Publications by authors named "Chenyang Li"

150 Publications

Analytic Energy Gradients for the Driven Similarity Renormalization Group Multireference Second-Order Perturbation Theory.

J Chem Theory Comput 2021 Nov 29. Epub 2021 Nov 29.

Department of Chemistry and Cherry Emerson Center for Scientific Computation, Emory University, Atlanta, Georgia 30322, United States.

We derive analytic energy gradients of the driven similarity renormalization group (DSRG) multireference second-order perturbation theory (MRPT2) using the method of Lagrange multipliers. In the Lagrangian, we impose constraints for a complete-active-space self-consistent-field reference wave function and the semicanonical orthonormal molecular orbitals. Solving for the associated Lagrange multipliers is found to share the same asymptotic scaling of a single DSRG-MRPT2 energy computation. A pilot implementation of the DSRG-MRPT2 analytic gradients is used to optimize the geometry of the singlet and triplet states of -benzyne. The equilibrium bond lengths and angles are similar to those computed via other MRPT2s and Mukherjee's multireference coupled cluster theory. An approximate DSRG-MRPT2 method that neglects the contributions of the three-body density cumulant is found to introduce negligible errors in the geometry of -benzyne, lending itself to a promising low-cost approach for molecular geometry optimizations using large active spaces.
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http://dx.doi.org/10.1021/acs.jctc.1c00980DOI Listing
November 2021

A Novel Rice Curl Dwarf-Associated Picornavirus Encodes a 3C Serine Protease Recognizing Uncommon EPT/S Cleavage Sites.

Front Microbiol 2021 13;12:757451. Epub 2021 Oct 13.

State Key Laboratory of Rice Biology, Institute of Biotechnology, Zhejiang University, Hangzhou, China.

Picornaviruses cause diseases in a wide range of vertebrates, invertebrates and plants. Here, a novel picornavirus was identified by RNA-seq technology from rice plants showing dwarfing and curling symptoms, and the name rice curl dwarf-associated virus (RCDaV) is tentatively proposed. The RCDaV genome consists of an 8,987 nt positive-stranded RNA molecule, excluding a poly(A) tail, that encodes two large polyproteins. Using cleavage assays, we have identified that the RCDaV 3C protease (3Cpro) as a serine protease recognizes the conserved EPT/S cleavage site which differs from the classic Q(E)/G(S) sites cleaved by most picornaviral 3C chymotrypsin-like cysteine proteases. Therefore, we comprehensively deciphered the RCDaV genome organization and showed that the two polyproteins of RCDaV can be cleaved into 12 mature proteins. We found that seven unclassified picornaviruses also encode a 3Cpro similar to RCDaV, and use the highly conserved EPT/S as the cleavage site. The precise genome organizations of these viruses were illustrated. Moreover, RCDaV and the seven unclassified picornaviruses share high sequence identities and similar genome organizations, and cluster into a distinct clade in the order . Our study provides valuable information for the understanding of picornaviral 3Cpros, deciphers the genome organization of a few relatively obscure picornaviruses, and lays the foundation for further pathogenesis research on these viruses.
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http://dx.doi.org/10.3389/fmicb.2021.757451DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8549817PMC
October 2021

Parity and risk of developing breast cancer according to tumor subtype: A systematic review and meta-analysis.

Cancer Epidemiol 2021 Dec 24;75:102050. Epub 2021 Oct 24.

Department of Epidemiology and Biostatistics, Key Laboratory of Molecular Cancer Epidemiology in Tianjin, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, People's Republic of China. Electronic address:

Background: Clinical breast cancer subtypes are categorized basing on the expression of hormone receptors and overexpression of the human epidermal growth factor receptor 2 (HER2). It is still unclear whether parity impact the risk of different breast cancer subtypes.

Methods: We searched eight mainstream databases for published epidemiologic studies that assessed the relationship between parity and risk of breast cancer subtypes up to January 12, 2021. Parity number were unified into nulliparity and ever parity. The random-effects or fixed-effect models were used to calculate the pooled odds ratios (ORs) and 95% confidence intervals (CIs) among different subtypes. Restricted cubic spline analysis with four knots was applied to determine the relationship of parity number and risk of breast cancer subtypes.

Results: We pooled sixteen case-control and four cohort studies, and performed an analysis including 7795 luminal A, 3576 luminal B, 1794 HER2-overexpressing, and 5192 triple-negative breast cancer cases among 1135131 participants. The combined ORs for ever parity versus nulliparity indicated a 34% reduction in luminal A risk (OR=0.66, 95% CI: 0.56-0.78), and a 29% reduction in luminal B risk (OR=0.71, 95% CI: 0.63-0.81), there was no significant association in HER2-overexpressing or TNBC risk. In the dose-response analysis, we observed a potentially non-linear and gradually increasing protective relationship between the number of parity and luminal breast cancer risk.

Conclusions: The effect of parity on breast cancer seems to vary among breast tumor subtypes, and it plays a protective role in luminal breast cancer.
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http://dx.doi.org/10.1016/j.canep.2021.102050DOI Listing
December 2021

Influence of Dietary Behaviors on Dyslipidemia in Pregnant Women and Its Effects on Physical Development of Fetuses and Infants: A Bidirectional Cohort Study.

Nutrients 2021 Sep 27;13(10). Epub 2021 Sep 27.

Department of Child and Adolescent Health, School of Public Health, China Medical University, Shenyang 110122, China.

Background: Gestational diabetes can alter the trajectory of fetal development, but there are few studies on the effects of abnormal lipid metabolism on physical development of infants. We aimed to explore the prevalence of maternal dyslipidemia, its influencing factors and effects on the physical development of fetuses and infants, as well as the role of leptin in this process.

Methods: Questionnaire surveys and main outcome measures were administered among 338 pairs of pregnant women and newborns.

Results: The detection rate of maternal dyslipidemia was 31.5%. The median levels of TG (triglyceride) and TG/HDL (high-density lipoprotein) ratio were higher in large-for-gestational-age (LGA) newborns. Birth weight was positively related to infants' height and weight at six months and one year old ( 0.05). Leptin was positively related to TG levels of pregnant women and newborns' birth weight ( 0.05). Logistic regression analysis showed that having greater than or equal to four meals a day (OR = 6.552, 95%CI = 1.014-42.338) and liking to eat lightly flavored food during pregnancy (OR = 1.887, 95%CI = 1.048-3.395) were independent risk factors of maternal dyslipidemia.

