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The incidence of diabetes is increasing annually, and the disease is uncurable due to its complex pathogenesis. Therefore, understanding diabetes pathogenesis and developing new treatments are crucial. This study showed that the NO donor SNP (8⯵M) significantly alleviated high glucose-induced developmental toxicity in zebrafish larvae. High glucose levels caused hyperglycemia, leading to oxidative stress and mitochondrial damage from excessive ROS accumulation. This promoted mitochondrial-dependent apoptosis and lipid peroxidation (LPO)-induced ferroptosis, along with immune inflammatory reactions that decreased mitochondrial function and altered intracellular grid morphology, causing imbalanced kinetics and autophagy. After SNP treatment, zebrafish larvae showed improved developmental toxicity and glucose utilization, reduced ROS accumulation, and increased antioxidant activity. The NO-sGC-cGMP signaling pathway, inhibited by high glucose, was significantly activated by SNP, improving mitochondrial homeostasis, increasing mitochondrial count, and enhancing mitochondrial function. It's worth noting that apoptosis, ferroptosis and immune inflammation were effectively alleviated. In summary, SNP improved high glucose-induced developmental toxicity by activating the NO-sGC-cGMP signaling pathway to reduce toxic effects such as apoptosis, ferroptosis and inflammation resulting from mitochondrial homeostasis imbalance.
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Homeostase , Larva , Mitocôndrias , Peixe-Zebra , Animais , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Homeostase/efeitos dos fármacos , Larva/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Glucose/metabolismo , Glucose/toxicidade , Óxido Nítrico/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Ferroptose/efeitos dos fármacosRESUMO
PURPOSE: The purpose of this research is to further understand the research status and summarize the research hotspots of sleep disorder and cancer, so as to provide insights into future researches. METHODS: In this research, the publications pertaining to sleep disorders and cancer from 1992 to 2022 was retrieved from SCIE and SSCI databases in the Web of Science Core Collection. The subject, journal, country/regions, institutions, author, and citations of publications were descriptively analyzed and visual analysis. RESULTS: From 1992 to December 2022, a total of 732 relevant literatures were retrieved from WOS SCIE and SSCI databases, the number of publications showed an increasing trend year by year. These articles were published in 252 journals, and the three most productive journals included Supportive Care in Cancer (80 publications), Psycho-oncology (32 publications), and Journal of Pain and Symptom Management (32 publications). The three most productive countries included the USA (367 publications, 50.1%), China (133 publications, 18.2%), and Canada (97 publications, 13.25%), with total citations of 12,684, 1866, and 5263. The three latest hot keywords in this field were sleep duration, validity, and inflammation. CONCLUSION: The USA, China, and Canada produced a lot of literature in the research field of sleep disorders and cancer, and had relatively great academic influence from 1992 to 2022. Researchers could pay more attention to the published in journals such as Journal of Clinical Oncology, Sleep, and Supportive Care in Cancer to timely grasp the latest progress and expand the breadth and depth in this area. Looking at the history of tumor and sleep disorder research in the past 20 years, the clinical treatment of sleep disorder caused by tumor and the direct bidirectional mechanism of the two may be a new focus of future research.
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Neoplasias , Transtornos do Sono-Vigília , Humanos , Oncologia , Bibliometria , CanadáRESUMO
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, and patients with HCC have a poor prognosis and low survival rates. Establishing a prognostic nomogram is important for predicting the survival of patients with HCC, as it helps to improve the patient's prognosis. This study aimed to develop and evaluate nomograms and risk stratification to predict overall survival (OS) and cancer-specific survival (CSS) in HCC patients. Data from 10,302 patients with initially diagnosed HCC were extracted from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2017. Patients were randomly divided into the training and validation set. Kaplan-Meier survival, LASSO regression, and Cox regression analysis were conducted to select the predictors of OS. Competing risk analysis, LASSO regression, and Cox regression analysis were conducted to select the predictors of CSS. The validation of the nomograms was performed using the concordance index (C-index), the Akaike information criterion (AIC), the Bayesian information criterion (BIC), Net Reclassification Index (NRI), Discrimination Improvement (IDI), the receiver operating characteristic (ROC) curve, calibration curves, and decision curve analyses (DCAs). The results indicated that factors including age, grade, T stage, N stage, M stage, surgery, surgery to lymph node (LN), Alpha-Fetal Protein (AFP), and tumor size were independent predictors of OS, whereas grade, T stage, surgery, AFP, tumor size, and distant lymph node metastasis were independent predictors of CSS. Based on these factors, predictive models were built and virtualized by nomograms. The C-index for predicting 1-, 3-, and 5-year OS were 0.788, 0.792, and 0.790. The C-index for predicting 1-, 3-, and 5-year CSS were 0.803, 0.808, and 0.806. AIC, BIC, NRI, and IDI suggested that nomograms had an excellent predictive performance with no significant overfitting. The calibration curves showed good consistency of OS and CSS between the actual observation and nomograms prediction, and the DCA showed great clinical usefulness of the nomograms. The risk stratification of OS and CSS was built that could perfectly classify HCC patients into three risk groups. Our study developed nomograms and a corresponding risk stratification system predicting the OS and CSS of HCC patients. These tools can assist in patient counseling and guiding treatment decision making.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , alfa-Fetoproteínas , Teorema de Bayes , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Nomogramas , Prognóstico , Distribuição AleatóriaRESUMO
