Compound hot-dry events greatly prolong the recovery time of dryland ecosystems.

Compound hot-dry events cause more severe impacts on terrestrial ecosystems than dry events, while the differences in recovery time (ΔRT) between hot-dry and dry events and their contributing factors remain unclear. Both remote sensing observations and eddy covariance measurements reveal that hot-dry events prolong the recovery time compared with dry events, with greater prolongation of recovery time in drylands than in humid regions. Random forest regression modeling demonstrates that the difference in vapor pressure deficit between hot-dry and dry events, with an importance score of 35%, is the major factor contributing to ΔRT. The severity of stomatal restriction exceeds that of non-stomatal limitation, which restricts the vegetation productivity that is necessary for the recovery process. These results emphasize the negative effect of vapor pressure deficit on vegetation recovery during hot-dry events and project an extension of drought recovery time considering elevated vapor pressure deficit in a warming world.

Ecosystem multifunctionality is more related to the indirect effects than to the direct effects of human management in China's drylands.

Drylands provide a wide range of important ecosystem functions but are sensitive to environmental changes, especially human management. Two major land use types of drylands are grasslands and croplands, which are influenced by intensive grazing activities and agricultural management, respectively. However, little is known about whether the ecosystem functioning of these two land use types is predominated affected by human management, or environmental factors (intrinsic environmental factors and factors modified by human management). This limits our understanding of the ecosystem functions under intensive human management in drylands. Here we reported a study where we collected data from 40 grassland and 30 cropland sites along an extensive aridity gradient in China's drylands to quantify the effects of human management intensity, intrinsic environmental factors (i.e., aridity), and environmental factors modified by human management (i.e., soil bulk density and plant density) on specific ecosystem functions (ecosystem multifunctionality, productivity, carbon storage, soil water, and soil nutrients). We found that the relative importance of each function differed between croplands and grasslands. Ecosystem functions varied with human management intensity, with lower productivity and plant carbon storage in grasslands under high grazing intensity than un-grazed, while multifunctionality and carbon storage increased with greater fertilization only in arid croplands. Furthermore, among environmental factors, soil bulk density had the greatest negative effects, which directly reduced multifunctionality in grasslands and indirectly reduced multifunctionality in croplands via suppressing crop density. Crop density was the major environmental factor that positively related to multifunctionality in croplands. However, these effects would be exacerbated with increasing aridity. Our study demonstrated that compared with the direct impacts of human management, environmental factors modified by human management (e.g., soil bulk density) are the major drivers of ecosystem functions, indicating that improving soil structure by alleviating human interferences (e.g., reducing livestock trampling) would be an effective way to restore ecosystem functions in drylands under global warming and drying.

Erratum: DTX3L E3 ligase targets p53 for degradation at poly ADP-ribose polymerase-associated DNA damage sites.

[This corrects the article DOI: 10.1016/j.isci.2023.106444.].

Cardiovascular protection of YiyiFuzi powder and the potential mechanisms through modulating mitochondria-endoplasmic reticulum interactions.

Cardiovascular diseases (CVD) remain the leading cause of death worldwide and represent a major public health challenge. YiyiFuzi Powder (YYFZ), composed of Coicis semen and Fuzi, is a classical traditional Chinese medicine prescription from the Synopsis of Golden Chamber dating back to the Han Dynasty. Historically, YYFZ has been used to treat various CVD, rooted in Chinese therapeutic principles. Network pharmacology analysis indicated that YYFZ may exhibit direct or indirect effects on mitochondria-endoplasmic reticulum (ER) interactions. This review, focusing on the cardiovascular protective effects of Coicis semen and Fuzi, summarizes the potential mechanisms by which YYFZ acts on mitochondria and the ER. The underlying mechanisms are associated with regulating cardiovascular risk factors (such as blood lipids and glucose), impacting mitochondrial structure and function, modulating ER stress, inhibiting oxidative stress, suppressing inflammatory responses, regulating cellular apoptosis, and maintaining calcium ion balance. The involved pathways include, but were not limited to, upregulating the IGF-1/PI3K/AKT, cAMP/PKA, eNOS/NO/cGMP/SIRT1, SIRT1/PGC-1α, Klotho/SIRT1, OXPHOS/ATP, PPARα/PGC-1α/SIRT3, AMPK/JNK, PTEN/PI3K/AKT, ß2-AR/PI3K/AKT, and modified Q cycle signaling pathways. Meanwhile, the MCU, NF-κB, and JAK/STAT signaling pathways were downregulated. The PERK/eIF2α/ATF4/CHOP, PERK/SREBP-1c/FAS, IRE1, PINK1-dependent mitophagy, and AMPK/mTOR signaling pathways were bidirectionally regulated. High-quality experimental studies are needed to further elucidate the underlying mechanisms of YYFZ in CVD treatment.