Conclusions: The prevalence of dyslipidemia was relatively high in pregnant women and was affected by dietary behaviors. Abnormal lipid levels during pregnancy could affect weight and length at birth, which might be associated with increasing leptin levels in cord blood, and then the weight of infants would be influenced by birth weight.
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http://dx.doi.org/10.3390/nu13103398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8538455PMC
September 2021

Narcolepsy Quality-of-Life Instrument with 21 Questions: A Translation and Validation Study in Chinese Pediatric Narcoleptics.

Nat Sci Sleep 2021 5;13:1701-1710. Epub 2021 Oct 5.

Sleep Medicine Center, Department of Respiratory and Critical Care Medicine, Peking University People's Hospital, Beijing, People's Republic of China.

Objective: This study aimed to translate and validate the narcolepsy quality-of-life instrument with 21 questions (NARQoL-21) in Chinese pediatrics with narcolepsy.

Methods: NARQoL-21 was translated following the 10 steps of scale translation. The translated version was tested by exploratory factor analysis (EFA), confirmatory factor analysis (CFA), known-group validity, criterion validity, Cronbach's α and test-rest reliability.

Results: The Chinese version of NARQoL-21 consisted of two factors: (psychosocial factors and future outlook factor), including 20 items. EFA yielded 3 domains for psychosocial factors and 1 domain for future outlook factor. The Chinese version had a negative correlation with the overall Modified Epworth Sleepiness Scale (r = -0.518, p<0.001) and meaningful difference in score between drug naïve and treated group (p<0.05). The Cronbach's α coefficient was higher than 0.7 and intraclass correlation coefficient (ICC) ranged from 0.75 to 0.905, indicating that it had good reliability.

Conclusion: The Chinese version of the NARQoL-21 is available and can be used to evaluate the health-related quality of life (HRQoL) of pediatric narcoleptics, despite that there is a shift in factors compared to the English version due to cultural differences. Future studies are recommended to further validate the scale in Chinese pediatrics with narcolepsy.
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http://dx.doi.org/10.2147/NSS.S322796DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8502071PMC
October 2021

A self-sacrifice template strategy to synthesize Co-LDH/MXene for lithium-ion batteries.

Chem Commun (Camb) 2021 Oct 28;57(86):11378-11381. Epub 2021 Oct 28.

State Key Laboratory of Metastable Materials Science and Technology, Yanshan University, Qinhuangdao 066004, China.

To overcome the limitations of both LDHs and MXenes, we develop a self-sacrifice template strategy using a zeolite imidazolate framework-67 (ZIF-67) to derive Co-LDH anchored on an MXene conductive substrate (Co-LDH/MXene). In this process, ZIF-67 grows on the MXene nanosheets, then spontaneously transforms into Co-LDH/MXene in aqueous solution at room temperature. As the LIB anode, it shows a reversible capacity of 854.9 and 398.0 mAh g at 0.1 and 1 A g, respectively. This work proposes a feasible synthesis method for the construction of a Co-LDH/MXene hybrid, which may be suitable for other MXenes.
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http://dx.doi.org/10.1039/d1cc04492cDOI Listing
October 2021

Antitumour effect of odoroside A and its derivative on human leukaemia cells through the ROS/JNK pathway.

Basic Clin Pharmacol Toxicol 2021 Oct 11. Epub 2021 Oct 11.

School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, Shenzhen, China.

Oleandrigenin-3-O-β-D-diginoside (a derivative of odoroside A), isolated and purified by our group, has seldom been explored for its pharmacological activity. This study aimed at clarifying the mechanisms towards the leukaemia-suppressive role of odoroside A (compound #1) and its derivative, oleandrigenin-3-O-β-D-diginoside (compound #2) isolated from Nerium oleander. Viability and nuclear morphology change were assessed by CCK-8 assay and fluorescence microscope, respectively. Then, the cell apoptosis and autophagy induced by the compounds were detected by flow cytometry and Western blot. Xenograft model of nude mice was also applied to measure the leukaemia-suppressive effects of compound #2 in vivo. The result displayed that compound #1 and compound #2 inhibited the proliferation of HL60 and K562 cells and stronger effects were found in HL60 than K562 cells. Both of the compounds induced a dose-dependent apoptosis and autophagy in HL60 cells, where compound #2 was more potent than compound #1. Compound #2 also demonstrated a time-dependent apoptosis and autophagy in HL60 cells. Furthermore, ROS generation and JNK phosphorylation occurred in a dose-dependent manner in the cells treated with compound #2. Mitochondria also played critical role, proved by the decrease of Bcl-2, the release of cyto c to cytosol and the activation of caspase-3 and caspase-9. Moreover, the antitumour effects of compound #2 were validated in the nude mouse xenograft model in vivo. Odoroside A and its derivative inhibited the growth of leukaemia by inducing apoptosis and autophagy through the activation of ROS/JNK pathway. These results suggest that the compounds can serve as potential antitumour agents against leukaemia, especially acute myeloid leukaemia (AML).
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http://dx.doi.org/10.1111/bcpt.13673DOI Listing
October 2021

Vitamin A alleviates heat stress-induced damage to hair follicle development in Rex rabbits.

J Sci Food Agric 2021 Oct 9. Epub 2021 Oct 9.

Department of Animal Science, Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Taian, China.

Background: Rex rabbits are important fur rabbits. Heat stress severely reduces the fur quality of Rex rabbits. The aim of this study was to experimentally investigate the effect of dietary vitamin A (VA) addition on hair follicle development and related signal pathways in Rex rabbits under heat stress.

Results: In the experiment, 90 Rex rabbits were randomly divided into three groups: control group (20-25 °C, fed basic diet), heat stress group (30-34 °C, fed basic diet), and heat stress + VA group (20-25 °C, fed 12 000 IU/kg VA in addition to the basic diet). VA could significantly increase the hair follicle density (P < 0.01), hair length (P < 0.05), and the ratio of secondary to primary hair follicles (P < 0.05). In addition, VA could significantly inhibit the expression of BMP2, BMP4, FGF5, TGF-β1, and miR-214 in heat-stressed Rex rabbits and significantly increase the expression of noggin, IGF1, IGF1R, Wnt10b, CTNNB1, SHH, and miR-203 and the levels of Wnt10b and p-β-catenin; however, there was no significant effect of VA on the expression of EGF and miR-205.

Conclusion: The dietary addition of VA can increase the hair follicle density and fur quality of heat-stressed Rex rabbits. Wnt10/β-catenin, insulin-like growth factor 1 (IGF1), fibroblast growth factor 5 (FGF5), noggin-BMP, and sonic hedgehog (SHH) signaling were associated with VA regulation under heat stress. It is possible that miR-205 and miR-194 contribute to the regulation of Wnt10/β-catenin and bone morphogenetic protein (BMP) signaling. © 2021 Society of Chemical Industry.
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http://dx.doi.org/10.1002/jsfa.11567DOI Listing
October 2021

Saponins from Nigella glandulifera seeds attenuate collagen-induced rheumatoid arthritis in rats via the OPG/RANKL/NF-κB and Ang/Tie-2 pathways.

