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In the background of global “carbon neutrality,” China Railway Express (CRE) is contributing to the long-term development of low-carbon environmental protection while promoting economic growth. Based on panel data of 284 cities at the prefecture level and above in China from 2003 to 2019, we empirically investigate the impact and mechanism of CRE opening on urban carbon emissions using the multi-period DID model and mediating effect model. Under the assumption of meeting parallel trends, we find that the opening of CRE considerably lowers urban carbon emissions by .78 percentage points as compared to the control group. This finding holds after placebo testing, PSM-DID estimation, replacing key variables, excluding other policies and disturbances from the opening of the high-speed railway (HSR), and overcoming endogeneity problems. According to the findings of the mechanism tests, the influence of transportation substitution, improved industrial structure, economic agglomeration, and trade openness are crucial mechanisms for reducing carbon emissions by opening CRE. Further heterogeneity tests show that the carbon reduction effect of CRE opening is more pronounced in east-central China, larger and non-resource-based cities. Therefore, this study suggests that the Chinese government should pay attention to the positive effect of CRE on environmental protection. The government should accelerate the construction of comprehensive transportation infrastructure while rationalizing the layout of economic activities and population clustering.

Lipid droplets (LDs) within atherosclerotic plaques are central to cardiovascular disease, yet their molecular composition remains largely unknown. More than 20 years experiences of developing LD purification method allowed us recently to successfully purify LDs from atherosclerotic plaques of patients undergoing carotid artery surgery, including three types, soft (lipid), mixed, and hard (calcified). In addition, the subpopulations of large LDs and small LDs were purified and studied, respectively. We report the first comprehensive proteo-lipidomic analysis of these LDs. Unexpectedly, about 19.3% of the plaque LD proteins belonged to cytoskeleton, while the content of lipid metabolism enzymes on plaque LDs was low. Our results show that the compositions of lipids and proteins were similar between two population LDs. Compared to soft (lipid) plaque LDs, LDs from mixed and hard (calcified) plaques had fewer metabolic enzymes and more cytoskeletal proteins. Lipidomics of the LD core uncovered an unexpected enrichment of polyunsaturated fatty acid cholesteryl esters (PUFA-CEs), which constituted 88.3% of all cholesterol esters. Notably, esters of the pro-inflammatory precursor arachidonic acid (AA) were among the most abundant species (16.5%). In addition, plaque LD were uniquely enriched in phospholipids including phosphatidic acid (PA), phosphatidylethanolamine plasmagens (PE-P), sphingomyelin (SM), and phosphatidylserine (PS). Our findings redefine the plaque LD as a dual-function “bad” organelle: a metabolically inert container for cholesterol ester, coated with cytoskeletons, and a massive reservoir for inflammatory precursors.

Genomic regions previously annotated as non-coding are now recognized sources of functional microproteins, termed the “dark proteome”, though their identification and characterization remain challenging. Addressing this, we developed a novel proteomic strategy combining lipid droplet (LD) enrichment with mass spectrometry against the database of sORF-derived proteins. This approach yielded the first reported LD-resident microprotein, LDANP1, and subsequently revealed other candidates from the same screen, such as MNP33, were localized to mitochondria. Here, we provide the first in-depth functional characterization of MNP33, a novel 28-amino acid protein encoded by an sORF within the Cdhr4 gene locus. We confirm MNP33 localizes to the inner mitochondrial membrane and demonstrate its interaction with the adenine nucleotide translocase 2 (ANT2). Functionally, MNP33 expression remodels mitochondrial bioenergetics, increasing basal respiration and proton leak while paradoxically elevating membrane potential, partly through modulating ANT2 activity linked to enhanced glycolysis. Furthermore, MNP33 shifts cellular lipid metabolism, favoring cholesteryl ester storage over triacylglycerols via stabilization of ACAT1, and is associated with closer ER-mitochondria contacts. MNP33 also induces ROS production and autophagy while inhibiting cell proliferation without increasing apoptosis. This study establishes MNP33 as a novel mitochondrial regulator emerging from the dark proteome, providing a mechanistic link between non-coding genetic elements, ANT2 function, mitochondrial bioenergetics, cellular metabolism, and stress responses. Our work highlights functional importances of the dark proteins and validates organelle-focused proteomics for discovering key cellular regulators.

As the key organelle governed lipid homeostasis, lipid droplets (LDs) in skeletal muscle plays a critical role in regulating systemic insulin sensitivity. In type 2 diabetes mellitus (T2DM) patients intramyocellular lipid (IMCL) content negatively associates with insulin sensitivity, while endurance athletes exhibit IMCL levels were positively correlated to insulin sensitivity, which is known as the athlete’s paradox. To solve this paradox, LDs were isolated from skeletal muscle samples of seven athletes and nine T2DM patients, and the first proteome dataset of human skeletal muscle LD was established. Comparative proteomic analysis revealed 733 upregulated proteins in athlete LDs, primarily enriched in mitochondria, and 755 downregulated proteins, mainly associated with cytoskeletal components, relative to T2DM patients. Integrated analysis with tissue proteomics further indicated enhanced energy metabolism activity of LD-anchored mitochondria (LDAM) in athletes. Notably, adipose triglyceride lipase (ATGL) was specifically upregulated by 2.97-fold on LDs in athletes, while its overall tissue expression remained unchanged. Moreover, deletion of ATGL in myoblasts significantly reduced insulin-stimulated AKT phosphorylation. Additionally, skeletal muscle LDs from db/db and ob/ob mice exhibited reduced levels of mitochondrial proteins and ATGL. Together, our findings reveal a LD-based solution for the athlete’s paradox, and identify ATGL as a key regulator of skeletal muscle insulin sensitivity. The results also suggest that the “bad LDs” in the skeletal muscle of T2DM patients are characterized by higher levels of cytoskeletal proteins, reduced LDAM, and lower ATGL compared to the “good LDs” observed in athletes.

