A gastrointestinal locally activating Janus kinase inhibitor to treat ulcerative colitis.

In this study, we integrated machine learning (ML), structure-tissue selectivity-activity-relationship (STAR), and wet lab synthesis/testing to design a gastrointestinal (GI) locally activating JAK inhibitor for ulcerative colitis treatment. The JAK inhibitor achieves site-specific efficacy through high local GI tissue selectivity while minimizing the requirement for JAK isoform specificity to reduce systemic toxicity. We used the ML model (CoGT) to classify whether the designed compounds were inhibitors or noninhibitors. Then we used the regression ML model (MTATFP) to predict their IC50 against related JAK isoforms of predicted JAK inhibitors. The ML model predicted MMT3-72, which was retained in the GI tract, to be a weak JAK1 inhibitor, while MMT3-72-M2, which accumulated in only GI tissues, was predicted to be an inhibitor of JAK1/2 and TYK2. ML docking methods were applied to simulate their docking poses in JAK isoforms. Application of these ML models enabled us to limit our synthetic efforts to MMT3-72 and MMT3-72-M2 for subsequent wet lab testing. The kinase assay confirmed MMT3-72 weakly inhibited JAK1, and MMT3-72-M2 inhibited JAK1/2 and TYK2. We found that MMT3-72 accumulated in the GI lumen, but not in GI tissue or plasma, but released MMT3-72-M2 accumulated in colon tissue with minimal exposure in the plasma. MMT3-72 achieved superior efficacy and reduced p-STAT3 in DSS-induced colitis. Overall, the integration of ML, the structure-tissue selectivity-activity-relationship system, and wet lab synthesis/testing could minimize the effort in the optimization of a JAK inhibitor to treat colitis. This site-specific inhibitor reduces systemic toxicity by minimizing the need for JAK isoform specificity.

Ferroptosis: a potential target for the treatment of atherosclerosis.

Atherosclerosis (AS), the main contributor to acute cardiovascular events, such as myocardial infarction and ischemic stroke, is characterized by necrotic core formation and plaque instability induced by cell death. The mechanisms of cell death in AS have recently been identified and elucidated. Ferroptosis, a novel iron-dependent form of cell death, has been proven to participate in atherosclerotic progression by increasing endothelial reactive oxygen species (ROS) levels and lipid peroxidation. Furthermore, accumulated intracellular iron activates various signaling pathways or risk factors for AS, such as abnormal lipid metabolism, oxidative stress, and inflammation, which can eventually lead to the disordered function of macrophages, vascular smooth muscle cells, and vascular endothelial cells. However, the molecular pathways through which ferroptosis affects AS development and progression are not entirely understood. This review systematically summarizes the interactions between AS and ferroptosis and provides a feasible approach for inhibiting AS progression from the perspective of ferroptosis.

Phosphorus desorption regulates phosphorus fraction dynamics in soil aggregates of revegetated ecosystems.

To elucidate the mechanisms and effects of phosphorus (P) desorption on P fractions in soil aggregates of revegetated ecosystems is fundamental for regulating the P supply and biogeochemical cycle. We selected four aggregate sizes (1-5, 0.5-1, 0.25-0.5, and <0.25 mm) from a desert revegetation chronosequence (11, 31, 40, 57, and 65 years) as our study targets and used the Freundlich model to reveal the dynamics of P desorption and changes in P fractions. The results showed that the calibrated model [Formula: see text] for different size aggregates in seven deserts (two natural and five revegetated) described the P desorption characteristics well. In soil aggregates of revegetated deserts, smaller aggregates with higher specific surface area did not desorb more P, nor did older aggregates after revegetation. The natural P desorption process in aggregates resulted in significant changes in Ca2-P, Ca8-P, Al-P and Fe-P fractions (p < 0.05), and revegetation years also affected P fraction dynamics significantly (p < 0.05). This study highlights that the calibrated kinetic model in the revegetated soil aggregates elucidated the P desorption characteristics, and that the P desorption process drove P fraction changes.

