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1.
Altern Ther Health Med ; 29(2): 206-212, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36525353

RESUMO

Context: Since December 2019, medical practitioners discovered a novel coronavirus causing an acute respiratory-tract infection in some hospitals in Wuhan, Hubei Province. COVID-19 has spread globally, making it an epidemic worldwide at present. Understanding the mental-health responses of college students to COVID-19 can help a school staff to better guide students seeking education. Objective: The study aimed to explore the differences between nonmedical and medical college students during the COVID-19 epidemic in their cognitive interest about the disease, preventive behaviors, psychological effects, and job-search intentions, hoping to provide more targeted measures for virus-coping education for college students. Design: The research team conducted a cross-sectional study, using an anonymous online questionnaire. Setting: The study took place at Shanghai, China. Participants: Participants were 1648 college students studying different specialties in various provinces of China, 485 nonmedical students and 1163 medical students. Outcome Measures: The survey's questions covered the respondents': (1) general demographic characteristics, (2) cognitive interest and knowledge about COVID-19 and its infectiousness as well as efforts at active learning about infectious diseases and viruses, (3) awareness of precautionary behaviors against COVID-19, (4) effects on mental health, and (5) effects on job-search intentions. The research team used descriptive statistics and Chi-square tests to analyze the survey data. Results: Among nonmedical students: (1) 297 participants (61.2%) were interested in learning about COVID-19, (2) 321 participants (66.2%) took the initiative to learn about the virus, (3) 301 participants (62.1%) took the initiative to learn about infectious disease, and (4) 151 participants (31.1%) watched medical-themed movies or TV series about COVID-19. Among medical students, the corresponding proportions were 772 participants (66.4%), 855 participants (73.5%), 791 participants (68.1%), and 791 participants (68.1%), respectively. Among nonmedical students, 223 participants (46.0%) had N95 masks available, 429 participants (88.5%) had disinfectant supplies available, 271 participants (55.9%) wore goggles in public places, 75 participants (15.5%) chose public transportation, and 77 participants (15.9%) were exposed to public places in the week prior to the survey. Among medical students, the corresponding proportions were 470 participants (40.4%), 935 participants (80.4%), 575 participants (49.4%), 243 participants (20.9%), and 297 participants (25.5%), respectively. Furthermore, COVID-19 had a stronger effect on medical students' psychology and job-search ambitions. Conclusions: The news about COVID-19 piqued the interest of medical students. Nonmedical students had stronger protective behavior than medical students. The COVID-19 outbreak had a significant influence on medical students' lives, studies, and moods. In addition, COVID-19 had a greater impact on the job-search intentions of medical students.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Intenção , Estudos Transversais , China/epidemiologia , Estudantes/psicologia , Cognição , Inquéritos e Questionários
2.
Anal Chem ; 94(8): 3467-3475, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35171581

RESUMO

Accurate full-length sequencing of a purified unknown protein is still challenging nowadays due to the error-prone mass-spectrometry (MS)-based methods. De novo identified peptide sequence largely contain errors, undermining the accuracy of assembly. Bias on the detectability of the peptides also makes low-coverage regions, resulting in gaps. Although recent advances on multi-enzyme hydrolysis and algorithms showed complete assembly of full-length protein sequences in a few examples, the robustness in practical application is still to be improved. Here, inspired by genome assembly strategies, we demonstrate a contig-scaffolding strategy to assemble protein sequences with high robustness and accuracy. This strategy integrates multiple unspecific hydrolysis methods to minimize the bias in the hydrolysis process. After de novo identification of the peptides, our assembly algorithm, named Multiple Contigs & Scaffolding (MuCS), assembles the peptide sequences in a multistep, i.e., contig-scaffold manner, with error correction in each step. MS data from different hydrolysis experiments complement each other for robust contig extension and error correction. We demonstrated that our strategy on three proteins and three replications all reached 100% coverage (except one with 98.85%) and 98.69-100% accuracy. It can also efficiently deal with the membrane protein, although the transmembrane region was missing due to the limitation of the MS. The three replicates reached 88.85-92.57% coverage and 97.57-100% accuracy. In sum, we provided a practical, robust, and accurate solution for full-length protein sequencing. The MuCS software is available at http://chi-biotech.com/mucs/.


