Biology subjects

Ren, M.

Publications and source records attributed to Ren, M..

At least 37 records · Page 2Linked to original sources

bioRxiv2024

Lysosome-acidifying nanoparticles rescue A30P α-synuclein induced neuronal death in cellular and Drosophila models of Parkinson's disease

Parkinsons disease (PD) is an age-related neurodegenerative disease characterized by histopathological hallmarks of Lewy bodies formed by accumulation of -synuclein (Syn) and progressive loss of dopaminergic neurons in the substantia nigra pars compacta of the midbrain, with clinical symptoms of motor deficits. Toxic protein accumulation of Syn in PD is associated with autolysosomal acidification dysfunction that contributes to defective autophagy-lysosomal degradation system. While lysosome-acidifying nanoparticles have been applied as therapeutics to ameliorate dopaminergic neurodegeneration in neurotoxin mediated or Syn aggregates induced mouse model of sporadic PD, lysosome-targeted approach has not yet been applied in synucleinopathy models of familial PD. Here, we report the first application of the new poly(ethylene tetrafluorosuccinate-co-succinate) (PEFSU)-based acidic nanoparticles (AcNPs) in A30P Syn overexpressing SH-SY5Y cells and Drosophila models of PD. In the cellular model, we showed that AcNPs restore lysosomal acidification, promote autophagic clearance of Syn, improve mitochondrial turnover and function, and rescue A30P Syn induced death in SH-SY5Y cells. In the Drosophila model, we demonstrated that AcNPs enhance clearance of Syn and rescue dopaminergic neuronal loss in fly brains and improve their locomotor activity. Our results highlight AcNPs as a new class of lysosome-acidifying therapeutic for treatment of PD and other proteinopathies in general.

neuroscience↗

bioRxiv2024

GABAAR-PPT1 palmitoylation homeostasis controls synaptic transmission and circuitry oscillation in CLN1 disease

CLN1 disease, also called infantile neuronal ceroid lipofuscinosis, is a fatal neurodegenerative disease caused by mutations in the CLN1 gene encoding palmitoyl protein thioesterase 1 (PPT1). To identify depalmitoylation substrate of PPT1 is crucial to understand CLN1 disease. In this study, we found that PPT1 depalmitoylates GABAAR 1 subunit at Cystein-260, while binding to Cystein-165 and -179. Mutations of PPT1 or its GABAAR 1 subunit binding site result in enhanced inhibitory synaptic transmission, strengthened and oscillation but disrupted phase coupling in CA1 region and impaired learning and memory in 1- to 2-months-old PPT1-deficient and Gabra1em1 mice. Our study highlights the critical role of PPT1 in maintaining GABAAR palmitoylation homeostasis and reveals a previously unknown molecular pathway in PPT1 induced diseases.

neuroscience↗

bioRxiv2024

Upregulation of the AMPK-FOXO1-PDK4 pathway is a primary mechanism of pyruvate dehydrogenase activity reduction and leads to increased glucose uptake in tafazzin-deficient cells

Barth syndrome (BTHS) is a rare disorder caused by mutations in the TAFAZZIN gene. Previous studies from both patients and model systems have established metabolic dysregulation as a core component of BTHS pathology. In particular, features such as lactic acidosis, pyruvate dehydrogenase (PDH) deficiency, and aberrant fatty acid and glucose oxidation have been identified. However, the lack of a mechanistic understanding of what causes these conditions in the context of BTHS remains a significant knowledge gap, and this has hindered the development of effective therapeutic strategies for treating the associated metabolic problems. In the current study, we utilized tafazzin-knockout C2C12 mouse myoblasts (TAZ-KO) and cardiac and skeletal muscle tissue from tafazzin-knockout mice to identify an upstream mechanism underlying impaired PDH activity in BTHS. This mechanism centers around robust upregulation of pyruvate dehydrogenase kinase 4 (PDK4), resulting from hyperactivation of AMP-activated protein kinase (AMPK) and subsequent transcriptional upregulation by forkhead box protein O1 (FOXO1). Upregulation of PDK4 in tafazzin-deficient cells causes direct phospho-inhibition of PDH activity accompanied by increased glucose uptake and elevated intracellular glucose concentration. Collectively, our findings provide a novel mechanistic framework whereby impaired tafazzin function ultimately results in robust PDK4 upregulation, leading to impaired PDH activity and likely linked to dysregulated metabolic substrate utilization. This mechanism may underlie previously reported findings of BTHS-associated metabolic dysregulation.

