Distinct signatures of gut microbiota and metabolites in primary biliary cholangitis with poor biochemical response after ursodeoxycholic acid treatment.

BACKGROUND: About 1/3 of primary biliary cholangitis (PBC) patients suffered from poor response worldwide. And these patients present intestinal disturbances. We aimed to identify signatures of microbiota and metabolites in PBC patients with poor response, comparing to patients with response. METHODS: This study enrolled 25 subjects (14 PBC patients with response and 11 PBC patients with poor response). Metatranscriptomics and metabolomics analysis were carried out on their fecal. RESULTS: PBC patients with poor response had significant differences in the composition of bacteria, characterized by decreased Gemmiger etc. and increased Ruminococcus etc. The differential microbiota functions characterized by decreased abundance of elongation factor Tu and elongation factor G base on the KO database, as well as decreased abundance of Replicase large subunit etc. based on the SWISS-PROT database. PBC with poor response also had significant differences in 17 kinds of bacterial metabolites, characterized by decreased level of metabolites vital in bile acids metabolism pathway (L-Cysteine etc.) and the all-trans-Retinoic acid, a kind of immune related metabolite. The altered microbiota was associated with the differential expressed metabolites and clinical liver function indicators. 1 bacterial genera, 2 bacterial species and 9 metabolites simultaneously discriminated PBC with poor response from PBC with response with high accuracy. CONCLUSION: PBC patients with poor response exhibit unique changes in microbiota and metabolite. Gut microbiota and metabolite-based algorithms could be used as additional tools for differential prediction of PBC with poor prognosis.

The feasibility of using pathobiome strains as live biotherapeutic products for human use.

The evaluation of pathobiome strains should be conducted at the strain level, involving the identification of the functional genes, while considering the impact of ecological niche and drug interactions. The safety, efficacy, and quality management of live biotherapeutic products (LBPs), especially pathobiome strains, have certain peculiarities. Promising development methods include the recombinant LBP and active metabolites.

Identification and Validation of SLC9A2 as A Potential Tumor Suppressor in Colorectal Cancer: Integrating Bioinformatics Analysis with Experimental Confirmation.

OBJECTIVE: To uncover the mechanisms underlying the development of colorectal cancer (CRC), we applied bioinformatic analyses to identify key genes and experimentally validated their possible roles in CRC onset and progression. METHODS: We performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis on differentially expressed genes (DEGs), constructed a protein-protein interaction (PPI) network to find the top 10 hub genes, and analyzed their expression in colon adenocarcinoma (COAD) and rectum adenocarcinoma (READ). We also studied the correlation between these genes and immune cell infiltration and prognosis and validated the expression of SLC9A2 in CRC tissues and cell lines using qRT-PCR and Western blotting. Functional experiments were conducted in vitro to investigate the effects of SLC9A2 on tumor growth and metastasis. RESULTS: We found 130 DEGs, with 45 up-regulated and 85 down-regulated in CRC. GO analysis indicated that these DEGs were primarily enriched in functions related to the regulation of cellular pH, zymogen granules, and transmembrane transporter activity. KEGG pathway analysis revealed that the DEGs played pivotal roles in pancreatic secretion, rheumatoid arthritis, and the IL-17 signaling pathway. We identified 10 hub genes: CXCL1, SLC26A3, CXCL2, MMP7, MMP1, SLC9A2, SLC4A4, CLCA1, CLCA4, and ZG16. GO enrichment analysis showed that these hub genes were predominantly involved in the positive regulation of transcription. Gene expression analysis revealed that CXCL1, CXCL2, MMP1, and MMP7 were highly expressed in CRC, whereas CLCA1, CLCA4, SLC4A4, SLC9A2, SLC26A3, and ZG16 were expressed at lower levels. Survival analysis revealed that 5 key genes were significantly associated with the prognosis of CRC. Both mRNA and protein expression levels of SLC9A2 were markedly reduced in CRC tissues and cell lines. Importantly, SLC9A2 overexpression in SW480 cells led to a notable inhibition of cell proliferation, migration, and invasion. Western blotting analysis revealed that the expression levels of phosphorylated ERK (p-ERK) and phosphorylated JNK (p-JNK) proteins were significantly increased, whereas there were no significant changes in the expression levels of ERK and JNK following SLC9A2 overexpression. Correlation analysis indicated a potential link between SLC9A2 expression and the MAPK signaling pathway. CONCLUSION: Our study suggests that SLC9A2 acts as a tumor suppressor through the MAPK pathway and could be a potential target for CRC diagnosis and therapy.

