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A new pathway of mitochondria-mediated cell death termed mitochondrial precursor over-accumulation stress (mPOS) is identified that could explain the link between mitochondrial dysfunction and misfolding of cytosolic proteins during ageing and disease; the pathway is triggered not only by mutations affecting the core protein import machineries, but also by conditions that interfere with mitochondrial inner membrane integrity and function, and a large network of genes that suppress mPOS in favour of cell survival is also identified. Protein transport related mitochondrial dysfunction Mitochondrial dysfunction and cellular protein homeostasis failure are hallmarks of many diseases and age-associated pathologies. Damaged mitochondria can lead to cell death through various mechanisms including energy deprivation. Two papers now describe an additional such mechanism: inefficient transport of mitochondrial proteins from ribosomes in the cytosol. Xiaowen Wang and Xin Jie Chen show that mitochondrial damage can block the import of nuclear-encoded proteins into mitochondria and cause cellular degeneration by triggering a pathway in the cytosol they name mitochondrial precursor over-accumulation stress (mPOS). The authors also identify an anti-degenerative network of compensatory processes — mostly associated with modulation of protein turnover and folding — that counteract mPOS in favour of cell survival. Agnieszka Chacinska and colleagues investigate the response to dysfunctional protein import into mitochondria through a detailed analysis of transcriptomic and proteomic changes within the cell. They too identify pathways that protect the cell against mitochondrial biogenesis defects, which mainly involve inhibiting protein synthesis and increased protein clearance by the proteasomal machinery. Mitochondria are multifunctional organelles whose dysfunction leads to neuromuscular degeneration and ageing. The multi-functionality poses a great challenge for understanding the mechanisms by which mitochondrial dysfunction causes specific pathologies. Among the leading mitochondrial mediators of cell death are energy depletion, free radical production, defects in iron–sulfur cluster biosynthesis, the release of pro-apoptotic and non-cell-autonomous signalling molecules, and altered stress signalling 1 , 2 , 3 , 4 , 5 . Here we identify a new pathway of mitochondria-mediated cell death in yeast. This pathway was named mitochondrial precursor over-accumulation stress (mPOS), and is characterized by aberrant accumulation of mitochondrial precursors in the cytosol. mPOS can be triggered by clinically relevant mitochondrial damage that is not limited to the core machineries of protein import. We also discover a large network of genes that suppress mPOS, by modulating ribosomal biogenesis, messenger RNA decapping, transcript-specific translation, protein chaperoning and turnover. In response to mPOS, several ribosome-associated proteins were upregulated, including Gis2 and Nog2, which promote cap-independent translation and inhibit the nuclear export of the 60S ribosomal subunit, respectively 6 , 7 . Gis2 and Nog2 upregulation promotes cell survival, which may be part of a feedback loop that attenuates mPOS. Our data indicate that mitochondrial dysfunction contributes directly to cytosolic proteostatic stress, and provide an explanation for the association between these two hallmarks of degenerative diseases and ageing. The results are relevant to understanding diseases (for example, spinocerebellar ataxia, amyotrophic lateral sclerosis and myotonic dystrophy) that involve mutations within the anti-degenerative network.

The carbon−carbon coupling at the Cu/Cu 2 O Schottky interface has been widely recognized as a promising approach for electrocatalytic CO 2 conversion into value-added alcohols. However, the limited selectivity of C 2+ alcohols persists due to the insufficient control over rectifying interface characteristics required for precise bonding of oxyhydrocarbons. Herein, we present an investigation into the manipulation of the coordination environment of Cu sites through an in-situ electrochemical reconstruction strategy, which indicates that the construction of low-coordinated Cu sites at the Cu/Cu 2 O interface facilitates the enhanced rectifying interfaces, and induces asymmetric electronic perturbation and faster electron exchange, thereby boosting C-C coupling and bonding oxyhydrocarbons towards the nucleophilic reaction process of *H 2 CCO-CO. Impressively, the low-coordinated Cu sites at the Cu/Cu 2 O interface exhibit superior faradic efficiency of 64.15  ±  1.92% and energy efficiency of ~39.32% for C 2+ alcohols production, while maintaining stability for over 50 h (faradic efficiency >50%, total current density = 200 mA cm −2 ) in a flow-cell electrolyzer. Theoretical calculations, operando synchrotron radiation Fourier transform infrared spectroscopy, and Raman experiments decipher that the low-coordinated Cu sites at the Cu/Cu 2 O interface can enhance the coverage of *CO and adsorption of *CH 2 CO and CH 2 CHO, facilitating the formation of C 2+ alcohols. Converting CO 2 into multicarbon products is highly desirable, but product selectivity needs improvement. Here the authors manipulate the coordination environment of Cu site through in-situ electrochemical reconstruction to enhance CO 2 conversion to C2+ alcohol.