Assuntos
Análise de Sequência de Proteína , Software , Algoritmos , Sequência de Aminoácidos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Proteínas/genética , Análise de Sequência de DNA/métodos , Análise de Sequência de Proteína/métodos
3.
J Virol ; 95(16): e0061721, 2021 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-34105996

RESUMO

The current pandemic of COVID-19 is caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The SARS-CoV-2 spike protein receptor-binding domain (RBD) is the critical determinant of viral tropism and infectivity. To investigate whether naturally occurring RBD mutations during the early transmission phase have altered the receptor binding affinity and infectivity, we first analyzed in silico the binding dynamics between SARS-CoV-2 RBD mutants and the human angiotensin-converting enzyme 2 (ACE2) receptor. Among 32,123 genomes of SARS-CoV-2 isolates (December 2019 through March 2020), 302 nonsynonymous RBD mutants were identified and clustered into 96 mutant types. The six dominant mutations were analyzed applying molecular dynamics simulations (MDS). The mutant type V367F continuously circulating worldwide displayed higher binding affinity to human ACE2 due to the enhanced structural stabilization of the RBD beta-sheet scaffold. The MDS also indicated that it would be difficult for bat SARS-like CoV to infect humans. However, the pangolin CoV is potentially infectious to humans. The increased infectivity of V367 mutants was further validated by performing receptor-ligand binding enzyme-linked immunosorbent assay (ELISA), surface plasmon resonance, and pseudotyped virus assays. Phylogenetic analysis of the genomes of V367F mutants showed that during the early transmission phase, most V367F mutants clustered more closely with the SARS-CoV-2 prototype strain than the dual-mutation variants (V367F+D614G), which may derivate from recombination. The analysis of critical RBD mutations provides further insights into the evolutionary trajectory of early SARS-CoV-2 variants of zoonotic origin under negative selection pressure and supports the continuing surveillance of spike mutations to aid in the development of new COVID-19 drugs and vaccines. IMPORTANCE A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused the pandemic of COVID-19. The origin of SARS-CoV-2 was associated with zoonotic infections. The spike protein receptor-binding domain (RBD) is identified as the critical determinant of viral tropism and infectivity. Thus, whether mutations in the RBD of the circulating SARS-CoV-2 isolates have altered the receptor binding affinity and made them more infectious has been the research hot spot. Given that SARS-CoV-2 is a novel coronavirus, the significance of our research is in identifying and validating the RBD mutant types emerging during the early transmission phase and increasing human angiotensin-converting enzyme 2 (ACE2) receptor binding affinity and infectivity. Our study provides insights into the evolutionary trajectory of early SARS-CoV-2 variants of zoonotic origin. The continuing surveillance of RBD mutations with increased human ACE2 affinity in human or other animals is critical to the development of new COVID-19 drugs and vaccines against these variants during the sustained COVID-19 pandemic.


Assuntos
Substituição de Aminoácidos , Enzima de Conversão de Angiotensina 2/genética , COVID-19/transmissão , Mutação , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genética , Enzima de Conversão de Angiotensina 2/química , Enzima de Conversão de Angiotensina 2/metabolismo , Sítios de Ligação , COVID-19/patologia , COVID-19/virologia , Expressão Gênica , Interações Hospedeiro-Patógeno/genética , Humanos , Cinética , Simulação de Dinâmica Molecular , Fenilalanina/química , Fenilalanina/metabolismo , Filogenia , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , SARS-CoV-2/classificação , SARS-CoV-2/metabolismo , SARS-CoV-2/patogenicidade , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/metabolismo , Termodinâmica , Valina/química , Valina/metabolismo , Virulência , Ligação Viral
4.
Clin Invest Med ; 41(1): E25-E30, 2018 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-29603688