Pyrosulfite-Involved Synthesis of Sulfides by Palladium-Catalyzed Decarboxylative Couplings.

The decarboxylative coupling using carboxylic acid and potassium metabisulfite, promoted by a palladium catalyst, is reported for the generation of sulfides. The coupling is performed using the easily available carboxylic acid and environmentally friendly inorganic sulfides as a divalent inorganic sulfur source. Not only aromatic acids but also aliphatic carboxylic acids are workable during the couplings. The method is applicable and practical to a scope of 20 examples and drug molecules.

A multisectoral and multidisciplinary endeavor: a review of diabetes self-management apps in China.

BACKGROUND: While the use of self-management apps has considerable promise to efficiently reduce the diabetes burden that disproportionally affects low- and middle-income countries (LMICs), and the multisectoral and multidisciplinary approaches have been encouraged to be used in diabetes management, little is known about the status of the integration of these approaches in the existing diabetes self-management apps. This review examines the diabetes apps in China as an indication of the current status of integrating multisectoral and multidisciplinary approaches in diabetes mHealth care in LMICs. METHODS: Eligible diabetes apps were searched on major Chinese app stores up to December 23, 2022. The app comprehensiveness index (ranging 0-80) regarding the app functions and diabetes management domains was created. The multisectoral and multidisciplinary features were summarized using indices derived from current guidance. RESULTS: Sixty-six apps were reviewed, all developed by private companies. The average comprehensiveness score was 16, with many major self-management domains and functions not represented among the reviewed apps. Forty apps (61%) involved multiple sectoral entities, with public/private and private/private collaborations being the most common collaborative combinations. Thirty-seven apps (56%) involved multiple disciplines, among which endocrinology/metabolism, nutrition, and cardiovascular medicine were the top three most common disciplines. Compared to non-multidisciplinary apps, multidisciplinary apps tended to provide more comprehensive services in apps (6.14 vs. 5.18, p = 0.0345). Different sectors and disciplines tended to work independently, without robust interactions, in providing diabetes management services in the reviewed apps. CONCLUSION: Multisectoral and multidisciplinary features has presented in the current diabetes self-management apps in China; however, it is still in its infancy and significant limitations existed. More engagement of civil society organizations and community groups and innovative collaborations between sectors and disciplines are needed to provide comprehensive, continuous, and patient-centered mHealth care for patients with diabetes in LMICs like China. Clear guidance for integrating and evaluating the multisectoral and multidisciplinary efforts in self-management apps is necessary to ensure the effective use of mHealth solutions for diabetes management in LMICs.

Transaldolase inhibits CD36 expression by modulating glutathione-p38 signaling, exerting protective effects against macrophage foam cell formation.

In atherosclerosis, macrophage-derived foam cell formation is considered to be a hallmark of the pathological process; this occurs via the uptake of modified lipoproteins. In the present study, we aim to determine the role of transaldolase in foam cell formation and atherogenesis and reveal the mechanisms underlying its role. Bone marrow-derived macrophages (BMDMs) isolated from mice successfully form foam cells after treatment with oxidized low-density lipoprotein (80 µg/mL). Elevated transaldolase levels in the foam cell model are assessed by quantitative polymerase chain reaction and western blot analysis. Transaldolase overexpression and knockdown in BMDMs are achieved via plasmid transfection and small interfering RNA technology, respectively. We find that transaldolase overexpression effectively attenuates, whereas transaldolase knockdown accelerates, macrophage-derived foam cell formation through the inhibition or activation of cholesterol uptake mediated by the scavenger receptor cluster of differentiation 36 (CD36) in a p38 mitogen-activated protein kinase (MAPK) signaling-dependent manner. Transaldolase-mediated glutathione (GSH) homeostasis is identified as the upstream regulator of p38 MAPK-mediated CD36-dependent cholesterol uptake in BMDMs. Transaldolase upregulates GSH production, thereby suppressing p38 activity and reducing the CD36 level, ultimately preventing foam cell formation and atherosclerosis. Thus, our findings indicate that the transaldolase-GSH-p38-CD36 axis may represent a promising therapeutic target for atherosclerosis.