cell biology↗

bioRxiv2024

Elucidating Resistance Mechanisms in Staphylococcus epidermidis: A High-Performing MALDI-TOF MS-Based Proteomic Approach for Predictive Modeling

The emergence of Staphylococcus epidermidis as a significant nosocomial pathogen necessitates advancements in more efficient antimicrobial resistance (AMR) profiling. However, existing culture-based antimicrobial susceptibility testing (AST) methods can take up to 96 hours, while holistic PCR assays can cost thousands of dollars. This study combines machine learning with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to develop predictive models for various antibiotics using a comprehensive dataset containing thousands of S. epidermidis isolates. Optimized machine learning models utilized feature selection and achieved high AUROC scores ranging from 0.80 to 0.95 while maintaining AUPRC scores up to 0.96 for balanced datasets. Shapley Additive exPlanations (SHAP) were employed to analyze relevant features and assess the significance of corresponding protein biomarkers while also verifying that predictive power was derived from the detection of proteins rather than noise. AMR prediction models were validated externally to evaluate model performance outside the original data collection site. The findings in this study demonstrate that combining machine learning with AMR profiling yields significant and relevant results, indicating that such an approach is a promising solution for rapid and cost-effective treatments for nosocomial infections. Models created to predict AMR can also aid in biomarker discovery. The workflow used in the present study is potentially applicable to other microbial pathogens in the future.

bioinformatics↗

bioRxiv2023

Revisiting the potency of Tbx2 expression in transforming outer hair cells into inner hair cells at multiple ages in vivo

The cochlea, the auditory organ, contains two types of sound receptors: inner hair cells (IHCs) and outer hair cells (OHCs). Tbx2 is expressed in IHCs but repressed in OHCs. The neonatal OHCs with Tbx2 misexpression transdifferentiate into IHC-like cells. However, the extent of the switch from OHCs to IHC-like cells and the underlying molecular mechanism remain poorly understood. Furthermore, it is unknown whether Tbx2 can transform fully mature adult OHCs into IHC-like cells. In this study, we employ single-cell transcriptomic analysis, revealing that 85.6% of IHC genes, including Slc17a8, are upregulated, whereas only 38.6% of OHC genes, including Ikzf2 and Slc26a5, are downregulated in neonatal OHCs with Tbx2 misexpression. Thus, our findings suggest that Tbx2 cannot fully reprogram neonatal OHCs into IHCs, contrary to previous assumptions. Consistently, Tbx2 also fails to fully reprogram cochlear progenitors into IHCs. Finally, Ikzf2 restoration alleviates the abnormalities present in the Tbx2+ OHCs, supporting the notion that Ikzf2 repression by Tbx2 contributes to the transdifferentiation of OHCs into IHC-like cells. Overall, our study reevaluates the effects of ectopic Tbx2 expression on OHC lineage development at different stages and provides molecular insights into how Tbx2 disrupts the gene expression profiles of OHCs. This research also lays the groundwork for future studies on OHC regeneration. Significance StatementUnderstanding the molecular and genetic mechanisms that govern the determination and stability of cochlear inner hair cells (IHCs) and outer hair cells (OHCs) would provide valuable insights into regenerating damaged IHCs and OHCs. In this manuscript, we conduct in vivo conditional overexpression of Tbx2 in cochlear sensory progenitors, neonatal OHCs and adult OHCs, respectively. Our findings challenge previous assumptions by revealing that Tbx2 expression alone can partially destabilize OHC fates but cannot fully convert OHCs into IHCs. Specifically, we demonstrate that the repression of Ikzf2 expression due to Tbx2 overexpression is one of the key pathways disrupting OHC fate.