Machine learning-based characterization of the gut microbiome associated with the progression of primary biliary cholangitis to cirrhosis.

BACKGROUND: Primary biliary cholangitis (PBC) is associated closely with the gut microbiota. This study aimed to explore the characteristics of the gut microbiota after the progress of PBC to cirrhosis. METHOD: This study focuses on utilizing the 16S rRNA gene sequencing method to screen for differences in gut microbiota in PBC patients who progress to cirrhosis. Then, we divided the data into training and verification sets and used seven different machine learning (ML) models to validate them respectively, calculating and comparing the accuracy, F1 score, precision, and recall, and screening the dominant intestinal flora affecting PBC cirrhosis. RESULT: PBC cirrhosis patients showed decreased diversity and richness of gut microbiota. Additionally, there are alterations in the composition of gut microbiota in PBC cirrhosis patients. The abundance of Faecalibacterium and Gemmiger bacteria significantly decreases, while the abundance of Veillonella and Streptococcus significantly increases. Furthermore, machine learning methods identify Streptococcus and Gemmiger as the predominant gut microbiota in PBC patients with cirrhosis, serving as non-invasive biomarkers (AUC = 0.902). CONCLUSION: Our study revealed that PBC cirrhosis patients gut microbiota composition and function have significantly changed. Streptococcus and Gemmiger may become a non-invasive biomarker for predicting the progression of PBC progress to cirrhosis.

Uric acid, high density lipoprotein cholesterol levels and their ratio are related to microbial enterotypes and serum metabolites in females with a blood stasis constitution.

BACKGROUND: Blood stasis constitution in traditional Chinese medicine (TCM) is believed to render individuals more susceptible to metabolic diseases. However, the biological underpinnings of this constitutional imbalance remain unclear. METHODS: This study explored the association between blood stasis constitution, serum metabolic markers including uric acid (UA), high-density lipoprotein cholesterol (HDLC), their ratio (UHR), serum metabolites, and gut microbiota. Clinical data, fecal and serum samples were acquired from 24 individuals with a blood stasis constitution and 80 individuals with a balanced constitution among healthy individuals from Guangdong. Gut microbiota composition analysis and serum metabolomics analysis were performed. RESULTS: Females with a blood stasis constitution had higher UA levels, lower HDLC levels, and higher UHR in serum, suggesting a higher risk of metabolic abnormalities. Analysis of the gut microbiome revealed two distinct enterotypes dominated by Bacteroides or Prevotella. Intriguingly, blood stasis subjects were disproportionately clustered within the Bacteroides-rich enterotype. Metabolomic analysis identified subtle differences between the groups, including lower phenylalanine and higher trimethylaminoacetone levels in the blood stasis. Several differential metabolites displayed correlations with HDLC, UA, or UHR, unveiling potential new markers of metabolic dysregulation. CONCLUSIONS: These findings elucidate the intricate interplay between host constitution, gut microbiota, and serum metabolites. The concept of blood stasis offers a unique perspective to identify subtle alterations in microbiome composition and metabolic pathways, potentially signaling underlying metabolic vulnerability, even in the presence of ostensibly healthy profiles. Continued investigation of this TCM principle may reveal critical insights into the early biological processes that foreshadow metabolic deterioration.