Woody encroachment: social-ecological impacts and sustainable management.

Woody plants are encroaching across terrestrial ecosystems globally, and this has dramatic effects on how these systems function and the livelihoods of producers who rely on the land to support livestock production. Consequently, the removal of woody plants is promoted widely in the belief that it will reinstate former grasslands or open savanna. Despite this popular management approach to encroachment, we still have a relatively poor understanding of the effects of removal on society, and of alternative management practices that could balance the competing needs of pastoral production, biodiversity conservation and cultural values. This information is essential for maintaining both ecological and societal benefits in encroached systems under predicted future climate changes. In this review, we provide a comprehensive synthesis of the social-ecological perspectives of woody encroachment based on recent studies and global meta-analyses by assessing the ecological impacts of encroachment and its effects on sustainable development goals (SDGs) when woody plants are retained and when they are removed. We propose a working definition of woody encroachment based on species- and community-level characteristics; such a definition is needed to evaluate accurately the effects of encroachment. We show that encroachment is a natural process of succession rather than a sign of degradation, with encroachment resulting in an overall 8% increase in ecosystem multifunctionality. Removing woody plants can increase herbaceous plant richness, biomass and cover, but at the expense of biocrust cover. The effectiveness of woody plant removal depends on plant identity, and where, when and how they are removed. Under current management practices, either removal or retention of woody plants can induce trade-offs among ecosystem services, with no management practice maximising all SDGs [e.g. SDG2 (end hunger), SDG13 (climate change), SDG 15 (combat desertification)]. Given that encroachment of woody plants is likely to increase under future predicted hotter and drier climates, alternative management options such as carbon farming and ecotourism could be effective land uses for areas affected by encroachment.

Hotspots of biogeochemical activity linked to aridity and plant traits across global drylands.

Perennial plants create productive and biodiverse hotspots, known as fertile islands, beneath their canopies. These hotspots largely determine the structure and functioning of drylands worldwide. Despite their ubiquity, the factors controlling fertile islands under conditions of contrasting grazing by livestock, the most prevalent land use in drylands, remain virtually unknown. Here we evaluated the relative importance of grazing pressure and herbivore type, climate and plant functional traits on 24 soil physical and chemical attributes that represent proxies of key ecosystem services related to decomposition, soil fertility, and soil and water conservation. To do this, we conducted a standardized global survey of 288 plots at 88 sites in 25 countries worldwide. We show that aridity and plant traits are the major factors associated with the magnitude of plant effects on fertile islands in grazed drylands worldwide. Grazing pressure had little influence on the capacity of plants to support fertile islands. Taller and wider shrubs and grasses supported stronger island effects. Stable and functional soils tended to be linked to species-rich sites with taller plants. Together, our findings dispel the notion that grazing pressure or herbivore type are linked to the formation or intensification of fertile islands in drylands. Rather, our study suggests that changes in aridity, and processes that alter island identity and therefore plant traits, will have marked effects on how perennial plants support and maintain the functioning of drylands in a more arid and grazed world.

Chinese herbal medicine Ginkgo biloba L. preparations for ischemic stroke: An overview of systematic reviews and meta-analyses.