developmental biology↗

bioRxiv2023

Highly accurate and robust protein sequence design with CarbonDesign

Protein sequence design, the inverse problem of protein structure prediction, plays a crucial role in protein engineering. Although recent deep learning-based methods have shown promising advancements, achieving accurate and robust protein sequence design remains an ongoing challenge. Here, we present CarbonDesign, a new approach that draws inspiration from successful ingredients of AlphaFold for protein structure prediction and makes significant and novel developments tailored specifically for protein sequence design. At its core, CarbonDesign explores Inverseformer, a novel network architecture adapted from AlphaFolds Evoformer, to learn representations from backbone structures and an amortized Markov Random Fields model for sequence decoding. Moreover, we incorporate other essential AlphaFold concepts into CarbonDesign: an end-to-end network recycling technique to leverage evolutionary constraints in protein language models and a multi-task learning technique to generate side chain structures corresponding to the designed sequences. Through rigorous evaluations on independent testing data sets, including the CAMEO and recent CASP15 data sets, as well as the predicted structures from AlphaFold, we show that CarbonDesign outperforms other published methods, achieving high accuracy in sequence generation. Moreover, it exhibits superior performance on de novo backbone structures obtained from recent diffusion generative models such as RFdiffusion and FrameDiff, highlighting its potential for enhancing de novo protein design. Notably, CarbonDesign also supports zero-shot prediction of the functional effects of sequence variants, indicating its potential application in directed evolution-based design. In summary, our results illustrate CarbonDesigns accurate and robust performance in protein sequence design, making it a promising tool for applications in bioengineering.

bioinformatics↗

bioRxiv2023

Knockout of cardiolipin synthase disrupts postnatal cardiac development by inhibiting the maturation of mitochondrial cristae

BackgroundCardiomyocyte maturation requires a massive increase in respiratory enzymes and their assembly into long-lived complexes of oxidative phosphorylation (OXPHOS). The molecular mechanisms underlying the maturation of cardiac mitochondria have not been established. MethodsTo determine whether the mitochondria-specific lipid cardiolipin is involved in cardiac maturation, we created a cardiomyocyte-restricted knockout (KO) of cardiolipin synthase (Crls1) in mice and studied the postnatal development of the heart. We also measured the turnover rates of proteins and lipids in cardiolipin-deficient flight muscle from Drosophila, a tissue that has mitochondria with high OXPHOS activity like the heart. ResultsCrls1KO mice survived the prenatal period but failed to accumulate OXPHOS proteins during postnatal maturation and succumbed to heart failure at the age of 2 weeks. Turnover measurements showed that the exceptionally long half-life of OXPHOS proteins is critically dependent on cardiolipin. ConclusionsCardiolipin is essential for the postnatal maturation of cardiomyocytes because it allows mitochondrial cristae to accumulate OXPHOS proteins to a high concentration and to shield them from degradation.

developmental biology↗

bioRxiv2023

GenBank genomics highlight the genomic features, genetic diversity and regulation of morphological, metabolic and disease-resistance traits in Nicotiana tabacum

Nicotiana tabacum is a model organism in plant molecular and pathogenic research and has significant potential in the production of biofuels and active pharmaceutical compounds in synthetic biology. Because of the large allotetraploid genome of tobacco, its genomic features, genetic diversity and genetic regulation of many complex traits remain unknown. In this study, we present a nearly complete chromosome-scale assembly of N. tabacum and provide evidence that homoeologous exchange between subgenomes and epigenetic remodelling are likely mechanisms of genome stabilization and subgenome coordination following polyploidization. By leveraging GenBank-scale sequencing and phenotyping data from 5196 lines, geography at the continent scale, rather than types assigned on the basis of curing crop practices, was found to be the most important correlate of genetic structure. Using 178 marker{square}trait associations detected in genome-wide association analysis, a reference genotype-to-phenotype map was built for 39 morphological, developmental, and disease-resistance traits. A novel gene, auxin response factor 9 (Arf9), associated with wider leaves after being knocked out, was fine-mapped to a single nucleotide polymorphism (SNP). This point mutation alters the translated amino acid from Ala203 to Pro203, likely preventing homodimer formation during DNA binding. Our analysis also revealed signatures of positive and polygenic selection for multiple traits during the process of selective breeding. Overall, this study demonstrated the power of leveraging GenBank genomics to gain insights into the genomic features, genetic diversity, and regulation of complex traits in N. tabacum, laying a foundation for future research on plant functional genomics, crop breeding, and the production of biopharmaceuticals and biofuels.

genetics↗

bioRxiv2023

Defective mechanosensory transduction of the new inner hair cells prevents hearing recover in the damaged cochlea

