Publications by authors named "Tiantian Ma"

70 Publications

Treatment of SARS-CoV-2-induced pneumonia with NAD and NMN in two mouse models.

Cell Discov 2022 Apr 29;8(1):38. Epub 2022 Apr 29.

State Key Laboratory of Molecular Developmental Biology, CAS Center for Excellence in Brain Science and Intelligence Technology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.

The global COVID-19 epidemic has spread rapidly around the world and caused the death of more than 5 million people. It is urgent to develop effective strategies to treat COVID-19 patients. Here, we revealed that SARS-CoV-2 infection resulted in the dysregulation of genes associated with NAD metabolism, immune response, and cell death in mice, similar to that in COVID-19 patients. We therefore investigated the effect of treatment with NAD and its intermediate (NMN) and found that the pneumonia phenotypes, including excessive inflammatory cell infiltration, hemolysis, and embolization in SARS-CoV-2-infected lungs were significantly rescued. Cell death was suppressed substantially by NAD and NMN supplementation. More strikingly, NMN supplementation can protect 30% of aged mice infected with the lethal mouse-adapted SARS-CoV-2 from death. Mechanically, we found that NAD or NMN supplementation partially rescued the disturbed gene expression and metabolism caused by SARS-CoV-2 infection. Thus, our in vivo mouse study supports trials for treating COVID-19 patients by targeting the NAD pathway.
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http://dx.doi.org/10.1038/s41421-022-00409-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9053567PMC
April 2022

Insight into the dynamic microbial community and core bacteria in composting from different sources by advanced bioinformatics methods.

Environ Sci Pollut Res Int 2022 Apr 25. Epub 2022 Apr 25.

College of Resources and Environmental Sciences, China Agricultural University, Beijing, 100193, China.

Microbial communities are important for high composting efficiency and good quality composts. This study was conducted to compare the changes of physicochemical and bacterial characteristics in composting from different raw materials, including chicken manure (CM), duck manure (DM), sheep manure (SM), food waste (FW), and vegetable waste (VW). The role and interactions of core bacteria and their contribution to maturity in diverse composts were analyzed by advanced bioinformatics methods combined sequencing with co-occurrence network and structural equation modeling (SEM). Results indicated that there were obviously different bacterial composition and diversity in composting from diverse sources. FW had a low pH and different physiochemical characteristics compared to other composts but they all achieved similar maturity products. Redundancy analysis suggested total organic carbon, phosphorus, and temperature governed the composition of microbial species but key factors were different in diverse composts. Network analysis showed completely different interactions of core bacterial community from diverse composts but Thermobifida was the ubiquitous core bacteria in composting bacterial network. Sphaerobacter and Lactobacillus as core genus were presented in the starting mesophilic and thermophilic phases of composting from manure (CM, DM, SM) and municipal solid waste (FW, VW), respectively. SEM indicated core bacteria had the positive, direct, and the biggest (> 80%) effects on composting maturity. Therefore, this study presents theoretical basis to identify and enhance the core bacteria for improving full-scale composting efficiency facing more and more organic wastes.
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http://dx.doi.org/10.1007/s11356-022-20388-7DOI Listing
April 2022

Molecular mechanisms underlying cTAGE5/MEA6-mediated cargo transport and biological functions.

J Genet Genomics 2022 Apr 15. Epub 2022 Apr 15.

Center for Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

Coat protein complex II (COPII)-coated vesicles are responsible for transporting the cargoes from the endoplasmic reticulum (ER) to different destinations. cTAGE5/MEA6 is essential for the development and function of different organs. It regulates the assembly of COPII carrier and cargo trafficking through direct or indirect interaction with COPII components. cTAGE5/MEA6 mainly coordinates with another scaffold protein, TANGO1, to play essential roles in the trafficking and secretion of both large and small cargoes in multiple organs. In this mini-review, we would like to discuss the molecular mechanisms underlying cTAGE5/MEA6-mediated cargo transport and biological functions.
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http://dx.doi.org/10.1016/j.jgg.2022.04.001DOI Listing
April 2022

Association of Serum Adipokines and Resting Energy Expenditure in Patients With Chronic Kidney Disease.

Front Nutr 2022 15;9:828341. Epub 2022 Mar 15.

Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.

Background And Aim: Metabolic disorders are prevalent in patients with chronic kidney disease (CKD) and may lead to protein energy wasting (PEW). Adipokines improve connections between PEW and energy metabolism. We aimed to determine the relationship between adipokine levels and resting energy expenditure (REE) in patients with CKD.

Methods: A total of 208 patients in non-dialyzed CKD stages 3-5 were enrolled in this cross-sectional study. Serum adipokines (leptin, adiponectin, and interleukin 6 (IL-6) were measured using enzyme-linked immunosorbent assay. Patient's REE was measured using indirect calorimetry. Fat mass (FM) and lean tissue mass (LTM) were measured using multiple-frequency bioimpedance analysis. Spearman correlation analyses and multivariate linear regression models were used to assess the association between serum adipokines and REE.

Results: The mean age was 52.7 ± 14.6 years, and 26.9, 26.4, and 46.7% of our participants had CKD stages 3, 4, and 5, respectively. The median values of serum adiponectin, leptin, and IL-6 were 470.4 (range, 291.1-802.2), 238.1 (range, 187.9-418.4), and 4.0 (range, 2.4-9.5) pg/mL, respectively. The male participants had significantly lower FM% ( = 0.001) and lower leptin levels ( < 0.001) than the female participants. After adjusting for age, diabetes, high-sensitivity C-reactive protein, intact parathyroid hormone, LTM, and FM, multiple linear regression analysis revealed that serum leptin levels were significantly positively associated with REE in men rather than in women ( < 0.05). Serum adiponectin levels were inversely associated with REE in men, but this association disappeared while FM was additionally adjusted. Adiponectin levels in women were not correlated with REE ( > 0.05). IL-6 was not significantly associated with REE in either men or women.

Conclusions: A sex-specific relationship between serum adipokines (leptin and adiponectin) and REE was observed in patients with CKD stages 3-5, which was partly confounded by FM.
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http://dx.doi.org/10.3389/fnut.2022.828341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8965443PMC
March 2022

The Subcellular Localization of RRAGD.

J Am Soc Nephrol 2022 05 31;33(5):1046-1048. Epub 2022 Mar 31.

Department of Nephrology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China

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http://dx.doi.org/10.1681/ASN.2022010006DOI Listing
May 2022

Long noncoding RNA SNHG8 promotes chemoresistance in gastric cancer via binding with hnRNPA1 and stabilizing TROY expression.

Dig Liver Dis 2022 Mar 27. Epub 2022 Mar 27.

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. Electronic address:

Aims: To determine SNHG8's function and potential mechanisms in gastric cancer (GC) chemoresistance.