RESUMO

PURPOSE: As a novel hepatokine, fetuin B involves in various functions of energy metabolism. Recent advance reveals a complex interaction between bone and liver via the secretion of hepatokines. The association between serum fetuin B and osteoporosis was evaluated in a 4-year hospital-based prospective study of 1,370 Chinese postmenopausal women. METHODS: Bone mineral densities (BMDs) were obtained on femoral neck and lumbar spines by dual energy X-ray absorptiometry. Serum fetuin B level was tested by enzyme-linked immunosorbent assay. RESULTS: Of the 1,370 participants in the baseline study (2012), 650 subjects were included in the 4-year follow-up study (2016). Serum fetuin B level presented higher in subjects with osteoporosis (106.7 ± 17.6 µg/ml) than it in controls (86.3 ± 17.5 µg/ml) (P < 0.001). Meanwhile, fetuin B positively correlated with triglycerides (r = 0.227, P = 0.001), femoral BMD (r = -0.426, P < 0.001) and lumbar BMD (r = -0.332, P < 0.001). At the 4-year follow-up, 116 subjects had developed osteoporosis. Serum fetuin B concentration was significantly higher in subjects who developed (P < 0.001). The osteoporosis incidence increased from Q1 9.9%, Q2 14.7%, and Q3 17.8% to Q4 30.2% (P for trend < 0.001), among the quartiles of baseline fetuin B. A higher fetuin B baseline level was linked to the incidence of osteoporosis (adjusted OR = 1.179, 95% CI [1.119 - 1.243], P = 0.009). CONCLUSION: Serum fetuin B levels increased with the development of osteoporosis.


Assuntos
Fetuína-B/metabolismo , Osteoporose/sangue , Idoso , Idoso de 80 Anos ou mais , Densidade Óssea , Feminino , Colo do Fêmur/metabolismo , Colo do Fêmur/patologia , Seguimentos , Humanos , Incidência , Vértebras Lombares/metabolismo , Vértebras Lombares/patologia , Masculino , Pessoa de Meia-Idade , Osteoporose/epidemiologia , Osteoporose/patologia , Estudos Prospectivos , Triglicerídeos/sangue
5.
Zhonghua Yi Xue Za Zhi ; 95(44): 3620-4, 2015 Nov 24.
Artigo em Zh | MEDLINE | ID: mdl-26813378

RESUMO

OBJECTIVE: To confirm the existence of purkinje fibers in rabbit outflow tract tissue and explore the role of Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel 4 (HCN4) protein in idiopathic ventricular tachycardia. METHODS: A total of ten New Zealand white rabbits were randomly selected to observe whether there were pukinje fibers in outflow tract by the methods of HE staining and immunohistochemical detection of midsize neurofilament (NF-M). Forty rabbits were randomly divided into four groups: normal control group (SO), ventricular tachycardia group (VT), ventricular tachycardia+ esmolol intervention group (VT+ ESM) and ventricular tachycardia+ ivabradine intervention group (VT+ IVA). Immunohistochemistry was used to detect the expression of HCN4 protein in ventricular outflow tract; the required output voltage amplitude was recorded when ventricular tachycardia was induced; the times and duration of spontaneous ventricular tachycardia when stimulation stopped were also recorded for each group. RESULTS: (1)Purkinje fibers existed in the myocardial tissue of rabbit outflow tract. (2)HCN4 protein expression significantly increased in VT group compared with SO group (left ventricular: 97.6 ± 16.7 vs 29.0 ± 8.0, P<0.01; right ventricular: 92.7 ± 12.3 vs 26.0 ± 10.8, P<0.01), the expression of HCN4 protein obviously reduced in VT+ IVA group compared with VT group (left ventricular: 32.0 ± 9.4 vs 97.6 ± 16.7, P<0.01; right ventricular: 30.8 ± 12.4 vs 92.7 ± 12.3, P<0.01). (3)The output voltage amplitude required to induce the desired ventricular tachycardia in VT+ ESM group and VT+ IVA group were higher than the VT group, under the same high frequency stimulation (P<0.01); the times and duration of spontaneous ventricular tachycardia in VT+ ESM group and VT+ IVA group significantly reduced when the stimulation stopped, compared with the VT group (both P<0.01). CONCLUSIONS: (1)Purkinje fibers exist in ventricular outflow tract, which may be the histological origin of the ventricular tachycardia. (2)HCN4 protein is up-regulated in ventricular outflow tract when ventricular tachycardia occurs. (3)Esmolol and ivabradine can prevent and reduce the occurrence of ventricular tachycardia, and as the specific inhibitor of the HCN channel, the effect of ivabradine is more obvious.