Multifaceted role of ferroptosis in cardiovascular disease.

Ferroptosis is a newly identified form of non-apoptotic cell death characterised primarily by iron-dependent lipid peroxidation. It differs morphologically, biochemically, and genetically from other forms of cell death, such as apoptosis, autophagy, and necrosis. Although the molecular mechanism underlying ferroptosis remains unclear, multiple biological processes, such as iron metabolism, lipid peroxides, and systems, such as the glutathione system and the tetrahydrobiopterin/coenzyme Q10 system, appear to be involved. While the contribution of ferroptotic mechanisms to human diseases is not clear, recent studies have identified a number of ferroptosis-related genes. Cardiovascular diseases are the main cause of death globally. In this review, we outline the progress regarding the emerging role of ferroptosis in the pathogenesis of cardiac pathophysiological conditions and the association of ferroptosis with cardiomyopathy, myocardial ischemia-reperfusion injury, heart failure, and atherosclerosis. We further summarise newly discovered ferroptotic targets for the development of therapies for cardiovascular diseases. Finally, we discuss the current challenges and future research directions in cardiovascular disease treatments.

Genetics behind Cerebral Disease with Ocular Comorbidity: Finding Parallels between the Brain and Eye Molecular Pathology.

Cerebral visual impairments (CVIs) is an umbrella term that categorizes miscellaneous visual defects with parallel genetic brain disorders. While the manifestations of CVIs are diverse and ambiguous, molecular diagnostics stand out as a powerful approach for understanding pathomechanisms in CVIs. Nevertheless, the characterization of CVI disease cohorts has been fragmented and lacks integration. By revisiting the genome-wide and phenome-wide association studies (GWAS and PheWAS), we clustered a handful of renowned CVIs into five ontology groups, namely ciliopathies (Joubert syndrome, Bardet-Biedl syndrome, Alstrom syndrome), demyelination diseases (multiple sclerosis, Alexander disease, Pelizaeus-Merzbacher disease), transcriptional deregulation diseases (Mowat-Wilson disease, Pitt-Hopkins disease, Rett syndrome, Cockayne syndrome, X-linked alpha-thalassaemia mental retardation), compromised peroxisome disorders (Zellweger spectrum disorder, Refsum disease), and channelopathies (neuromyelitis optica spectrum disorder), and reviewed several mutation hotspots currently found to be associated with the CVIs. Moreover, we discussed the common manifestations in the brain and the eye, and collated animal study findings to discuss plausible gene editing strategies for future CVI correction.

Dynamics of soil organic carbon and nitrogen and their relations to hydrothermal variability in dryland.

Carbon (C) and nitrogen (N) cycles of terrestrial ecosystems play key roles in global climate change and ecosystem sustainability. In recent decades, climate change has threatened the nutrient balance of dryland ecosystems. However, its impact on soil organic carbon (SOC) and soil total nitrogen (STN) in drylands of China are still unclear. In this study, the structural equation model (SEM) was used to explain the relationship between environmental variables used by the best model and SOC or STN. Then Adaptive Boosting Regressor (AdaBoost), Gradient Boosting Regression (GBRT), Extreme gradient boosting Regression (XGBoost) and Random Forest Regression (RF) were used to establish the prediction model of SOC and STN based on soil samples along with environmental variables. The performance of these models was assessed based on a 10-fold cross-validation method using three statistical indicators. Finally, we predicted the SOC and STN of soil samples from 2000 to 2019 based on the best model. Overall, the RF model performed better at predicting SOC and STN in drylands than the other three prediction models (AdaBoost, GBRT, XGBoost). Climate factors were the main factors affecting SOC and STN in the study area. In the Alashan, a dryland in northern China, the precipitation in the growing season increased from 2000 to 2019, at a rate of 12.9 mm/decade. During the same period, the annual sunshine duration significantly decreased by 66 h/decade. Along with interannual hydrothermal variability, SOC showed a fluctuating upward trend at a rate of 0.04 g/kg/decade, while STN exhibited a fluctuating downward trend at 0.003 g/kg/decade from 2000 to 2019. Due to the effects of climate change, dryland were considered as potential sites for carbon sequestration. However, due to the annual hydrothermal variance causing dynamic annual changes, it was deemed unstable. Moreover, it would cause STN loss, which might reduce soil fertility. More attention should be paid to STN monitoring in dryland in the future.