Methods: We assessed SNHG8 expression in GC cell lines, GC/CDDP cell lines (cell lines treated with cisplatin), and 42 GC tissues and SNHG8 levels in the lncRNA microarray analysis of AGS/CDDP and AGS cell lines. We also examined GC cell viability in vivo and in vitro and its apoptosis level with Flow cytometry assays. SNHG8 was localized in subcells using fluorescence in situ hybridization (FISH) and cell fraction assays, hnRNPA1's link to SNHG8 was determined utilizing RNA immunoprecipitation (RIP) and FISH assays, gene expression profiles were assessed employing RNA transcriptome sequencing, and hnRNPA1's relationship with TROY was ascertained with the RIP assay.

Results: SNHG8 increased significantly in GC cell lines and GC tissues. However, a decrease in its expression promoted sensitivity to chemotherapy and inhibited DNA damage repair in vitro and in vivo. SNHG8 appeared to regulate TROY expression via linking with hnRNPA1. Reducing TROY levels considerably stimulated GC cell chemosensitivity, whereas heightening them partially rescued the rate of chemoresistance caused by downregulating SNHG8.

Conclusion: In summary, the "SNHG8/hnRNPA1-TROY" axis is crucial to GC chemoresistance.
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http://dx.doi.org/10.1016/j.dld.2022.02.011DOI Listing
March 2022

Foliar Herbivory Reduces Rhizosphere Fungal Diversity and Destabilizes the Co-occurrence Network.

Front Microbiol 2022 8;13:846332. Epub 2022 Mar 8.

State Key Laboratory of Crop Stress Adaptation and Improvement, School of Life Sciences, Henan University, Kaifeng, China.

Insect herbivores can adversely impact terrestrial plants throughout ontogeny and across various ecosystems. Simultaneously, the effects of foliar herbivory may extend belowground, to the soil microbial community. However, the responses in terms of the diversity, assembly, and stability of rhizosphere fungi to aboveground herbivory remain understudied. Here, using high-throughput sequencing, the effects of foliar insect herbivory on rhizosphere fungal microbes were investigated in a common garden experiment that manipulated herbivory intensity and time from herbivore removal. The number of observed fungal species was reduced by a greater herbivory intensity, with some species evidently sensitive to herbivory intensity and time since herbivore removal. Rhizofungal assembly processes were altered by both herbivory intensity and time since herbivore removal. Further, we found evidence that both factors strongly influenced fungal community stability: a high intensity of herbivory coupled with a shorter time since herbivore removal resulted in low stability. These results suggest that foliar herbivory can adversely alter fungal diversity and stability, which would in turn be harmful for plant health. Fortunately, the effect seems to gradually diminish with time elapsed after herbivore removal. Our findings provide a fresh, in-depth view into the roles of rhizofungi in enhancing the adaption ability of plants under environmental stress.
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http://dx.doi.org/10.3389/fmicb.2022.846332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8957981PMC
March 2022

Multifunctional Gelatin-Nanoparticle-Modified Chip for Enhanced Capture and Non-Destructive Release of Circulating Tumor Cells.

Micromachines (Basel) 2022 Feb 28;13(3). Epub 2022 Feb 28.

Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan 430072, China.

Circulating tumor cells (CTCs) in cancer patients' peripheral blood have been demonstrated to be a significant biomarker for metastasis detection, disease prognosis, and therapy response. Due to their extremely low concentrations, efficient enrichment and non-destructive release are needed. Herein, an FTO chip modified with multifunctional gelatin nanoparticles (GNPs) was designed for the specific capture and non-destructive release of CTCs. These nanoparticles share a similar dimension with the microvilli and pseudopodium of the cellular surface; thus, they can enhance adhesion to CTCs, and then GNPs can be degraded by the enzyme matrix metalloproteinase (MMP-9), gently releasing the captured cells. In addition, the transparency of the chip makes it possible for fluorescence immunoassay identification in situ under a microscope. Our chip attained a high capture efficiency of 89.27%, a release efficiency of 91.98%, and an excellent cellular viability of 96.91% when the concentration of MMP-9 was 0.2 mg/mL. Moreover, we successfully identified CTCs from cancer patients' blood samples. This simple-to-operate, low-cost chip exhibits great potential for clinical application.
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http://dx.doi.org/10.3390/mi13030395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8955365PMC
February 2022

Combined BSA-Seq Based Mapping and RNA-Seq Profiling Reveal Candidate Genes Associated with Plant Architecture in .

Int J Mol Sci 2022 Feb 23;23(5). Epub 2022 Feb 23.

National Center of Rapeseed Improvement in Wuhan, National Key Laboratory of Crop Genetic Improvement, College of Plant Science and Technology, Huazhong Agricultural University, Wuhan 430070, China.

Plant architecture involves important agronomic traits affecting crop yield, resistance to lodging, and fitness for mechanical harvesting in . Breeding high-yield varieties with plant architecture suitable for mechanical harvesting is the main goal of rapeseed breeders. Here, we report an accession of (4942C-5), which has a dwarf and compact plant architecture in contrast to cultivated varieties. A BC population was constructed by crossing a normal plant architecture line, 8008, with the recurrent parent 4942C-5. To investigate the molecular mechanisms underlying plant architecture, we performed phytohormone profiling, bulk segregant analysis sequencing (BSA-Seq), and RNA sequencing (RNA-Seq) in BC plants with contrasting plant architecture. Genetic analysis indicated the plant architecture traits of 4942C-5 were recessive traits controlled by multiple genes. The content of auxin (IAA), gibberellin (GA), and abscisic acid (ABA) differed significantly between plants with contrasting plant architecture in the BC population. Based on BSA-Seq analysis, we identified five candidate intervals on chromosome A01, namely those of 0 to 6.33 Mb, 6.45 to 6.48 Mb, 6.51 to 6.53 Mb, 6.77 to 6.79 Mb, and 7 to 7.01 Mb regions. The RNA-Seq analysis revealed a total of 4378 differentially expressed genes (DEGs), of which 2801 were up-regulated and 1577 were down-regulated. There, further analysis showed that genes involved in plant hormone biosynthesis and signal transduction, cell structure, and the phenylpropanoid pathway might play a pivotal role in the morphogenesis of plant architecture. Association analysis of BSA-Seq and RNA-Seq suggested that seven DEGs involved in plant hormone signal transduction and a WUSCHEL-related homeobox (WOX) gene () might be candidate genes responsible for the dwarf and compact phenotype in 4942C-5. These findings provide a foundation for elucidating the mechanisms underlying rapeseed plant architecture and should contribute to breed new varieties suitable for mechanization.
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http://dx.doi.org/10.3390/ijms23052472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8910715PMC
February 2022

Randomized Study on the Efficacy of Standard Versus Low Roxadustat Dose for Anemia in Patients on Peritoneal Dialysis.

Kidney Int Rep 2022 Mar 27;7(3):455-464. Epub 2021 Dec 27.

Renal Division, Department of Medicine, Peking University First Hospital, Beijing, PR China.

Introduction: We aimed to investigate whether a lower starting dose of roxadustat (∼1-1.4 mg/kg) converted from erythropoiesis-stimulating agent (ESA) could achieve a comparable hemoglobin (Hb) target (≥100 and ≤120 g/l) compared with the standard weight-based dose (∼1.5-2 mg/kg) at week 12 through a peritoneal dialysis (PD) cohort.

