Publications by authors named "J Li"

139,895 Publications

Sequencing of the gene in a cohort of infertile Chinese men reveals novel mutations in patients with teratozoospermia.

J Med Genet 2022 Aug 16. Epub 2022 Aug 16.

Department of Obstetrics/Gynecology, Joint Laboratory of Reproductive Medicine (SCU-CUHK), Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China

Background: The information of in human reproduction is very limited, resulting in the unclear link between variants and male infertility.

Methods: Whole exome sequencing and Sanger sequencing to identify the potential pathogenic variation of in infertile men, Papanicolaou staining and electron microscopy to investigate the spermatozoa morphology, western blotting and immunofluorescence staining to confirm the pathogenicity of the identified variants, and proteomic analysis and coimmunoprecipitation to clarify the potential molecular mechanism.

Results: A total of 31 variants were identified in 227 infertile patients. Three deleterious biallelic variants, including a novel compound heterozygous variant of c.1105delG (p.A369Qfs*15) and c.1853T>C (p.F618S), a new homozygous splicing mutation of c.1297+5G>A and a reported homozygous nonsense mutation of c.1209T>A (p.Y403*), were detected in three affected individuals with oligoasthenoteratozoospermia, showing a biallelic pathogenic mutation frequency of 1.3% (3/227). No biallelic pathogenic mutation was found in 692 fertile men. Morphology analysis showed abnormalities in sperm morphology in the patients harbouring mutations. Western blotting and immunofluorescence staining confirmed the nearly absent ZMYND15 expression in the sperm of the patients. Mechanistically, ZMYND15 might regulate spermatogenesis by interacting with key molecules involved in sperm development, such as DPY19L2, AKAP4 and FSIP2, and might also mediate the expression of the autophagy-associated protein SPATA33 to maintain sperm individualisation and unnecessary cytoplasm removal.

Conclusion: Our findings broaden the variant and phenotype spectrum of in male infertility, and reveal the potential signalling pathway of ZMYND15 regulating spermatogenesis, finally confirming the essential role of in human fertility.
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http://dx.doi.org/10.1136/jmg-2022-108727DOI Listing
August 2022

SDH mutations confer complex cross-resistance patterns to SDHIs in Corynespora cassiicola.

Pestic Biochem Physiol 2022 Aug 28;186:105157. Epub 2022 Jun 28.

Shandong Provincial Key Laboratory for the Biology of Vegetable Diseases and Insect Pests, College of Plant Protection, Shandong Agricultural University, 61 Daizong Street, Tai'an, Shandong 271018, China; Key Laboratory of Pesticide Toxicology and Application Technique, College of Plant Protection, Shandong Agricultural University, 61 Daizong Street, Tai'an, Shandong 271018, China. Electronic address:

Succinate dehydrogenase inhibitors (SDHIs) are one of the most frequently used fungicides in cucumber fields in China. Our previous studies indicated that the sensitivity profile of Corynespora cassiicola, the causal agent of Corynespora leaf spot, to different SDHIs varied greatly; however, the underlying mechanism remains unclear. The 50% effective concentration (EC) values of boscalid, fluopyram, fluxapyroxad and isopyrazam in C. cassiicola collected from 2017 to 2020 shifted, with resistance frequencies of 79.83%, 78.43%, 83.19% and 49.86%, respectively. The sequence alignment of sdhB/C/D of resistant strains revealed that eight single amino acid mutations (B-H278Y/L, B-I280V, C-S73P, C-N75S, C-H134R, D-D95E and D-G109V), and three dual-mutations (B-I280V&C-S73P, B-I280V&C-N75S and C-S73P&C-N75S) conferred various SDHI resistance levels and cross-resistance profiles. The expression level of the sdhB/C/D gene and succinate dehydrogenase (SDH) activity in the mutants were significantly altered by the presence of SDHIs, compared with the wild type strain. Additionally, molecular docking results suggested that the missense mutation influenced the crystal structure of SDH and subsequently interfered with the interaction bonds and bond distances among the target protein and chemicals. In brief, amino acid mutations altered the fungicide response of target gene expression, SDH activity and the binding features of SDH-ligand complexes and subsequently conferred multiple resistance levels and complex cross-resistance patterns to SDHIs in C. cassiicola. The evaluation of C. cassiicola resistance to SDHIs provided a significant foundation for efficient chemical development and integrated CLS management strategies.
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http://dx.doi.org/10.1016/j.pestbp.2022.105157DOI Listing
August 2022

A novel naturally Phe206Tyr mutation confers tolerance to ALS-inhibiting herbicides in Alopecurus myosuroides.

Pestic Biochem Physiol 2022 Aug 29;186:105156. Epub 2022 Jun 29.