Structural and Interfacial Engineering of Ni2P/Fe3O4 Porous Nanosheet Arrays for Efficient Oxygen Evolution Reaction.

Rational design of transition-metal phosphide (TMPs)-based electrocatalysts can effectively promote oxygen evolution reaction (OER). Herein, the novel efficient Ni2P/Fe3O4 porous nanosheets arrays supported on Ni foam (Ni2P/Fe3O4/NF) as alkaline OER catalysts were synthesized using structural and interfacial engineering. The three-dimensional (3D) porous hierarchical structure of Ni2P/Fe3O4/NF provides abundant active sites for OER and facilitates the electrolyte diffusion of ions and O2 liberation. Furthermore, the strong interfacial coupling and synergistic effect between Ni2P and Fe3O4 modify the electronic structure, resulting in the enhanced intrinsic activity. Consequently, the optimized Ni2P/Fe3O4/NF exhibits excellent OER performance with low overpotentials of 213 and 240 mV at 60 and 100 mA cm-2 in 1.0 M KOH, respectively, better than the RuO2/NF and most Ni/Fe-based OER catalysts. Impressively, it can maintain its catalytic activity for at least 20 h at 60 mA cm-2. In addition, the relationship between the structure and performance is fully elucidated by the experimental characterizations, indicating that the metal oxyhydroxides in situ generated on the surface of catalysts are responsible for the high OER activity.

The Correlation between Gut Microbiota and Serum Metabolomic in Elderly Patients with Chronic Heart Failure.

OBJECTIVE: Chronic heart failure (CHF) refers to a state of persistent heart failure that can be stable, deteriorated, or decompensated. The mechanism and pathogenesis of myocardial remodeling remain unknown. Based on 16S rDNA sequencing and metabolomics technology, this study analyzed the gut microbiota and serum metabolome in elderly patients with CHF to provide new insights into the microbiota and metabolic phenotypes of CHF. METHODS: Blood and fecal samples were collected from 25 elderly patients with CHF and 25 healthy subjects. The expression of inflammatory factors in blood was detected by ELISA. 16S rDNA sequencing was used to analyze the changes in microorganisms in the samples. The changes of small molecular metabolites in serum samples were analyzed by LC-MS/MS. Spearman correlation coefficients were used to analyze the correlation between gut microbiota and serum metabolites. RESULTS: Our results showed that the IL-6, IL-8, and TNF-α levels were significantly increased, and the IL-10 level was significantly decreased in the elderly patients with CHF compared with the healthy subjects. The diversity of the gut microbiota was decreased in the elderly patients with CHF. Moreover, Escherichia Shigella was negatively correlated with biocytin and RIBOFLAVIN. Haemophilus was negatively correlated with alpha-lactose, cellobiose, isomaltose, lactose, melibiose, sucrose, trehalose, and turanose. Klebsiella was positively correlated with bilirubin and ethylsalicylate. Klebsiella was negatively correlated with citramalate, hexanoylcarnitine, inosine, isovalerylcarnitine, methylmalonate, and riboflavin. CONCLUSION: The gut microbiota is simplified by the disease, and serum small-molecule metabolites evidently change in elderly patients with CHF. Serum and fecal biomarkers could be used for elderly patients with CHF screening.

