Publications by authors named "Ling Ma"

458 Publications

Melatonin regulates the cross-talk between autophagy and apoptosis by SIRT3 in testicular Leydig cells.

Biochem Biophys Res Commun 2021 Apr 3;555:182-189. Epub 2021 Apr 3.

Reproductive Medicine Center, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, PR China; Clinical Medicine Research Center of Prenatal Diagnosis and Birth Health in Hubei Province, Wuhan, 430071, Hubei, PR China. Electronic address:

Autophagy and apoptosis, as major modes of cell death, play critical roles in cellular homeostasis. Our previous study demonstrated that the cross-talk between autophagy and apoptosis regulated cadmium-induced testicular injury and self-recovery, influencing male fertility. However, the underlying mechanism remains blurry. Herein, our subfertility rat model indicated that cadmium-induced autophagy and apoptosis were ameliorated by the activation of SIRT3 and blunted by the inhibition of SIRT3 in rat testis. Further, generating SIRT3 overexpression and knockdown models in TM3 mouse Leydig cells, we found that melatonin (SIRT3 activator) and overexpression of SIRT3 rescued cadmium-induced autophagy and apoptosis in TM3 cells. Knockdown of SIRT3 induced autophagy and apoptosis, which failed to be reversed by melatonin in TM3 cells. Taken together, SIRT3 functions as a pivotal protective factor in testicular Leydig cells injury, and melatonin regulates the cross-talk between autophagy and apoptosis by SIRT3, ameliorating cadmium-induced testicular injury.
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http://dx.doi.org/10.1016/j.bbrc.2021.03.138DOI Listing
April 2021

Exact acceleration of complex real-time model checking based on overlapping cycle.

PeerJ Comput Sci 2020 4;6:e272. Epub 2020 May 4.

School of Information Engineering, Zhengzhou University, Zhengzhou, Henan, China.

When real-time systems are modeled as timed automata, different time scales may lead to substantial fragmentation of the symbolic state space. Exact acceleration solves the fragmentation problem without changing system reachability. The relatively mature technology of exact acceleration has been used with an appended cycle or a parking cycle, which can be applied to the calculation of a single acceleratable cycle model. Using these two technologies to develop a complex real-time model requires additional states and consumes a large amount of time cost, thereby influencing acceleration efficiency. In this paper, a complex real-time exact acceleration method based on an overlapping cycle is proposed, which is an application scenario extension of the parking-cycle technique. By comprehensively analyzing the accelerating impacts of multiple acceleratable cycles, it is only necessary to add a single overlapping period with a fixed length without relying on the windows of acceleratable cycles. Experimental results show that the proposed timed automaton model is simple and effectively decreases the time costs of exact acceleration. For the complex real-time system model, the method based on an overlapping cycle can accelerate the large scale and concurrent states which cannot be solved by the original exact acceleration theory.
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http://dx.doi.org/10.7717/peerj-cs.272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924618PMC
May 2020

Generation of an induced pluripotent stem cell line from a patient with global development delay carrying DYRK1A mutation (c.1730T>A) and a gene correction isogenic iPSC line.

Stem Cell Res 2021 Mar 20;53:102305. Epub 2021 Mar 20.

Stem Cell Research Center, Institute of Pediatrics, Children's Hospital, Fudan University, 399 Wanyuan Road, Shanghai 201102, China; Key Laboratory of Birth Defects, Children's Hospital of Fudan University, Shanghai, China. Electronic address:

Mental retardation autosomal dominant 7 (MRD7), or DYRK1A Related Intellectual Disability Syndrome (OMIM 614104) is a developmental syndrome with microcephaly, intellectual disability, language delay and epileptic seizures. Haploinsufficiency of DYRK1A is the cause of MRD7. Here, we generated an induced pluripotent stem cell (iPSC) line with the mutation (DYRK1Ac.1730T>A) from the Peripheral blood mononuclear cell (PBMC) of a MRD7 patient along with an isogenic gene-corrected control iPSC line by CRISPR/Cas9 genome editing. Both iPSC lines showed full pluripotency, normal karyotype and differentiation capacity without integrating vectors. These DYRK1A mutant and isogenic gene-corrected iPSC control line provides a useful model to study the underlying molecular mechanisms of MRD7.
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http://dx.doi.org/10.1016/j.scr.2021.102305DOI Listing
March 2021

Efficiency and safety: comparison between preoperative analgesia and postoperative analgesia using non-steroidal anti-inflammatory drugs in patients receiving arthroscopic knee surgery in a multicenter, randomized, controlled study.

Inflammopharmacology 2021 Apr 2. Epub 2021 Apr 2.

Department of Anesthesiology, Daqing Oilfield General Hospital, No. 9 Zhongkang Road, Sartu District, Daqing, 163001, China.

Background: This study aimed to compare the efficiency regarding postoperative pain control, consumption of rescue drug, patients' satisfaction and the safety of preoperative analgesia versus postoperative analgesia using non-steroidal anti-inflammatory drugs (NSAIDs) in patients who received arthroscopic knee surgery (AKS).

Methods: Four hundred and sixty-four patients who received AKS were recruited in this multicenter, randomized, controlled study. Subsequently, they were randomized into PRE group (N = 232) and POST group (N = 232). In PRE group, patients received celecoxib, meloxicam or rofecoxib from 2 h pre-operation (Pre (- 2 h)) to 48 h post-operation for analgesia. In POST group, patients received celecoxib, meloxicam or rofecoxib from 4 to 48 h post-operation for analgesia.

Results: h and 12 h; pain VAS at passive movement was reduced in PRE group than POST group at 6 h, 12 h and 24 h. Additionally, consumption of rescue drug (pethidine) was decreased, while overall satisfaction was increased in PRE group compared to POST group. As for adverse events, the incidences of nausea, vomiting, constipation, drowsiness and dizziness were similar between PRE group and POST group. In subgroup analysis, the pain VAS score at passive movement at 6 h and nausea and constipation incidences were distinctive among subgroups categorized by meloxicam, celecoxib and rofecoxib administration. However, no difference of other assessments was found among subgroups categorized by meloxicam, celecoxib and rofecoxib administration.