There is increasing evidence that miRNAs play an important role in the prognosis of HCC. There is currently a lack of acknowledged models that accurately predict patient prognosis. The aim of this study is to create a miRNA-based model to precisely forecast a patient's prognosis and a miRNA-mRNA network to investigate the function of a targeted mRNA. TCGA miRNA dataset and survival data of HCC patients were downloaded for differential analysis. The outcomes of variance analysis were subjected to univariate and multivariate Cox regression analyses and LASSO analysis. We constructed and visualized prognosis-related models and subsequently used violin plots to probe the function of miRNAs in tumor cells. We predicted the target mRNAs added those to the String database, built PPI protein interaction networks, and screened those mRNA using Cytoscape. The hub mRNA was subjected to GO and KEGG analysis to determine its biological role. Six of them were associated with prognosis: hsa-miR-139-3p, hsa-miR-139-5p, hsa-miR-101-3p, hsa-miR-30d-5p, hsa-miR-5003-3p, and hsa-miR-6844. The prognostic model was highly predictive and consistently performs, with the C index exceeding 0.7 after 1, 3, and 5 years. The model estimated significant differences in the Kaplan-Meier plotter and the model could predict patient prognosis independently of clinical indicators. A relatively stable miRNA prognostic model for HCC patients was constructed, and the model was highly accurate in predicting patients with good stability over 5 years. The miRNA-mRNA network was constructed to explore the function of mRNA.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Prognóstico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Redes Reguladoras de Genes , MicroRNAs/genética , MicroRNAs/metabolismoAssuntos
Procedimentos Cirúrgicos do Sistema Digestório , Gastroparesia , Neoplasias Gástricas , Humanos , Gastroparesia/etiologia , Gastroparesia/cirurgia , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/complicações , Fatores de Risco , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversosRESUMO
The Convention on Biological Diversity seeks to conserve at least 30% of global land and water areas by 2030, which is a challenge but also an opportunity to better preserve biodiversity, including flowering plants (angiosperms). Herein, we compiled a large database on distributions of over 300,000 angiosperm species and the key functional traits of 67,024 species. Using this database, we constructed biodiversity-environment models to predict global patterns of taxonomic, phylogenetic, and functional diversity in terrestrial angiosperms and provide a comprehensive mapping of the three diversity facets. We further evaluated the current protection status of the biodiversity centers of these diversity facets. Our results showed that geographical patterns of the three facets of plant diversity exhibited substantial spatial mismatches and nonoverlapping conservation priorities. Idiosyncratic centers of functional diversity, particularly of herbaceous species, were primarily distributed in temperate regions and under weaker protection compared with other biodiversity centers of taxonomic and phylogenetic facets. Our global assessment of multifaceted biodiversity patterns and centers highlights the insufficiency and unbalanced conservation among the three diversity facets and the two growth forms (woody vs. herbaceous), thus providing directions for guiding the future conservation of global plant diversity.
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Magnoliopsida , Filogenia , Biodiversidade , Plantas , Ecossistema , Conservação dos Recursos NaturaisRESUMO
Despite the continuous advancement of surgical resection techniques, postoperative tumor recurrence and metastasis remain a huge challenge. Here, we constructed an injectable curcumin/doxorubicin-loaded nanoparticle (NanoCD) hydrogel, which could effectively inhibit tumor regrowth and metastasis via reshaping the tumor immune microenvironment (TIME) for highly effective postsurgical cancer treatment. NanoCD was prepared by the controlled assembly of curcumin (CUR) and doxorubicin (DOX) via π-π stacking and hydrogen bonding in the presence of human serum albumin. To facilitate prolonged treatment of postsurgical tumors, NanoCD was further incorporated into the temperature-sensitive Poloxamer 407 gel (NanoCD@Gel) for intracavity administration. Mechanistically, DOX induced the generation of intracellular reactive oxygen species (ROS) and CUR reduced the ROS metabolism by inhibiting thioredoxin reductase (TrxR). The synergy of DOX and CUR amplified intracellular ROS levels and thus resulted in enhanced immunogenic cell death (ICD) of tumor cells. Upon being injected into the tumor cavity after resection, the in situ-generated NanoCD@Gel allowed the local release of CUR and DOX in a controlled manner to induce local chemotherapy and persistently activate the antitumor immune response, thereby achieving enhanced immunogenic chemotherapy with reduced systemic toxicity. Our work provides an elegant strategy for persistently stimulating effective antitumor immunity to prevent postsurgical tumor recurrence and metastasis.