ABSTRACTHearing loss is a major health problem worldwide. Numerous attempts at regenerating functional hair cells (HCs) have been unsuccessful, but little is known about the main barrier that prevents us from achieving it and improving the hearing ability after damage. Here, we developed an in vivo genetic mouse model, by which the inner HCs (IHCs), the primary sound receptors innervated by the auditory neurons, were specifically damaged and the neighboring nonsensory supporting cells (SCs) were transformed into IHCs by ectopic expression of transient Atoh1 and permanent Tbx2. Despite [~]477 new IHCs were regenerated per cochlea and their differentiation status was more advanced than reported previously, no significant hearing improvement was achieved. By taking advantage of this unique model, we further found that the new IHCs expressed the functional marker vGlut3, harbored the similar transcriptomic profiles and electrophysiological properties as the endogenous IHCs. However, the mechanosensory transduction (MET) current could not be recorded in the new IHCs. Thus, our study indicated that the defective MET should be the main barrier that stops us from restoring the hearing capacity in the damaged cochlea and would pave the way for regenerating IHCs in vivo.

neuroscience↗

bioRxiv2022

ExposomeX: Integrative Exposomic Platform Expediates Discovery of "Exposure-Biology-Disease" Nexus

Exposome has become the hotspot of next-generation health studies. To date, there is no available effective platform to standardize the analysis of exposomic data. In this study, we aim to propose one new framework of exposomic analysis and build up one novel integrated platform "ExposomeX" to expediate the discovery of the "Exposure-Biology-Disease" nexus. We have developed 13 standardized modules to accomplish six major functions including statistical learning (E-STAT), exposome database search (E-DB), mass spectrometry data processing (E-MS), meta-analysis (E-META), biological link via pathway integration and protein-protein interaction (E-BIO) and data visualization (E-VIZ). Using ExposomeX, we can effectively analyze the multiple-dimensional exposomics data and investigate the "Exposure-Biology-Disease" nexus by exploring mediation and interaction effects, understanding statistical and biological mechanisms, strengthening prediction performance, and automatically conducting meta-analysis based on well-established literature databases. The performance of ExposomeX has been well validated by re-analyzing two previous multi-omics studies. Additionally, ExposomeX can efficiently help discover new associations, as well as relevant in-depth biological pathways via protein-protein interaction and gene ontology network analysis. In sum, we have proposed a novel framework for standardized exposomic analysis, which can be accessed using both R and online interactive platform (http://www.exposomex.cn/).

bioinformatics↗

bioRxiv2022

Distinct super-enhancer elements differentially control Il2ra gene expression in a cell-type specific fashion

The IL-2 receptor -chain (IL-2R/CD25) is constitutively expressed on DN2/DN3 thymocytes and Treg cells but induced by IL-2 on mature T and NK cells. Il2ra expression is regulated by a super-enhancer extensively bound by STAT5 in mature T cells. Here, we demonstrate that STAT5 cooperates with Notch to induce/maintain Il2ra/CD25 expression in DN2/DN3 cells. Moreover, we systematically investigated CD25 regulation using a series of mice with deletions spanning STAT5 binding elements. Deleting the upstream super-enhancer region mainly affected constitutive CD25 expression on DN2/DN3 thymocytes and Tregs, whereas deleting an intronic region primarily decreased IL-2-induced CD25 on peripheral T and NK cells. Thus, distinct elements preferentially control constitutive versus inducible expression in a cell-type-specific manner, with the MED1 coactivator co-localizing with specific STAT5 binding sites. Moreover, the intronic region was a dominant element whose deletion altered the structure throughout the super-enhancer in mature T cells. These results demonstrate differential functions for distinct super-enhancer elements, thereby indicating ways to manipulate CD25 expression in a cell-type specific fashion.

immunology↗

bioRxiv2022

A Mechanistic Study on the Cellular Uptake, Intracellular Trafficking, and Antisense Gene Regulation of Bottlebrush Polymer-Conjugated Oligonucleotides