The study focuses on the energy consumption (EC) and environmental pollution caused by carbon consumption in China’s development. The Yangtze River Delta (YRD) region is selected as the primary focus of investigation. To gain insight into the relationship between China’s economic growth (EG) and carbon reduction (CR), two major research elements, the impact of each on the other is examined. The study mainly uses decoupling models and influence models to analyze the decoupling relationship and effectiveness between CR and EG. The research results showed that there was a difference between long-term and short-term effects. The short-term effect in the YRD region was manifested as a continuously improving decoupling state, while the long-term effect was manifested as the significant impact of population and per capita Gross Domestic Product on CR. The effect value of EC factor was 0.43, while the effect value of CR factor was 0.07. In functional comparison, the role of EC factors was more significant.

Background Tropical stenothermal fish exhibit special tolerance and response to cold stress. However current knowledge of the molecular mechanisms response to cold stress in aquatic ectotherms is largely drawn from eurythermal or extreme stenothermal species. The tiger barb Puntius tetrazona is a tropical stenothermal fish, with great popularity in aquarium trade and research. Results To investigate the response mechanism of P. tetrazona to low temperature, fish were exposed to increasing levels of acute cold stress. Histopathological analysis showed that the brain, gill, liver and muscle tissues appeared serious damage after cold stress (13 °C). Brain, gill, liver and muscle tissues from control (CTRL) groups (27 °C) and COLD stress groups (13 °C) of eight-month fish (gender-neutral) were sampled and assessed for transcriptomic profiling by high-throughput sequencing. 83.0 Gb of raw data were generated, filtered and assembled for de novo transcriptome assembly. According to the transcriptome reference, we obtained 392,878 transcripts and 238,878 unigenes, of which 89.29% of the latter were annotated. There were 23,743 differently expressed genes (DEGs) been filtered from four pairs of tissues (brain, gill, liver and muscle) between these cold stress and control groups. These DEGs were mainly involved in circadian entrainment, circadian rhythm, biosynthesis of steroid and fatty acid. There were 64 shared DEGs between the four pairs of groups, and five were related to ubiquitylation/deubiquitylation. Our results suggested that ubiquitin-mediated protein degradation might be necessary for tropical stenothermal fish coping with acute cold stress. Also, the significant cold-induced expression of heat shock 70 kDa protein ( HSP70 ) and cold-induced RNA-binding protein ( CIRBP ) was verified. These results suggested that the expression of the molecular chaperones HSP70 and CIRBP in P. tetrazona might play a critical role in coping with acute cold stress. Conclusions This is the first transcriptome analysis of P. tetrazona using RNA-Seq technology. Novel findings about tropical stenothermal fish under cold stress (such as HSP70 and CIRBP genes) are presented here. This study contributes new insights into the molecular mechanisms of tropical stenothermal species response to acute cold stress .

Dermatophytosis is a common superficial infection caused by dermatophytes, a group of pathogenic keratinophilic fungi. Apart from invasion against skin barrier, host immune responses to dermatophytes could also lead to pathologic inflammation and tissue damage to some extent. Therefore, it is of great help to understand the pathogenesis of dermatophytes, including fungal virulence factors and anti-pathogen immune responses. This review aims to summarize the recent advances in host-fungal interactions, focusing on the mechanisms of anti-fungal immunity and the relationship between immune deficiency and chronic dermatophytosis, in order to facilitate novel diagnostic and therapeutic approaches to improve the outcomes of these patients.