Conclusion: Preoperative analgesia using NSAIDs is more efficient and equivalently tolerable compared to postoperative analgesia using NSAIDs in patients who receive AKS.
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http://dx.doi.org/10.1007/s10787-021-00792-0DOI Listing
April 2021

MicroRNA-23a-5p regulates cell proliferation, migration and inflammation of TNF-α-stimulated human fibroblast-like MH7A synoviocytes by targeting TLR4 in rheumatoid arthritis.

Exp Ther Med 2021 May 12;21(5):479. Epub 2021 Mar 12.

Department of Rheumatology and Immunology, Southwest Medical University Affiliated Hospital, Luzhou, Sichuan 646000, P.R. China.

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial joint inflammation. RA synovial fibroblasts (RASFs) constitute a major cell subset of the RA synovia. MicroRNAs (miRNAs/miRs) have been reported to serve a role in the activation and proliferation of RASFs. The present study aimed to investigate the effects and underlying mechanisms of miR-23a-5p on RA progression. Peripheral blood was collected from patients with RA (n=20) to analyze the expression levels of miR-23a-5p. The effects of miR-23a-5p on cell apoptosis, proliferation and migration in MH7A cells were determined in TNF-α-treated human fibroblast-like synoviocytes (MH7A cells) by flow cytometry, colony formation assay and Transwell assay, respectively. The cell cycle distribution was evaluated using flow cytometry. The binding relationship between miR-23a-5p and toll-like receptor (TLR) 4 was analyzed using a dual luciferase reporter gene assay. ELISA and reverse transcription-quantitative PCR assays were used to detect the levels of the inflammatory factors IL-6, IL-1β and IL-10. The expression levels of apoptosis- and migration-related proteins were analyzed using western blotting. The results of the present study revealed that the expression levels of miR-23a-5p were significantly downregulated in the plasma of patients with RA and in MH7A cells. In addition, the TNF-α-induced increase in the cell proliferative and migratory rates and the production of IL-6 and IL-1β were markedly inhibited following miR-23a-5p overexpression. The TNF-α-induced decreases in MH7A cell apoptosis were also reversed following miR-23a-5p overexpression. Additionally, transfection with miR-23a-5p mimics significantly inhibited the activation of the TLR4/NF-κB signaling pathway in TNF-α-treated MH7A cells by targeting TLR4. Notably, TLR4 overexpression weakened the effects of miR-23a-5p mimic on cell proliferation, apoptosis, migration, inflammation and the TLR4/NF-κB signaling pathway in TNF-α-induced MH7A cells. In conclusion, the findings of the present study indicated that the miR-23a-5p/TLR4/NF-κB axis may serve as a promising target for RA diagnosis and treatment.
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http://dx.doi.org/10.3892/etm.2021.9910DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7976437PMC
May 2021

Population exposure-efficacy and exposure-safety analyses for rucaparib in patients with recurrent ovarian carcinoma from Study 10 and ARIEL2.

Gynecol Oncol 2021 Mar 19. Epub 2021 Mar 19.

Clinical Pharmacology, Clovis Oncology, Inc., Boulder, CO, USA.

Objective: To evaluate correlations between rucaparib exposure and selected efficacy and safety endpoints in patients with recurrent ovarian carcinoma using pooled data from Study 10 and ARIEL2.

Methods: Efficacy analyses were limited to patients with carcinomas harboring a deleterious BRCA1 or BRCA2 mutation who had received ≥2 prior lines of chemotherapy. Safety was evaluated in all patients who received ≥1 rucaparib dose. Steady-state daily area under the concentration-time curve (AUC) and maximum concentration (C) for rucaparib were calculated for each patient and averaged by actual dose received over time (AUC and C) using a previously developed population pharmacokinetic model.

Results: Rucaparib exposure was dose-proportional and not associated with baseline patient weight. In the exposure-efficacy analyses (n = 121), AUC was positively associated with independent radiology review-assessed RECIST response in the subgroup of patients with platinum-sensitive recurrent disease (n = 75, p = 0.017). In the exposure-safety analyses (n = 393, 40 mg once daily to 840 mg twice daily [BID] starting doses), most patients received a 600 mg BID rucaparib starting dose, with 27% and 21% receiving 1 or ≥2 dose reductions, respectively. C was significantly correlated with grade ≥2 serum creatinine increase, grade ≥3 alanine transaminase/aspartate transaminase increase, platelet decrease, fatigue/asthenia, and maximal hemoglobin decrease (p < 0.05).

Conclusion: The exposure-response analyses provide support for the approved starting dose of rucaparib 600 mg BID for maximum clinical benefit with subsequent dose modification only following the occurrence of a treatment-emergent adverse event in patients with BRCA-mutated recurrent ovarian carcinoma.
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http://dx.doi.org/10.1016/j.ygyno.2021.03.015DOI Listing
March 2021

The CREB Regulated Transcription Coactivator 2 Suppresses HIV-1 Transcription by Preventing RNA Pol II from Binding to HIV-1 LTR.

Virol Sin 2021 Mar 15. Epub 2021 Mar 15.

Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical School, Beijing, 100050, China.

The CREB-regulated transcriptional co-activators (CRTCs), including CRTC1, CRTC2 and CRTC3, enhance transcription of CREB-targeted genes. In addition to regulating host gene expression in response to cAMP, CRTCs also increase the infection of several viruses. While human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) promoter harbors a cAMP response element and activation of the cAMP pathway promotes HIV-1 transcription, it remains unknown whether CRTCs have any effect on HIV-1 transcription and HIV-1 infection. Here, we reported that CRTC2 expression was induced by HIV-1 infection, but CRTC2 suppressed HIV-1 infection and diminished viral RNA expression. Mechanistic studies revealed that CRTC2 inhibited transcription from HIV-1 LTR and diminished RNA Pol II occupancy at the LTR independent of its association with CREB. Importantly, CRTC2 inhibits the activation of latent HIV-1. Together, these data suggest that in response to HIV-1 infection, cells increase the expression of CRTC2 which inhibits HIV-1 gene expression and may play a role in driving HIV-1 into latency.
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http://dx.doi.org/10.1007/s12250-021-00363-1DOI Listing
March 2021

Narrative review of stem cell therapy for ischemic brain injury.