Assuntos
Ventrículos do Coração , Taquicardia Ventricular , Animais , Eletrocardiografia , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização , Coelhos
6.
J Clin Microbiol ; 52(12): 4388-90, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25297323

RESUMO

Seven imipenem-resistant Pseudomonas aeruginosa isolates were recovered from the sputum samples of pneumonia patients in southwestern China. They had identical antibiotic resistance patterns and indistinguishable pulsed-field gel electrophoresis profiles. Nucleotide sequence analysis revealed a 4-bp (AGTC) insertion in the oprD gene, resulting in a frameshift in the cognate open reading frame. These isolates became imipenem susceptible when the chromosomal oprD lesion was complemented, indicating that the 4-bp insertion in the oprD gene resulted in imipenem resistance.


Assuntos
Surtos de Doenças , Mutação da Fase de Leitura , Pneumonia Bacteriana/microbiologia , Porinas/genética , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , China/epidemiologia , DNA Bacteriano/química , DNA Bacteriano/genética , Eletroforese em Gel de Campo Pulsado , Teste de Complementação Genética , Genótipo , Humanos , Imipenem/farmacologia , Unidades de Terapia Intensiva , Masculino , Testes de Sensibilidade Microbiana , Dados de Sequência Molecular , Tipagem Molecular , Mutagênese Insercional , Pneumonia Bacteriana/epidemiologia , Infecções por Pseudomonas/epidemiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/isolamento & purificação , Análise de Sequência de DNA , Escarro/microbiologia
7.
Proc Natl Acad Sci U S A ; 108(12): 4870-5, 2011 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-21383157

RESUMO

The large tumor suppressor 1 (LATS1) is a serine/threonine kinase and tumor suppressor found down-regulated in a broad spectrum of human cancers. LATS1 is a central player of the emerging Hippo-LATS suppressor pathway, which plays important roles in cell proliferation, apoptosis, and stem cell differentiation. Despite the ample data supporting a role for LATS1 in tumor suppression, how LATS1 is regulated at the molecular level remains largely unknown. In this study, we have identified Itch, a HECT class E3 ubiquitin ligase, as a unique binding partner of LATS1. Itch can complex with LATS1 both in vitro and in vivo through the PPxY motifs of LATS1 and the WW domains of Itch. Significantly, we found that overexpression of Itch promoted LATS1 degradation by polyubiquitination through the 26S proteasome pathway. On the other hand, knockdown of endogenous Itch by shRNAs provoked stabilization of endogenous LATS1 proteins. Finally, through several functional assays, we also revealed that change of Itch abundance alone is sufficient for altering LATS1-mediated downstream signaling, negative regulation of cell proliferation, and induction of apoptosis. Taking these data together, our study identifies E3 ubiquitin ligase Itch as a unique negative regulator of LATS1 and presents a possibility of targeting LATS1/Itch interaction as a therapeutic strategy in cancer.


