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1.
Mediators Inflamm ; 2021: 5573594, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34531703

RESUMO

Background: Abnormal endometrial repair after injury results in the formation of intrauterine adhesions (IUA) and a thin endometrium, which are key causes for implantation failure and infertility. Stem cell transplantation offers a potential alternative for some cases of severe Asherman's syndrome that cannot be treated with surgery or hormonal therapy. Umbilical cord-derived mesenchymal stem cells (UCMSCs) have been reported to repair the damaged endometrium. However, there is no report on the effects of UCMSCs previously seeded on human acellular amniotic matrix (AAM) on endometrial injury. Methods: Absolute ethanol was injected into rat uteri to damage the endometrium. UCMSCs previously seeded on AAM were surgically transplanted. Using a variety of methods, the treatment response was assessed by endometrial thickness, endometrial biomarker expression, endometrial receptivity, cell proliferation, and inflammatory factors. Results: Endometrial thickness was markedly improved after UCMSC-AAM transplantation. The expression of endometrial biomarkers, namely, vimentin, cytokeratin, and integrin ß3, in treated rats increased compared with untreated rats. In the UCMSC-AAM group, the VEGF expression decreased, whereas that of MMP9 increased compared with the injury group. Moreover, in the AAM group, the MMP9 expression increased. The expression of proinflammatory factors (IL-2, TNFα, and IFN-γ) in the UCMSC-AAM group decreased compared with the untreated group, whereas the expression of anti-inflammatory factors (IL-4, IL-10) increased significantly. Conclusions: UCMSC transplantation using AAM as the carrier can be applied to treat endometrial injury in rats. The successful preparation of lyophilized AAM provides the possibility of secondary infectious disease screening and amniotic matrix quality detection, followed by retrospective analysis. The UCMSC-AAM complex may promote the better application of UCMSCs on the treatment of injured endometrium.

2.
Hum Reprod ; 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34545401

RESUMO

STUDY QUESTION: What is the relationship between mitochondria of granulosa cells (GCs) and age and ovarian function in the patients under the POSEIDON classification? SUMMARY ANSWER: Our results revealed obvious abnormal mitochondrial-related changes in low prognosis IVF population, where age and the function of ovarian reserve exerted a divergent effect on mitochondrial content and function. WHAT IS KNOWN ALREADY: Mitochondria have an important role in the cross-talk between GCs and oocytes. However, factors affecting mitochondria of GCs and related mechanisms are still poorly understood. STUDY DESIGN, SIZE, DURATION: GCs samples were obtained from 119 infertile women undergoing IVF from September 2020 to February 2021. Six groups were investigated by the POSEIDON stratification: young with normal prognosis (C1), aging with normal prognosis (C2), young and low prognosis group with normal ovarian reserve (NOR) (G1), aging and low prognosis group with NOR (G2), young and low prognosis group with diminished ovarian reserve (DOR) (G3), and aging and low prognosis group with DOR (G4). PARTICIPANTS/MATERIALS, SETTING, METHODS: The morphology of GC mitochondria was observed by transmission electron microscopy. MtDNA copy number and mitochondrial replication-related genes were detected by real-time quantitative PCR (qPCR). Mitochondrial membrane potential (MMP) and cytosolic reactive oxygen species (ROS) were detected by confocal microscopy. Cellular glycolysis and aerobic respiratory capacity were analyzed by Seahorse XFe96 Analyzer, and related gene expression and protein levels were assessed by qPCR and Western blot. MAIN RESULTS AND THE ROLE OF CHANCE: Compared to the normal prognosis groups, mitochondrial morphology was impaired in the low prognosis groups, where the young groups (G1, G3) with low prognosis showed phenotypes undergoing oxidative stress (round, vacuolated, swollen with decreased matrix density) and the aging groups (G2, G4) revealed typical aging characteristics (an irregular shape with heterogeneous matrix density and cord-like cristae). Additionally, the degree of corresponding change and damage was more obvious in patients with DOR (G3, G4) regardless of age. For mitochondrial content, the mtDNA copy number in GCs was significantly negatively correlated with age in the low prognosis groups (ß = -0.373, P = 0.005). Interestingly, the relationship between mtDNA copy number and anti-Mullerian hormone score differed between the two age groups with low prognosis, with a negative correlation in the young groups (ß = -0.639, P = 0.049) and a positive correlation in the aging groups (ß = 0.505, P = 0.039). In addition, significantly reduced mitochondrial activity (MMP, ROS) and cell metabolism (both glycolysis and OXPHOS) were observed in the low prognosis groups, with the most obvious decrease being observed in the DOR population. However, the metabolism of the GCs in normal prognosis aging women (C2) shifted from OXPHOS to anaerobic glycolysis. LIMITATIONS, REASONS FOR CAUTION: Owing to the difficulties involved in primary GC collection and culture, the sample size was limited. WIDER IMPLICATIONS OF THE FINDINGS: Mitochondrial abnormality is closely linked to the low prognostic outcome in IVF patients. Supplementing the functional mitochondrial content or improving mitochondrial function by autologous mitochondrial transfer or mitochondrial-related regulating drugs may help improve the clinical outcomes in patients with a low prognosis, especially for those with DOR. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Natural Science Foundation of China (No. 21737001), the Peking University Clinical Medicine + X Youth Project (PKU2020LCXQ011), the Research and Development Program of Peking University People's Hospital (No. RDH2017-03; No. RDX2019-06) and the Application of Clinical Features of Capital Special Subject (Z171100001017130). There were no competing interests. TRIAL REGISTRATION NUMBER: This study was registered with the Chinese Clinical Trial Register (Clinical Trial Number: ChiCTR2100045531).