Methods: A 12-week multicenter randomized, parallel-controlled, open-label, pilot clinical trial enrolled adult patients who had undergone PD treatment for >3 months with renal anemia. Participants were randomized in blocks of 4 in a 1:1 ratio to either the standard-dose group ( 50) or the low-dose group ( 50). The primary end point was the proportion of patients achieving the Hb target at week 12.

Results: Baseline demographic and clinical characteristics of the 2 groups were comparable. There was no difference in the proportion of patients who met the Hb target at week 12, that is, 26 patients (52%) versus 31 patients (62%) in the low-dose group and standard-dose group, respectively ( = 0.31). The Hb levels significantly increased in both groups from baseline to week 12; the median change of Hb levels was 5.0 (0.0-14.3) g/l ( < 0.001) for the standard-dose group and 6.0 (-3.3 to 16.3) g/l for the low-dose group ( = 0.005) ( = 0.581 for between groups).

Conclusion: This study suggests that a lower starting dose of roxadustat effectively achieves the Hb target as standard-dose does among patients on PD. (ClinicalTrials.gov number, NCT04454879).
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http://dx.doi.org/10.1016/j.ekir.2021.12.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8897289PMC
March 2022

Adverse events of special interest following the use of BNT162b2 in adolescents: a population-based retrospective cohort study.

Emerg Microbes Infect 2022 Dec;11(1):885-893

Department of Paediatrics and Adolescent Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China.

Accruing evidence suggests an increased risk of myocarditis in adolescents from messenger RNA COVID-19 vaccines. However, other potential adverse events remain under-researched. We conducted a retrospective cohort study of adolescents aged 12-18 with a territory-wide electronic healthcare database of the Hong Kong population linked with population-based vaccination records and supplemented with age- and sex-specific population numbers. Two age- and sex-matched retrospective cohorts were formed to observe 28 days following the first and second doses of BNT162b2 and estimate the age- and sex-adjusted incidence rate ratios between the vaccinated and unvaccinated. Thirty AESIs adapted from the World Health Organization's Global Advisory Committee on Vaccine Safety were examined. Eventually, the first-dose cohort comprised 274,881 adolescents (50.25% received the first dose) and the second-dose cohort 237,964 (50.29% received the second dose). Ninety-four (34.2 per 100,000 persons) adolescents in the first-dose cohort and 130 (54.6 per 100,000 persons) in the second-dose cohort experienced ≥1 AESIs. There were no statistically significant differences in the risk of any AESI associated with BNT162b2 except myocarditis [first-dose cohort: incidence rate ratio (IRR) = 9.15, 95% confidence interval (CI) 1.14-73.16; second-dose cohort: IRR = 29.61, 95% CI 4.04-217.07] and sleeping disturbances/disorders after the second dose (IRR = 2.06, 95% CI 1.01-4.24). Sensitivity analysis showed that, with myocarditis excluded as AESIs, no significantly elevated risk of AESIs as a composite outcome associated with vaccination was observed (= 0.195). To conclude, the overall absolute risk of AESIs was low with no evidence of an increased risk of AESIs except myocarditis and sleeping disturbances/disorders.
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http://dx.doi.org/10.1080/22221751.2022.2050952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8942549PMC
December 2022

Case Report: Chronic Lymphocytic Leukemia With Recurrent Complement-Mediated Thrombotic Microangiopathy and C3 Glomerulonephritis.

Front Med (Lausanne) 2022 10;9:813439. Epub 2022 Feb 10.

Laboratory of Electron Microscopy, Ultrastructural Pathology Center, Peking University First Hospital, Beijing, China.

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is a monoclonal B cell lymphocytosis that produces nephrotoxic monoclonal immunoglobulin (MIg). However, the role of MIg in CLL and how it affects CLL patient survival are still unknown. Here, we report a case of MIg with renal significance (MGRS) associated with CLL. A 59-year-old Chinese woman complaining of abdominal pain, skin purpura, and typical soy-colored urine was admitted to the hospital for investigation. Laboratory tests revealed that she had microangiopathic hemolytic anemia, thrombocytopenia, acute kidney injury (AKI), and hypocomplementemia. She also reported cryoglobulinemia, thrombotic microangiopathy (TMA), and AKI 2 years previously. Peripheral blood smears at that time showed 4% schistocytes, a negative Coombs' test, and elevated lactate dehydrogenase (LDH). Based on a diagnosis of complement-mediated TMA, the patient was treated by plasmapheresis and achieved clinical disease remission. However, the serum hypocomplement 4 and cryoglobulinemia persisted. Further investigation showed elevated B lymphocytes and monoclonal serum IgMκ; however, the cryoprecipitate contained monoclonal IgMκ and polyclonal IgG, as well as immunoglobulins κ and λ. After plasmapheresis, her LDH, platelets, and complement 3 (C3) levels returned to normal. Biopsies of the bone marrow and an enlarged subclavicular lymph node revealed CLL/SLL. Renal pathological findings indicated significant arteriolar endothelial cells myxoid edema and glomerular endothelial cells swelling, however no thromboli, cryoglobulin formation and vasculitis were observed. We also found mild mesangial proliferative C3 glomerulonephritis and renal interstitial CLL cells infiltration. Collectively, these clinical and pathological manifestations were attributed to monoclonal IgMκ, which triggered C3 activation. MGRS associated with CLL was finally confirmed. Six cycles of rituximab, cyclophosphamide, verodoxin, and dexamethasone therapy were administered, after which she received ibrutinib. The patient experienced disease remission, and her serum C4 level returned to normal. Cryoglobulin and IgMκ were not detected. This is a special presentation of CLL/SLL with monoclonal IgMκ, which is a type of MGRS. Activation of the complement system by MIg led to TMA with C3 glomerulonephritis. Treatment for TMA and CLL/SLL should be initiated in a timely manner to improve patient prognosis.
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http://dx.doi.org/10.3389/fmed.2022.813439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8866726PMC
February 2022

Multimorbidity and adverse events of special interest associated with Covid-19 vaccines in Hong Kong.

Nat Commun 2022 01 20;13(1):411. Epub 2022 Jan 20.

Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.

Prior research using electronic health records for Covid-19 vaccine safety monitoring typically focuses on specific disease groups and excludes individuals with multimorbidity, defined as ≥2 chronic conditions. We examine the potential additional risk of adverse events 28 days after the first dose of CoronaVac or Comirnaty imposed by multimorbidity. Using a territory-wide public healthcare database with population-based vaccination records in Hong Kong, we analyze a retrospective cohort of patients with chronic conditions. Thirty adverse events of special interest according to the World Health Organization are examined. In total, 883,416 patients are included and 2,807 (0.3%) develop adverse events. Results suggest vaccinated patients have lower risks of adverse events than unvaccinated individuals, multimorbidity is associated with increased risks regardless of vaccination, and the association of vaccination with adverse events is not modified by multimorbidity. To conclude, we find no evidence that multimorbidity imposes extra risks of adverse events following Covid-19 vaccination.
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http://dx.doi.org/10.1038/s41467-022-28068-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8776841PMC
January 2022

Circadian clock regulates granulosa cell autophagy through NR1D1-mediated inhibition of ATG5.