Reconstructing premorbid gait patterns is critical for developing personalized rehabilitation strategies and assistive devices for patients with movement disorders. To achieve this aim, a predictive model is developed to estimate the walking dynamic features with individual parameters without requiring complex gait tests. First, an empirical kinematic model predicting the joint angle on the basis of leg length and walking cadence is derived. Consequently, dynamic models for the single support phase and double support phase are established, and a linear transformation strategy is proposed in the double support phase for optimization. Using inverse dynamic approaches, the model can ultimately predict the joint angle, joint moment, and ground reaction force across the entire gait cycle using only leg length, body mass, and walking cadence. The dynamic parameters predicted with the model are compared with experimental data for validation, and the results demonstrate the effectiveness of the proposed model.

Objective Neurodegenerative diseases affect millions of families around the world, while various wearable sensors and corresponding data analysis can be of great support for clinical diagnosis and health assessment. This systematic review aims to provide a comprehensive overview of the existing research that uses wearable sensors and features for the diagnosis of neurodegenerative diseases. Methods A systematic review was conducted of studies published between 2015 and 2022 in major scientific databases such as Web of Science, Google Scholar, PubMed, and Scopes. The obtained studies were analyzed and organized into the process of diagnosis: wearable sensors, feature extraction, and feature selection. Results The search led to 171 eligible studies included in this overview. Wearable sensors such as force sensors, inertial sensors, electromyography, electroencephalography, acoustic sensors, optical fiber sensors, and global positioning systems were employed to monitor and diagnose neurodegenerative diseases. Various features including physical features, statistical features, nonlinear features, and features from the network can be extracted from these wearable sensors, and the alteration of features toward neurodegenerative diseases was illustrated. Moreover, different kinds of feature selection methods such as filter, wrapper, and embedded methods help to find the distinctive indicator of the diseases and benefit to a better diagnosis performance. Conclusions This systematic review enables a comprehensive understanding of wearable sensors and features for the diagnosis of neurodegenerative diseases.

China has the largest population of patients with dementia in the world, imposing a heavy burden on the public and health care systems. More than 100 epidemiological studies on dementia have been done in China, but the estimates of the prevalence and incidence remain inconsistent because of the use of different sampling methods. Despite improved access to health services, inadequate diagnosis and management for dementia is still common, particularly in rural areas. The Chinese Government issued a new policy to increase care facilities for citizens older than 65 years, but most patients with dementia still receive care at home. Western medicines for dementia symptoms are widely used in China, but many patients choose Chinese medicines even though they have little evidence supporting efficacy. The number of clinical trials of Chinese and western medicines has substantially increased as a result of progress in research on new antidementia drugs but international multicentre studies are few in number. Efforts are needed to establish a national system of dementia care enhance training in dementia for health professionals, and develop global collaborations to prevent and cure this disease.

produces artemisinin, an effective antimalarial drug. In recent decades, the later steps of artemisinin biosynthesis have been thoroughly investigated; however, little is known about the early steps of artemisinin biosynthesis. Comparative transcriptomics of glandular and filamentous trichomes and CO radioisotope study have shown that the 2-C-methyl-D-erythritol-4-phosphate (MEP) pathway, rather than the mevalonate pathway, plays an important role in artemisinin biosynthesis. In this study, we have cloned three ( ) genes from . ( , , and ); the DXS enzyme catalyzes the first and rate-limiting enzyme of the MEP pathway. We analyzed the expression of these three genes in different tissues in response to multiple treatments. Phylogenetic analysis revealed that each of the three genes belonged to a distinct clade. Subcellular localization analysis indicated that all three AaDXS proteins are targeted to chloroplasts, which is consistent with the presence of plastid transit peptides in their N-terminal regions. Expression analyses revealed that the expression pattern of in specific tissues and in response to different treatments, including methyl jasmonate, light, and low temperature, was similar to that of artemisinin biosynthesis genes. To further investigate the tissue-specific expression pattern of , the promoter of was cloned upstream of the gene and was introduced in arabidopsis. Histochemical staining assays demonstrated that was mainly expressed in the trichomes of Arabidopsis leaves. Together, these results suggest that might be the only member of the DXS family in that is involved in artemisinin biosynthesis.

Cross-talks (e.g., host-driven iron withdrawal and microbial iron uptake between host gastrointestinal tract and commensal microbes) regulate immunotolerance and intestinal homeostasis. However, underlying mechanisms that regulate the cross-talks remain poorly understood. Here, we show that bacterial products up-regulate iron-transporter transferrin and transferrin acts as an immunosuppressor by interacting with cluster of differentiation 14 (CD14) to inhibit pattern recognition receptor (PRR) signaling and induce host immunotolerance. Decreased intestinal transferrin is found in germ-free mice and human patients with ulcerative colitis, which are characterized by impaired intestinal immunotolerance. Intestinal transferrin and host immunotolerance are returned to normal when germ-free mice get normal microbial commensalism, suggesting an association between microbial commensalism, transferrin, and host immunotolerance. Mouse colitis models show that transferrin shortage impairs host’s tolerogenic responses, while its supplementation promotes immunotolerance. Designed peptide blocking transferrin–CD14 interaction inhibits immunosuppressive effects of transferrin. In monkeys with idiopathic chronic diarrhea, transferrin shows comparable or even better therapeutic effects than hydrocortisone. Our findings reveal that by up-regulating host transferrin to silence PRR signaling, commensal bacteria counteract immune activation induced by themselves to shape host immunity and contribute for intestinal tolerance.