3.
Org Lett ; 23(18): 7100-7105, 2021 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-34436910

RESUMO

An efficient method for the Lewis acid promotion of the synthesis 9-phosphoryl fluorenes has been reported. This method focuses on ketone phosphonylation to form a C-P bond and a C-C bond between diphenylmethanone and H-phosphinate esters, H-phosphites, and H-phosphine oxides via phospha-aldol elimination, in which a series of 9-phosphoryl fluorene derivatives were selectively obtained in moderate to excellent yields.

4.
J Proteomics ; 248: 104353, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34418580

RESUMO

Stress-induced immunosuppression is one of the most widespread problems in the poultry industry. Understanding the molecular regulatory mechanism of immunosuppression induced by stress in the chicken spleen would provide a scientific foundation for the prevention of stress reactions and antistress molecular breeding in poultry. To assess the protein expression profile of spleen tissue in a stress-included immunosuppression model, we performed a TMT-based proteomic analysis of chicken spleen tissue in a Dex-induced immunosuppression model (group C) and a control group (group A). We identified 590 differentially abundant proteins (DAPs) in chicken spleen tissue. These DAPs were significantly enriched in the following functional categories: ECM-receptor interaction, DNA replication, p53 signaling pathway, PI3K-Akt signaling pathway and NF-kappa B signaling pathway. Integrative analysis of the proteome and our previous transcriptome data revealed 62 DAPs showing correlations with the expression of their encoding mRNAs. Complementary proteome- and transcriptome-level analyses revealed a complex molecular network of stress-included immunosuppression. DPP4 and ALDH1A3 were the most significantly upregulated DAPs. GBP and OASL were identified as important nodes in the network related to stress-induced immunosuppression. The candidate genes identified in this study may be useful for the marker-based breeding of new chicken varieties with reduced stress levels. SIGNIFICANCE: This study provides a large amount of new information about the spleen proteome of the Dex-induced immunosuppression in chicks, as well as the correlation of transcriptome and proteome. Analysis of this resource has enabled us to examine mechanism of protein and transcript diversification, which expands the understanding of the complexity of the mechanism of stress-induced immunosuppression.