BACKGROUND: Ginkgo biloba L. preparations (GBLPs) are a class of Chinese herbal medicine used in the adjuvant treatment of ischemic stroke (IS). Recently, several systematic reviews (SRs) and meta-analyses (MAs) of GBLPs for IS have been published. OBJECTIVE: This overview aims to assess the quality of related SRs and MAs. SEARCH STRATEGY: PubMed, Embase, Cochrane Library, Web of Science, Chinese Biological Medicine, China National Knowledge Infrastructure, Wanfang, and Chinese Science and Technology Journals databases were searched from their inception to December 31, 2022. INCLUSION CRITERIA: SRs and MAs of randomized controlled trials (RCTs) that explored the efficacy of GBLPs for patients with IS were included. DATA EXTRACTION AND ANALYSIS: Two independent reviewers extracted data and assessed the methodological quality, risk of bias (ROB), reporting quality, and credibility of evidence of the included SRs and MAs using A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2), Risk of Bias in Systematic Reviews (ROBIS), the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA), and the Grading of Recommendations Assessment, Development and Evaluation (GRADE), respectively. Additionally, descriptive analysis and data synthesis were conducted. RESULTS: Twenty-nine SRs/MAs involving 119 outcomes were included in this review. The overall methodological quality of all SRs/MAs was critically low based on AMSTAR 2, and 28 had a high ROB based on the ROBIS. According to the PRISMA statement, the reporting items of the included SRs/MAs are relatively complete. The results based on GRADE showed that of the 119 outcomes, 8 were rated as moderate quality, 24 as low quality, and 87 as very low quality. Based on the data synthesis, GBLPs used in conjunction with conventional treatment were superior to conventional treatment alone for decreasing neurological function scores. CONCLUSION: GBLPs can be considered a beneficial supplemental therapy for IS. However, because of the low quality of the existing evidence, high-quality RCTs and SRs/MAs are warranted to further evaluate the benefits of GBLPs for treating IS. Please cite this article as: Meng TT, You YP, Li M, Guo JB, Song XB, Ding JY, Xie XL, Li AQ, Li SJ, Yin XJ, Wang P, Wang Z, Wang BL, He QY. Chinese herbal medicine Ginkgo biloba L. preparations for ischemic stroke: An overview of systematic reviews and meta-analyses. J Integr Med. 2024;22(2): 163-179.

Accuracy of blood-based biomarkers for staging liver fibrosis in chronic liver disease: A systematic review supporting the AASLD Practice Guideline.

BACKGROUND AND AIMS: Blood-based biomarkers have been proposed as an alternative to liver biopsy for noninvasive liver disease assessment in chronic liver disease. Our aims for this systematic review were to evaluate the diagnostic utility of selected blood-based tests either alone, or in combination, for identifying significant fibrosis (F2-4), advanced fibrosis (F3-4), and cirrhosis (F4), as compared to biopsy in chronic liver disease. APPROACH AND RESULTS: We included a comprehensive search of databases including Ovid MEDLINE(R), EMBASE, Cochrane Database, and Scopus through to April 2022. Two independent reviewers selected 286 studies with 103,162 patients. The most frequently identified studies included the simple aspartate aminotransferase-to-platelet ratio index and fibrosis (FIB)-4 markers (with low-to-moderate risk of bias) in HBV and HCV, HIV-HCV/HBV coinfection, and NAFLD. Positive (LR+) and negative (LR-) likelihood ratios across direct and indirect biomarker tests for HCV and HBV for F2-4, F3-4, or F4 were 1.66-6.25 and 0.23-0.80, 1.89-5.24 and 0.12-0.64, and 1.32-7.15 and 0.15-0.86, respectively; LR+ and LR- for NAFLD F2-4, F3-4, and F4 were 2.65-3.37 and 0.37-0.39, 2.25-6.76 and 0.07-0.87, and 3.90 and 0.15, respectively. Overall, the proportional odds ratio indicated FIB-4 <1.45 was better than aspartate aminotransferase-to-platelet ratio index <0.5 for F2-4. FIB-4 >3.25 was also better than aspartate aminotransferase-to-platelet ratio index >1.5 for F3-4 and F4. There was limited data for combined tests. CONCLUSIONS: Blood-based biomarkers are associated with small-to-moderate change in pretest probability for diagnosing F2-4, F3-4, and F4 in viral hepatitis, HIV-HCV coinfection, and NAFLD, with limited comparative or combination studies for other chronic liver diseases.

StratoLAMP: Label-free, multiplex digital loop-mediated isothermal amplification based on visual stratification of precipitate.

Multiplex, digital nucleic acid detections have important biomedical applications, but the multiplexity of existing methods is predominantly achieved using fluorescent dyes or probes, making the detection complicated and costly. Here, we present the StratoLAMP for label-free, multiplex digital loop-mediated isothermal amplification based on visual stratification of the precipitate byproduct. The StratoLAMP designates two sets of primers with different concentrations to achieve different precipitate yields when amplifying different nucleic acid targets. In the detection, deep learning image analysis is used to stratify the precipitate within each droplet and determine the encapsulated targets for nucleic acid quantification. We investigated the effect of the amplification reagents and process on the precipitate generation and optimized the assay conditions. We then implemented a deep-learning image analysis pipeline for droplet detection, achieving an overall accuracy of 94.3%. In the application, the StratoLAMP successfully achieved the simultaneous quantification of two nucleic acid targets with high accuracy. By eliminating the need for fluorescence, StratoLAMP represents a unique concept toward label-free, multiplex nucleic acid assays and an analytical tool with great cost-effectiveness.