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Curcumina , Nanopartículas , Humanos , Curcumina/farmacologia , Hidrogéis , Espécies Reativas de Oxigênio , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/prevenção & controle , Linhagem Celular Tumoral , Doxorrubicina , Microambiente TumoralRESUMO
The Arctic is warming at a rate four times the global average, while also being exposed to other global environmental changes, resulting in widespread vegetation and ecosystem change. Integrating functional trait-based approaches with multi-level vegetation, ecosystem, and landscape data enables a holistic understanding of the drivers and consequences of these changes. In two High Arctic study systems near Longyearbyen, Svalbard, a 20-year ITEX warming experiment and elevational gradients with and without nutrient input from nesting seabirds, we collected data on vegetation composition and structure, plant functional traits, ecosystem fluxes, multispectral remote sensing, and microclimate. The dataset contains 1,962 plant records and 16,160 trait measurements from 34 vascular plant taxa, for 9 of which these are the first published trait data. By integrating these comprehensive data, we bridge knowledge gaps and expand trait data coverage, including on intraspecific trait variation. These data can offer insights into ecosystem functioning and provide baselines to assess climate and environmental change impacts. Such knowledge is crucial for effective conservation and management in these vulnerable regions.
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Clima , Ecossistema , Animais , Aves , Conhecimento , SvalbardRESUMO
Global changes over the past few decades have caused species distribution shifts and triggered population declines and local extinctions of many species. The International Union for Conservation of Nature (IUCN) Red List of Threatened Species (Red List) is regarded as the most comprehensive tool for assessing species extinction risk and has been used at regional, national, and global scales. However, most Red Lists rely on the past and current status of species populations and distributions but do not adequately reflect the risks induced by future global changes. Using distribution maps of >4,000 endemic woody species in China, combined with ensembled species distribution models, we assessed the species threat levels under future climate and land-cover changes using the projected changes in species' suitable habitats and compared our updated Red List with China's existing Red List. We discover an increased number of threatened species in the updated Red List and increased threat levels of >50% of the existing threatened species compared with the existing one. Over 50% of the newly identified threatened species are not adequately covered by protected areas. The Yunnan-Guizhou Plateau, rather than the Hengduan Mountains, is the distribution center of threatened species on the updated Red Lists, as opposed to the threatened species on the existing Red List. Our findings suggest that using Red Lists without considering the impacts of future global changes will underestimate the extinction risks and lead to a biased estimate of conservation priorities, potentially limiting the ability to meet the Kunming-Montreal global conservation targets.
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Clima , Espécies em Perigo de Extinção , Animais , China , Extinção Biológica , MadeiraRESUMO
Artificial enzymes have demonstrated therapeutic benefits against diverse malignant tumors, yet their antitumor potencies are still severely compromised by non-selective catalysis, low atomic-utilization efficiency, and undesired off-target toxicity. Herein, it is reported that peroxidase-like biomineralized copper (II) carbonate hydroxide nanocrystals inside single albumin nanocages (CuCH-NCs) act as a pH-activatable proenzyme to achieve tumor-selective and synergistic chemodynamic/chemo-immunotherapy against aggressive triple-negative breast cancers (TNBCs). These CuCH-NCs show pH-sensitive Cu2+ release, which spontaneously undergoes glutathione (GSH)-mediated reduction into Cu+ species for catalyzing the evolution of H2 O2 into hydroxyl radicals (·OH) in a single-atom-like manner to cause chemodynamic cell injury, and simultaneously activates non-toxic disulfiram to cytotoxic complex for yielding selective chemotherapeutic damage via blocking cell proliferation and amplifying cell apoptosis. CuCH-NCs exhibit considerable tumor-targeting capacity with deep penetration depth, thus affording preferable efficacy against orthotopic breast tumors through synergistic chemodynamic/chemotherapy, together with good in vivo safety. Moreover, CuCH-NCs arouse distinct immunogenic cell death effect and upregulate PD-L1 expression upon disulfiram combination, and thus synergize with anti-PD-L1 antibody to activate adaptive and innate immunities, together with relieving immunosuppression, finally yielding potent antitumor efficacy against both primary and metastatic TNBCs. These results provide insights into smart and high-performance proenzymes for synergistic therapy against aggressive cancers.