5.
Tissue Cell ; 72: 101596, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34333229

RESUMO

The role of autophagy in the transplantation of induced pluripotent stem cells (iPSCs)-derived neural stem cells (NSCs) to treat spinal cord injury (SCI) and neurogenic bladder was investigated in this study. NSCs derived from human iPSCs were identified by and immunofluorescence assay. To clarify the role of autophagy, iPSCs were treated with either an autophagy inducer (rapamycin), or an autophagy inhibitor (chloroquine). Cell Counting kit-8 (CCK-8), western blot and flow cytometry were used to detect the effect of autophagy on the viability and differentiation of iPSCs. Sixty Wistar rats were selected to establish the SCI model and treated with iPSCs-derived NSCs transplantation. The effect of autophagy on the bladder function of rats with different treatments was evaluated by Basso, Beattie, and Bresnahan (BBB) score, bladder function score, bladder weight measurement, Hematoxylin & Eosin (H&E) staining, and Masson staining. The results of in vitro experiment showed that rapamycin enhanced the cell activity of iPSCs, increased the number of nestin positive cells, up-regulated Beclin-1 and LC3BI/II expressions, and down-regulated p62 expression. And the results of in vivo experiment showed that rapamycin improved exercise ability and bladder function, partially restored bladder weight, and significantly reduced bladder tissue damage in SCI rats. However, chloroquine showed the opposite results. The differentiation of iPSCs into NSCs could be promoted by induced autophagy, while neurogenic bladder of SCI was restored by autophagy activation.

6.
Sci Rep ; 11(1): 16910, 2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34413375

RESUMO

Various biochemical functions of organisms are performed by protein-protein interactions (PPIs). Therefore, recognition of protein-protein interactions is very important for understanding most life activities, such as DNA replication and transcription, protein synthesis and secretion, signal transduction and metabolism. Although high-throughput technology makes it possible to generate large-scale PPIs data, it requires expensive cost of both time and labor, and leave a risk of high false positive rate. In order to formulate a more ingenious solution, biology community is looking for computational methods to quickly and efficiently discover massive protein interaction data. In this paper, we propose a computational method for predicting PPIs based on a fresh idea of combining orthogonal locality preserving projections (OLPP) and rotation forest (RoF) models, using protein sequence information. Specifically, the protein sequence is first converted into position-specific scoring matrices (PSSMs) containing protein evolutionary information by using the Position-Specific Iterated Basic Local Alignment Search Tool (PSI-BLAST). Then we characterize a protein as a fixed length feature vector by applying OLPP to PSSMs. Finally, we train an RoF classifier for the purpose of identifying non-interacting and interacting protein pairs. The proposed method yielded a significantly better results than existing methods, with 90.07% and 96.09% prediction accuracy on Yeast and Human datasets. Our experiment show the proposed method can serve as a useful tool to accelerate the process of solving key problems in proteomics.

7.
Nanotechnology ; 2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34311450

RESUMO

Recently, prussian blue analogues (PBAs), as the most classical class of metal-organic frameworks, have been widely studied by scientists. Nevertheless, the inferior conductivity of PBAs restricts the application in supercapacitors. In this work, nickel cobalt hexacyanoferrate (Ni2CoHCF) had been produced via a simple co-precipitation approach and coated with polypyrrole on its surface. The conductivity of PBAs was improved by the polypyrrole coating. The Ni2CoHCF@PPy-400 microspheres were demonstrated to the outstanding specific capacity of 82 mAh g-1 at 1 A g-1. After 3,000 cycles, the Ni2CoHCF@PPy-400 microspheres had a long cycle life and 86% specific capacity retention rate at 5 A g-1. Additionally, it was coupled with activated carbon to build high-performance asymmetric supercapacitor (Ni2CoHCF@PPy-400//AC), which displayed a high energy density of 21.7 Wh kg-1 at the power density of 888 W kg-1 and good cycle stability after 5,000 cycles (a capacity retention rate of 85.2%). What is more, the results reveal that the Ni2CoHCF@PPy-400 microspheresare a prospective candidate for exceptional energy storage devices.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34269698