Am J Physiol Cell Physiol 2022 02 22;322(2):C231-C245. Epub 2021 Dec 22.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, People's Republic of China.

Autophagy of granulosa cells (GCs) is involved in follicular atresia, which occurs repeatedly during the ovarian development cycle. Several circadian clock genes are rhythmically expressed in both rodent ovarian tissues and GCs. Nuclear receptor subfamily 1 group D member 1 (NR1D1), an important component of the circadian clock system, is involved in the autophagy process through the regulation of autophagy-related genes. However, there are no reports illustrating the role of the circadian clock system in mouse GC autophagy. In the present study, we found that core circadian clock genes (, , , and ) and an autophagy-related gene () exhibited rhythmic expression patterns across 24 h in mouse ovaries and primary GCs. Treatment with SR9009, an agonist of NR1D1, significantly reduced the expression of , , and in mouse GCs. ATG5 expression was significantly attenuated by SR9009 treatment in mouse GCs. Conversely, knockdown increased ATG5 expression in mouse GCs. Decreased NR1D1 expression at both the mRNA and protein levels was detected in the ovaries of mice, along with elevated expression of ATG5. Dual-luciferase reporter assay and electrophoretic mobility shift assay showed that NR1D1 inhibited transcription by binding to two putative retinoic acid-related orphan receptor response elements within the promoter. In addition, rapamycin-induced autophagy and ATG5 expression were partially reversed by SR9009 treatment in mouse GCs. Taken together, our current data demonstrated that the circadian clock regulates GC autophagy through NR1D1-mediated inhibition of ATG5 expression, and thus, plays a role in maintaining autophagy homeostasis in GCs.
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http://dx.doi.org/10.1152/ajpcell.00267.2021DOI Listing
February 2022

Study on the Relationship Between the Expression of B Cell Mature Antigen and the Classification, Stage, and Prognostic Factors of Multiple Myeloma.

Front Immunol 2021 18;12:724411. Epub 2021 Nov 18.

Department of Hematology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

The expression level of BCMA in bone marrow of 54 MM patients was detected in this study to explore the relationship between the BCMA expression and the classification, stage, and prognostic factors of MM. The BCMA expression level of the stable group and remission group was lower than that of the newly diagnosed group and relapse group (P=0.001). There was no significant difference in BCMA expression of MM patients in different types and stages (P>0.05), but it was found that for the newly diagnosed MM patients, the BCMA expression level of IgG patients was higher than that of IgA or light-chain patients (rank average 11.20 5.44, P=0.014). There was no significant correlation between the BCMA expression and the age and serum creatinine of MM patients (P>0.05). And there was no significant difference in BCMA expression between patients with different levels of age and serum creatinine (P>0.05). But it was found that the BCMA expression level of the newly diagnosed MM patients was moderately positively correlated with their age (P=0.025, r=0.595). There was no significant correlation between the BCMA expression and serum β2-microglobulin, serum lactate dehydrogenase, free kap/lam ratio, and urine β2-microglobulin (P>0.05). But we found that the BCMA expression of patients with high serum β2-microglobulin was higher than that of patients with low serum β2-microglobulin (rank average 28.89 17.54, P=0.017). And the BCMA expression of patients with abnormal serum free kap/lam ratio was higher than that of patients with normal ratio (rank average 28.49 13.55, P=0.004). The BCMA expression was strongly positively correlated with 24-h urine protein, was moderately positively correlated with serum M protein and the percentage of plasma cells in bone marrow, was moderately negatively correlated with albumin and hemoglobin count, and was weakly positively correlated with serum corrected calcium (P<0.05). And it was found that the BCMA expression of positive serum immunofixation electrophoresis patients was higher than that of negative patients (rank average 29.94 16.75, P=0.017). And we try to clarify the relationship between the bone marrow BCMA expression and the peripheral blood sBCMA expression. However, we have not found a clear correlation between them so far (P>0.05).
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http://dx.doi.org/10.3389/fimmu.2021.724411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8637449PMC
January 2022

Decreased urinary uromodulin is potentially associated with acute kidney injury: a systematic review and meta-analysis.

J Intensive Care 2021 Nov 15;9(1):70. Epub 2021 Nov 15.

Department of Nephrology, Peking Union Medical College Hospital, No 1, Shuaifuyuan, Wangfujing St, Beijing, 100730, China.

Background: Urinary uromodulin (uUMOD) is one of the novel biomarkers for predicting AKI. However, currently available publications showed inconsistent results. We designed this meta-analysis to evaluate the potential association between uUMOD and AKI.

Methods: We searched research articles with no language restriction in Medline, Web of Science, Cochrane Library, Embase, and 3 Chinese datasets from inception to February 2021. We used random-effects models to estimate the standardized mean difference (SMD) between patients with AKI or not, while the leave-one-out method and random-effects meta-regression to evaluate the sensitivity and the impact of potential confounders such as age and surgery.

Results: The meta-analysis comprising 3148 subjects from 11 studies showed that the uUMOD of the AKI group is significantly lower than the non-AKI group (SMD: - 0.71; 95% confidence interval (CI), - 1.00, - 0.42, P < 0. 001, I = 78.8%). Subgroup analysis revealed the difference is also significant in a different age, surgery condition, and assay time but not acute rejection (AR) group, especially in children (SMD: - 1.21, 95% CI: - 1.80, - 0.61; P < 0.001) and patients undergoing surgery (SMD: - 1.03, 95% CI: - 1.75, - 0.30; P < 0.001). Lower uromodulin is associated with higher odds for AKI incidence (odds ratio = 2.47, 95% CI: 1.12, 5.47; P < 0.001, I = 89%). Meta-reggression found that age was associated with the SMD of uUMOD. The study outcome was reliably confirmed by the sensitivity analysis.

Conclusion: The present study suggested a negative association between uUMOD and AKI especially in children and surgical patients.
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http://dx.doi.org/10.1186/s40560-021-00584-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8591828PMC
November 2021

Genome-wide development and application of miRNA-SSR markers in genus.

Physiol Mol Biol Plants 2021 Oct 9;27(10):2269-2282. Epub 2021 Oct 9.

State Key Laboratory of Grassland Agro-Ecosystems, Key Laboratory of Grassland Livestock Industry Innovation, Ministry of Agriculture and Rural Affairs, Engineering Research Center of Grassland Industry, Ministry of Education, College of Pastoral Agriculture Science and Technology, Lanzhou University, Lanzhou, 730020 People's Republic of China.

