Publications by authors named "Xue Bai"

835 Publications

The immune protection induced by a serine protease from the Trichinella spiralis adult against Trichinella spiralis infection in pigs.

PLoS Negl Trop Dis 2021 May 10;15(5):e0009408. Epub 2021 May 10.

Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, China.

Trichinellosis is a major foodborne parasitosis caused by Trichinella spiralis. In the present study, a serine protease gene from an adult T. spiralis (Ts-Adsp) cDNA library was cloned, expressed in Escherichia coli and purified by Ni-affinity chromatography. Previous studies of our laboratory have found that mice vaccinated with recombinant Ts-Adsp protein (rTs-Adsp) exhibited partial protection against T. spiralis infection. In this study, the protective effect of rTs-Adsp against T. spiralis infection in pigs was further explored. The cell-mediated and humoral immune responses induced by rTs-Adsp were measured, including the dynamic trends of specific antibody levels (IgG, IgG1, IgG2a and IgM), as well as the levels of cytokines (IFN-γ, IL-2, IL-4, and IL-10) in the serum. Moreover, the changes in T lymphocytes, B lymphocytes, and neutrophils were measured to evaluate cellular immune responses in pigs vaccinated with rTs-Adsp. The results indicated that a Th1-Th2 mixed immune response with Th1 predominant was induced by rTs-Adsp after vaccination. Flow cytometric analysis showed that the proportions of CD4+ T cells, B cells, and neutrophils in the immunized groups were significantly increased. Furthermore, pigs vaccinated with rTs-Adsp exhibited a 50.9% reduction in the muscle larvae burden, compare with pigs from the PBS group five weeks after challenged. Our results suggested that rTs-Adsp elicited partial protection and it could be a potential target molecule for preventing and controlling Trichinella transmission from pigs to human.
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http://dx.doi.org/10.1371/journal.pntd.0009408DOI Listing
May 2021

Clinical and pathological analysis of renal biopsies of elderly patients in Northeast China: a single-center study.

Ren Fail 2021 Dec;43(1):851-859

The Department of Nephropathy, The Second Hospital of Jilin University, Changchun, China.

Purpose: To identify the clinical characteristics, histopathological features, and prognosis of kidney disease in a large cohort of elderly patients from Northeast China.

Methods: We retrospectively analyzed the renal disease spectrum in 7,122 patients who underwent renal biopsies at the Second Hospital of Jilin University from 2006 to 2020. Patients were grouped according to age: below 60 years (non-elderly group,  = 5923) and at least 60 years (elderly group,  = 1199). The clinical and pathological characteristics of renal biopsy patients in the groups were analyzed using the -test and chi-square test.

Results: Compared with the non-elderly group, the elderly group had significantly fewer patients with primary glomerulonephritis, but more patients with tubulointerstitial disorders ( < .05). The incidence of IgA nephropathy, mesangial proliferative glomerulonephritis, and lupus nephritis was significantly lower in elderly patients than in non-elderly patients. The incidence of membranous nephropathy, membranoproliferative glomerulonephritis, diabetic nephropathy, hypertensive nephropathy, systemic vasculitis-associated renal damage, and amyloid nephropathy was significantly higher in elderly patients than in non-elderly patients ( < .05). The incidence of perinephric hematoma (≥4 cm) in elderly patients with renal biopsy was lower than that in non-elderly patients. We noted that 79.9% of primary glomerulonephritis patients who received immunosuppressive therapy showed a remission rate of 83.5%.

Conclusion: The spectrum of kidney disease in the elderly is different from that in the younger population.
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http://dx.doi.org/10.1080/0886022X.2021.1923527DOI Listing
December 2021

Association of Sleep Duration and Screen Time With Anxiety of Pregnant Women During the COVID-19 Pandemic.

Front Psychol 2021 20;12:646368. Epub 2021 Apr 20.

Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

The COVID-19 pandemic has dramatically changed the patterns of lifestyle and posed psychological stress on pregnant women. However, the association of sleep duration and screen time with anxiety among pregnant women under the backdrop of the COVID-19 pandemic scenario has been poorly addressed. We conducted one large-scale, multicenter cross-sectional study which recruited 1794 pregnant women across middle and west China. Self-reported demographic characteristics, lifestyle, and mental health status were collected from 6th February to 8th May 2020. We investigated the association of sleep duration and screen time with the risk of anxiety by multivariable logistic regression analysis and linear regression analysis after adjusting potential confounders. The dose-response relationship of sleep duration and screen time with anxiety was visualized using a cubic spline plot. Our data revealed that almost 35% of pregnant women suffered from anxiety during the COVID-19 pandemic. Sleep duration was dose-dependently associated with a lower risk of anxiety among pregnant women (OR = 0.41, 95% CI: 0.27-0.63), while screen time exhibited a conversed effect (OR = 2.01, 95% CI:1.00-4.39). Notably, sleep duration (≥8 h/day) synergistically combined with screen time (3-7 h/day) to diminish the risk of anxiety (OR = 0.70, 95% CI: 0.50-0.99). Taken together, sleep duration and screen time were independently and jointly associated with anxiety ( < 0.05). Therefore, promoting a more active lifestyle and maintaining higher sleep quality could improve the mental health of pregnant women, especially under public health emergency.
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http://dx.doi.org/10.3389/fpsyg.2021.646368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093759PMC
April 2021

LncRNA MIAT impairs cardiac contractile function by acting on mitochondrial translocator protein TSPO in a mouse model of myocardial infarction.

Signal Transduct Target Ther 2021 May 3;6(1):172. Epub 2021 May 3.

Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China and Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang, P. R. China.

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http://dx.doi.org/10.1038/s41392-021-00538-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093248PMC
May 2021

Inhibition of TMEM16A by Natural Product Silibinin: Potential Lead Compounds for Treatment of Lung Adenocarcinoma.

Front Pharmacol 2021 14;12:643489. Epub 2021 Apr 14.

Key Laboratory of Molecular Biophysics, Hebei Province, Institute of Biophysics, School of Sciences, Hebei University of Technology, Tianjin, China.