J Ethnopharmacol 2022 Jan 5;283:114714. Epub 2021 Oct 5.

Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, PR China. Electronic address:

Ethnopharmacological Relevance: Nigella glandulifera Freyn et Sint. (N. glandulifera) seeds are widely used in traditional Uyghur medicine for a variety of immuno-inflammatory diseases. The total saponins from N. glandulifera seeds (TSNGS) have been shown to have analgesic, antioxidant, and anti-inflammatory effects that can alleviate joint pain and swelling.

Aim Of The Study: Rheumatoid arthritis (RA) is a chronic and progressive, debilitating autoimmune disease for which current treatments are not sufficiently effective and result in unsatisfactory side effects. This study aimed to mechanistically investigate the therapeutic effects of TSNGS on RA.

Materials And Methods: Qualitative analysis of TSNGS was performed using ultra-high-performance liquid chromatography-Q-Orbitrap-high-resolution mass spectrometry. Rats with collagen-induced arthritis (CIA), IL-1β-induced HFLS-RAs, and VEGF-induced HUVECs were analyzed to determine the efficacy and mechanism of TSNGS on RA.

Results: Twenty-one compounds were identified in TSNGS. TSNGS (10, 50, or 250 mg/kg) reduced the severity of arthritis, indicated by a lower arthritis score, reduced paw swelling, and body weight in rats with CIA. TSNGS ameliorated histopathological changes involving inflammatory infiltration, bone degeneration, and angiogenesis in knee and ankle joints. TSNGS improved the immuno-inflammatory response by restoring the levels of the cytokines IFN-γ, TNF-α, IL-1β, IL-6, IL-17A, IL-4, and IL-10, and increasing the number of CD4CD25 Tregs in the peripheral circulation and Foxp3 levels in knee joints in rats with CIA. Furthermore, TSNGS increased the OPG/RANKL ratio and downregulated p-p65 in serum and joint synovia. Inhibition of angiogenesis by TSNGS was associated with recovery of the angiogenesis-related Ang/Tie-2 signaling pathway.

Conclusions: It was established that TSNGS provides a therapeutic effect on RA by alleviating synovitis, bone degeneration, and angiogenesis via the OPG/RANKL/NF-κB and Ang/Tie-2 pathways and may be used for the treatment of RA.
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http://dx.doi.org/10.1016/j.jep.2021.114714DOI Listing
January 2022

Spin-free formulation of the multireference driven similarity renormalization group: A benchmark study of first-row diatomic molecules and spin-crossover energetics.

J Chem Phys 2021 Sep;155(11):114111

Department of Chemistry and Cherry Emerson Center for Scientific Computation, Emory University, Atlanta, Georgia 30322, USA.

We report a spin-free formulation of the multireference (MR) driven similarity renormalization group (DSRG) based on the ensemble normal ordering of Mukherjee and Kutzelnigg [J. Chem. Phys. 107, 432 (1997)]. This ensemble averages over all microstates of a given total spin quantum number, and therefore, it is invariant with respect to SU(2) transformations. As such, all equations may be reformulated in terms of spin-free quantities and they closely resemble those of spin-adapted closed-shell coupled cluster (CC) theory. The current implementation is used to assess the accuracy of various truncated MR-DSRG methods (perturbation theory up to third order and iterative methods with single and double excitations) in computing the constants of 33 first-row diatomic molecules. The accuracy trends for these first-row diatomics are consistent with our previous benchmark on a small subset of closed-shell diatomic molecules. We then present the first MR-DSRG application on transition-metal complexes by computing the spin splittings of the [Fe(HO)] and [Fe(NH)] molecules. A focal point analysis (FPA) shows that third-order perturbative corrections are essential to achieve reasonably converged energetics. The FPA based on the linearized MR-DSRG theory with one- and two-body operators and up to a quintuple-ζ basis set predicts the spin splittings of [Fe(HO)] and [Fe(NH)] to be -35.7 and -17.1 kcal mol, respectively, showing good agreement with the results of local CC theory with singles, doubles, and perturbative triples.
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http://dx.doi.org/10.1063/5.0059362DOI Listing
September 2021

Dietary lysine supplementation improves growth performance and skeletal muscle development in rabbits fed a low protein diet.

J Anim Physiol Anim Nutr (Berl) 2021 Sep 8. Epub 2021 Sep 8.

Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Department of Animal Science, Shandong Agricultural University, Taian, Shandong, China.

The purpose of this study was to investigate the effects on growth of Lysine (Lys) supplementation in a low protein diet. We also investigated the gene or protein expression related to skeletal muscle development and intestinal amino acid transporters, and determined the major signalling associated with Lys-regulating skeletal muscle development. 1000 healthy, weights averaging 938.6 ± 6.54 g weaned rabbits were randomly divided into five groups (five replicates in each group and 40 rabbits in each replicate). These groups consisted of the normal protein group (NP group, consuming a diet containing 16.27% protein), the low protein group (LP group, 14.15%-14.19% protein) and the LP group with an addition of 0.15%, 0.3% or 0.45% Lys. The trial included 7 d of pre-feeding and 28 d of exposure to the treatment. Compared with NP diet and LP diet, LP+0.3% Lys group improved growth performance (p < 0.05), full-bore weight and half-bore weight of rabbits (p < 0.05). The LP+0.3% Lys group also resulted in a decrease in the excretion of faecal nitrogen and urinary nitrogen (FN; UN; p < 0.05), and an increase in nitrogen utilisation rate (NUR; p < 0.05). LP diet increased the mRNA expression of MSTN and WWP1, and decreased the mRNA expression of IGF1 (p < 0.05). LP diet decreased the protein expression of P-P70S6K1, P-4EBP1 and P-S6 (p < 0.05). LP+0.3% Lys group attenuated the effects of LP diet on the expression of MSTN, WWP1, IGF1, P-P70S6K1, P-4EBP1 and P-S6 (p < 0.05). LP+0.3% Lys group resulted in an increase in mRNA expression of MyoD and protein expression of P-mTOR relative to the NP and LP groups (p < 0.05). In summary, the addition of Lys to a LP diet provides a theoretical basis for the popularisation and application of Lys in rabbit production.
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http://dx.doi.org/10.1111/jpn.13632DOI Listing
September 2021

Efficacy and Safety of Janus Kinase Inhibitors for the Treatment of Atopic Dermatitis: A Systematic Review and Meta-Analysis.

Dermatology 2021 Aug 27:1-11. Epub 2021 Aug 27.