Genetic diversity of plants is the brace of biodiversity and diversity within species, between species, and of ecosystems. SSR markers are the most preferable molecular marker tool that has been successfully used to study the genetic diversity of plant species. Development of miRNA-SSR markers has been deed in animals but is still limited in plants. In this study, 365 precursors miRNA were extracted from (Ma) genome and used to design Ma miRNA-SSR primers. 137 Ma primer pairs (79 from known and 58 from novel pre-miRNAs) were obtained. 66 pairs of Ma miRNA-SSR primers were selected with polymorphisms and expected fragment size. The polymorphisms of primers were evaluated in 60 individuals of 15 Ma accessions. A total of 66 primer pairs showed high polymorphism, with average polymorphic information content of 0.49 among 15 Ma accessions and 0.63 among 18 species, indicating that these primers have high polymorphisms. The number of alleles produced per primer ranged from 2 to 6 with an average of 3.6 alleles per locus in Ma accessions, and 2 to 10 numbers of alleles with a mean of 5.24 alleles per locus in spp. For further studies, the genetic relationship was examined and the cluster analysis showed that 15 Ma accessions were grouped in three groups, on the other hand, 18 species clustered into two groups. The analysis of molecular variance (AMOVA) revealed that 64.82% of the variation was found within the species and 35.18% between the species. The population structure analysis showed similar results with PCA analysis in that 18 species were grouped in two groups. In addition, 16,450 miRNA target genes were identified and used for GO and KEGG analysis. This is the first study to develop miRNA-SSR molecular markers in spp., which has a great potential for marker-assisted, genetic improvement, genotyping applications, QTL analysis, and molecular-assisted selection studies for plant breeders and other researchers.

Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-021-01086-z.
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http://dx.doi.org/10.1007/s12298-021-01086-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8526654PMC
October 2021

Trimethylamine-N-oxide (TMAO) and clinical outcomes in patients with end-stage kidney disease receiving peritoneal dialysis.

Perit Dial Int 2021 Nov 1:8968608211051809. Epub 2021 Nov 1.

Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.

Background: Trimethylamine-N-oxide (TMAO) is a gut bacteria-derived metabolite of l-carnitine and choline. A high concentration of TMAO has been proven to relate to cardiovascular disease (CVD), all-cause mortality and chronic kidney disease progression. We aimed to investigate the relation between the value of serum TMAO and outcomes for peritoneal dialysis (PD) patients.

Methods: This is a prospective cohort study with data retrospectively analysed. All incident PD patients were enrolled and followed up. Log-rank test, competing risk survival analysis and COX regression were performed to test the effect of serum TMAO on developing first-episode peritonitis, all-cause and CVD mortality.

Results: A wide distribution of serum TMAO concentration was observed in 513 PD patients, with a median level of 72.3 (43.7, 124.7) µmol/L. Patients with lower TMAO concentration were more likely to be without diabetes and hypertension. Patients with lower TMAO concentration showed better residual kidney function and solute clearance at baseline. Participants in the higher three TMAO quartiles showed an increased risk for first-episode peritonitis ( = 0.039). By competing risk survival analysis, after adjusting for age, sex, diabetes mellitus, CVD, body mass index, albumin, high-sensitive C-reactive protein, potassium, phosphorus, residual kidney function, normalised protein equivalent of total nitrogen appearance and calendar year of catheter implantation, patients in the higher three TMAO quartiles had a statistically or marginally higher risk for first-episode peritonitis compared with patients in the lowest quartile, with hazard ratio (HR) 1.65 (1.05, 2.58), 1.46 (0.92, 2.31) and 1.66 (1.05, 2.61), respectively. In the COX model, patients in the third quartile TMAO group had significantly higher CVD mortality risk compared with the lowest quartile group, as HR 2.27 (1.02, 5.05) after adjusting for various factors. As for all-cause mortality, TMAO did not show any associated effects.

Conclusions: Serum TMAO concentration is associated with the risk of first-episode peritonitis and CVD mortality in PD patients. No obvious association between serum TMAO and all-cause mortality was observed.
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http://dx.doi.org/10.1177/08968608211051809DOI Listing
November 2021

Distribution and speciation of arsenic in seasonally stratified reservoirs: Implications for biotransformation mechanisms governing interannual variability.

Sci Total Environ 2022 Feb 14;806(Pt 4):150925. Epub 2021 Oct 14.

Institute of Surface-Earth System Science, School of Earth System Science, Tianjin University, Tianjin 300072, China. Electronic address:

HPLC-ICPMS was used to analyze the spatiotemporal variation of As species in different sections and tributaries of the Aha Reservoir over four seasons, and the migration and transformation mechanisms were clarified by combined analysis of hydrochemical parameters and microbial composition. The results showed that the internal release of As from the reservoir sediments is mainly due to the reduction of iron oxide and the release of adsorbed As(V). The average proportion of As(III) increased from 27.2% in autumn to 46.5% in summer, 68.9% in winter, and up to 70.8% in spring. In spring and summer, the high concentration of As(III) and organic arsenic in the epilimnion under phosphorus restriction was caused by the reductive metabolism of phytoplankton after intake of As(V). The arsenic species in the metalimnion were mainly affected by the oxidation-reduction potential (ORP). In summer and autumn, As-oxidizing bacteria used As(III) as an electron donor, and nitrate played an important role as an electron acceptor, maintaining the dominance of As(V) in the hypolimnion. However, in winter and spring, temperature-controlled ORP was the main process, which was dominated by As(III). In conclusion, As species show annual cycles in different layers of seasonally thermal stratified reservoirs. It provides a systematic mechanism of As species transformation in reservoirs, especially the effect of biological transformation mechanism.
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http://dx.doi.org/10.1016/j.scitotenv.2021.150925DOI Listing
February 2022

Development of molecular markers based on LTR retrotransposon in the Cleistogenes songorica genome.

J Appl Genet 2022 Feb 23;63(1):61-72. Epub 2021 Sep 23.

State Key Laboratory of Grassland Agro-ecosystems, Key Laboratory of Grassland Livestock Industry Innovation, Ministry of Agriculture and Rural Affairs, Engineering Research Center of Grassland Industry, Ministry of Education, College of Pastoral Agriculture Science and Technology, Lanzhou University, Lanzhou, 730020, China.

Long terminal repeat retrotransposons (LTR-RTs) contribute a large fraction of many sequenced plant genomes and play important roles in genomic diversity and phenotypic variations. LTR-RTs are abundantly distributed in plant genomes, facilitating the development of markers based on LTR-RTs for a variety of genotyping purposes. Whole-genome analysis of LTR-RTs was performed in Cleistogenes songorica. A total of 299,079 LTR-RTs were identified and classified as Gypsy type, Copia type, or other type. LTR-RTs were widely distributed in the genome, enriched in the heterochromatic region of the chromosome, and negatively correlated with gene distribution. However, approximately one-fifth of genes were still interrupted by LTR-RTs, and these genes are annotated. Furthermore, four types of primer pairs (PPs) were designed, namely, retrotransposon-based insertion polymorphisms, inter-retrotransposon amplified polymorphisms, insertion site-based polymorphisms, and retrotransposon-microsatellite amplified polymorphisms. A total of 350 PPs were screened in 23 accessions of the genus Cleistogenes, of which 80 PPs showed polymorphism, and 72 PPs showed transferability among Gramineae and non-Gramineae species. In addition, a comparative analysis of homologous LTR-RTs was performed with other related grasses. Taken together, the study will serve as a valuable resource for genotyping applications for C. songorica and related grasses.
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http://dx.doi.org/10.1007/s13353-021-00658-9DOI Listing
February 2022

AKT3 and related molecules as potential biomarkers responsible for cryptorchidism and cryptorchidism-induced azoospermia.