Assuntos
Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Repressoras/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Animais , Apoptose/genética , Células COS , Proliferação de Células , Chlorocebus aethiops , Estabilidade Enzimática/genética , Células HEK293 , Células HeLa , Humanos , Neoplasias/enzimologia , Neoplasias/genética , Neoplasias/terapia , Complexo de Endopeptidases do Proteassoma/genética , Complexo de Endopeptidases do Proteassoma/metabolismo , Ligação Proteica/genética , Proteínas Serina-Treonina Quinases/genética , Proteínas Repressoras/genética , Transdução de Sinais/genética , Proteínas Supressoras de Tumor/genética , Ubiquitina-Proteína Ligases/genética
8.
Sci Rep ; 14(1): 14550, 2024 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-38914604

RESUMO

Floating seedling cultivation technique is a novel seedling method in cotton and it provides an ideal model to study cotton growing under waterlogging stress. Morphological character and proteomic profile of the primary root from the seedling cultured by the new technology were evaluated in this study. Compared to seedlings cultured by the traditional method, the diameter of the taproot from floating technology is small at all five seedling stages from one-leaf stage to five-leaf stage. There are similar changes between the thickness of cortex and diameter of stele, which increased from the one- to the two-leaf stage but decreased from the two- to the five-leaf stage. At the one-leaf stage, the number and volume of mitochondria in the primary root-tip cells were less than those in the control. At the two-leaf stage, there was significantly less electron-dense material in the primary root-tip cells than those in the control group. From the one- to the two-leaf stage, the vacuole volume was significantly smaller than that in the control. Total 28 differentially expressed proteins were revealed from aquatic and control group roots of cotton seedlings at the three-leaf stage by two-dimensional electrophoresis, which included 24 up-regulated and four down-regulated proteins. The relative expression of the phosphoglycerate kinase (PGK) gene in aquatic roots increased from the one- to the four-leaf stage but declined rapidly from the four- to the five-leaf stage. The relative expression of the 14-3-3b gene tended to decrease from the one- to the five-leaf stage. The PGK and 14-3-3b genes were specifically expressed in the aquatic roots at the three-leaf stage. In brief, these changes induced waterlogging resistance in the aquatic roots of cotton seedlings in the floating nursery, thereby causing the roots to adapt to the aquatic environment, promoting the growth and development of cotton seedlings.


Assuntos
Gossypium , Proteínas de Plantas , Raízes de Plantas , Proteômica , Plântula , Gossypium/metabolismo , Gossypium/genética , Proteômica/métodos , Raízes de Plantas/metabolismo , Raízes de Plantas/crescimento & desenvolvimento , Plântula/metabolismo , Plântula/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Regulação da Expressão Gênica de Plantas , Estresse Fisiológico , Proteoma/metabolismo
9.
Int Immunopharmacol ; 130: 111805, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38457930

RESUMO

OBJECTIVE: To elucidate the mechanism of Pentraxin 3 (PTX3) in the pathogenesis of psoriasiform dermatitis using Ptx3-knockout (Ptx3-KO) background mice. METHODS: An Imiquimod (IMQ)-induced murine psoriatic model was created using Ptx3-KO (Ptx3-/-) and wild-type (Ptx3+/+) mice. Skin lesion severity and expression of inflammatory mediators (IL-6 and TNFα) were assessed using PASI score and ELISA, respectively. Cutaneous tissues from the two mice groups were subjected to histological analyses, including HE staining, Masson staining, and Immunohistochemistry (IHC). The PTX3, iNOS, COX2, and Arg1 expressions were quantified and compared between the two groups. We used RNA-seq to clarify the underlying mechanisms of the disease. Flow cytometry was used to analyze systemic Th17 cell differentiation and macrophage polarization. RESULT: The psoriatic region exhibited a higher PTX3 expression than the normal cutaneous area. Moreover, PTX3 was upregulated in HaCaT cells post-TNFα stimulation. Upon IMQ stimulation, Ptx3-/- mice displayed a lower degree of the psoriasiform dermatitis phenotype compared to Ptx3+/+ mice. Consistent with the RNA-seq results, further experiments confirmed that compared to the wild-type group, the PTX3-KO group exhibited a generally lower IL-6, TNFα, iNOS, and COX2 expression and a contrasting trend in macrophage polarization. However, no significant difference in Th17 cell activation was observed between the two groups. CONCLUSIONS: This study revealed that PTX3 was upregulated in psoriatic skin tissues and TNFα-stimulated HaCaT cells. We also discovered that PTX3 deficiency in mice ameliorated the psoriasiform dermatitis phenotype upon IMQ stimulation. Mechanistically, PTX3 exacerbates psoriasiform dermatitis by regulating macrophage polarization rather than Th17 cell differentiation.