Department of Dermatology, Shengjing Hospital of China Medical University, Shenyang, China.

Background: Current therapeutic options for atopic dermatitis (AD) are limited. Janus kinase (JAK) inhibitors may be viable alternatives.

Objectives: To assess the efficacy and safety of JAK inhibitors for AD treatment.

Methods: We searched PubMed, Embase, the Cochrane Controlled Register of Trials, Web of Science, Global Resource of Eczema Trials database, and ClinicalTrials.gov from inception to September 1, 2020. Randomized clinical trials (RCTs) comparing JAK inhibitors with placebo/vehicle treatment for AD patients were included. The primary study outcomes included (1) the change (%) from the Eczema Area and Severity Index (EASI) baseline expressed as weighted mean difference (WMD) and 95% confidence interval (95% CI), and (2) the Investigator's Global Assessment (IGA) response and safety outcomes expressed as relative risk (RR) and 95% CI.

Results: We included 14 RCTs published in 13 studies (3,822 patients). Treatment with JAK inhibitors significantly improved IGA response (RR 2.83, 95% CI 2.25-3.56, p < 0.001) and EASI score (WMD -28.82, 95% CI -34.48 to -23.16, p < 0.001). JAK inhibitor treatment achieved the largest improvement in both IGA response (RR 3.59, 95% CI 2.66-4.84, p < 0.001) and EASI score (WMD -42.00, 95% CI -48.64 to -35.36, p < 0.001) by week 4 of treatment. Topical JAK inhibitors were significantly more efficacious than oral inhibitors. Upadacitinib treatment for 4 weeks was most effective in reducing EASI score (WMD -53.92, 95% CI -69.26 to -38.58, p < 0.001), while abrocitinib for 4 weeks led to the most effective IGA response (RR 5.47, 95% CI 2.74-10.93, p < 0.001). There was no difference in the frequency of adverse events (AEs) leading to discontinuation; however, JAK inhibitors use, especially abrocitinib, led to a higher incidence of treatment-emergent AEs (RR 1.25, 95% CI 1.10-1.42, p = 0.001).

Conclusion: Our results imply that JAK inhibitors are an effective and safe AD treatment. Nevertheless, further trials with longer duration and head-to-head comparisons of different JAK inhibitors are needed.
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http://dx.doi.org/10.1159/000518541DOI Listing
August 2021

The month of birth has a seasonal effect in Chinese patients with narcolepsy and cataplexy.

J Clin Sleep Med 2021 Aug 26. Epub 2021 Aug 26.

Sleep Medicine Center, Department of Respiratory and Critical Care Medicine, Peking University People's Hospital, Beijing, China.

Study Objectives: We assess the yearly seasonal, environmental effects on birth pattern in Chinese patients later diagnosed with narcolepsy and cataplexy, and explored if this effect persisted in patients with symptoms onset date before, following and after 2009 H1N1 pandemic.

Methods: A total of 1942 patients with birth data information and diagnosed narcolepsy with cataplexy were included in this study. The birth month and seasonal effect of 1064 patients born from 1970 to 2000 were compared to controls (n=2,028,714) from the general population. Furthermore, birth season effect in 1373 patients with definite disease onset month were compared among patients with onset date before (n=595), following (n=325), and after (n=453) H1N1 pandemic.

Results: Patients with narcolepsy and cataplexy had a significantly different seasonality from the general population (p = 0.027). The monthly distribution of birth month yielded a peak in November (odds ratio = 1.23 [95%CI, 1.01-1.49], p=0.042) and a trough in April (odds ratio = 0.68 [95%CI,0.52-0.88], p=0.004). No significant difference was observed in the birth month across patients with symptoms onset dates before, following and after the 2009 H1N1 pandemic (p=0.603).

Conclusions: This reveal across many years of seasonal effect in Chinese narcolepsy cataplexy supports a role for early-life environmental influences on disease development.
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http://dx.doi.org/10.5664/jcsm.9626DOI Listing
August 2021

miR-486 Promotes the Invasion and Cell Cycle Progression of Ovarian Cancer Cells by Targeting CADM1.

Anal Cell Pathol (Amst) 2021 5;2021:7407086. Epub 2021 Aug 5.

Department of Hematology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou 450008, China.

Objective: To explore the role and possible underlying mechanism of miR-486 in ovarian cancer (OC) cells.

Methods: The expression of miR-486 and CADM1 was detected by qRT-PCR in OC tissues and adjacent nontumor tissues and OC cell lines. The dual-luciferase reporter gene system was used to determine the targeting relationship between miR-486 and CADM1. CCK-8, colony formation assay, Transwell, and flow cytometry were performed to detect cell proliferation, cell invasion, cell cycle progression, and the apoptotic cell death, respectively. Western blot was carried out to detect the expression of CADM1 protein and the proteins associated with cell cycle progression.

Results: miR-486 was significantly upregulated in OC tissues and cells, while CADM1 expression was significantly downregulated. Dual-luciferase reporter assays further confirmed that CADM1 was a target gene of miR-486. Interference with miR-486 could inhibit the proliferation and invasion and promoted the apoptosis of SKOV3 cells. Knocking down both miR-486 and CADM1 significantly increased the SKOV3 cell proliferation, invasion, and the number of cells transitioning from the G0/G1 phase into the S phase of cell cycle and reduced the cellular apoptosis. Western blot analysis revealed that the expression of cell cycle progression-related proteins (CyclinD1, CyclinE, and CDK6) was significantly reduced, and the p21 expression was increased when interfering with both miR-486 and CADM1 expression.

Conclusion: Our results suggested that miR-486 could act as a tumor promoter by targeting CADM1 and be a potential therapeutic target for the treatment of OC.
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http://dx.doi.org/10.1155/2021/7407086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8360751PMC
August 2021

REV-ERBα agonist SR9009 suppresses IL-1β production in macrophages through BMAL1-dependent inhibition of inflammasome.

Biochem Pharmacol 2021 10 26;192:114701. Epub 2021 Jul 26.