Urban-rural differences in the prevalence and correlates of mild cognitive impairment in community-dwelling older adults in Taiwan: The EMCIT study.

BACKGROUND: Taiwan is a rapidly aging society. The elderly with mild cognitive impairment (MCI) have increased risk of dementia, and this is a population-based report using standard neuropsychological tests and expert consensus diagnosis to assess the MCI prevalence and its associated factors in Taiwan. METHOD: The Epidemiology of Mild Cognitive Impairment study in Taiwan (EMCIT) is a community-based, prospective cohort study. Independently-living individuals aged ≧60 years in a rural area (n = 122) and in an urban area (n = 348) of New Taipei City, Taiwan, completed detailed neuropsychological tests at the cohort baseline. Diagnosis of MCI was ascertained through expert consensus based on 2011 NIA-AA criteria. RESULTS: Of 470 participants recruited between 2017 and 2019 (mean age 71.2 ± 5.4 years), the prevalence of MCI was higher in the rural area than in the urban area (25.1% vs. 10.8%, p < 0.001) after standardized for age, gender, and level of education. Having lower education and having depression symptoms were consistently associated with increased risk of MCI in both urban and rural areas (p < 0.05). Being male and diabetes were additionally associated with MCI prevalence in urban areas. CONCLUSION: In this community-based prospective cohort study in Taiwan, the prevalence of MCI in the rural community was much higher than that in the urban community. Different strategies may be needed to targeted different types of communities.

[Study on history of processing and drying of Angelicae sinensis].

Angelicae sinensis Radix( ASR) is a commonly used medicinal material in Chinese medicine,widely used in clinical practice of Chinese medicine,Gansu province is the genuine production area of ASR. This paper studies the evolution law of drying method of ASR,the results showed that drying process was the key affection of the medicinal properties and quality of ASR,and it was an important reflection of the authentic properties of ASR. The drying history of ASR has gradually changed from the earliest shade drying to various drying methods. The Chinese Pharmacopoeia stipulates that the drying method of ASR is"fumigation drying",and the traditional drying method can not meet the processing needs of the origin. In recent years,the new drying methods and drying effects on the quality of ASR are more.

[Study on low temperature moisture regain drying characteristics of different grades of Angelicae Sinensis Radix based on Weibull distribution function].

The drying process of different grades of Angelicae Sinensis Radix under low temperature and resurgence conditions was simulated based on the Weibull distribution function,in order to clarify the low-temperature moisture regain drying characteristics of different grades of Angelicae Sinensis Radix,and explore the effect of grade and drying conditions on the drying process of Angelicae Sinensis Radix. Research results indicated that the Weibull function can be used to simulate different grades of Angelicae Sinensis Radix low-temperature moisture regain drying process,and the lower the drying temperature,the smaller the grade,and the better the simulation effect. The grade and drying temperature showed a significant effect on the low-temperature moisture regain drying process of Angelicae Sinensis Radix,and the effect of temperature on the relative moisture regain rate of Angelicae Sinensis Radix was greater than the grade. The relative moisture regain rate of different grades of Angelicae Sinensis Radix at 40 ℃ was higher than 55 ℃,and the relative moisture regain rate at 40 ℃ was first class > second class > third class. After drying,the moisture ratio at 40 ℃ was lower than that at 55 ℃; the effect of the grade on the effective diffusion coefficient of dry water was greater than the temperature. Under different conditions of 40 ℃ and 55 ℃ moisture regain,the effective diffusion coefficient of water was between 2. 941 6×10-6-7. 991 5×10-6 and3. 093 8×10-6-8. 483 8×10-6 for different grades. Under the same temperature conditions,the effective diffusion coefficient of water was first class > second class > third class. Therefore,Weibull function can be used to study and simulate the drying characteristics of different grades of Angelicae Sinensis Radix under low-temperature moisture regain conditions,providing experimental basis for the improvement of traditional drying technology of Angelicae Sinensis Radix and the optimization of drying process of different specifications or grades of Angelicae Sinensis Radix.