Assuntos
Proteína C-Reativa , Dermatite , Psoríase , Componente Amiloide P Sérico , Animais , Camundongos , Proteína C-Reativa/genética , Proteína C-Reativa/metabolismo , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Dermatite/metabolismo , Dermatite/patologia , Modelos Animais de Doenças , Imiquimode/farmacologia , Interleucina-6/metabolismo , Macrófagos/patologia , Psoríase/metabolismo , Psoríase/patologia , Componente Amiloide P Sérico/genética , Componente Amiloide P Sérico/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Humanos , Progressão da Doença , Camundongos Knockout , Camundongos Endogâmicos C57BL
10.
Front Microbiol ; 15: 1363776, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38605717

RESUMO

Objective: The objective of this study is to investigate the causal relationship between gut microbiota and juvenile idiopathic arthritis, and to identify and quantify the potential role of plasma metabolites as mediators. Methods: Using summary-level data from genome-wide association studies, a two-sample Mendelian randomization was conducted involving 131 gut microbiota genus, 1,400 plasma metabolites, and juvenile idiopathic arthritis. Additionally, a two-step approach was employed to quantify the proportion of the effect of gut microbiota on juvenile idiopathic arthritis mediated by plasma metabolites. Effect estimation primarily utilized Inverse Variance Weighting, with further validation using Bayesian weighted Mendelian randomization. Results: In our MR analysis, a positive correlation was observed between Rikenellaceae and the risk of juvenile idiopathic arthritis, while Dorea showed a negative correlation with juvenile idiopathic arthritis risk. Mediation analysis indicated that Furaneol sulfate levels acted as a mediator between Dorea and juvenile idiopathic arthritis, with an indirect effect proportion of 19.94, 95% CI [8.86-31.03%]. Conclusion: Our study confirms a causal relationship between specific microbial genus and juvenile idiopathic arthritis, and computes the proportion of the effect mediated by plasma metabolites, offering novel insights for clinical interventions in juvenile idiopathic arthritis.

11.
Front Microbiol ; 15: 1325466, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38384268

RESUMO

Objective: Investigating the causal relationship between Lachnospiraceae and Appendicular lean mass (ALM) and identifying and quantifying the role of Aminopeptidase O Protein (AOPEP) as a potential mediator. Methods: The summary statistics data of gut microbiota composition from the largest available genome-wide association study (GWAS) meta-analysis conducted by the MiBioGen Consortium (n = 13,266). Appendicular lean mass data were obtained from the UK-Biobank (n = 450,243). We conducted bidirectional two-sample Mendelian randomization (MR) analysis using summary-level data from GWAS to investigate the causal relationship between Lachnospiraceae and ALM. Additionally, we employed a drug-targeted MR approach to assess the causal relationship between AOPEP and ALM. Finally, a two-step MR was employed to quantitatively estimate the proportion of the effect of Lachnospiraceae on ALM that is mediated by AOPEP. Cochran's Q statistic was used to quantify heterogeneity among instrumental variable estimates. Results: In the MR analysis, it was found that an increase in genetically predicted Lachnospiraceae [OR = 1.031, 95% CI (1.011-1.051), P = 0.002] is associated with an increase in ALM. There is no strong evidence to suggest that genetically predicted ALM has an impact on Lachnospiraceae genus [OR = 1.437, 95% CI (0.785-2.269), P = 0.239]. The proportion of genetically predicted Lachnospiraceae mediated by AOPEP was 34.2% [95% CI (1.3%-67.1%)]. Conclusion: Our research reveals that increasing Lachnospiraceae abundance in the gut can directly enhance limb muscle mass and concurrently suppress AOPEP, consequently mitigating limb muscle loss. This supports the potential therapeutic modulation of gut microbiota for sarcopenia. Interventions such as drug treatments or microbiota transplantation, aimed at elevating Lachnospiraceae abundance and AOPEP inhibition, synergistically improve sarcopenia in the elderly, thereby enhancing the overall quality of life for older individuals.