School of Biomedical Sciences, CUHK Shenzhen Research Institute, Heart and Vascular Institute, Chinese University of Hong Kong, Hong Kong Special Administrative Region. Electronic address:

The circadian clock plays an important role in adapting organisms to the daily light/dark cycling environment. Recent research findings reveal the involvement of the circadian clock not only in physiological functions but also in regulating inflammatory responses under pathological situations. Previous studies showed that the time-of-day variance of leucocyte circulation and pro-inflammatory cytokines secretion could be directly regulated by the clock-related proteins, including BMAL1 and REV-ERBα in a 24-hour oscillation pattern. To investigate the molecular mechanism behind the regulation of inflammation by the core clock components, we focus on the inflammatory responses in macrophages. Using bone marrow-derived macrophages from wild type and myeloid selective BMAL1-knockout mice, we found that the production of inflammatory cytokines, particularly IL-1β, was dependent on the timing of the lipopolysaccharide (LPS) stimulation in macrophages. Pharmacological activation of REV-ERBα with SR9009 significantly suppressed the LPS-induced inflammation in vitro and in vivo. Particularly, the effect of SR9009 on inhibiting NLRP3-mediated IL-1β and IL-18 production in macrophages was dependent on BMAL1 expression. Further analysis of the metabolic activity in LPS-treated mice showed that knockout of BMAL1 in macrophages exacerbated the hypometabolic state and delayed the recovery from LPS-induced endotoxemia even in the presence of SR9009. These results demonstrated an anti-inflammatory role of REV-ERBα in endotoxin-induced inflammation, during which the secretion of IL-1β through the NLRP3 inflammasome pathway inhibited by SR9009 was regulated by BMAL1.
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http://dx.doi.org/10.1016/j.bcp.2021.114701DOI Listing
October 2021

Factors Associated with Depression and Sub-Dimension Symptoms in Adolescent Narcolepsy.

Nat Sci Sleep 2021 6;13:1075-1082. Epub 2021 Jul 6.

Department of General Internal Medicine, Peking University People's Hospital, Beijing, 100044, People's Republic of China.

Objective: We evaluate the association between depression symptoms, clinical features (disease onset-age, disease duration, sleep-related hallucination), sleepiness, and polysomnography parameters in adolescent narcolepsy type 1 patients.

Methods: Eighty-three adolescent narcolepsy type 1 patients were involved in this cross-sectional study. Patients completed questionnaires evaluating depression symptoms (Center for Epidemiologic Studies Depression Scale) and sleepiness (Epworth Sleepiness Scale). Parameters from polysomnography and multiple sleep latency test were also collected.

Results: Patients with depression symptoms (62.7%) have later disease onset-age. Depression symptoms were associated with sleep-related hallucination (OR = 2.75). Six independent variables were associated with sub-dimensional depression symptoms, including sleep latency, sleep efficiency, sleep-related hallucination, Epworth sleepiness scale, disease duration, and disease onset-age.

Conclusion: Sleep-related hallucination is associated with total depression symptoms in adolescent narcolepsy. Subjective sleepiness is associated with depressed affect, somatic symptoms, and interpersonal problems. Lower sleep efficiency is associated with a lack of positive affect.
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http://dx.doi.org/10.2147/NSS.S312000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273757PMC
July 2021

Effect and Mechanism of TL1A Expression on Epithelial-Mesenchymal Transition during Chronic Colitis-Related Intestinal Fibrosis.

Mediators Inflamm 2021 25;2021:5927064. Epub 2021 Jun 25.

Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, No. 80 Huanghe Road, Yuhua District, Shijiazhuang, Hebei, China.

Background And Aims: Recent evidences reveal that epithelial to mesenchymal transition (EMT) exacerbates the process of intestinal fibrosis. Tumor necrosis factor-like ligand 1A (TL1A) is a member of the tumor necrosis family (TNF), which can take part in the development of colonic inflammation and fibrosis by regulating immune response or inflammatory factors. The purpose of this study was to elucidate the possible contribution of TL1A in onset and progression of intestinal inflammation and fibrosis through EMT.

Methods: Colonic specimens were obtained from patients with inflammatory bowel disease (IBD) and control individuals. The expression levels of TL1A and EMT-related markers in intestinal tissues were evaluated. Furthermore, the human colorectal adenocarcinoma cell line, HT-29, was stimulated with TL1A, anti-TL1A antibody, or BMP-7 to assess EMT process. In addition, transgenic mice expressing high levels of TL1A in lymphoid cells were used to further investigate the mechanism of TL1A in intestinal fibrosis.

Results: High levels of TL1A expression were detected in the intestinal specimens of patients with ulcerative colitis and Crohn's disease and were negatively associated with the expression of an epithelial marker (E-cadherin), while it was positively associated with the expression of interstitial markers (FSP1 and -SMA). Transgenic mice with high expression of TL1A were more sensitive to dextran sodium sulfate and exhibited severe intestinal inflammation and fibrosis. Additionally, the TGF-1/Smad3 pathway may be involved in TL1A-induced EMT, and the expression of IL-13 and EMT-related transcriptional molecules (e.g., ZEB1 and Snail1) was increased in the intestinal specimens of the transgenic mice. Furthermore, TL1A-induced EMT can be influenced by anti-TL1A antibody or BMP-7 .

Conclusions: TL1A participates in the formation and process of EMT in intestinal fibrosis. This new knowledge enables us to better understand the pathogenesis of intestinal fibrosis and identify new therapeutic targets for its treatment.
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http://dx.doi.org/10.1155/2021/5927064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253633PMC
June 2021

Mist1 promoted inflammation in colitis model via K+-ATPase NLRP3 inflammasome by SNAI1.

Pathol Res Pract 2021 Aug 12;224:153511. Epub 2021 Jun 12.

Department of Gastroenterology, The Fourth Medical Center of Chinese PLA General Hospital, Beijing 100048, China. Electronic address:

Ulcerative colitis (UC) is a chronic inflammatory intestinal disease. Genetic susceptibility, gut microbiota and mucosal immune dysfunction play important roles in the pathogenesis and development of UC. We investigate the effect of Mist1 in model of colitis and its underlying mechanism. The expressions of Mist1 in patients with colitis tissue were up-regulated. Meanwhile, Mist1 mRNA and protein expressions in DSS-induced colitis mice model were also induced and Mist1 mRNA and protein expressions of LPS induced THP-1 cell were also up-regulated. we found Mist1 human protein promoted inflammation in DSS-induced colitis mice by NLRP3. So, we up-regulated Mist1 expression and over-expression of Mist1 promoted IL-1β and NLRP3 protein expression levels in vitro model. However, down-regulation of Mist1 suppressed IL-1β and NLRP3 protein expression levels in vitro model. Next, SNAI1 is a shooting point of Mist1 in the effects of Mist1 in colitis. The inhibition of SNAI1 reduced the effects of Mist1 on NLRP3 inflammasome in vitro model. Activation of SNAI1 induced the effects of Mist1 on NLRP3 inflammasome in vitro model. Lastly, anti-SNAI1 human protein lowered the effects of Mist1 human protein on NLRP3 inflammasome in DSS-induced colitis mice. We demonstrated that Mist1 promoted inflammation in colitis model via NLRP3 inflammasome by SNAI1, whereas the absence of these macrophages led to a significant improvement in colitis treatment.
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http://dx.doi.org/10.1016/j.prp.2021.153511DOI Listing
August 2021

Development of Broad-Spectrum Antiviral Agents-Inspiration from Immunomodulatory Natural Products.