Transl Pediatr 2021 Feb;10(2):435-445

Stem Cell Research Center, Institute of Pediatrics, Children's Hospital, Fudan University, Shanghai, China.

Ischemic brain injury is a common cause of long-term neurological deficits in children as well as adults, and no efficient treatments could reverse the sequelae in clinic till now. Stem cells have the capacity of self-renewal and multilineage differentiation. The therapeutic efficacy of stem cell transplantation for ischemic brain injury have been tested for many years. The grafts could survive and mature in the ischemic brain environment. Stem cell transplantation could improve functional recovery of ischemic brain injury models in pre-clinical trials. The potential mechanisms included cell replacement, release of neurotrophic and anti-inflammatory factors, immunoregulation as well as activation of endogenous neurogenesis. Besides, many clinical trials were conducted and some of trials already had preliminary results. From the current published data, cell transplantation for clinical application is safe and feasible. No severe adverse events and tumorigenesis were reported. While the therapeutic efficacy of stem cell therapy in clinic still needs more evidences. In this review, we overviewed the studies about stem cell therapy for ischemic brain injury. Different types of stem cells used for transplantation as well as the therapeutic mechanisms were discussed in detail. The related pre-clinical and clinical trials were summarized into two separate tables. In addition, we also discussed the unsolved problems and concerns about stem cell therapy for ischemic brain injury that need to be overcome before clinic transformation.
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http://dx.doi.org/10.21037/tp-20-262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944170PMC
February 2021

Regorafenib-Attenuated, Bleomycin-Induced Pulmonary Fibrosis by Inhibiting the TGF-β1 Signaling Pathway.

Int J Mol Sci 2021 Feb 17;22(4). Epub 2021 Feb 17.

State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300353, China.

Idiopathic pulmonary fibrosis (IPF) is a fatal and age-related pulmonary disease. Nintedanib is a receptor tyrosine kinase inhibitor, and one of the only two listed drugs against IPF. Regorafenib is a novel, orally active, multi-kinase inhibitor that has similar targets to nintedanib and is applied to treat colorectal cancer and gastrointestinal stromal tumors in patients. In this study, we first identified that regorafenib could alleviate bleomycin-induced pulmonary fibrosis in mice. The in vivo experiments indicated that regorafenib suppresses collagen accumulation and myofibroblast activation. Further in vitro mechanism studies showed that regorafenib inhibits the activation and migration of myofibroblasts and extracellular matrix production, mainly through suppressing the transforming growth factor (TGF)-β1/Smad and non-Smad signaling pathways. In vitro studies have also indicated that regorafenib could augment autophagy in myofibroblasts by suppressing TGF-β1/mTOR (mechanistic target of rapamycin) signaling, and could promote apoptosis in myofibroblasts. In conclusion, regorafenib attenuates bleomycin-induced pulmonary fibrosis by suppressing the TGF-β1 signaling pathway.
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http://dx.doi.org/10.3390/ijms22041985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922359PMC
February 2021

Transcriptional networks identify synaptotagmin-like 3 as a regulator of cortical neuronal migration during early neurodevelopment.

Cell Rep 2021 Mar;34(9):108802

Stem Cell Center, Children's Hospital of Fudan University, Shanghai 201102, China. Electronic address:

Human brain development is a complex process involving neural proliferation, differentiation, and migration that are directed by many essential cellular factors and drivers. Here, using the NetBID2 algorithm and developing human brain RNA sequencing dataset, we identify synaptotagmin-like 3 (SYTL3) as one of the top drivers of early human brain development. Interestingly, SYTL3 exhibits high activity but low expression in both early developmental human cortex and human embryonic stem cell (hESC)-derived neurons. Knockout of SYTL3 (SYTL3-KO) in human neurons or knockdown of Sytl3 in embryonic mouse cortex markedly promotes neuronal migration. SYTL3-KO causes an abnormal distribution of deep-layer neurons in brain organoids and reduces presynaptic neurotransmitter release in hESC-derived neurons. We further demonstrate that SYTL3-KO-accelerated neuronal migration is modulated by high expression of matrix metalloproteinases. Together, based on bioinformatics and biological experiments, we identify SYTL3 as a regulator of cortical neuronal migration in human and mouse developing brains.
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http://dx.doi.org/10.1016/j.celrep.2021.108802DOI Listing
March 2021

A Complete Genome Sequence of the Wood Stem Endophyte BY6 Strain Possessing Plant Growth-Promoting and Antifungal Activities.

Biomed Res Int 2021 30;2021:3904120. Epub 2021 Jan 30.

Heilongjiang Provincial Key Laboratory of Forest Sustainable Management and Environmental Microbial Engineering, Northeast Forestry University, Harbin 150040, China.

An endophytic bacterium BY6 was isolated from the wood stems of healthy  ×  var. (PdPap). The BY6 strain can inhibit pathogenic fungus in PdPap and promote growth of PdPap seedlings. In the present study, we used the Pacific Biosciences long-read sequencing platform, a single-molecule real-time (SMRT) technology for strain BY6, to perform complete genome sequencing. The genome size was 3,898,273 bp, the number of genes was 4,045, and the average GC content was 47.33%. A complete genome of strain BY6 contained 110 secondary metabolite gene clusters. Nine of the secondary metabolite gene clusters exhibited antifungal activity and promoted growth functions primarily involved in the synthesis of surfactin, bacteriocins, accumulated iron ions, and related antibiotics. Gene clusters provide genetic resources for biotechnology and genetic engineering, and enhance understanding of the relationship between microorganisms and plants.
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http://dx.doi.org/10.1155/2021/3904120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869414PMC
January 2021

Conditioned medium from primary cytotrophoblasts, primary placenta-derived mesenchymal stem cells, or sub-cultured placental tissue promoted HUVEC angiogenesis in vitro.