RESUMO

ABSTRACT: Proper medication compliance is critical for the integrity of clinical practice, directly related to the success of clinical trials to evaluate both pharmacological and device-based therapies. Here, we established a liquid chromatography tandem mass spectrometry (LC-MS/MS) method to accurately detect 55 chemical entities in human urine sample, which accounting for the most commonly used 172 antihypertensive drugs in China. The established method had good accuracy, intra-day and inter-day precision for all analyses in both bench tests and validated in 21 hospitalized patients. We utilized this method to monitor and ensure drug compliance, and exclude the inferring impacts of medication compliance as a key confounder for our pivotal trial of a catheter-based, renal mapping and selective renal denervation to treat hypertension. It is found that in the urine samples from 92 consecutive subjects, 85 subjects (92.4%) were consistent with their prescriptions after 28 days run-in periods, 90 (97.8%) and 85 (95.5%) patients completely complied with their medications during the 3-month and 6-month follow-up period, respectively. Thus, using LC-MS/MS method with specificity, accuracy and precision, we ensured drug compliance of patients, excluded the key confounder of drug interferences and ensured the quality of our device-based clinical trial for treatment of hypertension.

9.
Mol Biol Evol ; 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34329477

RESUMO

Domestication and breeding have reshaped the genomic architecture of chicken, but the retention and loss of genomic elements during these evolutionary processes remain unclear. We present the first chicken pan-genome constructed using 664 individuals, which identified an additional ∼66.5 Mb sequences that are absent from the reference genome (GRCg6a). The constructed pan-genome encoded 20,491 predicated protein-coding genes, of which higher expression level are observed in conserved genes relative to dispensable genes. Presence/absence variation (PAV) analyses demonstrated that gene PAV in chicken was shaped by selection, genetic drift, and hybridization. PAV-based GWAS identified numerous candidate mutations related to growth, carcass composition, meat quality, or physiological traits. Among them, a deletion in the promoter region of IGF2BP1 affecting chicken body size is reported, which is supported by functional studies and extra samples. This is the first time to report the causal variant of chicken body size QTL located at chromosome 27 which was repeatedly reported. Therefore, the chicken pan-genome is a useful resource for biological discovery and breeding. It improves our understanding of chicken genome diversity and provides materials to unveil the evolution history of chicken domestication.

10.
Sci Rep ; 11(1): 12020, 2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-34103637

RESUMO

Bemisia tabaci is one of the most notorious agricultural pests in the world. A vicious circle among insect resistance, dose increased, environment and human body impaired as the overuse of synthetic pesticides are becoming increasingly evident. Entomopathogenic Beauveria sp. is known as an effective natural enemy to control B. tabaci. Therefore, this study aimed to purify and identify the biological compounds from Beauveria sp. LY2 via extensive chromatographic techniques, NMR and MS and evaluated for their insecticidal activities against B. tabaci via contact and feeding assay. The outcome identified that one new cerebroside, cerebroside F (1), nine known compounds, cerebroside B (2), bassiatin (3), methyl 1,4-dihydro-4-oxo-2-quinolinecarboxylate (4), cerevisterol (5), 9-hydroxycerevisterol (6), 6-dehydrocerevisterol (7), (22E,24R)-ergosta-8(14),22-diene-3ß,5α,6ß,7α-tetrol (8), melithasterol B (9) and ergosterol peroxide (10) were isolated. Among the known compounds, methyl 1,4-dihydro-4-oxo- 2-quinolinecarboxylate (4) was isolated from natural origin for the first time. It is demonstrable from the results that compounds 3, 4 and 7 strongly featured insecticidal activities against B. tabaci, being the LC50 value as 10.59, 19.05, 26.59 µg/mL respectively in contact as well as 11.42, 5.66, 5.65 µg/mL respectively in feeding experiment. Moreover, no adverse effect on plant growth/height or phytotoxicity was observed on pepper, cucumber, tomato and cotton. The data from the current study has provided the foundation for the use of newly purified compounds against Bemisia tabaci as an alternative to synthetic chemical compounds.