: Effective anticancer therapy can be achieved by identifying novel tumor-specific drug targets and screening of new drugs. Recently, TMEM16A has been identified to be overexpressed in lung adenocarcinoma, and inhibitors of TMEM16A showed obvious antitumor efficacy. : YFP fluorescence quenching and whole-cell patch clamp experiments were used to explore the inhibitory effect of silibinin on TMEM16A. Molecular docking and site-directed mutagenesis were performed to confirm the binding sites of silibinin and TMEM16A. MTT assay, wound healing assay, and annexin-V assay were used to detect the effect of silibinin on cancer cell proliferation, migration, and apoptosis. shRNA was transfected into LA795 cells to knock down the expression of endogenous TMEM16A. Tumor xenograft mice combined with Western blot experiments reveal the inhibitory effect and mechanism of silibinin . : Silibinin concentration dependently inhibited the whole-cell current of TMEM16A with an IC of 30.90 ± 2.10 μM. The putative binding sites of silibinin in TMEM16A were K384, R515, and R535. The proliferation and migration of LA795 cells were downregulated by silibinin, and the inhibition effect can be abolished by knockdown of the endogenous TMEM16A. Further, silibinin was injected to tumor xenograft mice which exhibited significant antitumor activity without weight loss. Finally, Western blotting results showed the mechanism of silibinin inhibiting lung adenocarcinoma was through apoptosis and downregulation of cyclin D1. : Silibinin is a novel TMEM16A inhibitor, and it can be used as a lead compound for the development of lung adenocarcinoma therapy drugs.
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http://dx.doi.org/10.3389/fphar.2021.643489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079988PMC
April 2021

EEF1D facilitates milk lipid synthesis by regulation of PI3K-Akt signaling in mammals.

FASEB J 2021 May;35(5):e21455

Department of Animal Genetics and Breeding, College of Animal Science and Technology, Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry of Agriculture and Rural Affairs, National Engineering Laboratory for Animal Breeding, China Agricultural University, Beijing, China.

Mammal's milk is an abundantly foremost source of proteins, lipids, and micronutrients for human nutrition and health. Understanding the molecular mechanisms underlying synthesis of milk components provides practical benefits to improve the milk quality via systematic breeding program in mammals. Through RNAi with EEF1D in primary bovine mammary epithelial cells, we phenotypically observed aberrant formation of cytoplasmic lipid droplets and significantly decreased milk triglyceride level by 37.7%, and exploited the mechanisms by which EEF1D regulated milk lipid synthesis via insulin (PI3K-Akt), AMPK, and PPAR pathways. In the EEF1D CRISPR/Cas9 knockout mice, incompletely developed mammary glands at 9th day postpartum with small or unformed lumens, and significantly decreased triglyceride concentration in milk by 23.4% were observed, as well as the same gene expression alterations in the three pathways. For dairy cattle, we identified a critical regulatory mutation modifying EEF1D transcription activity, which interpreted 7% of the genetic variances of milk lipid yield and percentage. Our findings highlight the significance of EEF1D in mammary gland development and milk lipid synthesis in mammals.
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http://dx.doi.org/10.1096/fj.202000682RRDOI Listing
May 2021

Inversing supramolecular chirality and boosting circularly polarized luminescence of pyrene moieties a gel matrix.

Soft Matter 2021 Apr;17(16):4328-4334

Key laboratory of Nanosystem and Hierarchical Fabrication, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China.

Alkyl-substituted l/d-glutamide derivatives (L/D-SG) were designed as gelators to fabricate host gel matrices. Pyrene-appended l/d-glutamide derivatives (Py-LG/Py-DG) were employed as guest luminophores to investigate chiral packing and emission behavior in gel matrices. It was found that Py-LG and Py-DG are prone to form P- and M-chirally packed assemblies in DMSO gels, respectively. However, the chiral packing was inversed, and CPL was boosted after Py-LG/Py-DG was embedded in the L/D-SG gel matrix. M-chiral packing together with left-handed excimer emission ((-)-CPL) was observed in the Py-LG immobilized L-SG gel matrix, while P-chiral packing together with right-handed excimer emission ((+)-CPL) was found in the Py-DG immobilized L-SG gel matrix. It is more interesting to find that the molecular chirality of the matrix gelator did not affect the supramolecular chirality of pyrene assemblies. Either l or a d-matrix gelator can inverse the supramolecular chirality of the pure gel, but did not follow the chirality of the matrix. It was found that the gel matrix converts intralayer pyrene-pyrene (Py-Py) packing in the pure pyrene gel to interlayer Py-Py packing, thus giving an opposite chirality. The study not only deepened our understanding of the supramolecular chirality transfer but also unveiled the effects of an inert gel matrix in regulating the chiroptical properties.
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http://dx.doi.org/10.1039/d1sm00262gDOI Listing
April 2021

Bioinformatics analysis of mRNA and miRNA microarray to identify the key miRNA-mRNA pairs in cisplatin-resistant ovarian cancer.

BMC Cancer 2021 Apr 23;21(1):452. Epub 2021 Apr 23.

Department of Gynecology and Obstetrics, Dalian Municipal Central Hospital, Affiliated to Dalian Medical University, Dalian, 116011, China.

Background: Ovarian cancer (OC) is a gynecological malignancy with the highest mortality rate. Cisplatin (DDP) based chemotherapy is a standard strategy for ovarian cancer. Despite good response rates for initial chemotherapy, almost 80% of the patients treated with DDP based chemotherapy will experience recurrence due to drug-resistant, which will ultimately result in fatality. The aim of the present study was to examine the pathogenesis and potential molecular markers of cisplatin-resistant OC by studying the differential expression of mRNAs and miRNAs between cisplatin resistant OC cell lines and normal cell lines.

Methods: Two mRNA datasets (GSE58470 and GSE45553) and two miRNA sequence datasets (GSE58469 and GSE148251) were downloaded from the Gene expression omnibus (GEO) database. Differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) were screened by the NetworkAnalyst. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to analyze the biological functions of DEGs. The protein-protein interaction network was constructed using STRING and Cytoscape software to identify the molecular mechanisms of key signaling pathways and cellular activities. FunRich and MiRNATip databases were used to identify the target genes of the DEMs.