Antitumoral Cascade-Targeting Ligand for IL-6 Receptor-Mediated Gene Delivery to Glioma.

The effective treatment of glioma is largely hindered by the poor transfer of drug delivery systems across the blood-brain barrier (BBB) and the difficulty in distinguishing healthy and tumorous cells. In this work, for the first time, an interleukin-6 receptor binding I6P7 peptide was exploited as a cascade-targeting ligand in combination with a succinoyl tetraethylene pentamine (Stp)-histidine oligomer-based nonviral gene delivery system (I6P7-Stp-His/DNA). The I6P7 peptide provides multiple functions, including the cascade-targeting potential represented by a combined BBB-crossing and subsequent glioma-targeting ability, as well as a direct tumor-inhibiting effect. I6P7-Stp-His/DNA nanoparticles (NPs) mediated higher gene expression in human glioma U87 cells than in healthy human astrocytes and a deeper penetration into glioma spheroids than scrambled peptide-modified NPs. Transport of I6P7-modified, but not the control, NPs across the BBB was demonstrated in vitro in a transwell bEnd.3 cell model resulting in transfection of underlying U87 cells and also in vivo in glioma-bearing mice. Intravenous administration of I6P7-Stp-His/plasmid DNA (pDNA)-encoding inhibitor of growth 4 (pING4) significantly prolonged the survival time of orthotopic U87 glioma-bearing mice. The results denote that I6P7 peptide is a roborant cascade-targeting ligand, and I6P7-modified NPs might be exploited for efficient glioma therapy.

ATP-Binding Cassette Transporter VcaM from Vibrio cholerae is Dependent on the Outer Membrane Factor Family for Its Function.

Vibrio cholerae ATP-binding cassette transporter VcaM (V. cholerae ABC multidrug resistance pump) has previously been shown to confer resistance to a variety of medically important drugs. In this study, we set to analyse its properties both in vitro in detergent-solubilised state and in vivo to differentiate its dependency on auxiliary proteins for its function. We report the first detailed kinetic parameters of purified VcaM and the rate of phosphate (Pi) production. To determine the possible functional dependencies of VcaM on the tripartite efflux pumps we then utilized different E. coli strains lacking the principal secondary transporter AcrB (Acriflavine resistance protein), as well as cells lacking the outer membrane factor (OMF) TolC (Tolerance to colicins). Consistent with the ATPase function of VcaM we found it to be susceptible to sodium orthovanadate (NaOV), however, we also found a clear dependency of VcaM function on TolC. Inhibitors targeting secondary active transporters had no effects on either VcaM-conferred resistance or Hoechst 33342 accumulation, suggesting that VcaM might be capable of engaging with the TolC-channel without periplasmic mediation by additional transporters. Our findings are indicative of VcaM being capable of a one-step substrate translocation from cytosol to extracellular space utilising the TolC-channel, making it the only multidrug ABC-transporter outside of the MacB-family with demonstrable TolC-dependency.

[Analysis Characteristics of Inorganic Elements in Different Organs of Hedysarum polybotrys in Different Growing Variation].

Objective: To study the characteristics of inorganic elements in different organs of Hedysarum polybotrys in different growing variation, including root, rhizome, leaf, flower and fruit. Methods: The content of 13 inorganic elements in different organs were detected by using flame atomic absorption method, and then the characteristics of inorganic elements in different organs of Hedysarum polybotrys in different growing variation were analyzed. Results: There were abundant inorganic elements in root, rhizome, leaf, flower and fruit, the change in the contents of inorganic elements at different growing variation related to the season. The contents of Fe,Cu,Ca,Mn,Zn, Mg, Cr, Co, Na, Li,Ni and K were regularly changed with the change of growing variation, and Cd was not deteced. The content of Cu and Ca order was leaf > root > rhizome, and the content of Mn at leaf was higher than that at other organs during June to October. Conclusion: The results provide scientific basis for the harvest time of Hedysari Radix and the development of non-medicinal portions.