GWAS unravels acid phosphatase ACP2 as a photosynthesis regulator under phosphate starvation conditions through modulating serine metabolism in rice.

Inorganic phosphorus (Pi) deficiency significantly impacts plant growth, development, and photosynthetic efficiency. This study evaluated 206 rice accessions from a MiniCore population under both Pi-sufficient (Pi+) and Pi-starvation (Pi-) conditions in the field to assess photosynthetic phosphorus use efficiency (PPUE), defined as the ratio of AsatPi- to AsatPi+. A genome-wide association study and differential gene expression analyses identified an acid phosphatase gene (ACP2) that responds strongly to phosphate availability. Overexpression and knockout of ACP2 led to a 67% increase and 32% decrease in PPUE, respectively, compared with wild type. Introduction of an elite allele A, by substituting the v5 SNP G with A, resulted in an 18% increase in PPUE in gene-edited ACP2 rice lines. The phosphate-responsive gene PHR2 was found to transcriptionally activate ACP2 in parallel with PHR2 overexpression, resulting in an 11% increase in PPUE. Biochemical assays indicated that ACP2 primarily catalyzes the hydrolysis of phosphoethanolamine and phospho-L-serine. In addition, serine levels increased significantly in the ACP2v8G-overexpression line, along with a concomitant decrease in the expression of all nine genes involved in the photorespiratory pathway. Application of serine enhanced PPUE and reduced photorespiration rates in ACP2 mutants under Pi-starvation conditions. We deduce that ACP2 plays a crucial role in promoting photosynthesis adaptation to Pi starvation by regulating serine metabolism in rice.

Fine mapping identifies independent HLA associations in autoimmune hepatitis type 1.

Background & Aims: Association studies have greatly refined the important role of the major histocompatibility complex (MHC) region in autoimmune hepatitis (AIH). However, the effects of human leucocyte antigen (HLA) polymorphisms on AIH are not well established. The aim of this study is to systematically characterise the association of MHC variants with AIH in our well-defined cohort of patients. Methods: We performed an imputation-based analysis on the extensive association observed within the MHC region using the Han-MHC reference panel, and tested the comprehensive associations of HLA polymorphisms with AIH in 1622 Chinese AIH type 1 patients and 10,466 population controls. Results: A total of 588 HLA variants were significantly associated with AIH, with HLA-B∗35:01 (p = 8.17 × 10-304; odds ratio [OR] = 7.32) contributing the strongest signal. Stepwise conditional analysis revealed additional independent signals at HLA-B∗08:01 (p = 1.35 × 10-33; OR = 4.26) and rs7765379 (p = 5.08 × 10-18; OR = 1.66). A strong link between the lead HLA variant and clinical phenotypes of AIH was observed: patients with HLA-B∗35:01 were less frequently positive for ANA and tended to have higher serum AST and ALT levels at diagnosis, but lower serum IgG levels. Conclusions: Our study reveals three novel and independent variants at HLA-B∗35:01, HLA-B∗08:01, and rs7765379 associated with AIH across the whole MHC region in the Han Chinese population. The findings illustrate the value of the MHC region in AIH and provide a new perspective for the immunogenetics of AIH. Impact and implications: This study revealed three novel and independent variants associated with autoimmune hepatitis across the whole major histocompatibility complex region in the Han Chinese population. These findings are significant in identifying autoantigens, providing insights into the activation of the autoimmune processes, and further advancing our understanding of the immunogenetic basis underlying autoimmune hepatitis.

Photochemically induced chloromethylation/cyclization of benzimidazole derivatives with CCl4/CHCl3.

Herein, it is reported that a series of trichloromethyl/dichloromethyl substituted benzimidazole derivatives have been synthesized by dechlorination of CCl4/CHCl3 to form polychloromethyl radicals and cyclization with an unactivated olefin under a purple LED lamp. The protocol features a wide substrate scope, high atom economy, and excellent regioselectivity, and is easy to scale up.