11.
Spectrochim Acta A Mol Biomol Spectrosc ; 261: 120078, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34147737

RESUMO

A novel gelator molecular based on quinolone (MN) has been successfully designed and synthesized. The gelator MN could self-assemble to form a supramolecular gel (OMN), which showed obvious aggregation-induced emission (AIE) in iso-Propyl alcohol (i-PrOH). Furthermore, the supramolecular organogel OMN realized ultrasensitive detection of Fe3+ and Cu2+ in aqueous medium and fluorescent quenching at 427 nm. The sensing mechanism between supramolecular gel and metal ions was fully investigated via FE-SEM, FT-IR, XRD and XPS. Meanwhile, a thin film based on responsive supramolecular gel OMN was prepared, which could be used as multi-stimuli-responsive fluorescent display materials for the detection of Fe3+ and Cu2+.


Assuntos
Quinolinas , Íons , Espectrometria de Fluorescência , Espectroscopia de Infravermelho com Transformada de Fourier
12.
BMC Genomics ; 22(1): 428, 2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34107898

RESUMO

BACKGROUND: Estrogen plays an essential role in female development and reproductive function. In chickens, estrogen is critical for lipid metabolism in the liver. The regulatory molecular network of estrogen in chicken liver is poorly understood. To identify estrogen-responsive genes and estrogen functional sites on a genome-wide scale, we determined expression profiles of mRNAs, lncRNAs, and miRNAs in estrogen-treated ((17ß-estradiol)) and control chicken livers using RNA-Sequencing (RNA-Seq) and studied the estrogen receptor α binding sites by ChIP-Sequencing (ChIP-Seq). RESULTS: We identified a total of 990 estrogen-responsive genes, including 962 protein-coding genes, 11 miRNAs, and 17 lncRNAs. Functional enrichment analyses showed that the estrogen-responsive genes were highly enriched in lipid metabolism and biological processes. Integrated analysis of the data of RNA-Seq and ChIP-Seq, identified 191 genes directly targeted by estrogen, including 185 protein-coding genes, 4 miRNAs, and 2 lncRNAs. In vivo and in vitro experiments showed that estrogen decreased the mRNA expression of PPARGC1B, which had been reported to be linked with lipid metabolism, by directly increasing the expression of miR-144-3p. CONCLUSIONS: These results increase our understanding of the functional network of estrogen in chicken liver and also reveal aspects of the molecular mechanism of estrogen-related lipid metabolism.


Assuntos
MicroRNAs , RNA Longo não Codificante , Animais , Galinhas/genética , Galinhas/metabolismo , Estrogênios , Feminino , Metabolismo dos Lipídeos/genética , Fígado/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo
13.
Neurourol Urodyn ; 40(6): 1593-1599, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34058024

RESUMO

BACKGROUND: The controversy on the best surgical approach for vesicovaginal fistula (VVF) repair remains due to the scarcity of high-level evidences. We aim to analyze the efficacy and safety of the laparoscopic transvesical (LT) and laparoscopic extravesical (LE) approaches to posthysterectomy VVF (PH-VVF). METHODS: Data of 64 patients with PH-VVFs who were laparoscopicly treated in the First Affiliated Hospital of Nanchang University and the Hangzhou Third Hospital from January 2011 to November 2019 were retrospectively collected. The operative time (OT), estimated bleeding volume (EBV), postoperative bladder function and complications, hospital stay length (HSL), surgery success rate, and recurrence were compared between the two groups. RESULTS: In all, there were no significant differences in baseline characteristics between those two arms. Both approaches were successfully performed without open conversion in either group. The LT group was significantly corrected with a shorter mean OT than the LE group (p < 0.001), regardless of the fistula's position. No significant differences existed in the mean EBV and HSL between the two interventions (p = 0.136 and p = 0.210, respectively). The tendency of postoperative complications and success rates of surgery were also comparable in both groups. The patients in the LT group had similar bladder functions to those in LE group. The recurrence occurred in one patient in each arm during the follow-up periods of 12-36 months. CONCLUSIONS: The LT approach is significantly related to a shorter OT than the LE approach without compromising the safety and success rates in repairing PH-VVF.