Results: A total of 380 DEGs, and 5 DEMs were identified. Protein-protein interaction (PPI) network of DEGs containing 379 nodes and 1049 edges was constructed, and 4 key modules and 24 hub genes related to cisplatin-resistant OC were screened. Two hundred ninety-nine target genes of the 5 DEMs were found out. Subsequently, one of these 299 target genes (UBB) belonging to the hub genes of GSE58470 and GSE45553 was identified by MCODE and CytoHubba,which was regulated by one miRNA (mir-454).

Conclusions: One miRNA-mRNA regulatory pairs (mir-454-UBB) was established. Taken together, our study provided evidence concerning the alteration genes involved in cisplatin-resistant OC, which will help to unravel the mechanisms underlying drug resistant.
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http://dx.doi.org/10.1186/s12885-021-08166-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063430PMC
April 2021

[Activation of Permonosulfate by Rhodamine B for BPA Degradation Under Visible Light Irradiation].

Huan Jing Ke Xue 2021 May;42(5):2353-2359

School of Environmental and Municipal Engineering, Xi'an University of Architecture and Technology, Xi'an 710055, China.

Although the activation method of permonosulfate has been gradually developed, its practical application is severely restricted by the high cost and difficult recovery of the catalyst, thereby resulting in secondary pollution. In this study, the application potential of self-decolorization of dyes and degradation of other pollutants through persulfate(PS) activation was examined by building a self-decolorization system. The results showed that the dyes could activate PS under visible light irradiation, which could realize not only the self-decolorization of dyes, but also the degradation of other pollutants. The degradation rates of rhodamine B and bisphenol A could reach 80% and 90%, respectively. This process included both free radical reaction pathways and nonradical reaction pathways. The active oxidants produced in the system included superoxide radicals, sulfate radicals, hydroxyl radicals, and singlet oxygen. The self-decolorization efficiency of dyes was related to the type of dyes, initial concentration of the dyes, dosage of PS, and initial pH of the solution. Meanwhile, the initial concentrations of the dyes and other pollutants had a great influence on the degradation of other pollutants. This study provides a new idea for economic and environmental protection in the PS activation method, and has broad application prospects in the treatment of printing and dyeing wastewater.
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http://dx.doi.org/10.13227/j.hjkx.202010097DOI Listing
May 2021

Ginsenoside Rh4 alleviates antibiotic-induced intestinal inflammation by regulating the TLR4-MyD88-MAPK pathway and gut microbiota composition.

Food Funct 2021 Apr 19;12(7):2874-2885. Epub 2021 Mar 19.

Shaanxi Key Laboratory of Degradable Biomedical Materials and Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, Taibai North Road 229, Xi'an, Shaanxi 710069, China.

Ginsenoside Rh4, as a bioactive component obtained from Panax notoginseng, has excellent pharmacological properties. However, its role in regulating gut microbiota and intestinal inflammation is still poorly understood. Thus, the aim of this study is to investigate the effect of Rh4 on gut microbiota, especially antibiotic-induced microbiota perturbation, and the underlying mechanisms. C57BL/6 mice were given different doses of Rh4 after the establishment of a gut microbiota disturbance model with antibiotics. Our data revealed that Rh4 administration could greatly improve the pathological phenotype, gut barrier disruption, and intestinal inflammation in mice that had been antibiotic-induced. Notably, it was found that Rh4 significantly inhibited the TLR4-MyD88-MAPK signaling pathway. In addition, Rh4 treatment could significantly increase the number of short chain fatty acids (SCFAs) and bile acids (BAs). These changes were accompanied with beneficial alterations in gut microbiota diversity and composition. In conclusion, Rh4 improves intestinal inflammation and induces potentially beneficial changes in the gut microbiota, which are conducive to revealing host-microbe interactions.
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http://dx.doi.org/10.1039/d1fo00242bDOI Listing
April 2021

Increased Production of Short-Chain Fatty Acids in Microbacteria Fermentation Treated by Fullerenols.

J Nanosci Nanotechnol 2021 Oct;21(10):5352-5362

CAS Key Laboratory for Biomedical Effects of Nanomaterial and Nanosafety, Institute of High Energy Physics, Chinese Academy of Science (CAS), Beijing 100049, China.

Fullerenol nanoparticles were found to significantly modulate the gut microbiota and selectively enrich the short-chain fatty acids (SCFAs) production by adjusting the gut microbacteria in mice models. In this research, we screened the from seven strains and investigated the interactions and mechanism between the and fullerenol NPs fermentation. The results shows that fullerenol NPs increased the amounts of acetate and butyrate of without significant bacteria growth in the complete medium. The activities of the butyryl-CoA: acetate CoA transferase (BUT), which are the main pathway to produce butyrate, were reduced while the activities of the butyrate kinase (BUK) were enhanced simultaneously. Surprisingly, fullerenol NPs promoted the growth of and in low glucose medium, but they could not be direct carbon source in the culture. Moreover, when cocultured with and the bifidobacterial strains in fullerenols, the biomass and acetate production of were markedly increased while butyrate was decreased significantly.
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http://dx.doi.org/10.1166/jnn.2021.19341DOI Listing
October 2021

Identification of the specific long-noncoding RNAs involved in night-break mediated flowering retardation in Chenopodium quinoa.

BMC Genomics 2021 Apr 19;22(1):284. Epub 2021 Apr 19.

Key Laboratory of Coarse Cereal Processing, Ministry of Agriculture and Rural Affairs, Sichuan Engineering & Technology Research Center of Coarse Cereal Industralization, School of Food and Biological Engineering, Chengdu University, Chengluo road 2025, Shiling town, Longquanyi District, Chengdu, 610106, Sichuan Province, P.R. China.

Background: Night-break (NB) has been proven to repress flowering of short-day plants (SDPs). Long-noncoding RNAs (lncRNAs) play key roles in plant flowering. However, investigation of the relationship between lncRNAs and NB responses is still limited, especially in Chenopodium quinoa, an important short-day coarse cereal.