Ralstonia solanacearum Suppresses Tomato Root Growth by Downregulation of a Wall-Associated Receptor Kinase.

The root architecture of a range of host plants is altered in response to Ralstonia solanacearum infection. This work aimed to identify host genes involved in root development during R. solanacearum infection. A deficient mutant of the type III secretion system regulator hrpB was created in R. solanacearum GMI1000. The hrpB mutant was impaired in virulence but showed a similar suppressive effect as wild-type GMI1000 on tomato root development. Based on comparative transcriptome analysis, 209 genes were found that showed the same changed expression pattern in GMI1000 and hrpB mutant infected roots relative to uninoculated roots. Among them, the wall-associated receptor kinase WAKL20 was substantially downregulated in GMI1000 and hrpB mutant infected roots. Knockdown of WAKL20 led to a shorter primary root length and fewer lateral roots in tomato as well as in Nicotiana benthamiana. The WAKL20 is a pivotal target suppressed by R. solanacearum to shape the altered root development during infection.

Handling multi-objective optimization problems with a comprehensive indicator and layered particle swarm optimizer.

The multi-objective particle swarm optimization algorithm has several drawbacks, such as premature convergence, inadequate convergence, and inadequate diversity. This is particularly true for complex, high-dimensional, multi-objective problems, where it is easy to fall into a local optimum. To address these issues, this paper proposes a novel algorithm called IMOPSOCE. The innovations for the proposed algorithm mainly contain three crucial factors: 1) an external archive maintenance strategy based on the inflection point distance and distribution coefficient is designed, and the comprehensive indicator (CM) is used to remove the non-dominated solutions with poor comprehensive performance to improve the convergence of the algorithm and diversity of the swarm; 2) using the random inertia weight strategy to efficiently control the movement of particles, balance the exploration and exploitation capabilities of the swarm, and avoid excessive local and global searches; and 3) offering different flight modes for particles at different levels after each update to further enhance the optimization capacity. Finally, the algorithm is tested on 22 typical test functions and compared with 10 other algorithms, demonstrating its competitiveness and outperformance on the majority of test functions.

Multi-objective particle swarm optimization with reverse multi-leaders.

Despite being easy to implement and having fast convergence speed, balancing the convergence and diversity of multi-objective particle swarm optimization (MOPSO) needs to be further improved. A multi-objective particle swarm optimization with reverse multi-leaders (RMMOPSO) is proposed as a solution to the aforementioned issue. First, the convergence strategy of global ranking and the diversity strategy of mean angular distance are proposed, which are used to update the convergence archive and the diversity archive, respectively, to improve the convergence and diversity of solutions in the archives. Second, a reverse selection method is proposed to select two global leaders for the particles in the population. This is conducive to selecting appropriate learning samples for each particle and leading the particles to quickly fly to the true Pareto front. Third, an information fusion strategy is proposed to update the personal best, to improve convergence of the algorithm. At the same time, in order to achieve a better balance between convergence and diversity, a new particle velocity updating method is proposed. With this, two global leaders cooperate to guide the flight of particles in the population, which is conducive to promoting the exchange of social information. Finally, RMMOPSO is simulated with several state-of-the-art MOPSOs and multi-objective evolutionary algorithms (MOEAs) on 22 benchmark problems. The experimental results show that RMMOPSO has better comprehensive performance.

Multivariate logistic regression analysis of clinical characteristics and risk factors of cognitive impairment after cerebral ischemic stroke: implications for clinical treatment.