Transl Pediatr 2021 Jul;10(7):1805-1817

Department of Urology, Capital Institute of Pediatrics, Beijing, China.

Background: Cryptorchidism is a common congenital malformation strongly related to future oligospermia and male infertility. Normally functioning early-stage spermatogonia are vital to ensure fertility. The present study aimed to identify new differentially expressed genes (DEGs) associated with signaling pathways related to spermatogonial stem cell (SSC) maintenance during early spermatogenesis.

Methods: GEO2R was used to screen for genes differentially regulated in cryptorchidism using mRNA expression profiling data in the GEO database. DAVID was used to perform GO and KEGG enrichment analysis of DEGs to analyze their functions. A protein-protein interaction (PPI) network of DEGs was constructed using the STRING database. The hub genes in the PPI networks were identified using Maximal Clique Centrality (MCC) in Cytohubba, and the top 50 genes were displayed as hub genes using Cytoscape software. Then, the miRNAs targeting hub genes were predicted using miRWalk and an mRNA-miRNA interaction network was constructed using Cytoscape. We took the intersection of these target miRNAs and the differentially expressed miRNAs identified from a non-coding RNA sequencing dataset, GSE149084. Furthermore, the intersected miRNAs and their predicted target genes were validated in the testicular tissue of rats with cryptorchidism.

Results: A total of 474 DEGs were identified, most of which were annotated to the PI3K-AKT-mTOR signaling pathway. Hub genes related to the pathway were predicted to be targeted by 27 miRNAs. Further miRNA mining revealed that miRNA-7-5p and miRNA-519d-3p were both dysregulated in cryptorchidism patients. Further, we found that these two miRNAs were predicted with high confidence to share a common target gene, AKT3. In the testicular tissue of rats with cryptorchidism, miRNA-519d-3p was upregulated while miRNA-7-5p and AKT3 were downregulated. We also found that AKT3 plays an essential role in regulating SSC state through the PI3K-AKT-mTOR signaling pathway and that AKT3 is one of the key genes related to SSC self-renewal, proliferation, and differentiation.

Conclusions: The PI3K-AKT-mTOR signaling pathway functions in SSC maintenance, and alterations in this pathway may explain defects in spermatogenesis. AKT3-related miRNAs, including hsa-miR-7-5p and hsa-miR-519d-3p, might be responsible for cryptorchidism and cryptorchidism-induced azoospermia and serve as potential biomarkers.
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http://dx.doi.org/10.21037/tp-21-31DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8349953PMC
July 2021

Circadian regulation of apolipoprotein gene expression affects testosterone production in mouse testis.

Theriogenology 2021 Oct 14;174:9-19. Epub 2021 Aug 14.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, 712100, Shaanxi, China; Key Laboratory of Animal Biotechnology of the Ministry of Agriculture and Rural Affairs, Northwest A&F University, Yangling, 712100, Shaanxi, China. Electronic address:

The circadian clock system plays an important role in regulating testosterone synthesis in mammals. Male Bmal1 mice are infertile with low serum testosterone levels and decreased expression of testicular steroidogenic genes, suggesting that circadian clock genes regulate testosterone biosynthesis by activating steroidogenic gene transcription. However, whether the circadian clock regulates testosterone production via other genes remains unknown. Using Bmal1 mice and their wild-type (WT) siblings, we aimed to identify additional genes by which the circadian clock regulates testosterone synthesis. WT and Bmal1 mouse testes sections had similar normal morphologies, although there was a decrease in testicular spermatozoa in the Bmal1 mice. Low serum testosterone levels were detected in the Bmal1 mice. RNA sequencing identified 37 and 48 genes that were differentially expressed between WT and Bmal1 mouse testes at circadian time (CT2 and CT14), respectively. The cholesterol metabolism pathway was significantly enriched in the KEGG pathway analysis, and there was lower expression of three apolipoprotein genes (Apoa1, Apoa2, and Apoc3) at CT2 in the testes of Bmal1 mice than in those of WT mice. These decreases in Apoa1, Apoa2, and Apoc3 expression were verified by quantitative polymerase chain reaction analysis, which also revealed downregulation of the expression of the circadian clock (Per2, Dbp, and Nr1d1) and steroidogenic (StAR, Cyp11a1, and Hsd17b3) genes. The expression of circadian clock genes was relatively stable in WT mice over a 20-h period, whereas there was clear circadian rhythmic expression of Apoa1, Apoa2, Apoc3, StAR, Cyp11a1, Hsd3b2, and Hsd17b3. Bmal1 mice showed severely reduced expression of testicular circadian clock genes at three time points (CT4, CT12, and CT20), and a reduction in mRNA expression levels of Apo (Apoa1, Apoa2, and Apoc3) and steroidogenic (StAR, Cyp11a1, Hsd3b2, and Hsd17b3) genes. Oil Red O staining showed decreased lipid aggregation in the Leydig cells of Bmal1 mouse testes. Considering the vital role of Apo genes in high-density lipoprotein formation and cholesterol transport, the present data suggest that the circadian clock system regulates testosterone production by orchestrating the rhythmic expression of Apo genes. These data extend our understanding of the role of the circadian clock in regulating testosterone production in mammals.
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http://dx.doi.org/10.1016/j.theriogenology.2021.06.023DOI Listing
October 2021

A novel frameshift mutation in the gene causing Aarskog-Scott syndrome patient with hypogonadism: a case report.

Transl Pediatr 2021 May;10(5):1377-1385

Department of Urology, Capital Institute of Pediatrics, Beijing, China.

Aarskog-Scott syndrome (AAS) is most commonly inherited as an X-linked recessive genetic disease caused by mutations. AAS patients are most frequently male, and the clinical manifestations of facial abnormalities, skeletal deformities, and abnormal genitalia comprise a characteristic triad of diagnostic features. The results on the clinical and molecular analysis of a family that reveals a novel gene frameshift mutation in an 11-year-old boy displaying bilateral cryptorchidism associated with hypogonadism are reported here. This patient exhibited a characteristic triad of diagnostic features of ASS, including short stature, facial abnormalities, joint laxity, and typical scrotal fold. Whole-exome sequencing revealed the novel hemizygous mutation c.500delA in exon 3 of the patient's gene, resulting after a frameshift in the Tyr167 residue, while his mother is heterozygous of the same variant. Further in silico studies were performed to identify the pathological consequence of this gene mutation. Thus, our study shows that frameshifts disrupting the RhoGEF gene domain of represent the most prevalent causal mutations underlying AAS and expand the phenotypic and mutational spectra of this disease. Improved understanding of the phenotypic and pathological heterogeneity accompanying mutation can greatly enhance the clinical prognostic capabilities in the future and aid genetic counseling for AAS patients.
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http://dx.doi.org/10.21037/tp-21-26DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192999PMC
May 2021

Phosphorus excess changes rock phosphate solubilization level and bacterial community mediating phosphorus fractions mobilization during composting.