Results: In this study, we performed strand-specific RNA-seq of leaf samples collected from quinoa seedlings treated by SD and NB. A total of 4914 high-confidence lncRNAs were identified, out of which 91 lncRNAs showed specific responses to SD and NB. Based on the expression profiles, we identified 17 positive- and 7 negative-flowering lncRNAs. Co-expression network analysis indicated that 1653 mRNAs were the common targets of both types of flowering lncRNAs. By mapping these targets to the known flowering pathways in model plants, we found some pivotal flowering homologs, including 2 florigen encoding genes (FT (FLOWERING LOCUS T) and TSF (TWIN SISTER of FT) homologs), 3 circadian clock related genes (EARLY FLOWERING 3 (ELF3), LATE ELONGATED HYPOCOTYL (LHY) and ELONGATED HYPOCOTYL 5 (HY5) homologs), 2 photoreceptor genes (PHYTOCHROME A (PHYA) and CRYPTOCHROME1 (CRY1) homologs), 1 B-BOX type CONSTANS (CO) homolog and 1 RELATED TO ABI3/VP1 (RAV1) homolog, were specifically affected by NB and competed by the positive and negative-flowering lncRNAs. We speculated that these potential flowering lncRNAs may mediate quinoa NB responses by modifying the expression of the floral homologous genes.

Conclusions: Together, the findings in this study will deepen our understanding of the roles of lncRNAs in NB responses, and provide valuable information for functional characterization in future.
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http://dx.doi.org/10.1186/s12864-021-07605-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056640PMC
April 2021

Protein Corona Formation: Characterizations, Effects on Engineered Nanoparticles' Biobehaviors, and Applications.

Front Bioeng Biotechnol 2021 31;9:646708. Epub 2021 Mar 31.

School of Pharmacy, Nantong University, Nantong, China.

Understanding the basic interactions between engineered nanoparticles (ENPs) and biological systems is essential for evaluating ENPs' safety and developing better nanomedicine. Profound interactions between ENPs and biomolecules such as proteins are inevitable to occur when ENPs are administered or exposed to biological systems, for example, through intravenous injection, oral, or respiration. As a key component of these interactions, protein corona (PC) is immediately formed surrounding the outlayer of ENPs. PC formation is crucial because it gives ENPs a new biological identity by altering not only the physiochemical properties, but also the biobehaviors of ENPs. In the past two decades, most investigations about PC formation were carried out with systems which could not represent the true events occurring within systems. Most recently, studies of PC formation were reported, and it was found that the protein compositions and structures were very different from those formed . Herein, we provide an in-time review of the recent investigations of this PC formation of ENPs. In this review, commonly used characterization methods and compositions of PC are summarized firstly. Next, we highlight the impacts of the PC formation on absorption, blood circulation, biodistribution, metabolism, and toxicity of administered ENPs. We also introduce the applications of modulating PC formation in nanomedicine. We further discuss the challenges and future perspectives.
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http://dx.doi.org/10.3389/fbioe.2021.646708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044820PMC
March 2021

Thin-layered MoS nanoflakes vertically grown on SnO nanotubes as highly effective room-temperature NO gas sensor.

J Hazard Mater 2021 Apr 7;416:125830. Epub 2021 Apr 7.

Key Laboratory of Functional Inorganic Material Chemistry, Ministry of Education. School of Chemistry and Material Science, Heilongjiang University, Harbin 150080, PR China. Electronic address:

The unique properties of heterostructure materials make them become a promising candidate for high-performance room-temperature (RT) NO sensing. Herein, a p-n heterojunction consisting of two-dimensional (2D) MoS nanoflakes vertically grown on one-dimensional (1D) SnO nanotubes (NTs) was fabricated via electrospinning and subsequent hydrothermal route. The sulfur edge active sites are fully exposed in the MoS@SnO heterostructure due to the vertically oriented thin-layered morphology features. Moreover, the interface of p-n heterojunction provides an electronic transfer channel from SnO to MoS, which enables MoS act as the generous electron donor involved in NO gas senor detection. As a result, the optimized MoS@SnO-2 heterostructure presents an impressive sensitivity and selectivity for NO gas detection at RT. The response value is 34.67 (R/R) to 100 ppm, which is 26.5 times to that of pure SnO It also exhibits a fast response and recovery time (2.2 s, 10.54 s), as well as a low detection limit (10 ppb) and as long as 20 weeks of stability. This simple fabrication of high-performance sensing materials may facilitate the large-scale production of RT NO gas sensors.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125830DOI Listing
April 2021

Potential medicinal value of celastrol and its synthesized analogues for central nervous system diseases.

Biomed Pharmacother 2021 Apr 14;139:111551. Epub 2021 Apr 14.

Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, and State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), and Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, and Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi'an 712046, Shaanxi Province, China. Electronic address:

The central nervous system (CNS) is a vital part of the human nervous system, and the incidence of CNS disease is increasing year by year, which has become a major public health problem and a prominent social problem. At present, the drugs most commonly used in the clinic are receptor regulators, and neurotransmitter inhibitors, but they are accompanied by serious side effects. Therefore, the identification of new drugs and treatment strategies for CNS disease has been a research hotspot in the medical field. Celastrol, a highly bio-active pentacyclic triterpenoid isolated from Tripterygium wilfordii Hook. F, has been proved to have a wide range of pharmacological effects, such as anti-inflammation, immunosuppression, anti-obesity and anti-tumor activity. However, due to its poor water solubility, low bioavailability and toxicity, the clinical development and trials of celastrol have been postponed. However, in recent years, the extensive medical value of celastrol in the treatment of CNS diseases such as nervous system tumors, Alzheimer's disease, Parkinson's disease, cerebral ischemia, multiple sclerosis, spinal cord injury, and amyotrophic lateral sclerosis has gradually attracted intensive attention worldwide. In particular, celastrol has non-negligible anti-tumor efficacy, and as there are no 100% effective anti-tumor drugs, the study of its structural modification to obtain better leading compounds with higher efficiency and lower toxicity has aroused strong interest in pharmaceutical chemists. In this review, research progress on celastrol in CNS diseases and the synthesis of celastrol-type triterpenoid analogues and their application evaluation in disease models, such as CNS diseases and autotoxicity-related target organ cancers in the past decade are summarized in detail, in order to provide reference for future better application in the treatment of CNS diseases.
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http://dx.doi.org/10.1016/j.biopha.2021.111551DOI Listing
April 2021

Consensus Control for Heterogeneous Multivehicle Systems: An Iterative Learning Approach.