Background: Stroke ranks first among disease fatalities, and those who do survive stroke are prone to cognitive impairment. The aim of this study was to explore the clinical characteristics of post stroke cognitive impairment (PSCI) and the risk factors of PSCI using multivariate logistic regression. Methods: January 2018 to January 2021, the clinical data of 120 patients treated for cerebral ischemic stroke (CIS) at Chengde Central Hospital were retrospectively analyzed. In this study, patients were divided into 2 groups: a control group and a cognitive impairment group. The clinical characteristics of cognitive impairment following CIS were determined using multivariate logistic regression analysis to examine the risk factors and identify clinical implications. Results: This study included the assessment of overall cognitive function and daily living activities of 120 participants, 68 of whom experienced cognitive impairment, representing an incidence of 57%, while 43% patients represented no cognitive impairment after CIS. After the careful analysis of the data, there were remarkable differences in age, sex, education level, stroke history, infarction area, and infarction location (P<0.05). There was no remarkable difference in the history of hypertension, diabetes, atrial fibrillation, carotid intima thickness, smoking, or drinking (P>0.05). The degree of white matter degeneration, brain atrophy, and dominant hemisphere involvement was higher in the cognitive impairment group (P<0.05). The results of multivariate logistic regression analysis indicated that sex, age, education level, stroke history, infarction size, and infarction location were the main risk factors for cognitive impairment after CIS (P<0.05). Conclusions: Patients with cognitive impairment after CIS have imaging features of white matter degeneration, brain atrophy, and involvement of dominant hemispheres. The results of multivariate logistic regression analysis indicated that sex, age, education level, stroke history, infarct size, and infarct location were main risk factors of cognitive impairment after CIS.

ZIC2 induces pro-tumor macrophage polarization in nasopharyngeal carcinoma by activating the JUNB/MCSF axis.

Nasopharyngeal carcinoma (NPC) is a common malignant epithelial tumor of the head and neck that often exhibits local recurrence and distant metastasis. The molecular mechanisms are understudied, and effective therapeutic targets are still lacking. In our study, we found that the transcription factor ZIC2 was highly expressed in NPC. Although ZIC family members play important roles in neural development and carcinogenesis, the specific mechanism and clinical significance of ZIC2 in the tumorigenesis and immune regulation of NPC remain elusive. Here, we first reported that high expression of ZIC2 triggered the secretion of MCSF in NPC cells, induced M2 polarization of tumor-associated macrophages (TAMs), and affected the secretion of TAM-related cytokines. Mechanistically, ChIP-seq and RNA-seq analyses identified JUNB as a downstream target of ZIC2. Furthermore, ZIC2 was significantly enriched in the promoter site of JUNB and activated JUNB promoter activity, as shown by ChIP-qPCR and luciferase assays. In addition, JUNB and MCSF participated in ZIC2-induced M2 TAMs polarization. Thus, blocking JUNB and MCSF could reverse ZIC2-mediated M2 TAMs polarization. Moreover, Kaplan-Meier survival analyses indicated that high expression of ZIC2, JUNB, and CD163 was positively associated with a poor prognosis in NPC. Overexpression of ZIC2 induced tumor growth in vivo, with the increase of JUNB, MCSF secretion, and CD163. In summary, our study implies that ZIC2 induces M2 TAM polarization, at least in part through regulation of JUNB/MCSF and that ZIC2, JUNB, and CD163 can be utilized as prognostic markers for NPC and as therapeutic targets for cancer immunotherapy.

EDIL3 and VEGF Synergistically Affect Angiogenesis in Endothelial Cells.