Stem Cell Res Ther 2021 Feb 17;12(1):141. Epub 2021 Feb 17.

Department of Pathophysiology, College of Basic Medical Science, China Medical University, No.77, Puhe Road, Shenyang North New Area, Shenyang, 110122, Liaoning Province, China.

Background: As a large capillary network, the human placenta plays an important role throughout pregnancy. Placental vascular development is complex and delicate and involves many types of placental cells, such as trophoblasts, and mesenchymal stem cells. There has been no systematic, comparative study on the roles of these two groups of placental cells and the whole placental tissue in the placental angiogenesis. In this study, primary cytotrophoblasts (CTBs) from early pregnancy and primary human placenta-derived mesenchymal stem cells (hPDMSCs) from different stages of pregnancy were selected as the cell research objects, and full-term placental tissue was selected as the tissue research object to detect the effects of their conditioned medium (CM) on human umbilical vein endothelial cell (HUVEC) angiogenesis.

Methods: We successfully isolated primary hPDMSCs and CTBs, collected CM from these placental cells and sub-cultured placental tissue, and then evaluated the effects of the CM on a series of angiogenic processes in HUVECs in vitro. Furthermore, we measured the levels of angiogenic factors in the CM of placental cells or tissue by an angiogenesis antibody array.

Results: The results showed that not only placental cells but also sub-cultured placental tissue, to some extent, promoted HUVEC angiogenesis in vitro by promoting proliferation, adhesion, migration, invasion, and tube formation. We also found that primary placental cells in early pregnancy, whether CTBs or hPDMSCs, played more significant roles than those in full-term pregnancy. Placental cell-derived CM collected at 24 h or 48 h had the best effect, and sub-cultured placental tissue-derived CM collected at 7 days had the best effect among all the different time points. The semiquantitative angiogenesis antibody array showed that 18 of the 43 angiogenic factors had obvious spots in placental cell-derived CM or sub-cultured placental tissue-derived CM, and the levels of 5 factors (including CXCL-5, GRO, IL-6, IL-8, and MCP-1) were the highest in sub-cultured placental tissue-derived CM.

Conclusions: CM obtained from placental cells (primary CTBs or hPDMSCs) or sub-cultured placental tissue contained proangiogenic factors and promoted HUVEC angiogenesis in vitro. Therefore, our research is helpful to better understand placental angiogenesis regulation and provides theoretical support for the clinical application of placental components, especially sub-cultured placental tissue-derived CM, in vascular tissue engineering and clinical treatments.
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http://dx.doi.org/10.1186/s13287-021-02192-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890636PMC
February 2021

Quantitative Assessment of the Physical Virus Titer and Purity by Ultrasensitive Flow Virometry.

Angew Chem Int Ed Engl 2021 Apr 17;60(17):9351-9356. Epub 2021 Mar 17.

Department of Chemical Biology, MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, P. R. China.

Rapid quantification of viruses is vital for basic research on viral diseases as well as biomedical application of virus-based products. Here, we report the development of a high-throughput single-particle method to enumerate intact viral particles by ultrasensitive flow virometry, which detects single viruses as small as 27 nm in diameter. The nucleic acid dye SYTO 82 was used to stain the viral (or vector) genome, and a laboratory-built nano-flow cytometer (nFCM) was employed to simultaneously detect the side-scatter and fluorescence signals of individual viral particles. Using the bacteriophage T7 as a model system, intact virions were completely discriminated from empty capsids and naked viral genomes. Successful measurement of the physical virus titer and purity was demonstrated for recombinant adenoviruses, which could be used for gene delivery, therapeutic products derived from phage cocktails, and infected cell supernatants for veterinary vaccine production.
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http://dx.doi.org/10.1002/anie.202100872DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014667PMC
April 2021

Expert Consensus on Polymyxin Antimicrobial Susceptibility Testing and Clinical Interpretation.

Chin Med Sci J 2021 Jan 14. Epub 2021 Jan 14.

Department of Respiratory Medicine, the First Medical Center of PLA General Hospital, Beijing 100853, China.

The polymyxins are important antimicrobial agents against antibiotic-resistant gram-negative bacilli. In 2020, the Clinical and Laboratory Standards Institute modified the clinical breakpoints for polymyxin susceptibility test by eliminating the "susceptible" interpretive category, only reporting intermediate (≤ 2 mg/L) and resistant (≥ 4 mg/L). However, the European Committee on Antimicrobial Susceptibility Testing recommended the use of clinical breakpoints of ≤ 2 mg/L as susceptible and > 2 mg/L as resistant. The first-line laboratorians and clinicians in China have been perplexed by the inconsistence of international polymyxin clinical breakpoints and discouraged by the difficulty of conducting polymyxin susceptibility testing. Therefore, it is urgently needed to make it clear for the laboratorians in China to know how to accurately carry out polymyxin susceptibility testing and standardize the interpretation of susceptibility testing results. To this end, the experts from relevant fields were convened to formulate this consensus statement on the testing and clinical interpretation of polymyxin susceptibility. Relevant recommendations are proposed accordingly for laboratorians and clinicians to streamline their daily work.
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http://dx.doi.org/10.24920/003864DOI Listing
January 2021

Natural variations of TFIIAγ gene and LOB1 promoter contribute to citrus canker disease resistance in Atalantia buxifolia.

PLoS Genet 2021 01 25;17(1):e1009316. Epub 2021 Jan 25.

Key Laboratory of Horticultural Plant Biology Ministry of Education, Huazhong Agricultural University, Wuhan, the People's Republic of China.