China is transitioning into the digital economy era. The advancement of the digital economy could offer a fresh mechanism to attain carbon peak and carbon neutrality objectives. Applications of the digital economy, such as smart energy management, intelligent transport systems, and digital agricultural technologies, have significantly reduced carbon emissions by optimizing resource use, reducing energy waste, and improving production efficiency. This research does so by devising a theoretical model that looks into the multi-faceted power of the digital economy under a two-sector paradigm. Utilising a panel model, a mediation effect model and a spatial Durbin model to assess the digital economy’s power on carbon emissions. This research has determined that the digital economy can significantly diminish carbon emissions, with green tech innovations and industrial transformation being key contributors. The spatial spillover effect was used for the digital economy to aid in lowering carbon emissions in adjacent districts and upgrading better environmental stewardship. The influence of the digital economy has better performance in lowering carbon emissions in mid-western China than in the eastern area. This paper deepens understanding of the drivers of low-carbon growth and the significance, mechanism and regional disparities of the digital economy’s effect on reducing carbon emissions. It offers valuable policy insights and guidance for globally achieving digital economy growth, reducing carbon emissions and reaching carbon peak and neutrality goals.

Background Parkinson’s disease (PD) has emerged as a major global public health challenge. However, there is currently a lack of systematic analysis regarding the burden of PD and its long-term trends among people over 55 years of age. Methods This study utilizes data from the Global Burden of Disease 2021 database to analyze the prevalence, incidence, disability-adjusted life years (DALYs), and mortality rates of PD in individuals aged 55 and older from 1990 to 2021. The annual percentage change was calculated to assess the temporal trends of the disease burden. Point estimates and their corresponding ranges were reported with 95% uncertainty intervals. Results Globally, the prevalence, incidence, DALYs, and mortality rates of PD in individuals aged 55 and above significantly increased from 1990 to 2021, with all indicators being higher in males than in females. This trend was evident across all five Socio-Demographic Index (SDI) groups and in 21 regions worldwide. The number of prevalent cases, incident cases, DALYs, and deaths all showed significant increases and were positively correlated with SDI ( R  = 0.645, P  < 0.001). Among 185 countries, the incidence rate increased, with DALY rates rising in 74 countries and mortality rates rising in 65 countries. Notably, in the population aged 95 years and older, the prevalence and incidence of PD showed particularly remarkable increases, at 735% and 505%, respectively. Furthermore, the greatest increase in prevalence was observed in the 55–59 age group, especially in countries with Middle SDI and High-middle SDI regions. Conclusions This study indicates that the burden of PD in individuals aged 55 and above has significantly increased over the past three decades. This trend reflects the profound impact of global aging and socioeconomic development levels on the burden of PD, underscoring the urgency of addressing PD as a major global public health challenge.