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Nanopartículas , Neoplasias , Humanos , Precursores Enzimáticos , Cobre , Dissulfiram , Imunoterapia , Glutationa , Concentração de Íons de Hidrogênio , Linhagem Celular Tumoral , Peróxido de Hidrogênio , Microambiente TumoralRESUMO
Large amounts of enriched cadmium (Cd) in the environment seriously threatens the healthy and sustainable development of the aquaculture industry and greatly restricts the development of the food processing industry. Studying the distribution and toxic effects of Cd in fish, as well as the possible toxic effects of Cd on the human body, is very significant. A large number of studies have shown that the accumulation and distribution of Cd in fish are biologically specific, cause tissue differences, and seriously damage the integrity of tissue structure and function, the antioxidant defense system, the reproductive regulation system, and the immune system. The physiological, biochemical, enzyme, molecular, and gene expression levels change with different concentrations and times of Cd exposure, and these changes are closely related to the target sites of Cd action and tissues in fish. Therefore, the toxic effects of Cd on fish occur with multiple tissues, systems, and levels.
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BACKGROUND: Diabetes mellitus (DM) is an endocrine and metabolic disease caused by a variety of pathogenic factors, including genetic factors, environmental factors and behavior. In recent decades, the number of cases and the prevalence of diabetes have steadily increased, and it has become one of the most threatening diseases to human health in the world. Currently, insulin is the most effective and direct way to control hyperglycemia for diabetes treatment at a low cost. However, hypoglycemia is often a common complication of insulin treatment. Moreover, with the extension of treatment time, insulin resistance, considered the typical adverse symptom, can appear. Therefore, it is urgent to develop new targets and more effective and safer drugs for diabetes treatment to avoid adverse reactions and the insulin tolerance of traditional hypoglycemic drugs. SCOPE OF REVIEW: In recent years, it has been found that some fibroblast growth factors (FGFs), including FGF1, FGF19 and FGF21, can safely and effectively reduce hyperglycemia and have the potential to be developed as new drugs for the treatment of diabetes. FGF23 is also closely related to diabetes and its complications, which provides a new approach for regulating blood glucose and solving the problem of insulin tolerance. MAJOR CONCLUSIONS: This article reviews the research progress on the physiology and pharmacology of fibroblast growth factor in the treatment of diabetes. We focus on the application of FGFs in diabetes care and prevention.
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Diabetes Mellitus , Fatores de Crescimento de Fibroblastos , Hiperglicemia , Humanos , Glicemia/metabolismo , Diabetes Mellitus/tratamento farmacológico , Fatores de Crescimento de Fibroblastos/uso terapêutico , Hiperglicemia/tratamento farmacológico , Insulina/uso terapêuticoRESUMO
In recent decades, diabetes mellitus has become a major chronic disease threatening human health worldwide, and the age of patients tends to be younger; however, the pathogenesis remains unclear, resulting in many difficulties in its treatment. As an ideal model animal, zebrafish can simulate the processes of human diabetes well. In this study, we successfully established a model of diabetic zebrafish larvae in a previous work. Furthermore, transcriptome analysis was completed, and the results suggested that 10.59% of differentially expressed genes (DEGs) related to the apoptosis pathway need to be considered. Then, glucose-induced developmental toxicity, reactive oxygen species (ROS) accumulation, antioxidant system function, apoptosis and mitochondrial dysfunction were measured in zebrafish larvae. We hope that this study will provide valuable reference information for type 2 juvenile diabetes treatment.
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Apoptose , Peixe-Zebra , Animais , Embrião não Mamífero/metabolismo , Glucose/metabolismo , Glucose/farmacologia , Humanos , Larva/metabolismo , Mitocôndrias/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismoRESUMO
Plants have evolved many strategies for adaptation to extreme environments. Ca2+, acting as an important secondary messenger in plant cells, is a signaling molecule involved in plants' response and adaptation to external stress. In plant cells, almost all kinds of abiotic stresses are able to raise cytosolic Ca2+ levels, and the spatiotemporal distribution of this molecule in distant cells suggests that Ca2+ may be a universal signal regulating different kinds of abiotic stress. Ca2+ is used to sense and transduce various stress signals through its downstream calcium-binding proteins, thereby inducing a series of biochemical reactions to adapt to or resist various stresses. This review summarizes the roles and molecular mechanisms of cytosolic Ca2+ in response to abiotic stresses such as drought, high salinity, ultraviolet light, heavy metals, waterlogging, extreme temperature and wounding. Furthermore, we focused on the crosstalk between Ca2+ and other signaling molecules in plants suffering from extreme environmental stress.