Viruses 2021 06 28;13(7). Epub 2021 Jun 28.

Department of Pharmacy, School of Medicine, Health Science Center, Shenzhen University, Shenzhen 518060, China.

Developing broad-spectrum antiviral drugs remains an important issue as viral infections continue to threaten public health. Host-directed therapy is a method that focuses on potential targets in host cells or the body, instead of viral proteins. Its antiviral effects are achieved by disturbing the life cycles of pathogens or modulating immunity. In this review, we focus on the development of broad-spectrum antiviral drugs that enhance the immune response. Some natural products present antiviral effects mediated by enhancing immunity, and their structures and mechanisms are summarized here. Natural products with immunomodulatory effects are also discussed, although their antiviral effects remain unknown. Given the power of immunity and the feasibility of host-directed therapy, we argue that both of these categories of natural products provide clues that may be beneficial for the discovery of broad-spectrum antiviral drugs.
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http://dx.doi.org/10.3390/v13071257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310077PMC
June 2021

Price Attractiveness and Price Complexity: Why People Prefer Level-Payment Loans.

Front Psychol 2021 10;12:532696. Epub 2021 Jun 10.

School of Business and Administration, Northeastern University, Shenyang, China.

The improving sequence effect suggests that in choices between a rising earning and any other sequences, participants prefer the rising earning. Recent studies show that the improving sequence effect also exists in a loan context. As consumers have a strong preference for falling loan profiles, banks may consider to offer loans in which the loan repayments concentrate at the beginning of the loan term. In this paper, we examined the improving sequence effect in context of a car loan with three repayment plans expressed in temporally reframed prices (TRP). By regressing the evaluation of loan profiles on the perceived price attractiveness, price complexity, TRP and the interaction terms, we find that (1) the perceived price attractiveness and price complexity significantly predict the loan evaluation, and they also explain a significant proportion of variance in loan evaluation; (2) the TRP effect interacts with the improving sequence effect. Specifically, with the introduction of TRP, respondents prefer constant profiles over falling profiles. TRP may explain why level-payment loans are still popular in real world, though the improving sequence effect suggests otherwise.
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http://dx.doi.org/10.3389/fpsyg.2021.532696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222506PMC
June 2021

Long noncoding RNA taurine-up regulated gene 1 for the prognosis of osteosarcoma: A protocol for meta-analysis and bioinformatics analysis.

Medicine (Baltimore) 2021 Jun;100(24):e26182

Department of Orthopedics and Soft Surgery, Gansu Cancer Hospital, Lanzhou, Gansu Province, China.

Background: In recent years, a variety of long noncoding RNA (lncRNA) has been confirmed to be involved in the initiation and progression of osteosarcoma. Taurine-up regulated gene 1 (TUG1) plays an important role in the formation, invasion, and metastasis of osteosarcoma. Therefore, perhaps TUG1 is a potential biomarker for the prognosis of patients suffering from osteosarcoma. In this study, meta-analysis and bioinformatics were adopted to further explore the effects of TUG1 on the prognosis of patients with osteosarcoma and its potential molecular mechanism.

Methods: Embase, PubMed, Sinomed, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang database, and Vip Journal Integration Platform were searched from inception to May 2021. The relationship between TUG1 expression and survival outcome was estimated by hazard ratio (HRs) and 95% confidence interval (CIs). Meta-analysis was conducted on the Stata 16.0. The differential expression of TUG1 in osteosarcoma was analyzed by using UALCAN database, and the survival of TUG1 was analyzed as well. The target genes of TUG1 were predicted by RegRNA2.0 biology software, HMDD, targetscan and microTCDS, and TUG1-micoRNAs-mRNAs regulatory network was constructed. The predicted target genes obtained GeneOntology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signal transduction pathway enrichment analysis using FunRich platform.

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

Conclusion: This study will provide evidence-based medical evidence for the relationship between TUG1 and the prognosis of osteosarcoma. Furthermore, bioinformatics analysis will provide ideas for the exploration on osteosarcoma mechanism.

Ethics And Dissemination: The private information from individuals will not be published. This systematic review also should not damage participants' rights. Ethical approval is not available. The results will be published in a peer-reviewed journal or disseminated in relevant conferences.

Osf Registration Number: DOI 10.17605/OSF.IO/CW4BF.
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http://dx.doi.org/10.1097/MD.0000000000026182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213273PMC
June 2021

Effect of sodium butyrate on slaughter performance, serum indexes and intestinal barrier of rabbits.

J Anim Physiol Anim Nutr (Berl) 2021 Jun 6. Epub 2021 Jun 6.

Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Department of Animal Science, Shandong Agricultural University, Taian, China.

The purpose of this study was to investigate the effect of sodium butyrate on slaughter performance, serum indexes and the intestinal barrier in rabbits. Six hundred healthy weaned rabbits were randomly divided into three groups (5 replicates per group, 40 rabbits per replicate): control (fed a basal diet), sodium butyrate (fed a basal diet containing 0.5% sodium butyrate) and antibiotic (fed a basal diet containing 0.004% antibiotic). The trial lasted 35 days, including 7 days of pretesting and 28 days of formal testing. The results showed that dietary sodium butyrate supplementation increased the full-bore weight, the half-bore weight and the half-bore rate of rabbits. Meanwhile, the content of aspartate aminotransferase (AST) in serum was increased in rabbits fed the sodium butyrate diet. According to the intestinal barrier, after adding sodium butyrate to feed, the tight junction function of the rabbit intestine is enhanced, and the intestinal microbial composition is also improved. To sum up, after sodium butyrate was added to feed instead of antibiotics, slaughter performance was significantly enhanced, serum indexes were improved, and intestinal barrier function was also enhanced. Therefore, sodium butyrate can be added to feed as an additive and can replace antibiotics.
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http://dx.doi.org/10.1111/jpn.13571DOI Listing
June 2021

A novel therapeutic approach for inflammatory bowel disease by exosomes derived from human umbilical cord mesenchymal stem cells to repair intestinal barrier via TSG-6.

Stem Cell Res Ther 2021 05 29;12(1):315. Epub 2021 May 29.

Department of Gastroenterology, The Second Hospital of Hebei Medical University, No. 80 Huanghe Road, Yuhua District, Shijiazhuang, 050000, Hebei, China.