Citrus canker caused by Xanthomonas citri subsp. citri (Xcc) is one of the most devastating diseases in citrus industry worldwide. Most citrus cultivars such as sweet orange are susceptible to canker disease. Here, we utilized wild citrus to identify canker-resistant germplasms, and found that Atalantia buxifolia, a primitive (distant-wild) citrus, exhibited remarkable resistance to canker disease. Although the susceptibility gene LATERAL ORGAN BOUNDARIES 1 (LOB1) could also be induced in Atalantia after canker infection, the induction extent was far lower than that in sweet orange. In addition, three of amino acids encoded by transcription factor TFIIAγ in Atalantia (AbTFIIAγ) exhibited difference from those in sweet orange (CsTFIIAγ) which could stabilize the interaction between effector PthA4 and effector binding element (EBE) of LOB1 promoter. The mutation of AbTFIIAγ did not change its interaction with transcription factor binding motifs (TFBs). However, the AbTFIIAγ could hardly support the LOB1 expression induced by the PthA4. In addition, the activity of AbLOB1 promoter was significantly lower than that of CsLOB1 under the induction by PthA4. Our results demonstrate that natural variations of AbTFIIAγ and effector binding element (EBE) in the AbLOB1 promoter are crucial for the canker disease resistance of Atalantia. The natural mutations of AbTFIIAγ gene and AbLOB1 promoter in Atalantia provide candidate targets for improving the resistance to citrus canker disease.
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http://dx.doi.org/10.1371/journal.pgen.1009316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7861543PMC
January 2021

Knowledge, Attitudes, and Practices Toward COVID-19 Among Construction Industry Practitioners in China.

Front Public Health 2020 8;8:599769. Epub 2021 Jan 8.

The Bartlett School of Construction and Project Management, University College London, London, United Kingdom.

The COVID-19 pandemic has put labor-intensive industries at risk, among which the construction industry is a typical one. Practitioners in the construction industry are facing high probabilities of COVID-19 transmission, while their knowledge, attitudes, and practices (KAP) are critical to the prevention of virus spread. This study seeks to investigate the KAP of construction industry practitioners in China through an online questionnaire survey conducted from 15 to 30 June 2020. A total of 702 effective responses were received and analyzed. The results revealed that: (1) although an overwhelming percentage of respondents had the correct knowledge about COVID-19, there were significant respondents (15% of all) who were unsure or wrong about the human-to-human transmission of the virus; (2) practitioners generally showed an optimistic attitude about winning the battle against the COVID-19 pandemic and were satisfied with the governments' contingency measures; (3) practitioners tended to actively take preventive measures, although checking body temperature, wearing face masks, and keeping safe social distance still needs to be reinforced. This research is among the first to identify the KAP of construction industry practitioners toward the COVID-19 pandemic in China. Results presented here have implications for enhancing strategies to reduce and prevent COVID-19 spread in the construction industry.
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http://dx.doi.org/10.3389/fpubh.2020.599769DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820676PMC
February 2021

Pathogen-inducible OsMPKK10.2-OsMPK6 cascade phosphorylates the Raf-like kinase OsEDR1 and inhibits its scaffold function to promote rice disease resistance.

Mol Plant 2021 Apr 13;14(4):620-632. Epub 2021 Jan 13.

National Key Laboratory of Crop Genetic Improvement, National Center of Plant Gene Research (Wuhan), Huazhong Agricultural University, Wuhan 430070, China.

Mitogen-activated protein kinase (MAPK) cascades regulate a myriad of plant biological processes, including disease resistance. Plant genomes encode a large number of MAPK kinase kinases (MAPKKKs) that can be divided into two subfamilies, namely MEKK-like kinases and Raf-like kinases. Thus far, the functions of MEKK-like MAPKKKs have been relatively well characterized, but the roles of Raf-like MAPKKKs in plant MAPK cascades remain less understood. Here, we report the role of OsEDR1, a Raf-like MAPKKK, in the regulation of the MAPK cascade in rice response to the bacterial pathogen Xanthomonas oryzae pv. oryzicola (Xoc). We found that OsEDR1 inhibits OsMPKK10.2 (a MAPK kinase) activity through physical interaction. Upon Xoc infection, OsMPKK10.2 is phosphorylated at S304 to activate OsMPK6 (a MAPK). Interestingly, activated OsMPK6 phosphorylates OsEDR1 at S861, which destabilizes OsEDR1 and thus releases the inhibition of OsMPKK10.2, leading to increased OsMPKK10.2 activity and enhanced resistance of rice plants to Xoc. Taken together, these results provide new insights into the functions of Raf-like kinases in the regulation of the MAPK cascade in plant immunity.
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http://dx.doi.org/10.1016/j.molp.2021.01.008DOI Listing
April 2021

[Analysis of a pedigree affected with HSAS syndrome due to a noval variant of L1CAM gene].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2021 Jan;38(1):83-86

Reproductive Medicine Center, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China.

Objective: To explore the genetic basis for a fetus with hydrocephalus.

Methods: The fetus was found to have hydrocephalus upon ultrasonography duringthe second trimester. Following induced abortion, fetal tissue was collected for the extraction of DNA and whole exome sequencing.Sanger sequencing was used to verify the suspected variants in the family.

Results: The fetus was found to harbor a hemizygous c.620A>G (p.Tyr207Cys) variant of the L1CAM gene (OMIM 308840),for which his mother and sister were heterozygous carriers. The same variant was not found in his father, uncle and grandparents.Based on the standards and guidelines of the American College of Medical Genetics and Genomics, the variant was predicted to be likely pathogenic (PM1+PM2+PP3+PP4).

Conclusion: The hemizygous c.620A>G (p.Tyr207Cys) variant of the L1CAM gene probably underlay the hydrocephalus in this fetus.
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http://dx.doi.org/10.3760/cma.j.cn511374-20200113-00024DOI Listing
January 2021

Comprehensive review of surgical microscopes: technology development and medical applications.