14.
PLoS One ; 16(4): e0249288, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33857153

RESUMO

Circular RNAs (circRNAs) play important roles in adipogenesis. However, studies on circRNA expression profiles associated with the development of abdominal adipose tissue are lacking in chickens. In this study, 12 cDNA libraries were constructed from the abdominal adipose tissue of Chinese domestic Gushi chickens at 6, 14, 22, and 30 weeks. A total of 1,766 circRNAs were identified by Illumina HiSeq 2500 sequencing. These circRNAs were primarily distributed on chr1 through chr10 and sex chromosomes, and 84.95% of the circRNAs were from gene exons. Bioinformatic analysis showed that each circRNA has 35 miRNA binding sites on average, and 62.71% have internal ribosome entry site (IRES) elements. Meanwhile, these circRNAs were primarily concentrated in TPM < 0.1 and TPM > 60, and their numbers accounted for 18.90% and 80.51%, respectively, exhibiting specific expression patterns in chicken abdominal adipose tissue. In addition, 275 differentially expressed (DE) circRNAs were identified by comparison analysis. Functional enrichment analysis showed that the parental genes of DE circRNAs were primarily involved in biological processes and pathways related to lipid metabolism, such as regulation of fat cell differentiation, fatty acid homeostasis, and triglyceride homeostasis, as well as fatty acid biosynthesis, fatty acid metabolism, and glycerolipid metabolism. Furthermore, ceRNA regulatory networks related to abdominal adipose development were constructed. The results of this study indicated that circRNAs can regulate lipid metabolism, adipocyte proliferation and differentiation, and cell junctions during abdominal adipose tissue development in chickens through complex ceRNA networks between circRNAs, miRNAs, genes, and pathways. The results of this study may help to expand the number of known circRNAs in abdominal adipose tissue and provide a valuable resource for further research on the function of circRNAs in chicken abdominal adipose tissue.


Assuntos
Gordura Abdominal/metabolismo , RNA Circular/metabolismo , Gordura Abdominal/crescimento & desenvolvimento , Envelhecimento/genética , Animais , Sítios de Ligação , Diferenciação Celular/genética , Galinhas/genética , Biblioteca Gênica , Redes Reguladoras de Genes/genética , Metabolismo dos Lipídeos/genética , MicroRNAs/química , MicroRNAs/metabolismo , Transcriptoma
15.
ACS Nano ; 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33929826

RESUMO

Bulk nanopolycrystalline diamond (NPD) samples were deformed plastically within the diamond stability field up to 14 GPa and above 1473 K. Macroscopic differential stress Δσ was determined on the basis of the distortion of the 111 Debye ring using synchrotron X-ray diffraction. Up to ∼5(2)% strain, Debye ring distortion can be satisfactorily described by lattice strain theories as an ellipse. Beyond ∼5(2)% strain, lattice spacing d111 along the Δσ direction becomes saturated and remains constant with further deformation. Transmission electron microscopy on as-synthesized NPD shows well-bonded grain boundaries with no free dislocations within the grains. Deformed samples also contain very few free dislocations, while density of {111} twins increases with plastic strain. Individual grains display complex contrast, exhibiting increasing misorientation with deformation according electron diffraction. Thus, NPD does not deform by dislocation slip, which is the dominated mechanism in conventional polycrystalline diamond composites (PCDCs, grain size >1 µm). The nonelliptical Debye ring distortion is modeled by nucleating 12⟨110⟩ dislocations or their dissociated 16⟨112⟩ partials gliding in the {111} planes to produce deformation twinning. With increasing strain up to ∼5(2)%, strength increases rapidly to ∼20(1) GPa, where d111 reaches saturation. Strength beyond the saturation shows a weak dependence on strain, reaching ∼22(1) GPa at >10% strain. Overall, the strength is ∼2-3 times that of conventional PCDCs. Combined with molecular dynamics simulations and lattice rotation theory, we conclude that the rapid rise of strength with strain is due to defect-source strengthening, whereas further deformation is dominated by nanotwinning and lattice rotation.