Background: Exosomes as the main therapeutic vectors of mesenchymal stem cells (MSC) for inflammatory bowel disease (IBD) treatment and its mechanism remain unexplored. Tumor necrosis factor-α stimulated gene 6 (TSG-6) is a glycoprotein secreted by MSC with the capacities of tissue repair and immune regulation. This study aimed to explore whether TSG-6 is a potential molecular target of exosomes derived from MSCs (MSCs-Exo) exerting its therapeutic effect against colon inflammation and repairing mucosal tissue.

Methods: Two separate dextran sulfate sodium (DSS) and 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced IBD mouse models were intraperitoneally administered MSCs-Exo extracted from human umbilical cord MSC (hUC-MSC) culture supernatant. Effects of MSCs-Exo on intestinal inflammation, colon barrier function, and proportion of T cells were investigated. We explored the effects of MSCs-Exo on the intestinal barrier and immune response with TSG-6 knockdown. Moreover, recombinant human TSG-6 (rhTSG-6) was administered exogenously and colon inflammation severity in mice was evaluated.

Results: Intraperitoneal injection of MSCs-Exo significantly ameliorated IBD symptoms and reduced mortality rate. The protective effect of MSCs-Exo on intestinal barrier was demonstrated evidenced by the loss of goblet cells and intestinal mucosa permeability, thereby improving the destruction of tight junctions (TJ) structures and microvilli, as well as increasing the expression of TJ proteins. Microarray analysis revealed that MSCs-Exo administration downregulated the level of pro-inflammatory cytokines and upregulated the anti-inflammatory cytokine in colon tissue. MSCs-Exo also modulated the response of Th2 and Th17 cells in the mesenteric lymph nodes (MLN). Reversely, knockdown of TSG-6 abrogated the therapeutic effect of MSCs-Exo on mucosal barrier maintenance and immune regulation, whereas rhTSG-6 administration showed similar efficacy to that of MSCs-Exo.

Conclusions: Our findings suggested that MSCs-Exo protected against IBD through restoring mucosal barrier repair and intestinal immune homeostasis via TSG-6 in mice.
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http://dx.doi.org/10.1186/s13287-021-02404-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164818PMC
May 2021

Generation and Application of a Reporter Cell Line for the Quantitative Screen of Extracellular Vesicle Release.

Front Pharmacol 2021 16;12:668609. Epub 2021 Apr 16.

Moores Cancer Center, University of California, San Diego, La Jolla, CA, United States.

Extracellular vesicles (EVs) are identified as mediators of intercellular communication and cellular regulation. In the immune system, EVs play a role in antigen presentation as a part of cellular communication. To enable drug discovery and characterization of compounds that affect EV biogenesis, function, and release in immune cells, we developed and characterized a reporter cell line that allows the quantitation of EVs shed into culture media in phenotypic high-throughput screen (HTS) format. Tetraspanins CD63 and CD9 were previously reported to be enriched in EVs; hence, a construct with dual reporters consisting of CD63-Turbo-luciferase (Tluc) and CD9-Emerald green fluorescent protein (EmGFP) was engineered. This construct was transduced into the human monocytic leukemia cell line, THP-1. Cells expressing the highest EmGFP were sorted by flow cytometry as single cell, and clonal pools were expanded under antibiotic selection pressure. After four passages, the green fluorescence dimmed, and EV biogenesis was then tracked by luciferase activity in culture supernatants. The Tluc activities of EVs shed from CD63Tluc-CD9EmGFP reporter cells in the culture supernatant positively correlated with the concentrations of released EVs measured by nanoparticle tracking analysis. To examine the potential for use in HTS, we first miniaturized the assay into a robotic 384-well plate format. A 2210 commercial compound library (Maybridge) was then screened twice on separate days, for the induction of extracellular luciferase activity. The screening data showed high reproducibility on days 1 and 2 (78.6%), a wide signal window, and an excellent Z' factor (average of 2-day screen, 0.54). One hundred eighty-seven compounds showed a response ratio that was 3SD above the negative controls in both day 1 and 2 screens and were considered as hit candidates (approximately 10%). Twenty-two out of 40 re-tested compounds were validated. These results indicate that the performance of CD63Tluc-CD9EmGFP reporter cells is reliable, reproducible, robust, and feasible for HTS of compounds that regulate EV release by the immune cells.
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http://dx.doi.org/10.3389/fphar.2021.668609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085554PMC
April 2021

Farnesyl pyrophosphate is a new danger signal inducing acute cell death.

PLoS Biol 2021 04 26;19(4):e3001134. Epub 2021 Apr 26.

School of Life Sciences, Institute for Immunology, Ministry of Education Key Laboratory of Protein Sciences, Beijing Advanced Innovation Center for Structural Biology, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Beijing Key Lab for Immunological Research on Chronic Diseases, Tsinghua University, Beijing, China.

Cell death is a vital event in life. Infections and injuries cause lytic cell death, which gives rise to danger signals that can further induce cell death, inflammation, and tissue damage. The mevalonate (MVA) pathway is an essential, highly conserved and dynamic metabolic pathway. Here, we discover that farnesyl pyrophosphate (FPP), a metabolic intermediate of the MVA pathway, functions as a newly identified danger signal to trigger acute cell death leading to neuron loss in stroke. Harboring both a hydrophobic 15-carbon isoprenyl chain and a heavily charged pyrophosphate head, FPP leads to acute cell death independent of its downstream metabolic pathways. Mechanistically, extracellular calcium influx and the cation channel transient receptor potential melastatin 2 (TRPM2) exhibit essential roles in FPP-induced cell death. FPP activates TRPM2 opening for ion influx. Furthermore, in terms of a mouse model constructing by middle cerebral artery occlusion (MCAO), FPP accumulates in the brain, which indicates the function of the FPP and TRPM2 danger signal axis in ischemic injury. Overall, our data have revealed a novel function of the MVA pathway intermediate metabolite FPP as a danger signal via transient receptor potential cation channels.
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http://dx.doi.org/10.1371/journal.pbio.3001134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075202PMC
April 2021

Transcriptome analysis reveals gene responses to herbicide, tribenuron methyl, in Brassica napus L. during seed germination.

BMC Genomics 2021 Apr 23;22(1):299. Epub 2021 Apr 23.

College of Agronomy and Biotechnology, Southwest University, Chongqing, 400716, China.

Background: Tribenuron methyl (TBM) is an herbicide that inhibits sulfonylurea acetolactate synthase (ALS) and is one of the most widely used broad-leaved herbicides for crop production. However, soil residues or drifting of the herbicide spray might affect the germination and growth of rapeseed, Brassica napus, so it is imperative to understand the response mechanism of rape to TBM during germination. The aim of this study was to use transcriptome analysis to reveal the gene responses in herbicide-tolerant rapeseed to TBM stress during seed germination.