We have developed a non-cationic transfection vector in the form of a bottlebrush polymer-antisense oligonucleotide (ASO) conjugate. Termed pacDNA (polymer-assisted compaction of DNA), these agents show improved biopharmaceutical characteristics and antisense potency in vivo while suppressing non-antisense side effects. Nonetheless, there still lacks a mechanistic understanding regarding the cellular uptake, subcellular trafficking, and gene knockdown with pacDNA. Here, we show that the pacDNA enters human non-small cell lung cancer cells (NCI-H358) predominantly by scavenger receptor-mediated endocytosis and macropinocytosis, and trafficks via the endolysosomal pathway within the cell. The pacDNA significantly reduces a target gene expression (KRAS) in the protein level but not in the mRNA level, despite that the transfection of free ASOs causes ribonuclease H1 (RNase H)-dependent degradation of KRAS mRNA. In addition, the antisense activity of pacDNA is independent of ASO chemical modification, suggesting that the pacDNA functions as a steric blocker. TOC O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=148 SRC="FIGDIR/small/496353v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@56e08eorg.highwire.dtl.DTLVardef@1b09510org.highwire.dtl.DTLVardef@a785corg.highwire.dtl.DTLVardef@1641874_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2022

Development and Application of a Novel Simple Sequence Repeat Mining Algorithm Based on Regular Expression

Simple sequence repeats (SSRs) are molecular genetic markers that are powerful tools in genomics studies; SSR markers are routinely mined as a part of genetic workflows. Here, we developed a novel SSR mining algorithm based on regular expression that can reduce the complexity of commonly used SSR mining software. We used the following SSR mining regular expression: ({i, j}?) (\1) {k}, where i and j denote the minimum and maximum lengths of the motifs of the SSR sequence, respectively, and k is the minimum number of repeat motifs. From this SSR mining algorithm, we developed an SSR sequence analysis software (named "regexSSRw") that is capable of mining eligible SSR loci from FASTA format sequences; regexSSRw can be accessed at https://github.com/renm79/rgxSSRw. This SSR mining algorithm can aid a range of applications, from being used by programmers in the development of SSR mining software to being implemented by scholars into their SSR marker workflow.

bioinformatics↗

bioRxiv2022

Tbx2 is essential for cochlear inner hair cell development and regeneration

Atoh1 is essential for the development of outer hair cells (OHCs) and inner hair cells (IHCs) in the mammalian cochlea. Whereas Ikzf2 is necessary for OHC development, the key gene for IHC development remains unknown. We found that deleting Tbx2 in neonatal IHCs led to their trans-differentiation into OHCs, by repressing 26.7% of IHC and inducing 56.3% of OHC genes, including Ikzf2. More importantly, persistent expression of Tbx2 together with transient Atoh1 effectively reprogramed non-sensory supporting cells into new IHCs expressing functional IHC marker vGlut3. The differentiation status of these new IHCs is much more advanced than those previously reported. Thus, Tbx2 is essential for IHC development, and its co-upregulation with Atoh1 in supporting cells represents a new approach for treating IHC degeneration-related deafness.

developmental biology↗

bioRxiv2021

Dual expression of Atoh1 and Ikzf2 promotes transformation of adult cochlear supporting cells into outer hair cells

Mammalian cochlear outer hair cells (OHCs) are essential for hearing. OHC degeneration causes severe hearing impairment. Previous attempts of regenerating new OHCs from cochlear supporting cells (SCs) had yielded cells lacking Prestin, a key motor protein for OHC function. Thus, regeneration of Prestin+ OHCs remains a challenge for repairing OHC damage in vivo. Here, we reported that successful in vivo conversion of adult cochlear SCs into Prestin+ OHC-like cells could be achieved by simultaneous expression of Atoh1 and Ikzf2, two key transcriptional factors necessary for OHC development. New OHC-like cells exhibited upregulation of hundreds of OHC genes and downregulation of SC genes. Single cell transcriptomic analysis demonstrated that the differentiation status of these OHC-like cells was much more advanced than previously achieved. Thus, we have established an efficient approach to promote regeneration of Prestin+ OHCs and paved the way for repairing damaged cochlea in vivo via transdifferentiation of SCs.

developmental biology↗

bioRxiv2020

Genome Wide Characterization, Identification And Expression Analysis Of Erf Gene Family In Cotton