IEEE Trans Neural Netw Learn Syst 2021 Apr 15;PP. Epub 2021 Apr 15.

This article investigates the consensus tracking problem of the heterogeneous multivehicle systems (MVSs) under a repeatable control environment. First, a unified iterative learning control (ILC) algorithm is presented for all autonomous vehicles, each of which is governed by both discrete- and continuous-time nonlinear dynamics. Then, several consensus criteria for MVSs with switching topology and external disturbances are established based on our proposed distributed ILC protocols. For discrete-time systems, all vehicles can perfectly track to the common reference trajectory over a specified finite time interval, and the corresponding digraphs may not have spanning trees. Existing approaches dealing with the continuous-time systems generally require that all vehicles have strictly identical initial conditions, being too ideal in practice. We relax this unpractical assumption and propose an extra distributed initial state learning protocol such that vehicles can take different initial states, leading to the fact that the finite time tracking is achieved ultimately regardless of the initial errors. Finally, a numerical example demonstrates the effectiveness of our theoretical results.
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http://dx.doi.org/10.1109/TNNLS.2021.3071413DOI Listing
April 2021

Interleukin-17D regulates group 3 innate lymphoid cell function through its receptor CD93.

Immunity 2021 Apr;54(4):673-686.e4

Institute for Immunology and School of Medicine, Tsinghua University, Beijing 100084, China; Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, Shanghai 200127, China. Electronic address:

The interleukin (IL)-17 family, consisting of six members, promotes host defense but can in some context promote the development of autoimmune disease. Here, we examined the role of IL-17D, a poorly understood member in the IL-17 family. IL-17D was expressed primarily by colonic epithelial cells. Il17d mice were more susceptible to acute colitis, bacterial infection and experimentally induced colon cancer than their wildtype counterparts. Il17d deficiency impaired IL-22 production by group 3 innate lymphoid cells (ILC3s) and reduced expression of IL-22-dependent antimicrobial peptides, RegIIIβ and RegIIIγ, in colon tissue at steady state and in colitis; this was associated with changes in microbial composition and dysbiosis. Protein purification studies revealed that IL-17D bound not canonical IL-17 receptors, but rather CD93, a glycoprotein expressed on mature ILC3s. Mice lacking Cd93 in ILC3s exhibited impaired IL-22 production and aggravated colonic inflammation in experimental colitis. Thus, an IL-17D-CD93 axis regulates ILC3 function to preserve intestinal homeostasis.
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http://dx.doi.org/10.1016/j.immuni.2021.03.018DOI Listing
April 2021

N-Acetylcysteine Combined With Dexamethasone Treatment Improves Sudden Sensorineural Hearing Loss and Attenuates Hair Cell Death Caused by ROS Stress.

Front Cell Dev Biol 2021 18;9:659486. Epub 2021 Mar 18.

Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Sudden sensorineural hearing loss (SSNHL) is a common emergency in the world. Increasing evidence of imbalance of oxidant-antioxidant were found in SSNHL patients. Steroids combined with antioxidants may be a potential strategy for the treatment of SSNHL. In cochlear explant experiment, we found that N-acetylcysteine (NAC) combined with dexamethasone can effectively protect hair cells from oxidative stress when they were both at ineffective concentrations alone. A clinic trial was designed to explore whether oral NAC combined with intratympanic dexamethasone (ITD) as a salvage treatment has a better therapeutic effect. 41 patients with SSNHL were randomized to two groups. 23 patients in control group received ITD therapy alone, while 18 patient s in NAC group were treated with oral NAC and ITD. The patients were followed-up on day 1st (initiation of treatment) and day 14th. Overall, there was no statistical difference in final pure-tone threshold average (PTA) improvement between those two groups. However, a significant hearing gain at 8,000 Hz was observed in NAC group. Moreover, the hearing recovery rates of NAC group is much higher than that in control group. These results demonstrated that oral NAC in combination with ITD therapy is a more effective therapy for SSNHL than ITD alone.
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http://dx.doi.org/10.3389/fcell.2021.659486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014036PMC
March 2021

A Practical Nomogram to Predict Early Death in Advanced Epithelial Ovarian Cancer.

Front Oncol 2021 19;11:655826. Epub 2021 Mar 19.

Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China.

Ovarian cancer is a common gynecological malignancy, most of which is epithelial ovarian cancer (EOC). Advanced EOC is linked with a higher incidence of premature death. To date, no effective prognostic tools are available to evaluate the possibility of early death in patients with advanced EOC. Advanced (FIGO stage III and IV) EOC patients who were enrolled in the Surveillance, Epidemiology, and End Results database between 2004 and 2015 were regarded as subjects and studied. We aimed to construct a nomogram that can deliver early death prognosis in patients with advanced EOC by identifying crucial independent factors using univariate and multivariate logistic regression analyses to help deliver accurate prognoses. In total, 13,403 patients with advanced EOC were included in this study. Three hundred ninety-seven out of a total of 9,379 FIGO stage III patients died early. There were 4,024 patients with FIGO stage IV, 414 of whom died early. Nomograms based on independent prognostic factors have the satisfactory predictive capability and clinical pragmatism. The internal validation feature of the nomogram demonstrated a high level of accuracy of the predicted death. By analyzing data from a large cohort, a clinically convenient nomogram was established to predict premature death in advanced EOC. This tool can aid clinicians in screening patients who are at higher risk for tailoring treatment plans.
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http://dx.doi.org/10.3389/fonc.2021.655826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017286PMC
March 2021

Disruption of Epithelial Barrier of Caco-2 Cell Monolayers by Excretory Secretory Products of Might Be Related to Serine Protease.

Front Microbiol 2021 17;12:634185. Epub 2021 Mar 17.

Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Institute of Zoonosis, Jilin University, Changchun, China.