Results: 2414, 2286, and 1068 differentially expressed genes (DEGs) were identified in TBM-treated resistant vs sensitive lines, treated vs. control sensitive lines, treated vs. control resistant lines, respectively. GO analysis showed that most DEGs were annotated to the oxidation-reduction pathways and catalytic activity. KEGG enrichment was mainly involved in plant-pathogen interactions, α-linolenic acid metabolism, glucosinolate biosynthesis, and phenylpropanoid biosynthesis. Based on GO and KEGG enrichment, a total of 137 target genes were identified, including genes involved in biotransferase activity, response to antioxidant stress and lipid metabolism. Biotransferase genes, CYP450, ABC and GST, detoxify herbicide molecules through physical or biochemical processes. Antioxidant genes, RBOH, WRKY, CDPK, MAPK, CAT, and POD regulate plant tolerance by transmitting ROS signals and triggering antioxidant enzyme expression. Lipid-related genes and hormone-related genes were also found, such as LOX3, ADH1, JAZ6, BIN2 and ERF, and they also played an important role in herbicide resistance.

Conclusions: This study provides insights for selecting TBM-tolerant rapeseed germplasm and exploring the molecular mechanism of TBM tolerance during germination.
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http://dx.doi.org/10.1186/s12864-021-07614-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067372PMC
April 2021

Development of genic KASP SNP markers from RNA-Seq data for map-based cloning and marker-assisted selection in maize.

BMC Plant Biol 2021 Mar 26;21(1):157. Epub 2021 Mar 26.

Maize Research Institute, Sichuan Agricultural University, 211 Huiming Road, Wenjiang District, Chengdu City, 611000, Sichuan, China.

Background: Maize is one of the most important field crops in the world. Most of the key agronomic traits, including yield traits and plant architecture traits, are quantitative. Fine mapping of genes/ quantitative trait loci (QTL) influencing a key trait is essential for marker-assisted selection (MAS) in maize breeding. However, the SNP markers with high density and high polymorphism are lacking, especially kompetitive allele specific PCR (KASP) SNP markers that can be used for automatic genotyping. To date, a large volume of sequencing data has been produced by the next generation sequencing technology, which provides a good pool of SNP loci for development of SNP markers. In this study, we carried out a multi-step screening method to identify kompetitive allele specific PCR (KASP) SNP markers based on the RNA-Seq data sets of 368 maize inbred lines.

Results: A total of 2,948,985 SNPs were identified in the high-throughput RNA-Seq data sets with the average density of 1.4 SNP/kb. Of these, 71,311 KASP SNP markers (the average density of 34 KASP SNP/Mb) were developed based on the strict criteria: unique genomic region, bi-allelic, polymorphism information content (PIC) value ≥0.4, and conserved primer sequences, and were mapped on 16,161 genes. These 16,161 genes were annotated to 52 gene ontology (GO) terms, including most of primary and secondary metabolic pathways. Subsequently, the 50 KASP SNP markers with the PIC values ranging from 0.14 to 0.5 in 368 RNA-Seq data sets and with polymorphism between the maize inbred lines 1212 and B73 in in silico analysis were selected to experimentally validate the accuracy and polymorphism of SNPs, resulted in 46 SNPs (92.00%) showed polymorphism between the maize inbred lines 1212 and B73. Moreover, these 46 polymorphic SNPs were utilized to genotype the other 20 maize inbred lines, with all 46 SNPs showing polymorphism in the 20 maize inbred lines, and the PIC value of each SNP was 0.11 to 0.50 with an average of 0.35. The results suggested that the KASP SNP markers developed in this study were accurate and polymorphic.

Conclusions: These high-density polymorphic KASP SNP markers will be a valuable resource for map-based cloning of QTL/genes and marker-assisted selection in maize. Furthermore, the method used to develop SNP markers in maize can also be applied in other species.
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http://dx.doi.org/10.1186/s12870-021-02932-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004444PMC
March 2021

Retracted: Anthecotulide Sesquiterpene Lactone Exhibits Selective Anticancer Effects in Human Malignant Melanoma Cells by Activating Apoptotic and Autophagic Pathways, S-Phase Cell Cycle Arrest, Caspase Activation, and Inhibition of NF-κB Signalling Pathway.

Med Sci Monit 2021 Mar 25;27:e932353. Epub 2021 Mar 25.

Department of Dermatology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China (mainland).

Retracted, due to breach of publishing guidelines, following the identification of non-original and manipulated figure images. Reference: Chenyang Li, Xiuping Han: Anthecotulide Sesquiterpene Lactone Exhibits Selective Anticancer Effects in Human Malignant Melanoma Cells by Activating Apoptotic and Autophagic Pathways, S-Phase Cell Cycle Arrest, Caspase Activation, and Inhibition of NF-kappaB Signalling Pathway. Med Sci Monit 2019; 25:2852-2858. 10.12659/MSM.913771.
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http://dx.doi.org/10.12659/MSM.932353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009250PMC
March 2021

Virucidal activity of Moringa A from Moringa oleifera seeds against Influenza A Viruses by regulating TFEB.

Int Immunopharmacol 2021 Jun 18;95:107561. Epub 2021 Mar 18.

Department of Pharmacy, Shenzhen Key Laboratory of Novel Natural Health Care Products, Innovation Platform for Natural Small Molecule Drugs, Engineering Laboratory of Shenzhen Natural Small Molecule Innovative Drugs, School of Medicine, Health Science Center, Shenzhen University, Shenzhen 518060, China. Electronic address:

Influenza A viruses (IAVs) are highly contagious pathogens infecting human and numerous animals. The viruses cause millions of infection cases and thousands of deaths every year, making IAVs a continual threat to global health. Our study demonstrated the virucidal activity of Moringa A as a new compound from Moringa oleifera seeds against IAVs. It inhibits virus replication in host cells and protects infected cells from the cytopathic effect induced by IAVs. The EC50andEC90 values of Moringa A for IAVs were 1.27 and 5.30 μM, respectively, when RAW264.7 cells were infected at MOI of 1. The different treatment experiments revealed that Moringa A has a significant inhibitory effect on the IAVs both before and afterdrug addition. Moringa A was observed to decrease the inflammatory cytokines TNF-α, IL-6, IL-1β, and IFN-β in H1N1 infected RAW264.7 cells. Finally, Moringa A was found to inhibit the expression and nuclear transfer of the cellular protein transcription factor EB (TFEB) and weaken the autophagy in infected cells, which could be an important antiviral mechanism. Our study demonstrates Moringa A has potent antiviral activity against IVAs, which could be due to the autophagy inhibition property.
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http://dx.doi.org/10.1016/j.intimp.2021.107561DOI Listing
June 2021
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