AbstractObjectiveTo estimate the risks of daily hospital admissions for cause specific major cardiovascular diseases associated with short term exposure to ambient fine particulate matter (aerodynamic diameter ≤2.5 μm; PM2.5) pollution in China.DesignNational time series study.Setting184 major cities in China.Population8 834 533 hospital admissions for cardiovascular causes in 184 Chinese cities recorded by the national database of Urban Employee Basic Medical Insurance from 1 January 2014 to 31 December 2017.Main outcome measuresDaily counts of city specific hospital admissions for primary diagnoses of ischaemic heart disease, heart failure, heart rhythm disturbances, ischaemic stroke, and haemorrhagic stroke among different demographic groups were used to estimate the associations between PM2.5 and morbidity. An overdispersed generalised additive model was used to estimate city specific associations between PM2.5 and cardiovascular admissions, and random effects meta-analysis used to combine the city specific estimates.ResultsOver the study period, a mean of 47 hospital admissions per day (standard deviation 74) occurred for cardiovascular disease, 26 (53) for ischaemic heart disease, one (five) for heart failure, two (four) for heart rhythm disturbances, 14 (28) for ischaemic stroke, and two (four) for haemorrhagic stroke. At the national average level, an increase of 10 μg/m3 in PM2.5 was associated with a 0.26% (95% confidence interval 0.17% to 0.35%) increase in hospital admissions on the same day for cardiovascular disease, 0.31% (0.22% to 0.40%) for ischaemic heart disease, 0.27% (0.04% to 0.51%) for heart failure, 0.29% (0.12% to 0.46%) for heart rhythm disturbances, and 0.29% (0.18% to 0.40%) for ischaemic stroke, but not with haemorrhagic stroke (−0.02% (−0.23% to 0.19%)). The national average association of PM2.5 with cardiovascular disease was slightly non-linear, with a sharp slope at PM2.5 levels below 50 μg/m3, a moderate slope at 50-250 μg/m3, and a plateau at concentrations higher than 250 μg/m3. Compared with days with PM2.5 up to 15 μg/m3, days with PM2.5 of 15-25, 25-35, 35-75, and 75 μg/m3 or more were significantly associated with increases in cardiovascular admissions of 1.1% (0 to 2.2%), 1.9% (0.6% to 3.2%), 2.6% (1.3% to 3.9%), and 3.8% (2.1% to 5.5%), respectively.According to projections, achieving the Chinese grade 2 (35 μg/m3), Chinese grade 1 (15 μg/m3), and World Health Organization (10 μg/m3) regulatory limits for annual mean PM2.5 concentrations would reduce the annual number of admissions for cardiovascular disease in China. Assuming causality, which should be done with caution, this reduction would translate into an estimated 36 448 (95% confidence interval 24 441 to 48 471), 85 270 (57 129 to 113 494), and 97 516 (65 320 to 129 820), respectively.ConclusionsThese data suggest that in China, short term exposure to PM2.5 is associated with increased hospital admissions for all major cardiovascular diseases except for haemorrhagic stroke, even for exposure levels not exceeding the current regulatory limits.

The consumption of ultra-processed foods (UPFs) has surged globally, raising significant public health concerns due to their associations with a range of adverse health outcomes. This review aims to elucidate potential health impacts of UPF intake and underscore the importance of considering diet quality when interpreting study findings. UPF group, as classified by the Nova system based on the extent of industrial processing, contains numerous individual food items with a wide spectrum of nutrient profiles, as well as differential quality as reflected by their potential health effects. The quality of a given food may well misalign with the processing levels so that a UPF food can be nutritious and healthful whereas a non-UPF food can be of low quality and excess intake of which may lead to adverse health consequences. The current review argues that it is critical to focus on the nutritional content and quality of foods and their role within the overall dietary pattern rather than only the level of processing. Further research should dissect health effects of diet quality and food processing, investigate the health impacts of ingredients that render the UPF categorization, understand roles of metabolomics and the gut microbiome in mediating and modulating the health effects of food processing, and consider environmental sustainability in UPF studies. Emphasizing nutrient-dense healthful foods and dietary patterns shall remain the pivotal strategy for promoting overall health and preventing chronic diseases.

To increase the stability of selenium in nano state and further improve its antioxidant and skin whitening ability, Bombyx batryticatus polypeptide (BBPP) was prepared. The optimum synthesis conditions of Bombyx batryticatus polypeptide nano-selenium (BBPP-SeNPs) were determined by a double-peak method. BBPP-SeNPs were characterized by transmission electron microscope (TEM), Fourier transform infrared spectroscopy (FT-IR), and particle size analysis (PSS). The 1,1-Diphenyl-2-picrylhydrazyl (DPPH), 2,2’-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS), superoxide anion free radical scavenging rate, and total antioxidant capacity of BBPP, vitamin C (VC), and BBPP-SeNPs were measured for comparison. The inhibitory ability of BBPP and BBPP-SeNPs on tyrosinase was measured. Using mouse modeling, the skin whitening ability of VC and BBPP-SeNPs was measured. The results showed that the optimal conditions were obtained when the concentration of BBPP was 0.16 mg/mL, sodium selenite was 0.01 mol/L, ultrasound was carried out for 30 min, ascorbic acid was added in 0.04 mol/L, and stirring temperature was 20 °C for 4 h. The antioxidant capacity of BBPP-SeNPs has significantly improved. It can be observed that BBPP-SeNPs has obvious scavenging ability on skin-reactive oxygen species through a Reactive Oxygen Species (ROS) staining section. Through Hematoxylin–Eosin (H&E) staining, it can be proven that BBPP-SeNPs has a high security threshold.