Background: Angiogenesis is one of the histologically predominant characteristics of psoriasis. Vascular endothelial growth factor (VEGF) and epidermal growth factor-like repeats and discoidin I-like domains 3 (EDIL3) have critical effects on angiogenesis. Both these proteins are vital proangiogenic factors in tumor occurrence and progression; however, the relationship between EDIL3 and VEGF with psoriasis remains unclear. Objective: We aimed to elucidate the role of EDIL3 and VEGF and the involved mechanisms in psoriasis-associated angiogenesis. Methods: EDIL3 and VEGF expression in cutaneous tissue was determined by immunohistochemical assay. The effects of EDIL3 on VEGF, VEGFR2, and the growth, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) were analyzed by Western blotting assay, cell counting kit-8 assay, Transwell assay, and Matrigel tube formation assay. Results: EDIL3 and VEGF levels in psoriatic lesions significantly increased as compared to those in normal individuals and showed a positive relationship with the Psoriasis Area and Severity Index. The downregulation of EDIL3 decreased VEGF and VEGFR2 expression in HUVECs. Moreover, the decreased expression of EDIL3 and VEGF reduced the growth, invasion, and tube formation abilities of HUVECs, while EDIL3 resistance to VEGF and VEGFR2 was restored by using the EDIL3 recombinant protein. Conclusion: These results suggest that psoriasis is also characterized by EDIL3 and VEGF-mediated angiogenesis. Thus, EDIL3 and VEGF could serve as novel targets for treating psoriasis.

Study of 43 SLE patients with autoimmune liver cirrhosis: emphasis on clinical features and differences from lupus without cirrhosis.

OBJECTIVE: To investigate the clinical characteristics of systemic lupus erythematosus accompanied by autoimmune liver cirrhosis (SLE-ALC) patients and differences from the non-cirrhosis group. METHODS: Forty-three patients with SLE-ALC were enrolled in this study from 2653 patients with SLE in Peking University People's Hospital. A descriptive case-control study was performed between SLE-ALC patients and the entry time-matched non-cirrhosis group. RESULTS: Among the 43 SLE-ALC patients, 41 (95.3%) were female. Eight patients (18.6%) were first found to have cirrhosis and then diagnosed with SLE. Eighteen patients (41.9%) had jaundice and 27 (62.8%) had esophageal and gastric varices. The age of SLE-ALC patients was 51.1 ± 17.2 years, which was significantly older than the non-cirrhosis group (P < 0.001). Lung involvement was more common as initial manifestations in SLE-ALC patients during the SLE course (P=0.027). Compared with the non-cirrhosis group, SLE-ALC patients had worse liver function. A significantly higher rate of hematological system involvement (anemia, leucopenia, and thrombocytopenia) and a higher level of immunoglobulins were observed in SLE-ALC patients (P<0.05). Moreover, SLE-ALC patients displayed a lower positive rate of anti-double-stranded DNA and anti-ribosomal P protein (P<0.05). The most common radiologic manifestations are ascitic fluid (72.1%) and splenomegaly (71.4%) in SLE-ALC patients. Six SLE-ALC patients underwent liver biopsy, and interface hepatitis was present in all patients. CONCLUSIONS: Cirrhosis is rare in SLE patients but is manifested as a unique pattern of clinical features characterized by late-onset age, lung involvement, high immunoglobulins, and impaired liver function.

MicroRNA-214-3p protects against myocardial ischemia-reperfusion injury by targeting demethylase lysine demethylase 3A.

Objective: Many studies have explored the roles of microRNAs (miRs) in myocardial ischemia/reperfusion injury (MI/RI), while the function of miR-214-3p in MI/RI remained obscure. This study aims to unravel the regulatory mechanism of miR-214-3p in MI/RI via targeting histone demethylase lysine demethylase 3A (KDM3A). Methods: MI/RI rat model was established by ligating the left anterior descending coronary artery. MiR-214-3p and KDM3A expression in myocardial tissues of MI/RI rats was examined. Then, the serum oxidative stress factors, inflammatory factors, pathological changes of myocardial tissues, cardiomyocyte apoptosis, and fibrosis of myocardial tissues were detected in MI/RI rats intervening with miR-214-3p or KDM3A expression. The targeting relation between miR-214-3p and KDM3A was validated. Results: MiR-214-3p was low-expressed while KDM3A was high-expressed in MI/RI rat model. Up-regulated miR-214-3p or down-regulated KDM3A protected against MI/RI via mitigating serum oxidative response, reducing the levels of inflammatory factors, alleviating the pathological changes of myocardial tissues, and decreasing cardiomyocyte apoptosis and fibrosis of myocardial tissue. KDM3A amplification reversed the therapeutic effects of elevated miR-214-3p on MI/RI. KDM3A was targeted by miR-214-3p. Conclusion: miR-214-3p hinders cardiomyocyte apoptosis and myocardial injury in MI/RI rats via regulating KDM3A. Thus, miR-214-3p may function as a potential candidate for MI/RI treatment.