Bioresour Technol 2021 Oct 19;337:125433. Epub 2021 Jun 19.

College of Resources and Environmental Science, Beijing Key Laboratory of Biodiversity and Organic Farming, China Agricultural University, Beijing 100193, China; Organic Recycling Institute (Suzhou) of China Agricultural University, Wuzhong District, Suzhou 215128, China.

This study investigated the changes of phosphorus (P) fractions, bacterial community and their response to available P or carbon (C):P during composting with different rock phosphate (RP) addition levels. Results showed that adding RP at 10% or 15% promoted the rise of temperature, maturity and Olsen P accumulation in composting, which had a higher amount of RP solubilization than other groups. Available P changed bacterial composition and decreased diversity in composts. RP solubilization efficiency was negatively correlated to C:P ratio and the highest (22.7%) when 10% RP was added, in which bacterial community changed from "function redundancy" to "intensive P-solubilization". Low C:P ratio (〈300) increased the RP solubilization ratio especially within 135-160. Therefore, this study proposed that adding P-rich substrates to decrease C:P ratio could regulate P-solubilizers' activity for increasing RP solubilization efficiency during composting.
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http://dx.doi.org/10.1016/j.biortech.2021.125433DOI Listing
October 2021

Glyphosate exposure attenuates testosterone synthesis via NR1D1 inhibition of StAR expression in mouse Leydig cells.

Sci Total Environ 2021 Sep 25;785:147323. Epub 2021 Apr 25.

Northwest A&F University, Yangling 712100, Shaanxi, China; Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling 712100, Shaanxi, China; Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, Northwest A&F University, Yangling 712100, Shaanxi, China. Electronic address:

Glyphosate is a broad-spectrum herbicide that impairs testosterone synthesis in mammals. Leydig cells (LCs), the primary producers of testosterone, demonstrate rhythmic expression of circadian clock genes both in vivo and in vitro. The nuclear receptor NR1D1 is an important clock component that constitutes the subsidiary transcriptional/translational loop in the circadian clock system. Nr1d1 deficiency resulted in diminished fertility in both male and female mice. However, whether NR1D1 is involved in the glyphosate-mediated inhibition of testosterone synthesis in LCs remains unclear. Here, the involvement of NR1D1 in glyphosate-mediated inhibition of testosterone synthesis was investigated both in vitro and in vivo. Glyphosate exposure of TM3 cells significantly increased Nr1d1 mRNA levels, but decreased Bmal1, Per2, StAR, Cyp11a1, and Cyp17a1 mRNA levels. Western blotting confirmed elevated NR1D1 and reduced StAR protein levels following glyphosate exposure. Glyphosate exposure also reduced testosterone production in TM3 cells. In primary LCs, glyphosate exposure also upregulated Nr1d1 mRNA levels and downregulated the mRNA levels of other clock genes (Bmal1 and Per2) and steroidogenic genes (StAR, Cyp17a1, Cyp11a1, and Hsd3b2), and inhibited testosterone synthesis. Moreover, glyphosate exposure significantly reduced the amplitude and shortened the period of PER2::LUCIFERASE oscillations in primary LCs isolated from mPer2 knock-in mice. Four weeks of oral glyphosate upregulated NR1D1 at both the mRNA and protein levels in mouse testes, and this was accompanied by a reduction in StAR expression. Notably, serum testosterone levels were also drastically reduced in mice treated with glyphosate. Moreover, dual-luciferase reporter and EMSA assays revealed that in TM3 cells NR1D1 inhibits the expression of StAR by binding to a canonical RORE element present within its promoter. Together, these data demonstrate that glyphosate perturbs testosterone synthesis via NR1D1 mediated inhibition of StAR expression in mouse LCs. These findings extend our understanding of how glyphosate impairs male fertility.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147323DOI Listing
September 2021

Genome-Wide Identification and Development of LTR Retrotransposon-Based Molecular Markers for the Genus.

Plants (Basel) 2021 Apr 28;10(5). Epub 2021 Apr 28.

The State Key Laboratory of Grassland Agro-Ecosystems, Key Laboratory of Grassland Livestock Industry Innovation, Ministry of Agriculture and Rural Affairs, College of Pastoral Agriculture Science and Technology, Lanzhou University, Lanzhou 730020, China.

is an important genus of legumes with industrial and medicinal value, partly due to the production of coumarin. To explore the genetic diversity and population structure of , 40 accessions were analyzed using long terminal repeat (LTR) retrotransposon-based markers. A total of 585,894,349 bp of LTR retrotransposon sequences, accounting for 55.28% of the genome, were identified using bioinformatics tools. A total of 181,040 LTR retrotransposons were identified and classified as , , or another type. A total of 350 pairs of primers were designed for assessing polymorphisms in 15 accessions. Overall, 47 polymorphic primer pairs were screened for their availability and transferability in 18 species. All the primer pairs were transferable, and 292 alleles were detected at 47 LTR retrotransposon loci. The average polymorphism information content (PIC) value was 0.66, which indicated that these markers were highly informative. Based on unweighted pair group method with arithmetic mean (UPGMA) dendrogram cluster analysis, the 18 species were classified into three clusters. This study provides important data for future breeding programs and for implementing genetic improvements in the genus.
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http://dx.doi.org/10.3390/plants10050890DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146837PMC
April 2021

Novel equation for estimating resting energy expenditure in patients with chronic kidney disease.

Am J Clin Nutr 2021 06;113(6):1647-1656

Renal Division, Department of Medicine, Peking University First Hospital; Institute of Nephrology, Peking University; Key Laboratory of Renal Disease, Ministry of Health; Key Laboratory of Renal Disease, Ministry of Education; Research Units of Diagnosis and Treatment of Immune-mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China.

Background: In chronic kidney disease (CKD), determining energy expenditure is the precondition for recommending energy intake in nutrition management.

Objectives: We aimed to develop and validate a resting energy expenditure (REE) equation for patients with CKD.

Methods: This cross-sectional study enrolled 300 patients with CKD (stages 3-5) according to inclusion and exclusion criteria. Stepwise linear regression analysis was used to derive a new REE equation (eREE-CKD) according to actual REE (aREE) measured using indirect calorimetry in the development dataset. The eREE-CKD value was then validated with aREE in the validation dataset and compared with values from existing equations obtained in general populations, namely, the Harris-Benedict, Mifflin, WHO, and Schofield equations in terms of bias, precision, and accuracy.