Authors:
Ling Ma Baowei Fei

J Biomed Opt 2021 Jan;26(1)

The Univ. of Texas at Dallas, United States.

Significance: Surgical microscopes provide adjustable magnification, bright illumination, and clear visualization of the surgical field and have been increasingly used in operating rooms. State-of-the-art surgical microscopes are integrated with various imaging modalities, such as optical coherence tomography (OCT), fluorescence imaging, and augmented reality (AR) for image-guided surgery.

Aim: This comprehensive review is based on the literature of over 500 papers that cover the technology development and applications of surgical microscopy over the past century. The aim of this review is threefold: (i) providing a comprehensive technical overview of surgical microscopes, (ii) providing critical references for microscope selection and system development, and (iii) providing an overview of various medical applications.

Approach: More than 500 references were collected and reviewed. A timeline of important milestones during the evolution of surgical microscope is provided in this study. An in-depth technical overview of the optical system, mechanical system, illumination, visualization, and integration with advanced imaging modalities is provided. Various medical applications of surgical microscopes in neurosurgery and spine surgery, ophthalmic surgery, ear-nose-throat (ENT) surgery, endodontics, and plastic and reconstructive surgery are described.

Results: Surgical microscopy has been significantly advanced in the technical aspects of high-end optics, bright and shadow-free illumination, stable and flexible mechanical design, and versatile visualization. New imaging modalities, such as hyperspectral imaging, OCT, fluorescence imaging, photoacoustic microscopy, and laser speckle contrast imaging, are being integrated with surgical microscopes. Advanced visualization and AR are being added to surgical microscopes as new features that are changing clinical practices in the operating room.

Conclusions: The combination of new imaging technologies and surgical microscopy will enable surgeons to perform challenging procedures and improve surgical outcomes. With advanced visualization and improved ergonomics, the surgical microscope has become a powerful tool in neurosurgery, spinal, ENT, ophthalmic, plastic and reconstructive surgeries.
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http://dx.doi.org/10.1117/1.JBO.26.1.010901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780882PMC
January 2021

Relationship between long non-coding RNA and prognosis of patients with coronary heart disease after percutaneous coronary intervention: A protocol for systematic review and meta-analysis.

Medicine (Baltimore) 2020 Dec;99(51):e23525

Department of Cardiovascular Medicine, 940th Hospital of PLA Joint Service Support Force, Lanzhou, Gansu, China.

Background: Long non-coding RNA (lncRNA) can predict the prognosis of patients with coronary heart disease (CHD) after obtaining percutaneous coronary intervention (PCI), while this conclusion still needs to be further confirmed. Therefore, this study attempted to explore the relationship between lncRNA and prognosis in CHD patients after PCI.

Methods: The database was retrieved from China National Knowledge Infrastructure (CNKI), Chinese Biomedical literature Database (CBM), Chinese Scientific and Journal Database (VIP), Wan Fang database, PubMed, and EMBASE. Hazard ratios (HRs) and its 95% confidence interval (CIs) were applied to assess the prognostic effects of lncRNA on overall survival (OS). RevMan 5.3 and STATA 16.0 software were used to perform meta-analysis.

Results: The results of this meta-analysis would be submitted to peer-reviewed journals for publication.

Conclusion: This review provided a comprehensive overview of the relationship between lncRNA and prognosis in CHD patients after PCI, and offered recommendations for clinical practices or guidelines.
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http://dx.doi.org/10.1097/MD.0000000000023525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7748174PMC
December 2020

Corrigendum to "Mental health outcomes among Chinese prenatal and postpartum women after the implementation of universal two-child policy". [Journal of Affective Disorders 264 (2020) 187-192].

J Affect Disord 2021 Feb 11;281:1002. Epub 2020 Dec 11.

The National Clinical Research Center for Mental Disorders, Beijing Key Laboratory of Mental Disorders & Advanced Innovation Center for Human Brain Protection, Beijing Anding Hospital, Capital Medical University, Beijing, China; Department of Psychiatry, University of Oxford, Oxford, UK. Electronic address:

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http://dx.doi.org/10.1016/j.jad.2020.11.010DOI Listing
February 2021

Cyanuric chloride-imidazole dendrimer functionalized nanoparticles as an adsorbent for magnetic solid phase extraction of quaternary ammonium compounds from fruit and vegetable puree based infant foods.

J Chromatogr A 2021 Jan 6;1636:461735. Epub 2020 Dec 6.

School of Public Health, Hebei Medical University, Shijiazhuang 050017, PR China; Hebei Key Laboratory of Environment and Human Health, Shijiazhuang 050017, PR China. Electronic address:

A novel magnetic solid-phase extraction (MSPE) material (FeO@SiO-NH-G2) had been prepared and employed for adsorption and analysis of seven quaternary ammonium compounds (QACs) in infant fruit and vegetable products coupled with high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). In this paper, FeO@SiO-NH-G2 was synthesized based on FeO@SiO-NH and dendrimer (G2) consisting of cyanuric chloride and imidazole. The morphology, configuration and magnetic behavior of the magnetic material were characterized by transmission electron microscopy (TEM), Fourier transform infrared spectrometry (FT-IR), X-ray diffraction (XRD), and vibrating sample magnetometer (VSM). Critical parameters affecting extraction efficiency, such as the adsorbent amount, sample pH, extraction time, the type of eluent, and desorption time, were optimized. The proposed method provided good linearity with the correlation coefficients (R) of 0.9992-0.9999, low limits of detection (LODs) (0.05-0.50 μg kg) and limits of quantitation (LOQs) (0.20-2.00 μg kg). The satisfactory method recoveries in three spiked infant fruit and vegetable products samples were between 80.12% and 101.35% with the relative standard deviations (RSDs) less than 12.04%. In summary, the established method was an effective sample preparation method and showed good prospect for the analysis of QACs in complex matrices.
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http://dx.doi.org/10.1016/j.chroma.2020.461735DOI Listing
January 2021

Generation of an induced pluripotent stem cell line from an Alström Syndrome patient with ALMS1 mutation (c.3902C > A, c.6436C > T) and a gene correction isogenic iPSC line.