Xuanfei Baidu decoction in the treatment of coronavirus disease 2019 (COVID-19): Efficacy and potential mechanisms.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide and become a major global public health concern. Although novel investigational COVID-19 antiviral candidates such as the Pfizer agent PAXLOVID™, molnupiravir, baricitinib, remdesivir, and favipiravir are currently used to treat patients with COVID-19, there is still a critical need for the development of additional treatments, as the recommended therapeutic options are frequently ineffective against SARS-CoV-2. The efficacy and safety of vaccines remain uncertain, particularly with the emergence of several variants. All 10 versions of the National Health Commission's diagnosis and treatment guidelines for COVID-19 recommend using traditional Chinese medicine. Xuanfei Baidu Decoction (XFBD) is one of the "three Chinese medicines and three Chinese prescriptions" recommended for COVID-19. This review summarizes the clinical evidence and potential mechanisms of action of XFBD for COVID-19 treatment. With XFBD, patients with COVID-19 experience improved clinical symptoms, shorter hospital stay, prevention of the progression of their symptoms from mild to moderate and severe symptoms, and reduced mortality in critically ill patients. The mechanisms of action may be associated with its direct antiviral, anti-inflammatory, immunomodulatory, antioxidative, and antimicrobial properties. High-quality clinical and experimental studies are needed to further explore the clinical efficacy and underlying mechanisms of XFBD in COVID-19 treatment.

Plant functional traits explain long-term differences in ecosystem services between artificial forests and natural grasslands.

Declining ecosystem services have prompted numerous studies aiming at developing more sustainable management practices for vegetation restoration. Advances in functional ecology indicate that the sustainable management of afforestation ecosystems should be performed based on plant functional traits, which provides pivotal knowledge for long-term sustainable vegetation restoration. Currently, the mechanism of how plant functional traits affect long term ecosystem services in restored areas is still unclear. This study investigates plant functional traits and the associated ecosystem services from artificial forestlands (Robinia pseudoacacia, Caragana korshinskii) and natural grasslands following different durations of vegetation restoration (10, 20, 30 and 40 years) in the Danangou watershed, a loess hilly-gully region in the Loess Plateau, China. The results showed that 1) the water conservation services of artificial forestlands first decreased and then increased over time, whereas the soil conservation service had an opposite trend; in turn, natural grassland led to a consistent increase in soil conservation and carbon sequestration services over time. 2) Artificial forestlands had greater soil conservation and carbon sequestration services than natural grassland but had lower water conservation services. 3) Leaves had a greater impact on carbon sequestration and water conservation services than did root length and root biomass density. 4) Root biomass density had a greater effect on soil conservation services than did leaf carbon content and soil organic matter. 5) Leaf carbon content, specific root length, and root biomass density had significant effects on the trade-off value between any two ecosystem services with increasing time after restoration of artificial forestland. 6) Specific leaf area had a greater effect on the trade-off values among the three services than did the other functional traits in the natural grassland. In arid ecosystems, natural grasslands are the best restoration strategy given their higher water conservation services. However, in soil erosion-affected areas, restoration through artificial forestlands is more appropriate. To mitigate the trade-offs between ecosystem services, it is recommended that artificial forestlands be thinned before the leaf carbon content, specific root length, and root biomass density reach a maximum (i.e., mature forestland).

Soil erodibility for water and wind erosion and its relationship to vegetation and soil properties in China's drylands.