The physical barrier is composed of epithelial cells which are joined together through intercellular connections. It serves to prevent pathogenic microorganisms from departing the intestinal lumen to invade the host. The excretory secretory (ES) products of are critical for invasion. However, whether ES products of can act on the intestinal barrier is still unknown. In this study, the role of ES products of muscle larvae (-ML-ES) in host invasion was studied by establishing an cell monolayers model. Barrier integrity analysis by a transmembrane resistance test and a paracellular permeability assay revealed that the -ML-ES was able to destroy barrier function. It occurred a reduction in the expression of tight junction (TJ) proteins, which was induced by serine protease. Furthermore, Western bolt analysis indicated that -ML-ES reduced the expression of TJ proteins the MAPK signaling pathway. Based on these data, we conclude that serine protease are likely the main factors from -ML-ES that affect host intestinal barrier integrity by reducing the expression of TJs the P38-MAPK signaling pathway. Serine protease in -ML-ES might be a key invasion factor in .
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http://dx.doi.org/10.3389/fmicb.2021.634185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013981PMC
March 2021

Selection and Validation of Reference Genes for qRT-PCR Analysis in the Oil-Rich Tuber Crop Tiger Nut () Based on Transcriptome Data.

Int J Mol Sci 2021 Mar 4;22(5). Epub 2021 Mar 4.

CAS Key Laboratory of Tropical Plant Resources and Sustainable Use, Xishuangbanna Tropical Botanical Garden, Innovation Academy for Seed Design, Chinese Academy of Sciences, Menglun, Mengla 666303, China.

Tiger nut (), a perennial C plant of the family, is an unconventional crop that is distinguished by its oil-rich tubers, which also possesses the advantages of strong resistance, wide adaptability, short life periods, and large biomass. To facilitate studies on gene expression in this species, we identified and validated a series of reference genes (RGs) based on transcriptome data, which can be employed as internal controls for qRT-PCR analysis in tiger nut. Fourteen putative candidate RGs were identified and evaluated across nine different tissues of two cultivars, and the RGs were analyzed using three different algorithms (geNorm, NormFinder, and BestKeeper). The stability rankings of the candidate RGs were merged into consensus lists with RankAggreg. For the below-ground storage organ of tiger nut, the optimal RGs were and in different developmental stages of tubers. and were the most stably expressed RGs among all tissues, while and exhibited the lowest expression stability. , and were compared to normalize the expression levels of the () and () genes across the same tissues. Our results showed that the RGs identified in this study, which exhibit more uniform expression patterns, may be utilized for the normalization of qRT-PCR results, promoting further research on gene expression in various tissues of tiger nut.
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http://dx.doi.org/10.3390/ijms22052569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961719PMC
March 2021

Cloudy Apple Juice Fermented by Prevents Obesity via Modulating Gut Microbiota and Protecting Intestinal Tract Health.

Nutrients 2021 Mar 17;13(3). Epub 2021 Mar 17.

College of Food Science and Engineering, Northwest A&F University, Yangling 712100, China.

Obesity and hyperglycemia are two serious chronic diseases that are increasing in incidence worldwide. This research aimed to develop a fermented cloudy apple juice with good hyperglycemia intervention activities. Here, cloudy apple juice (CAJ), cloudy apple juice rich in polyphenols (CAJP) and fermented cloudy apple juice rich in polyphenols (FCAJP) were prepared sequentially, and then the effects of the three apple juices on weight, lipid level, gut microbiota composition and intestinal tract health were evaluated for obese mice induced by a high-fat diet. The research findings revealed that the FCAJP showed potential to inhibit the weight gain of mice, reduce fat accumulation, and regulate the blood lipid levels of obese mice by decreasing the ratio of the Firmicutes/Bacteroidotas, improving the Sobs, Ace, and Chao indexes of the gut microbiota and protecting intestinal tract health. In addition, the FCAJP augmented the abundance of Akkermansia and Bacteroides, which were positively related to SCFAs in cecal contents. This study inferred that FCAJP could be developed as a healthy food for preventing obesity and hyperglycemia.
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http://dx.doi.org/10.3390/nu13030971DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002442PMC
March 2021

A Versatile Optoelectronic Tweezer System for Micro-Objects Manipulation: Transportation, Patterning, Sorting, Rotating and Storage.

Micromachines (Basel) 2021 Mar 6;12(3). Epub 2021 Mar 6.

School of Mechanical Engineering & Automation, Beihang University, Beijing 100191, China.

Non-contact manipulation technology has a wide range of applications in the manipulation and fabrication of micro/nanomaterials. However, the manipulation devices are often complex, operated only by professionals, and limited by a single manipulation function. Here, we propose a simple versatile optoelectronic tweezer (OET) system that can be easily controlled for manipulating microparticles with different sizes. In this work, we designed and established an optoelectronic tweezer manipulation system. The OET system could be used to manipulate particles with a wide range of sizes from 2 μm to 150 μm. The system could also manipulate micro-objects of different dimensions like 1D spherical polystyrene microspheres, 2D rod-shaped euglena gracilis, and 3D spiral microspirulina. Optical microscopic patterns for trapping, storing, parallel transporting, and patterning microparticles were designed for versatile manipulation. The sorting, rotation, and assembly of single particles in a given region were experimentally demonstrated. In addition, temperatures measured under different objective lenses indicate that the system does not generate excessive heat to damage bioparticles. The non-contact versatile manipulation reduces operating process and contamination. In future work, the simple optoelectronic tweezers system can be used to control non-contaminated cell interaction and micro-nano manipulation.
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http://dx.doi.org/10.3390/mi12030271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000357PMC
March 2021

Bioinformatic Prediction and Production of Four Recombinant Proteins from Different Developmental Stages of and Testing of Their Diagnostic Sensitivity in Mice.

Iran J Parasitol 2021 Jan-Mar;16(1):122-135

National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, WHO Collaborating Center for Tropical Diseases, Key Laboratory of Parasite and Vector Biology, National Health and Family Planning Commission, Shanghai 200025, China.

Background: Trichinellosis is a serious food-borne parasitic zoonosis, thus finding high quality antigens is the key to serodiagnosis of trichinosis. This article reports the characterization and sensitivity of four recombinant proteins expressed by four genes (, , , and ) from different developmental stages of for the diagnosis of trichinellosis in mice.