Stem Cell Res 2020 12 17;49:102089. Epub 2020 Nov 17.

Department of Neonatology, Children's Hospital of Fudan University, Shanghai, China; Key Laboratory of Neonatal Diseases, Ministry of Health, Children's Hospital of Fudan University, Shanghai 201102, China. Electronic address:

To develop a disease model for the human Alström Syndrome (AS), we used the episomal reprogramming system and CRISPR/Cas9 technology to generate an induced pluripotent stem cell (iPSC) line with the compound heterozygous patient mutation (ALMS1 c.3902C > A, c.6436C > T) along with an isogenic gene-corrected control iPSC line. Both iPSC lines showed normal karyotype, expressed pluripotent markers, and differentiated into cells of three embryonic germ layer. These AS mutant and isogenic iPSC control line will be of great use in investigating the disease mechanisms, drug screening and treatment in patients.
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http://dx.doi.org/10.1016/j.scr.2020.102089DOI Listing
December 2020

USP38 Couples Histone Ubiquitination and Methylation via KDM5B to Resolve Inflammation.

Adv Sci (Weinh) 2020 Nov 11;7(22):2002680. Epub 2020 Oct 11.

MOE Key Laboratory of Gene Function and Regulation State Key Laboratory of Biocontrol School of Life Sciences Sun Yat-sen University Guangzhou Guangdong 510006 China.

Chromatin modifications, such as histone acetylation, ubiquitination, and methylation, play fundamental roles in maintaining chromatin architecture and regulating gene transcription. Although their crosstalk in chromatin remodeling has been gradually uncovered, the functional relationship between histone ubiquitination and methylation in regulating immunity and inflammation remains unclear. Here, it is reported that USP38 is a novel histone deubiquitinase that works together with the histone H3K4 modifier KDM5B to orchestrate inflammatory responses. USP38 specifically removes the monoubiquitin on H2B at lysine 120, which functions as a prerequisite for the subsequent recruitment of demethylase KDM5B to the promoters of proinflammatory cytokines and during LPS stimulation. KDM5B in turn inhibits the binding of NF-B transcription factors to the and promoters by reducing H3K4 trimethylation. Furthermore, USP38 can bind to KDM5B and prevent it from proteasomal degradation, which further enhances the function of KDM5B in the regulation of inflammation-related genes. Loss of in mice markedly enhances susceptibility to endotoxin shock and acute colitis, and these mice display a more severe inflammatory phenotype compared to wild-type mice. The studies identify USP38-KDM5B as a distinct chromatin modification complex that restrains inflammatory responses through manipulating the crosstalk of histone ubiquitination and methylation.
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http://dx.doi.org/10.1002/advs.202002680DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675183PMC
November 2020

Controllable Preparation of 3D Graphene with Different Morphologies for High-Performance Electrode Materials.

ACS Omega 2020 Nov 5;5(45):29038-29042. Epub 2020 Nov 5.

College of Chemistry and Chemical Engineering, Jinzhong University, Jinzhong 030619, P. R. China.

Synthesis of three-dimensional (3D) graphene with controlled morphologies has been achieved by changing the freeze-drying process of graphene in this paper. The obtained vertically aligned graphene (VAGN) is stand-up and has a uniform, dense, and porous network, while the obtained graphene foam (GF) just has a cross-linked 3D porous framework. In addition, the possible growth mechanisms of these nanostructures have been studied based on the experimental results. Furthermore, the effects of morphologies on their electrochemical performances have been investigated. The result shows that the VAGN-based supercapacitor has a higher specific capacitance () of 182 F g at 0.5 A g than that of GF (160 F g at 0.5 A g). The supercapacitors prepared by VAGN and GF retain about 95.7 and 92.7% of , respectively, after 2000 charge-discharge processes. When the power density of the supercapacitor prepared by VAGN is about 50.3 W kg, its maximum energy density can reach 7.05 Wh kg, which is higher than that of GF. This shows that VAGN has better electrochemical performance than GF. It might be because the aligned structure of VAGN plays an important role in reducing the internal resistance of the electrodes and accelerating ion and electron transport. Three-dimensional graphene with different morphologies might have potential applications as electrode materials for supercapacitors.
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http://dx.doi.org/10.1021/acsomega.0c03507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675539PMC
November 2020

Mixed-lineage leukaemia 1 contributes to endometrial stromal cells progesterone responsiveness during decidualization.

J Cell Mol Med 2021 Jan 17;25(1):297-308. Epub 2020 Nov 17.

Reproductive Medicine Center, Zhongnan Hospital of Wuhan University, Wuhan, China.

Studies have reported that non-receptive endometrium or abnormal decidualization was closely related to recurrent implantation failure (RIF). MLL1 is a histone H3 lysine 4 trimethylation (H3K4me3) transferase that regulates the transcriptional activation of target genes. The role of MLL1 has been underexplored during decidualization. In our research, we found the expression of MLL1 was closely related to endometrial receptivity, and it was responsible to hormone stimulation. Inhibiting the function of MLL1 by MM102 reduced the transformation of HESCs. Furthermore, down-regulation of MLL1 by siRNA transfection significantly decreased PGR and its target genes expression. MLL1 act as a co-activator of ERα, and both of them were recruited to PGR regulatory regions, thus promote PGR transcription. Our study showed that MLL1 plays a key role in promoting progesterone signalling transmission.
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http://dx.doi.org/10.1111/jcmm.16030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810960PMC
January 2021

Structural insights into the photoactivation of Arabidopsis CRY2.

Nat Plants 2020 12 16;6(12):1432-1438. Epub 2020 Nov 16.

National Key Laboratory of Crop Genetic Improvement and National Centre of Plant Gene Research, Huazhong Agricultural University, Wuhan, China.