Drylands with fragile socio-ecological systems are vulnerable to soil erosion. China's drylands face the dual threat of water (WAE) and wind erosion (WIE). To mitigate soil erosion in drylands, China has implemented numerous ecological restoration measures. However, whether vegetation and soil have different effects on soil erodibility for water erosion (soil erodibility, K) and wind erosion (soil erodible fraction, EF) in drylands is unclear, hindering decision makers to develop suitable ecological restoration strategies. Here, we conducted a large-scale belt transect survey to explore the spatial variation of K and EF in China's drylands, and examined the linear and nolinear effects of aridity (aridity index), vegetation (fractional vegetation cover and below-ground biomass), and soil properties (bulk density, total nitrogen, and total phosphorus) on K and EF. The results showed in China's drylands that the K ranges from 0.02 to 0.07, with high values recorded in the northern Loess Plateau and the eastern Inner Mongolia Plateau. The EF ranges from 0.26 to 0.98, and shows longitudinal zonation with higher values in the east and lower values in the west. Aridity has a negative linear effect on K and an inverse U-shaped nonlinear effect on EF. Aridity can affect K and EF by suppressing vegetation growth and disrupting soil properties. However, K and EF had different responses to some vegetation and soil variables. K and EF had opposite relationships with soil bulk density, and EF was significantly affected by fractional vegetation cover, while K was not. Overall, the effects of aridity and soil properties on soil erodibility were more pronounced than those from vegetation, whose effect on soil erodibility was limited. This study provides relevant information to support reducing soil water and wind erosion by highlighting the hotspot areas of soil erodibility, relevant for implementing vegetation restoration and soil conservation measures in drylands.

Divergent responses of ecosystem services to afforestation and grassland restoration in the Tibetan Plateau.

Afforestation and grassland restoration have been proposed as important pathways for nature-based solutions. However, the effects of different ecological restoration projects on multiple ecosystem services are poorly understood, inhibiting our ability to maximize ecosystem services for further restoration. Here, we provide a comprehensive assessment of the impact of different ecological projects on ecosystem services (carbon storage, water conservation, soil retention), using a pairwise comparative study of samples from 90 project-control pairs in the Tibetan Plateau. Our results found that afforestation increased carbon storage (31.3%) and soil retention (37.6%), but the effects of grassland restoration on services were mixed, while the overall changes in water conservation were negligible. Prior land use/measures and the age of project implementation were key factors in regulating ecosystem service responses. For example, afforestation on bare land increased carbon storage and soil retention but indirectly decreased water conservation by influencing vegetation cover, while cropland afforestation increased water and soil retention. Ecosystem services increased with project age after afforestation. For grassland restoration, short-term recovery increased carbon storage but was not effective in improving water and soil retention. Climate and topography also directly or indirectly controlled the response of ecosystem services by affecting the changes in total nitrogen, total porosity, clay and fractional vegetation cover following the projects. This study improves our current understanding of the mechanisms underlying the responses of ecosystem services to afforestation and grassland restoration. Our results suggest that sustainable restoration management taking into account prior land use/measures, implementation age, climate, topography and other resources is critical for optimizing ecosystem services.

Heterogeneity changes of active bacterial community on cigar filler leaves after fermentation based on metagenome.

Microorganisms play an important role in cigar fermentation. To further explore the dynamic changes of bacterial community composition, the changes of surface bacterial diversity of cigar filler leaves were investigated in the present study by high-throughput sequencing technology. It was found that the surface bacterial richness was declined after fermentation, and the dominant microorganisms on the surface of cigar filler leaves evolved from Pseudomonas spp. and Sphingomonas spp. before fermentation to Staphylococcus spp. after fermentation. The chemical composition and sensory quality evaluation of cigar filler leaves were closely related to the changes of surface bacterial community. The changes of the dominant surface bacterial community led to the differences of metabolic functions, among which the metabolic pathways such as the synthesis of secondary metabolites, carbon metabolism, and amino acid biosynthesis were significantly different. The results provide a basis for clarifying the roles of bacteria in fermentation of cigar filler leaves.

DTX3L E3 ligase targets p53 for degradation at poly ADP-ribose polymerase-associated DNA damage sites.

P53 is a master transcriptional regulator and effector of the DNA damage response (DDR) that localizes to DNA damage sites, in part, via an interaction with PARP1. However, the mechanisms that regulate p53 abundance and activity at PARP1-decorated DNA damage sites remain undefined. The PARP9 (BAL1) macrodomain-containing protein and its partner DTX3L (BBAP) E3 ligase are rapidly recruited to PARP1-PARylated DNA damage sites. During an initial DDR, we found that DTX3L rapidly colocalized with p53, polyubiquitylated its lysine-rich C-terminal domain, and targeted p53 for proteasomal degradation. DTX3L knockout significantly increased and prolonged p53 retention at PARP-decorated DNA damage sites. These findings reveal a non-redundant, PARP- and PARylation-dependent role for DTX3L in the spatiotemporal regulation of p53 during an initial DDR. Our studies suggest that targeted inhibition of DTX3L may augment the efficacy of certain DNA-damaging agents by increasing p53 abundance and activity.