ERF is a subfamily of AP2/EREBP superfamily, contained single AP2 domain. The overexpression of ERF genes steered to abiotic stress tolerance and pathogen resistance in transgenic plants. Here, a genome-wide analysis of ERF gene family within two diploid species (G. arboreum & G. raimondii) and two tetraploid species (G. barbadense, G. hirsutum) was performed. A total of 118, 120, 213, 220 genes contained sequence single AP2 domain were identified in G. arboreum, G. raimondii, G. barbadense and G. hirsutum respectively. The identified genes were unevenly distributed across 13/26 chromosomes of A and D genomes of cotton. Genome comparison revealed that segmental duplication may have played crucial roles in the expansion of the cotton ERF gene family, and tandem duplication also played a minor role. Analysis of RNA-Seq data indicated that cotton ERF gene expression levels varied across different tissues and in response to different abiotic stress. Overall, our results could provide valuable information for better understanding the evolution of cotton ERF genes and lays a foundation for future investigation in cotton.

bioinformatics↗

bioRxiv2020

Transcriptome analysis of an albino mutant in Haworthia cooperi var. pilifera

Photosynthetic organisms appear green due to the accumulation of chlorophyll (Chl) pigments in their chloroplasts. Although the genes encoding key enzymes related to Chl biosynthesis have been well characterized in herbaceous plants, such as rice, Arabidopsis and maize, white leaf mutants have not yet been fully studied in succulent plants. In this work, we explored the molecular mechanism of leaf color formation in an albino mutant (HUA) of Haworthia cooperi var. pilifera. We investigated the differentially expressed genes (DEGs) between HUA and control plants (wild type, LV) by transcriptome sequencing. Approximately 2,586 genes (1,996 downregulated and 590 upregulated) were found to be differentially expressed in HUA compared with LV using a threshold of ratio change [≥] 2 and false discovery rate (FDR) [≤]0.05. GO analysis predicted that these DEGs participate in 12 cellular component, 20 biological process and 13 molecular function terms. Among the DEGs were well-recognized genes associated with chloroplast division and the biosynthesis of plant pigments, including chlorophyll, carotenoids and anthocyanin, as well as various transcription factor families. Overall, these results can help confirm the molecular regulatory mechanisms controlling leaf pigmentation and provide a comprehensive resource for breeding colorful leaf phenotypes in succulent plants.

genetics↗

bioRxiv2020

The Biogeography of Fungal Communities Across Different Chinese Wine-producing Regions Associated with Environmental Factors and Spontaneous Fermentation Performance

Chinese Marselan grapes are believed to possess the potential to become a characteristic regional variety, whose quality is internationally recognized. The fermentation-related mycobiota from six climatically diverse Marselan-producing regions in China were analyzed via high-throughput sequencing (HTS), while the influence of environmental factors was evaluated as well. The results implied that the phyla Ascomycota and genus Aureobasidium dominated the fungal communities in 166 Marselan must and ferment samples. Significant differences were detected in the fungal microbiota from the regions, as well as the wineries, while these discrepancies decreased as the fermentation progressed. Moreover, the difference in fungal communities between the wineries exceeded the variation involving the regions, and higher diversity was identified in the types of species than in the compositions. Geoclimatic elements (Gc) and physicochemical indexes (Pi) exerted a significant effect on the fungal must consortium, explaining 58.17% of the taxonomic information. Therefore, a correlation was proposed between the spontaneous fermentation performance, as well as the polyphenol (PP) content, and their association with fungal taxonomic composition. In addition to enriching the knowledge regarding the wine microbiome and its influencing factors, this study may provide a new strategy for harnessing autochthonous "microbial terroir". ImportanceWine microbiome and their metabolism play a crucial role in wine quality. Chinese wine-producing regions are widely distributed with diverse geoclimatic conditions, this study reports a most comprehensive biogeography of fermentation-related fungal communities performed to date, taking the Chinese promising Marselan grape variety as the research object. It reveals significant differences in the fungal microbiota of Marselan must and ferment from different regions and wineries, and higher otherness between species type than that between species composition. The study also reports the main geoclimatic and physicochemical factors shaping fungal flora. Moreover, a correlation was proposed among the spontaneous fermentation performance with fungal taxonomic composition and polyphenol content. Taken together, the results shed light on the wine fungal communities and its influencing factors, which is crucial for vineyard and fermentation microorganism management, and may also provide a new strategy for harnessing autochthonous "microbial terroir" by utilizing spontaneous fermentation.

microbiology↗