16.
Nat Commun ; 12(1): 1383, 2021 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-33654063

RESUMO

In this study, we investigate the seroprevalence of SARS-CoV-2 antibodies among blood donors in the cities of Wuhan, Shenzhen, and Shijiazhuang in China. From January to April 2020, 38,144 healthy blood donors in the three cities were tested for total antibody against SARS-CoV-2 followed by pseudotype SARS-CoV-2 neutralization tests, IgG, and IgM antibody testing. Finally, a total of 398 donors were confirmed positive. The age- and sex-standardized SARS-CoV-2 seroprevalence among 18-60 year-old adults (18-65 year-old in Shenzhen) was 2.66% (95% CI: 2.24%-3.07%) in Wuhan, 0.033% (95% CI: 0.0029%-0.267%) in Shenzhen, and 0.0028% (95% CI: 0.0001%-0.158%) in Shijiazhuang, respectively. Female sex and older-age were identified to be independent risk factors for SARS-CoV-2 seropositivity among blood donors in Wuhan. As most of the population of China remained uninfected during the early wave of the COVID-19 pandemic, effective public health measures are still certainly required to block viral spread before a vaccine is widely available.


Assuntos
SARS-CoV-2/patogenicidade , Anticorpos Antivirais/sangue , Doadores de Sangue/estatística & dados numéricos , COVID-19/sangue , COVID-19/epidemiologia , COVID-19/imunologia , China/epidemiologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Testes de Neutralização , Prevalência , Fatores de Risco , SARS-CoV-2/imunologia
17.
Cancer Rep (Hoboken) ; 4(4): e1361, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33788425

RESUMO

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) exposure had been reported to be a risk factor of mtDNAcn in our early study. However, the effect of metabolic enzymes' genetic polymorphisms on mtDNAcn in PAHs-Exposure workers has not been fully evaluated. AIM: The aim of the study was to explore the effect of metabolic enzymes' genetic polymorphisms on mtDNAcn in PAHs-Exposure. METHODS AND RESULTS: We investigated the effects of metabolic enzymes' genetic polymorphisms on mtDNAcn among 544 coke oven workers and 238 office staffs. The mtDNAcn of peripheral blood leukocytes was measured using the Real-time quantitative polymerase chain reaction (PCR) method. PCR and restriction fragment length was used to detect five polymorphisms in GSTT1, GSTM1, GSTP1 rs1695, CYP2E1 rs6413432, and CYP2E1 rs3813867. The mtDNAcn in peripheral blood leukocytes was significantly lower in the exposure group than that in the control group (p < .001). The 1-OHPYR had an increasing trend with the genotypes AA→AG → GG of GSTP1 rs1695 in the control group. Generalized linear model indicated that the influencing factors of mtDNAcn were PAHs-exposure [ß (95% CI) = -0.420 (-0.469, -0.372), p < .001], male [ß (95% CI) = -0.058 (-0.103, -0.012), p = .013], and AA genotype for GSTP1 rs1695 [ß (95% CI) = -0.051 (-0.095, -0.008), p = .020]. CONCLUSION: The individuals carrying the AA genotype of GSTP1 rs1695 may have a lower mtDNAcn due to their weaker detoxification of PAHs.

18.
Virol Sin ; 36(4): 736-745, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33616891

RESUMO

Human rhinovirus (HRV) is one of the most important cold-causing pathogens in humans. Piwi-interacting RNAs (piRNAs) are a recently discovered class of small non-coding RNAs whose best-understood function is to repress mobile element (ME) activity in animal germline. However, the profile of human/host piRNA during HRV infection is largely unknown. Here we performed high-throughput sequencing of piRNAs from H1-HeLa cells infected with HRV16 at 12 h, 24 h, and 36 h. The results showed that 22,151,664, 24,362,486 and 22,726,546 piRNAs displayed differential expression after HRV16 infection for three time points. A significant differential expression of 21 piRNAs was found in all time points and further verified by RT-qPCR, including 7 known piRNAs and 14 newly found piRNAs. In addition, piRNA prediction was performed on Piano using the SVM algorithm and transposon information. It found that novel_pir78110, novel_pir78107, novel_pir78097, novel_pir78094 and novel_pir76584 are associated with the DNA/hobo of Drosophila, Ac of maize and Tam3 of snapdragon (hAT)-Charlie transposon. The novel_pir97924, novel_pir105705 and novel_pir105700 recognize long interspersed nuclear elements 1 (LINE-1). The novel_pir33182 and novel_pir46604 are related to the long terminal repeat (LTR)/(Endogenous Retrovirus1) ERV1 repetitive element. The novel_pir73855 is related to the LTR/ERVK repetitive element. Both novel_pir70108 and novel_pir70106 are associated with the LTR/ERVL-MaLR repetitive element. The novel_pir15900 is associated with the DNA/hAT-Tip100 repetitive element. Overall, our results indicated that rhinovirus infection could reduce the expression of some piRNAs to facilitate upregulation of LINE-1 transcription or retrotransposons' expression, which is helpful to further explore the mechanism of rhinovirus infection.