The success of woody plant removal depends on encroachment stage and plant traits.

Woody plants (shrubs and trees) are encroaching across the globe, affecting livestock production and terrestrial ecosystem functioning. Despite the widespread practice, there has been no quantitative global assessment of whether removal of encroaching woody plants will re-instate productive grasslands and open savanna. Here we compiled a global database of 12,198 records from 524 studies on the ecosystem responses of both the encroachment and removal of woody plants, and show that removal fails to reverse encroachment impacts. Removing woody plants only reversed less than half of the reductions in herbaceous structure induced by encroachment, and woody expansion actually enhanced ecosystem functions (+8%). The effectiveness of removal varied with encroachment stage (that is, time since treatment) and the functional traits (for example, deciduousness and resprouting) of the focal woody species, and waned in drier regions. Our results suggest that assessment of woody plant communities before removal is critical to assess the likelihood of successful ecosystem recovery.

Bone-on-a-chip platforms and integrated biosensors: Towards advanced in vitro bone models with real-time biosensing.

Bone diseases, such as osteoporosis and bone defects, often lead to structural and functional deformities of the patient's body. Understanding the complicated pathophysiology and finding new drugs for bone diseases are in dire need but challenging with the conventional cell and animal models. Bone-on-a-chip (BoC) models recapitulate key features of bone at an unprecedented level and can potentially shift the paradigm of future bone research and therapeutic development. Nevertheless, current BoC models predominantly rely on off-chip analysis which provides only endpoint measurements. To this end, integrating biosensors within the BoC can provide non-invasive, continuous monitoring of the experiment progression, significantly facilitating bone research. This review aims to summarize research progress in BoC and biosensor integrations and share perspectives on this exciting but rudimentary research area. We first introduce the research progress of BoC models in the study of bone remodeling and bone diseases, respectively. We then summarize the need for BoC characterization and reported works on biosensor integration in organ chips. Finally, we discuss the limitations and future directions of BoC models and biosensor integrations as next-generation technologies for bone research.

The impact of the armed conflict in Afghanistan on vegetation dynamics.

Armed conflicts disturb the environment and impair land productivity. Afghanistan has been submerged in conflict for >20 years, affecting the environment dramatically. In this study, we used the Normalised difference vegetation index (NDVI) to investigate vegetation's spatial and temporal changes and the potential underpinned mechanisms. We found a 16.44 % increase in NDVI in Afghanistan from 2000 to 2021. The average NDVI growth rate was 11.33 % (within 5 km distance from the armed conflict), higher in the conflict group than in the non-conflict group. People migration may have reduced the human impacts on the environment. The relative contribution of armed conflict to vegetation growth was 3.17 %. Our results showed that the vegetation in Afghanistan increased, confirming the idea that depopulation increase greenness. Despite the reduced variance explained by the war (R2 values around 0.3), our study provides empirical evidence on the linkages between the war and vegetation change in Afghanistan.

Global trends and frontiers in research on coronary microvascular dysfunction: a bibliometric analysis from 2002 to 2022.

BACKGROUND: Coronary microvascular dysfunction (CMD) is a leading cause of ischemic heart disease. Over the past few decades, considerable progress has been made with respect to research on CMD. The present study summarized the current research hotspots and trends on CMD by applying a bibliometric approach. METHODS: Relevant publications between 2002 and 2022 were extracted from the Web of Science Core Collection. Visualization network maps of countries, institutions, authors, and co-cited authors were built using VOSviewer. CiteSpace was used for keyword analysis and the construction of a dual-map overlay of journals and a timeline view of co-cited references. RESULTS: 1539 CMD-related publications were extracted for bibliometric analysis. The annual publications generally showed an upward trend. The United States of America was the most prolific country, with 515 publications (33.5%). Camici P. G. was the most influential author, whereas the European Heart Journal, Circulation, and Journal of the American College of Cardiology were the most authoritative journals. Research hotspot analysis revealed that endothelial dysfunction as well as reduced nitric oxide production or bioavailability played critical roles in CMD development. Positron emission tomography was the most widely used imaging method for diagnosis. In addition, microvascular angina, hypertrophic cardiomyopathy, and heart failure have attracted much attention as the main clinical implications. Furthermore, international standards for CMD diagnosis and management may be the future research directions. CONCLUSIONS: This study offers a comprehensive view about the hotspots and development trends of CMD, which can assist subsequent researchers and guide future directions.