Direct Solvent-Derived Polymer-Coated Nitrogen-Doped Carbon Nanodots with High Water Solubility for Targeted Fluorescence Imaging of Glioma.

Cancer imaging requires biocompatible and bright contrast-agents with selective and high accumulation in the tumor region but low uptake in normal tissues. Herein, 1-methyl-2-pyrrolidinone (NMP)-derived polymer-coated nitrogen-doped carbon nanodots (pN-CNDs) with a particle size in the range of 5-15 nm are prepared by a facile direct solvothermal reaction. The as-prepared pN-CNDs exhibit stable and adjustable fluorescence and excellent water solubility. Results of a cell viability test (CCK-8) and histology analysis both demonstrate that the pN-CNDs have no obvious cytotoxicity. Most importantly, the pN-CNDs can expediently enter glioma cells in vitro and also mediate glioma fluorescence imaging in vivo with good contrast via elevated passive targeting.

Multimodal Connectivity-based Individual Parcellation and Analysis for Humans and Rhesus Monkeys.

Individual brains vary greatly in morphology, connectivity and organization. Individualized brain parcellation is capable of precisely localizing subject-specific functional regions. However, most individualization approaches examined single modality of data and have not generalized to nonhuman primates. The present study proposed a novel multimodal connectivity-based individual parcellation (MCIP) method, which optimizes within-region homogeneity, spatial continuity and similarity to a reference atlas with the fusion of personal functional and anatomical connectivity. Comprehensive evaluation demonstrated that MCIP outperformed state-of-the-art multimodal individualization methods in terms of functional and anatomical homogeneity, predictability of cognitive measures, heritability, reproducibility and generalizability across species. Comparative investigation showed a higher topographic variability in humans than that in macaques. Therefore, MCIP provides improved accurate and reliable mapping of brain functional regions over existing methods at an individual level across species, and could facilitate comparative and translational neuroscience research.

Response of Carbon-Fixing Bacteria to Patchy Degradation of the Alpine Meadow in the Source Zone of the Yellow River, West China.

This study aims to enlighten our understanding of the distribution of soil carbon-fixing bacteria (cbbL-harboring bacteria) and their community diversity in differently degraded patches at three altitudes. MiSeq high-throughput sequencing technology was used to analyze the soil carbon-fixing bacteria community diversity of degraded patches and healthy meadow at three altitudes. Redundancy analysis (RDA) and structural equation model (SEM) were used to analyze the correlation and influence path between environmental factors and carbon-fixing bacteria. The results showed that degradation reduced the relative abundance of Proteobacteria from 99.67% to 95.57%. Sulfurifustis, Cupriavidus, and Alkalispirillum were the dominant genera at the three altitudes. Hydrogenophaga and Ectothiorhodospira changed significantly with altitude. RDA results confirmed that available phosphorus (AP) was strongly and positively correlated with Proteobacteria. AP and total nitrogen (TN) were strongly and positively correlated with Hydrogenophaga. Grass coverage and sedge aboveground biomass were strongly and positively correlated with Sulfurifustis and Ectothiorhodospira, respectively. Elevation adversely affected the relative abundance of dominant carbon-fixing bacteria and diversity index by reducing the coverage of grass and soil volumetric moisture content (SVMC) indirectly, and also had a direct positive impact on the Chao1 index (path coefficient = 0.800). Therefore, increasing the content of nitrogen, phosphorus and SVMC and vegetation coverage, especially sedge and grass, will be conducive to the recovery of the diversity of soil carbon-fixing bacteria and improve the soil autotrophic microbial carbon sequestration potential in degraded meadows, especially in high-altitude areas.