Weed Science Department, Institute of Plant Protection, Shandong Academy of Agricultural Sciences, No. 202 of Gongye North Road, Jinan 250100, China. Electronic address:

Herbicide-resistant weeds pose a serious threat to world food production. The rapid and widespread development of target-site based resistance limits the application of herbicides. Alopecurus myosuroides Huds. (blackgrass) has spread rapidly in winter wheat regions in China, and the field recommended dose of ALS herbicides no longer controls blackgrass populations in recent years. A highly resistant population TW18(R) was collected in 2018 from Shandong Province. Dose-response assays showed that the TW18 was resistant to mesosulfuron-methyl, flucarbazone-sodium, and imazethapyr, with resistance index values of 5.96, 6.1, and 4.09, respectively. DNA sequencing of the TW18 population revealed a Phe206Tyr (F206Y) mutation in the ALS, which was not yet reported. Blackgrass ALS gene with the F206Y mutation (R gene) was expressed in Arabidopsis and rice. Transgenic studies have shown that both Arabidopsis and rice expressing this R gene have resistance to imazethapyr. However, it did not confer resistance to tribenuron methyl and florasulam in transgenic Arabidopsis. This study showed that the F206Y substitution caused herbicide resistance in blackgrass. To our knowledge, this is the first-reported F206Y mutation of a weed species in the natural environment. Transgenic plants showed this functional site could be utilized to generate imazethapyr-resistant rice to control herbicide-resistant weed damage.
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http://dx.doi.org/10.1016/j.pestbp.2022.105156DOI Listing
August 2022

A novel dibenzofuran from endophytic fungus Mycosphaerella nawae preferentially inhibits CD4 T cell activation and proliferation.

J Appl Microbiol 2022 Aug 16. Epub 2022 Aug 16.

School of Basic Medical Sciences & Forensic Medicine, Hangzhou Medical College, 310053, Hangzhou, China.

Aim: To obtain promising immunosuppressants from endophytic fungus.

Methods And Results: The endophytic fungus Mycosphaerella nawae (ZJLQ129) was isolated from the plant Smilax china L. and its secondary metabolites extracted and fractionated through column chromatography. The metabolites were further modified by a derivatization reaction with ammonium hydroxide. After isolation and derivatization, a new dibenzofuran named as (+)isomycousnine enamine (iME) was obtained. The structures of the derivatives were determined based on chemical evidences and extensive spectroscopic methods including 2D-NMR, DEPT and HRESI-MS spectra. The immune activities of iME were first evaluated on the proliferation and cytokines (IL-2 and IFN-γ) production of T and B cells by using MTT and ELISA methods, respectively. Then, its effects on the proliferation of T cell subsets (CD4 and CD8 T cells), as well as CD25 and CD69 expressions were also determined by flow cytometry. Finally, by using Cytometric Bead Array (CBA), the impacts of iME on the secretion of Th1/Th2/Th17 cytokines from purified CD4 T cells were assayed. The results showed that iME not only selectively suppressed the immune responses of T cells, but also preferentially inhibited the activation and proliferation of CD4 T cells.

Conclusion: A novel dibenzofuran derived from endophytic fungus Mycosphaerella nawae preferentially inhibits CD4 T cell activation and proliferation.

Significance And Impact Of The Study: This work obtained iME, a new dibenzofuran derived from endophytic fungus. iME has the capacity to inhibit CD4 T cell activation and therefore is a novel potential immunosuppressant for development in the future.
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http://dx.doi.org/10.1111/jam.15782DOI Listing
August 2022

Cardiac Substructures Dosimetric Predictors for Cardiac Toxicity After Definitive Radiotherapy in Esophageal Cancer.

Int J Radiat Oncol Biol Phys 2022 Aug 13. Epub 2022 Aug 13.

Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China; Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China. Electronic address:

Purpose: To investigate the predictive value of the cardiac substructures (CS) dosimetric parameters for cardiac toxicity after definitive radiotherapy in locally advanced esophageal cancer.

Methods And Materials: Between August 2010 and January 2016, 716 patients with stage II-III esophageal cancer receiving definitive radiotherapy at two institutions were divided into the training (n = 432) and external validation cohorts (n = 284). Dose-volume histogram parameters for the whole heart (WH) and CSs were extracted. Competing risks and Cox regressions analyses were performed. The predictive performance of the models was evaluated using the area under the receiver operating characteristic curve (AUC) and Brier score.

Results: With a median follow-up of 93 months, 68 patients (15.7%) developed grade ≥ 3 cardiac events (G3+ CEs), at a median of 13.5 months to first event. Multivariable analysis showed left ventricle (LV), left anterior descending (LAD), and mean left circumflex (LCX) variables were significantly associated with G3+ CEs. The AUCs and Brier scores demonstrated favorable predictive accuracies of the models integrating these CS variables when predicting G3+ CEs in the training and validation cohorts. However, compared to the WH variables, the CS variables did not significantly improve the prediction of G3+ CEs. Nevertheless, when G3+ acute coronary syndrome/congestive heart failure (ACS/CHF) CE was the outcome of interest, models based on the LAD or LCX variables were superior to the WH variable models in training and validation cohorts.

Conclusions: Models based on CSs variables showed favorable predictive accuracy for G3+ CEs. The LAD and LCX variables significantly improved the prediction of G3+ ACS/CHF events compared to the WH variables. Radiation doses to CSs, such as LCX and LAD, should be monitored to help reduce the occurrence of significant CEs in patients with esophageal cancer undergoing definitive radiotherapy.
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http://dx.doi.org/10.1016/j.ijrobp.2022.08.013DOI Listing
August 2022
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