19.
Clin Cancer Res ; 27(10): 2764-2772, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33627493

RESUMO

PURPOSE: Autologous chimeric antigen receptor T (CAR-T) cell therapy is an effective treatment for relapsed/refractory acute lymphoblastic leukemia (r/r ALL). However, certain characteristics of autologous CAR-T cells can delay treatment availability. Relapse caused by antigen escape after single-targeted CAR-T therapy is another issue. Therefore, we aim to develop CRISPR-edited universal off-the-shelf CD19/CD22 dual-targeted CAR-T cells as a novel therapy for r/r ALL. PATIENTS AND METHODS: In this open-label dose-escalation phase I study, universal CD19/CD22-targeting CAR-T cells (CTA101) with a CRISPR/Cas9-disrupted TRAC region and CD52 gene to avoid host immune-mediated rejection were infused in patients with r/r ALL. Safety, efficacy, and CTA101 cellular kinetics were evaluated. RESULTS: CRISPR/Cas9 technology mediated highly efficient, high-fidelity gene editing and production of universal CAR-T cells. No gene editing-associated genotoxicity or chromosomal translocation was observed. Six patients received CTA101 infusions at doses of 1 (3 patients) and 3 (3 patients) × 106 CAR+ T cells/kg body weight. Cytokine release syndrome occurred in all patients. No dose-limiting toxicity, GvHD, neurotoxicity, or genome editing-associated adverse events have occurred to date. The complete remission (CR) rate was 83.3% on day 28 after CTA101 infusion. With a median follow-up of 4.3 months, 3 of the 5 patients who achieved CR or CR with incomplete hematologic recovery (CR/CRi) remained minimal residual disease (MRD) negative. CONCLUSIONS: CRISPR/Cas9-engineered universal CD19/CD22 CAR-T cells exhibited a manageable safety profile and prominent antileukemia activity. Universal dual-targeted CAR-T cell therapy may offer an alternative therapy for patients with r/r ALL.

20.
Int J Cancer ; 148(2): 267-276, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33459350

RESUMO

Peptidylarginine deiminases (PADs) catalyze the conversion of arginine residues to citrulline residues on target proteins in the presence of calcium ions. This elaborate type of posttranslational modification is termed citrullination. PADs may regulate gene transcriptional activity via histone citrullination. There has been an increasing appreciation for the roles of PADs in a wide variety of biological processes. In this review article, we summarize recent evidence indicating that PADs and citrullinated proteins are involved in several physiological and pathological processes related to cancer. Of particular interest is that PAD2 and PAD4 exhibit characteristic expression levels, activities and specific biological effects in diverse types of cancer. We also list several PAD inhibitors, propose the possible mechanisms underlying the biological actions of PAD-mediated protein citrullination in experimental models and discuss the potential therapeutic value of PADs and their inhibitors for disease diagnosis and treatment.


Assuntos
Neoplasias/metabolismo , Proteína-Arginina Desiminase do Tipo 2/metabolismo , Proteína-Arginina Desiminase do Tipo 4/metabolismo , Animais , Arginina/metabolismo , Citrulina/metabolismo , Humanos , Neoplasias/enzimologia , Processamento de Proteína Pós-Traducional
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