The blue-light receptor cryptochrome (CRY) in plants undergoes oligomerization to transduce blue-light signals after irradiation, but the corresponding molecular mechanism remains poorly understood. Here, we report the cryogenic electron microscopy structure of a blue-light-activated CRY2 tetramer at a resolution of 3.1 Å, which shows how the CRY2 tetramer assembles. Our study provides insights into blue-light-mediated activation of CRY2 and a theoretical basis for developing regulators of CRYs for optogenetic manipulation.
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http://dx.doi.org/10.1038/s41477-020-00800-1DOI Listing
December 2020

Caspase-8 knockdown suppresses apoptosis, while induces autophagy and chemo-sensitivity in non-small cell lung cancer cells.

Am J Transl Res 2020 15;12(10):6478-6489. Epub 2020 Oct 15.

Faculty of Life Science and Technology, Kunming University of Science and Technology Kunming 655034, Yunnan Province, China.

Purpose: Drug resistance remains a major cause of relapse and therapeutic failure in non-small cell lung cancer (NSCLC). The purpose of this investigation is to explore the relationship between caspase-8 level and chemo-sensitivity, as well as its underlying mechanism in NSCLC cells.

Methods: NSCLC cell line, A549 cells was used to investigate the influence of caspase-8 on the biological behavior . The abundance of caspase-8 in A549 cells was manipulated by transfection lentivirus containing specific caspase-8 short hairpin RNA (sh-caspase-8) and caspase-8 overexpressed plasmid. Cell viability and the percentage of apoptotic cells was quantified using cell counting kit-8 (CCK-8) assay and flow cytometry following Annexin V-FITC/PI staining, respectively. The formation of acidic vesicle organelles (AVOs) was examined by acridine orange staining and visualized under a fluorescence microscope. The mRNA and protein levels of relative genes were determined by qRT-PCR and western blotting.

Results: Our results indicated that cells infected with sh-caspase-8 exhibited high knockdown efficiency. Knockdown of caspase-8 significantly reduced apoptosis of A549 cells. As evidenced by the decreased number of apoptotic cells and the reduction of Bcl-2/bax ratio. Interestingly, caspase-8 knockdown also enhanced autophagy in A549 cells. Additionally, knockdown of caspase-8 reduced the doxorubicin, carboplatin, cisplatin, and etoposide sensitivity towards A549 cells.

Conclusion: In summary, our results revealed that knockdown of caspase-8 could promote cell growth and autophagy, while reduce chemo-sensitivity and apoptotic cell death. These finding suggest caspase-8 might serve as a potential target to improve the chemo-sensitivity for NSCLC patients in clinical setting.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653624PMC
October 2020

Circular RNA circSEMA5A promotes bladder cancer progression by upregulating ENO1 and SEMA5A expression.

Aging (Albany NY) 2020 11 7;12(21):21674-21686. Epub 2020 Nov 7.

Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.

Bladder cancer (BC) is one of the most commonly diagnosed urologic carcinomas, with high recurrence and death rates. Circular RNAs (circRNAs) are a class of noncoding RNAs which are anomalously expressed in cancers and involved in the progression of cancers. In this study, we found that circSEMA5A was upregulated in BC tissues and cell lines. The overexpressed circSEMA5A was correlated with malignant characteristics of BC. In vitro data indicated that circSEMA5A promoted proliferation, suppressed apoptosis, facilitated migration, accelerated invasion, enhanced angiogenesis and promotes glycolysis of BC. Mechanistically, circSEMA5A served as a miRNA sponge for miR-330-5p to upregulates Enolase 1 (ENO1) expression and facilitated the activation of Akt and β-catenin signaling pathways. Then, we showed that circSEMA5A exerted its biological functions partially via miR-330-5p/ENO1 signaling. Moreover, circSEMA5A raised SEMA5A expression by recruiting EIF4A3 to enhance the mRNA stability of SEMA5A, and thereby accelerated BC angiogenesis. To sum up, circSEMA5A is upregulated in BC and facilitates BC progression by mediating miR-330-5p/ENO1 signaling and upregulating SEMA5A expression.
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http://dx.doi.org/10.18632/aging.103971DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695386PMC
November 2020

Decreased mixed lineage leukemia 1 is involved in endometriosis-related infertility.

J Mol Endocrinol 2021 01;66(1):45-57

Reproductive Medicine Center, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China.

The aberrant histone methylation patterns contribute to the pathogenesis of endometriosis (EM). Mixed lineage leukemia 1 (MLL1), a histone methyltransferase, is crucial for gene expression by catalyzing the trimethylation of histone 3 lysine 4 (H3K4me3) in gene promoter. This study aimed to explore whether MLL1 is involved in EM-related infertility. The expressions of MLL1 and H3K4me3 were analyzed in the eutopic endometria from EM women with infertility (n = 22) and the normal endometria from EM-free women (n = 22). Mouse EM model was established. The MLL1 and H3K4me3 expression patterns in mice endometria of early pregnancy were also investigated. Immortalized human endometrial stromal cells (iESCs) were cultured and underwent in vitro decidualization. The chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) was performed to find the target gene of MLL1 during decidual process. Results showed that both MLL1 and H3K4me3 decreased in the eutopic endometrium from EM patients compared to that in the normal endometrium. During early pregnancy and the decidual process, MLL1 and H3K4me3 were significantly upregulated in stromal cells. ChIP-seq and ChIP-qPCR found that the cytochrome c oxidase subunit 4I 2 (COX4I2) was directly targeted by MLL1. The dominance of COX4I2-containing enzyme induced the expression of hypoxia-inducible factor-2α (HIF-2α), whose expression in the peri-implantation endometrium is essential for embryo implantation. Further results showed that MLL1 was directly regulated by progesterone (P4) - P4 receptors (PRs). Our study proved that MLL1 was involved in EM-related infertility, which may provide a novel approach to treat the nonreceptive endometrium in EM patients.
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http://dx.doi.org/10.1530/JME-20-0193DOI Listing
January 2021