Methods: This study was conducted in Jilin University and National Institute of Parasitic Diseases of Chinese Center for Disease Control and Prevention in 2017-2018. The structures and functions of the proteins encoded by four genes were predicted by bioinformatics analysis. The four genes were cloned and expressed, and the recombinant proteins were purified. Anti- IgM and IgG antibodies in the sera of mice infected with from 1-45 d post-infection (dpi) were evaluated by ELISA.

Results: The optimal antigen epitopes of four proteins (P1, P2, P3, and P4) encoded by the four genes from T- and B-cells were predicted, and four purified recombinant proteins (r-P1, r-P2, r-P3, and r-P4) were successfully produced. For IgM, the antibody levels detected by the four recombinant antigens were approximately equal to the cut-off value. Anti- IgG antibodies were first detected by r-P1 at 8 dpi, followed by r-P2, r-P3, and r-P4 at 10 dpi, 14 dpi, and 16 dpi, respectively, and the antibody levels remained high until 45 dpi.

Conclusion: The recombinant antigens r-P1, r-P2, r-P3, and r-P4 could be antigens that react with antibodies, they showed high sensitivity in the detection of anti- IgG antibodies in mice. Among these proteins, r-P1 may be a candidate antigen for the detection of anti- IgG antibodies in the early infection phase and exhibited the best sensitivity among the antigens.
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http://dx.doi.org/10.18502/ijpa.v16i1.5531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988681PMC
March 2021

Palbociclib in advanced acral melanoma with genetic aberrations in the cyclin-dependent kinase 4 pathway.

Eur J Cancer 2021 May 23;148:297-306. Epub 2021 Mar 23.

Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma, Peking University Cancer Hospital & Institute, Beijing, China. Electronic address:

Background: Genetic aberrations in the cyclin-dependent kinase (CDK)4 pathway occur in 82% of patients with acral melanoma (AM), which is the predominant subtype of melanoma in China. We aimed to evaluate the anti-tumour activity of palbociclib, a selective CDK4/6 inhibitor, in patients with advanced AM with CDK4 pathway gene aberrations.

Methods: In this phase II trial, patients with advanced AM with CDK4 or/and CCND1 gain or/and CDKN2A loss were treated with oral palbociclib (125 mg) on days 1-21 of a 28-day cycle. The primary end-point was overall response rate (ORR). Secondary end-points were progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs). Whole-exome sequencing and multiplex immunohistochemistry of the available formalin-fixed, paraffin-embedded samples of nine patients were analysed to explore the predictive biomarkers of palbociclib response.

Results: Fifteen patients were enrolled. Three (20.0%) patients achieved tumour shrinkage at 8 weeks, including one with confirmed partial response. At data cut-off date, treatment was ongoing for one patient. The median PFS was 2.2 mo (range: 1.5-13.3 mo; 95% confidence interval [CI]: 1.9-2.5), and the median OS was 9.5 mo (range: 2.6-14.1 mo, 95% CI: 5.7-13.4). Eight patients died due to disease progression. The most common TRAEs were leukopenia (87%; Grade III/IV, 27%), neutropenia (80%; grade III/IV, 27%), and fatigue (53%; grade III/IV, 7%). Significant JAK2 deletions and SH2B3 amplifications were observed in patients who did not achieve any clinical benefit (CB) with palbociclib treatment. MCM7 amplification or protein expression level was found to be associated with CB.

Conclusions: Palbociclib monotherapy demonstrated preliminary efficacy and an acceptable safety profile in advanced AM patients with CDK4 pathway aberrations. Patients with amplification or high protein levels of MCM7 were more prone to benefit from palbociclib. The JAK-STAT pathway might play a role in the mechanism of action of palbociclib in AM.

Trial Registration Number: NCT03454919.

The Date Of Registration: March 6, 2018.
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http://dx.doi.org/10.1016/j.ejca.2021.02.021DOI Listing
May 2021

Single-cell sequencing technology in tumor research.

Clin Chim Acta 2021 Mar 22;518:101-109. Epub 2021 Mar 22.

Cancer Research Institute of Hengyang Medical College, University of South China Key Laboratory of Cancer Cellular and Molecular Pathology in Hunan Province, Hunan, Hengyang 421001, China. Electronic address:

Tumor heterogeneity is a key characteristic of malignant tumors and a significant obstacle in cancer treatment and research. Although bulk tissue sequencing has wide coverage and high accuracy, it can only represent the dominant cell signal information of each sample, while masking the unique gene expression of rare cells; therefore it cannot represent genes that are unstable within a subgroup, but unchanged in a majority of cells. With the progress of genomic technology, the emergence of single-cell sequencing (SCS) has effectively solved the above problem. Genetic, transcriptomic and epigenetic sequencing at the single-cell level provides an important basis for us to correctly classify the cell subsets of heterogeneous tumor populations and to reveal the process of complex changes in tumor cells at the molecular level. Single-cell sequencing technology has been applied to the field of cancer, revealing exciting discoveries in the potential mechanisms of tumor driver gene mutation, clonal evolution, invasion and metastasis. It also provides favorable conditions for developing new tumor biomarkers and providing more accurate and individualized targeted tumor therapy. Herein, we review the steps and methods of single-cell sequencing and highlight the application of SCS in tumor diagnosis and clinical treatment.
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http://dx.doi.org/10.1016/j.cca.2021.03.013DOI Listing
March 2021

The Regulation of ROS- and BECN1-Mediated Autophagy by Human Telomerase Reverse Transcriptase in Glioblastoma.

Oxid Med Cell Longev 2021 8;2021:6636510. Epub 2021 Mar 8.

Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor with high morbidity and mortality. Human telomerase reverse transcriptase (hTERT), the catalytic subunit of human telomerase, is overexpressed in most cancers including GBM. It is well known that hTERT can compensate telomere shortening to immortalize cells. However, in addition to the canonical function, hTERT has the roles beyond canonical telomere maintenance. To further understand the effects of hTERT on glioblastoma progression, we investigated the role of hTERT in regulating autophagy-a conserved pathway, by which cells deliver cellular organic material and impaired organelles to the lysosomes for degradation and recycle these cargos to produce energy under a stressful condition. Our results showed that downregulation of hTERT impaired autophagy levels by suppressing BECN1/beclin-1 and induced an increase of reactive oxygen species (ROS), which resulted in cell death ultimately. On the contrary, overexpression of BECN1 or treating cells with the antioxidant N-acetylcysteine (NAC) could restore the survival of hTERT knockdown cells. Our study will provide an additional basis of telomerase-targeting therapy for future clinical anticancer treatment.
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http://dx.doi.org/10.1155/2021/6636510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7963889PMC
March 2021

To be or not to be: relationship between grandparent status and health and wellbeing.

BMC Geriatr 2021 03 24;21(1):204. Epub 2021 Mar 24.

Department of Applied Social Sciences, The Hong Kong Polytechnic University, 11 Yuk. Choi Road, Hung Hum, Kowloon, Hong Kong.

Background: It is common for older people to become grandparents in later life. However, the impacts of grandparenting on their health and well-being remain ambiguous, especially in Chinese society, where the family is in the core of culture. The current study explored the relationship between grandparenthood and Chinese older people's health and psychological well-being in Hong Kong.

Methods: Cross-sectional data were collected from a sample of 1208 Hong Kong Chinese older people aged 55 and above through a telephone survey conducted in 2019. Participants were grouped into three categories: current grandparents (n = 507), grandparents-to-be (n = 275), and grandparents-not-to-be (n = 426). Multivariate linear regressions were performed to examine the relationship between grandparenting status and health and well-being outcomes, including self-rated physical health, mental health, resilience, and happiness. The potential moderating roles of older adults' demographic characteristics, including age, sex, education, marital status, financial status, were also examined.

Results: Bivariate analyses suggested statistically significant differences between health and well-being across the three groups of participants. Regression models showed that, compared with grandparents-not-to-be, being a current grandparent was associated with a significantly higher happiness level. Being a future grandparent was associated with significantly higher levels of happiness, resilience, and self-rated physical health. Moderating analyses showed that age, marital status, and educational level could moderate the relationship between grandparent status and resilience and self-rated mental health.

Conclusions: The current study offers preliminary insights into the significant relationship between grandparenthood and older adults' health and well-being. It calls for future studies to further explore the mechanisms between grandparenthood and the healthy ageing of different subgroups of older adults.
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http://dx.doi.org/10.1186/s12877-021-02052-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7989105PMC
March 2021

Multiplex Visualized Closed-Tube PCR with Hamming Distance 2 Code for 15 HPV Subtype Typing.

Anal Chem 2021 04 22;93(13):5529-5536. Epub 2021 Mar 22.

Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China.

Cervical cancer is the fourth leading cause of death in women, especially in developing countries. Specific and economic methodologies for HPV typing are crucial in cancer diagnosis and further disease control. However, routine assays based on real-time polymerase chain reaction (qPCR) or DNA-chip hybridization are either incapable of offering detailed subtype information or involve tedious open-tube operations with the risk of cross-contamination from PCR amplicons. Herein, we proposed a multiplex visualized closed-tube PCR (Multi-Vision) for HPV typing. Using gold nanoparticle probes (AuNPs) as a color change indicator combined with a Hamming distance 2 coding scheme, 13 high-risk HPVs and two subtypes associated with high-incidence benign lesions were successfully typed by performing six closed-tube PCRs. The assay demonstrates high specificity with no cross-reaction among different subtypes under several artificial sample concentrations (from 10 to 10 copies per reaction) and enables highly sensitive detection of as low as 0.5 copies/μL. Further, 105 clinical samples were successfully analyzed using our method with a high concordance rate of 99.05% (104/105) compared to a HPV typing kit. The inconsistent sample was confirmed by sequencing to be consistent with the typing results determined by our method, indicating that Multi-Vision could be a useful tool for HPV detection, especially in resource-limited regions.
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http://dx.doi.org/10.1021/acs.analchem.1c00035DOI Listing
April 2021

FixJ family regulator AcfR of Azorhizobium caulinodans is involved in symbiosis with the host plant.

BMC Microbiol 2021 Mar 9;21(1):80. Epub 2021 Mar 9.

Key Laboratory of Coastal Biology and Bioresource Utilization, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai, 264003, China.

Background: A wide variety of bacterial adaptative responses to environmental conditions are mediated by signal transduction pathways. Two-component signal transduction systems are one of the predominant means used by bacteria to sense the signals of the host plant and adjust their interaction behaviour. A total of seven open reading frames have been identified as putative two-component response regulators in the gram-negative nitrogen-fixing bacteria Azorhizobium caulinodans ORS571. However, the biological functions of these response regulators in the symbiotic interactions between A. caulinodans ORS571 and the host plant Sesbania rostrata have not been elucidated to date.

Results: In this study, we identified and investigated a two-component response regulator, AcfR, with a phosphorylatable N-terminal REC (receiver) domain and a C-terminal HTH (helix-turn-helix) LuxR DNA-binding domain in A. caulinodans ORS571. Phylogenetic analysis showed that AcfR possessed close evolutionary relationships with NarL/FixJ family regulators. In addition, six histidine kinases containing HATPase_c and HisKA domains were predicted to interact with AcfR. Furthermore, the biological function of AcfR in free-living and symbiotic conditions was elucidated by comparing the wild-type strain and the ΔacfR mutant strain. In the free-living state, the cell motility behaviour and exopolysaccharide production of the ΔacfR mutant were significantly reduced compared to those of the wild-type strain. In the symbiotic state, the ΔacfR mutant showed a competitive nodule defect on the stems and roots of the host plant, suggesting that AcfR can provide A. caulinodans with an effective competitive ability for symbiotic nodulation.

Conclusions: Our results showed that AcfR, as a response regulator, regulates numerous phenotypes of A. caulinodans under the free-living conditions and in symbiosis with the host plant. The results of this study help to elucidate the involvement of a REC + HTH_LuxR two-component response regulator in the Rhizobium-host plant interaction.
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http://dx.doi.org/10.1186/s12866-021-02138-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7945327PMC
March 2021