Key Mutant Genes and Biological Pathways Involved in Aspirin Resistance in the Residents of the Chinese Plateau Area.

INTRODUCTION: Aspirin is used to prevent and treat cardiovascular diseases; however, some patients develop aspirin resistance. AIM: We aimed to explore the potential molecular mechanisms underlying aspirin resistance in people living in the Chinese plateau area. METHODS: In total, 91 participants receiving aspirin treatment from the Qinghai plateau area were divided into the aspirin resistance and aspirin sensitivity groups. Genotyping was performed using the Sequence MASSarray. Differentially mutated genes between the two groups were analyzed using MAfTools. The annotation of differentially mutated genes was conducted based on the Metascape database. RESULTS AND DISCUSSION: In total, 48 differential SNP and 22 differential InDel mutant genes between the aspirin resistance and aspirin sensitivity groups were screened using Fisher's exact test (P < 0.05). After the χ2 test, a total of SNP mutant genes, including ZFPL1 and TLR3, and 19 InDel mutant genes were found to be differentially expressed between the two groups (P < 0.05). Functional analysis revealed that these differential SNP mutations were mainly enriched in aspirin resistance pathways, such as the Wnt signaling pathway. Furthermore, these genes were related to many diseases, including various aspirin indications. CONCLUSION: This study identified several genes and pathways that could be involved in arachidonic acid metabolic processes and aspirin resistance progression, which will provide a theoretical understanding of the molecular mechanism of aspirin resistance.

[Sensitivity baseline establishment and resistance risk assessment of Botrytis cinerea from Panax ginseng to prochloraz].

This study aimed to establish the baseline sensitivity of Botrytis cinerea from Panax ginseng to prochloraz, and ensure the fitness of prochloraz-resistant mutants and the cross-resistance of B. cinerea to prochloraz and commonly used fungicides for the prevention and control of gray mold including boscalid, pyraclostrobin, iprodione, and pyrimethanil. The sensitivity of B. cinerea from P. ginseng to fungicides was determined by the mycelial growth rate method. The prochloraz-resistant mutants were screened out through fungicide domestication and ultraviolet(UV) induction. The fitness of resistant mutants was determined through the stability of subculture, mycelial growth rate, and pathogenicity test. The cross-resistance between prochloraz and the four fungicides was determined by Person correlation analysis. The results showed that all B. cinerea strains tested were sensitive to prochloraz, and the EC_(50) value ranged from 0.004 8 to 0.062 9 µg·mL~(-1), with an average of 0.022 µg·mL~(-1). The sensitivity frequency distribution diagram showed that 89 B. cinerea strains were located within the main peak with a continuous single peak curve, and the average EC_(50) value of 0.018 µg·mL~(-1) was taken as the baseline sensitivity of B. cinerea to prochloraz. The fungicide domestication and UV induction obtained 6 resistant mutants, among which 2 strains were unstable and the other 2 strains showed decreased resistance after multiple generations of culture. Furthermore, the mycelial growth rate and spore yield of all resistant mutants were lower than those of their parents, and the pathogenicity of most mutants was lower than that of their parents. In addition, prochloraz had no obvious cross-resistance with boscalid, pyraclostrobin, iprodione, and pyrimethanil. In conclusion, prochloraz has great potential for controlling gray mold in P. ginseng, and the resistance risk of B. cinerea to prochloraz is low.