Results: The eREE-CKD equation: eREE-CKD (kcal) = (1 if male; 0 if female) × 106.0 - [1 if diabetes mellitus (DM); 0 if non-DM] × 51.6 - 4.7 × age (y) + 13.1 × weight (kg) + 645.5 (R2 = 0.779).The bias, precision, and accuracy (percentage of estimates that differed >20% from the measured REE) of the eREE-CKD equation were -0.4 (IQR: -29.8, 23.8) kcal, 98.4 (IQR: 79.5, 116.6) kcal, and 5.4%, respectively with indirect calorimetry as the reference method. Both bias and precision of the eREE-CKD were significantly better than the Harris-Benedict, WHO, and Schofield equations (P < 0.001) and similar to the Mifflin equation (P = 0.125 for bias and 0.268 for precision). Accuracy of the eREE-CKD was significantly better than the Harris-Benedict, WHO, Mifflin, and Schofield equations (P < 0.001). Bias, precision, and accuracy of the eREE-CKD equation were consistent when applied to subgroups categorized according to high-sensitivity C-reactive protein concentrations and CKD stages, respectively.

Conclusions: The eREE-CKD equation using age, sex, weight, and DM data could serve as a reliable tool for estimating REE in patients with CKD. This trial was registered at clinicaltrials.gov as NCT03377413.
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http://dx.doi.org/10.1093/ajcn/nqaa431DOI Listing
June 2021

Identification of the candidate lncRNA biomarkers for acute kidney injury: a systematic review and meta-analysis.

Expert Rev Mol Diagn 2021 01 20;21(1):77-89. Epub 2021 Feb 20.

Department of Nephrology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.

: This meta-analysis aims to summarize the studies of lncRNAs dysregulation in individual acute kidney injury (AKI) and identify the potential lncRNA biomarkers of AKI.: We systematically searched four databases to identify the lncRNA expression studies of AKI in animal models and patients. The lncRNAs expression data were extracted from 38 included studies, and lncRNA vote-counting strategy was applied to identify significant lncRNA biomarkers. The predicted targets of lncRNA biomarkers were obtained by searching Co-LncRNA, RBPmap, and LncBase v.2. Further, GO enrichment analysis and KEGG pathway analysis were performed.: We recognized a significant lncRNA signature of 21 up-regulated and 11 down-regulated lncRNAs, among which TapSAKI, XIST, MALAT1, CASC2, and HOXA-AS2 were dysregulated both in AKI rodent models and patients. About 28.0% of these lncRNAs mainly exist in the nucleus, which was also the most enriched GO cellular components term. The most relevant GO terms in biological process and molecular function associated with these lncRNAs were splicing, processing, and binding of mRNA.: The present meta-analysis identified 31 significant dysregulated lncRNAs from 38 studies. TapSAKI, XIST, MALAT1, CASC2, and HOXA-AS2 were considered as the potential predictive biomarkers and therapeutic targets of AKI.
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http://dx.doi.org/10.1080/14737159.2021.1873131DOI Listing
January 2021

Circadian clock gene BMAL1 controls testosterone production by regulating steroidogenesis-related gene transcription in goat Leydig cells.

J Cell Physiol 2021 09 17;236(9):6706-6725. Epub 2021 Feb 17.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China.

Testosterone is produced by Leydig cells (LCs) and undergoes diurnal changes in serum levels in rats, mice, and humans, but little is known in goats. The present study revealed that goat serum testosterone levels displayed diurnal rhythmic changes (peak time at ZT11.2). Immunohistochemical staining showed that BMAL1, a circadian clock protein, is highly expressed in goat LCs. ELISA revealed that both hCG (0-5 IU/ml) and 22R-OH-cholesterol (0-30 μM) addition stimulated testosterone synthesis in primary goat LCs in a dose-dependent manner. Treating goat LCs with hCG (5 IU/ml) significantly increased intracellular cAMP levels. Additionally, real-time quantitative polymerase chain reaction (PCR) analysis revealed that the circadian clock (BMAL1, PER1, PER2, DBP, and NR1D1) and steroidogenesis-related genes (SF1, NUR77, StAR, HSD3B2, CYP17A1, CYP11A1, and HSD17B3) showed rhythmic expression patterns in goat LCs following dexamethasone synchronization. Several Bmal1-Luc circadian oscillations were clearly observed in dexamethasone-treated goat LCs transfected with the pLV6-Bmal1-Luc plasmid. BMAL1 knockdown significantly downregulated mRNA levels of PER2, NR1D1, DBP, StAR, HSD3B2, SF1, NUR77, and GATA4, and dramatically decreased StAR and HSD3B2 protein levels and testosterone production. In contrast, BMAL1 overexpression significantly increased the mRNA and protein expression levels of StAR and HSD17B3 and enhanced testosterone production. Reporter assays revealed that goat BMAL1, or in combination with mouse CLOCK, activated goat HSD17B3 transcription in vitro. These data indicate that BMAL1 contributes to testosterone production by regulating transcription of steroidogenesis-related genes in goat LCs, providing a basis for further exploring the underlying mechanism by which the circadian clock regulates ruminant reproductive capability.
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http://dx.doi.org/10.1002/jcp.30334DOI Listing
September 2021

promotes prostaglandin E synthesis by upregulating transcription in response to increasing estradiol levels in pregnant mice.

Am J Physiol Endocrinol Metab 2021 04 8;320(4):E747-E759. Epub 2021 Feb 8.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, China.

Prostaglandin G/H synthase 2 (PTGS2) is a rate-limiting enzyme in prostaglandin synthesis. The present study assessed the role of the uterine circadian clock on transcription in response to steroid hormones during early pregnancy. We demonstrated that the core clock genes (, , , and ), , and and their encoded proteins, have rhythmic expression in the mouse uterus from to () of pregnancy. Progesterone (P) treatment of cultured uterus endometrial stromal cells (UESCs) isolated from reporter gene knock-in mice on D4 induced a phase shift in oscillations. This P-induced phase shift of oscillations was significantly attenuated by the P antagonist RU486. Additionally, the amplitude of oscillations was increased by estradiol (E) treatment in the presence of P. Consistently, the mRNA levels of clock genes ( and ), , and were markedly increased by E treatment of UESCs in the presence of P. Treatment with E also promoted prostaglandin E (PGE) synthesis by UESCs. Depletion of in UESCs by small-interfering RNA (siRNA) decreased the transcript levels of clock genes ( and ), , and compared with nonsilencing siRNA treatment. knockdown also inhibited PGE synthesis. Moreover, the mRNA expression levels of clock genes ( and ), , and , and their respective proteins were significantly decreased in the uterus of mice. Thus, these data suggest that in mice promotes PGE synthesis by upregulating in response to increases in E on D4 of pregnancy. Rhythmic expression of Bmal1 and Ptgs2 was observed in the uterus isolated from of pregnant mice. E increased the expression of Bmal1 and Ptg2 in UESCs isolated from mice on D4. The expression of Ptgs2 was significantly decreased in Bmal1-siRNA treated UESCs. knockdown also inhibited PGE synthesis. Thus, these data suggest that Bmal1 in mice promotes PGE synthesis by upregulating Ptgs2 in response to increases in E on D4 of pregnancy.
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http://dx.doi.org/10.1152/ajpendo.00466.2020DOI Listing
April 2021
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