~ 3.028). The effect value of particulate matter (PM) also increased with a longer cumulative lag time. In the single pollutant model, the highest risk of RD mortality was observed on the lag1-day of per 10 μg/m3 increase in PM2.5 exposure, with an excess risk ratio (ER) of 0.847% (95% CI: 0.335% ~ 1.362%). The largest cumulative effect was found at a lag of 8 days, with an ER of 1.546% (95% CI: 0.483% ~ 2.621%). A similar trend was found for PM10. For O3 exposure, the highest risk was observed on the lag1-day of per 10 μg/m3 increase, with an ER of 1.073% (95% CI: 0.502% ~ 1.647%), and the largest cumulative effect occurred at a lag of 2 days with an ER of 1.113% (95%CI: 0.386% ~ 1.844%). Results from the dual-pollutants model demonstrated that the effect of PM on the risk of RD mortality remained significant and slightly increased in magnitude. Moreover, composite pollutants exhibited a higher risk effect, reaching its peak after one week; however, there was a decrease in single-day cumulative effects as more pollutant types were included. Subgroup analysis showed that females, elderly individuals, and those exposed during warm seasons demonstrated greater susceptibility to PM exposure. The present study revealed a significant association between short-term exposure to high temperature, PM2.5, PM10 and O3 and the risk of RD mortality in Qingdao, even in dual- and composite-pollutants models. Furthermore, our findings indicate that females, the elderly population, and warm seasons exhibit heightened sensitivity to PM exposure.