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Hydrogen sulfide (H2S), a highly toxic gas, has become a polluting gas that cannot be ignored, while H2S exposure results in acute or chronic poisoning or even death in humans or animals and plants, but the relevant mechanisms remain poorly understood. In this study, 9-day-old zebrafish larvae were exposed continuously to culture medium containing 30 µM survival rate was counted on H2S, and our results indicated that H2S exposure increased intracellular ROS, Ca2+, NO and MDA contents and decreased SOD activity, meaning that H2S caused oxidative stress in embryo-larval stages of zebrafish. Furthermore, we found that transgenic zebrafish (cms Tg/+ AB) displayed a lower fluorescence intensity, and cytochrome c oxidase (COX) activity and JC-1 monomer fluorescence ratio increased under H2S treatment conditions. These findings indicated that H2S caused mitochondrial dysfunction. Moreover, in this experiment, after H2S treatment, the increase of apoptotic cells, activity of caspase 3 and transcription of typical apoptosis-associated genes including BCL2 associated agonist of cell death (Bad), and BCL2 associated X apoptosis (Baxa) and so on were found, which suggested that H2S caused apoptosis in zebrafish larvae. Therefore, our data meant that H2S-traggered oxidative stress mediate mitochondrial dysfunction, thus triggering apoptosis. In conclusion, oxidative stress triggered H2S-induced apoptosis via mitochondria pathway in embryo-larval stages of zebrafish.
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Apoptose , Sulfeto de Hidrogênio , Mitocôndrias , Estresse Oxidativo , Animais , Sulfeto de Hidrogênio/efeitos adversos , Larva/metabolismo , Mitocôndrias/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Peixe-Zebra/metabolismoRESUMO
Hydrogen sulfide (H2S) is considered the third gas signal molecule in recent years. A large number of studies have shown that H2S not only played an important role in animals but also participated in the regulation of plant growth and development and responses to various environmental stresses. Waterlogging, as a kind of abiotic stress, poses a serious threat to land-based waterlogging-sensitive plants, and which H2S plays an indispensable role in response to. In this review, we summarized that H2S improves resistance to waterlogging stress by affecting lateral root development, photosynthetic efficiency, and cell fates. Here, we reviewed the roles of H2S in plant resistance to waterlogging stress, focusing on the mechanism of its promotion to gained hypoxia tolerance. Finally, we raised relevant issues that needed to be addressed.
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Angiosperm sexual systems are fundamental to the evolution and distribution of plant diversity, yet spatiotemporal patterns in angiosperm sexual systems and their drivers remain poorly known. Using data on sexual systems and distributions of 68453 angiosperm species, we present the first global maps of sexual system frequencies and evaluate sexual system evolution during the Cenozoic. Frequencies of dioecy and monoecy increase with latitude, while hermaphrodites are more frequent in warm and arid regions. Transitions to dioecy from other states were higher than to hermaphroditism, but transitions away from dioecy increased since the Cenozoic, suggesting that dioecy is not an evolutionary end point. Transitions between hermaphroditism and dioecy increased, while transitions to monoecy decreased with paleo-temperature when paleo-temperature >0â. Our study demonstrates the biogeography of angiosperm sexual systems from a macroecological perspective, and enhances our understanding of plant diversity patterns and their response to climate change.
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Magnoliopsida , Evolução Biológica , Plantas , ReproduçãoRESUMO
Elevational range shifts of mountain species in response to climate change have profound impact on mountain biodiversity. However, current evidence indicates great controversies in the direction and magnitude of elevational range shifts across species and regions. Here, using historical and recent occurrence records of 83 plant species in a subtropical mountain, Mt. Gongga (Sichuan, China), we evaluated changes in species elevation centroids and limits (upper and lower) along elevational gradients, and explored the determinants of elevational changes. We found that 63.9% of the species shifted their elevation centroids upward, while 22.9% shifted downward. The changes in centroid elevations and range size were more strongly correlated with changes in lower than upper limits of species elevational ranges. The magnitude of centroid elevation shifts was larger than predicted by climate warming and precipitation changes. Our results show complex changes in species elevational distributions and range sizes in Mt. Gongga, and that climate change, species traits and climate adaptation of species all influenced their elevational movement. As Mt. Gongga is one of the global biodiversity hotspots, and contains many threatened plant species, these findings provide support to future conservation planning.