12.
Mutat Res ; 750(1-2): 139-46, 2013 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-23159492

RESUMO

1,3-Butadiene (BD) has been classified as a human carcinogen, group I; however, the relationship between polymorphisms of glutathione S-transferases that metabolize BD and chromosomal damage is not clear. The present study used sister chromatid exchange (SCE) and cytokinesis-block micronucleus (CBMN) assays to detect chromosomal damage in peripheral lymphocytes of 44 BD-exposed workers and 39 non-exposed healthy controls. PCR and PCR-RFLP were employed to detect three known glutathione S-transferase polymorphisms GSTT1, GSTM1, and GSTP1 (Ile105Val). The data demonstrated that the micronucleus (CBMN) frequency in BD-exposed workers was significantly higher than that in controls (frequency ratio (FR)=1.48, 95% CI: 1.14-1.91, P<0.01), and the CBMN frequency was higher in workers exposed to higher cumulative BD levels (FR=1.70, 95% CI: 1.28-2.27, P<0.01). However, differences in SCE frequency were not observed (FR=1.14, 95% CI: 0.81-1.61, P>0.05). Among exposed workers, chromosomal damage was related to BD exposure levels (FR=1.35, 95% CI: 1.02-1.80, P<0.05); age, older workers exhibited higher MN frequencies than younger workers (FR=1.45, 95% CI: 1.14-1.84, P<0.05); and years of work, those with more years of work exhibited higher MN frequencies than those with fewer years (FR=1.40, 95% CI: 1.10-1.77, P<0.05). Multivariate Poisson regression analysis showed that those who carried GSTM1 (-) (FR=1.48, 95% CI: 1.14-1.92) or GSTT1 (-) (FR=1.42, 95% CI: 1.10-1.83) genotypes, and especially those who carried both (FR=2.10, 95% CI: 1.43-3.09) exhibited significantly higher MN frequencies than those carrying GSTM1 (+), GSTT1 (+) genotypes or their combination. The GSTP1 Val genotype did not affect MN frequency (P>0.05). Our results suggested that higher levels of BD exposure in the workplace resulted in increased chromosomal damage, and that polymorphisms in GSTT1 and GSTM1 genes might modulate the genotoxic effects of BD exposure. Furthermore, the GSTT1 and GSTM1 polymorphisms exhibited an additive effect. Finally, urinary DHBMA was found to provide a biomarker that correlated with airborne BD levels.


Assuntos
Butadienos/toxicidade , Glutationa Transferase/genética , Polimorfismo Genético , Adulto , Povo Asiático/genética , Dano ao DNA , Feminino , Glutationa S-Transferase pi/genética , Humanos , Linfócitos/efeitos dos fármacos , Masculino , Testes para Micronúcleos , Pessoa de Meia-Idade , Troca de Cromátide Irmã
13.
J Cancer ; 14(11): 2093-2108, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37497411

RESUMO

Background: Regional lymph nodes (RLNs) removed combined with surgery is a standard option for patients at stage I to IIIA NSCLC. The objective of the study is to clarify the effect of removing different number of RLNs on survival outcomes for patients at stage IIIA N0 NSCLC. Methods: Patients at stage IIIA N0 NSCLC from 2004 to 2015 were identified from Surveillance, Epidemiology, and End Results (SEER) database. Prior propensity score method (PSM), survival time was compared among different number (0, 1-3 and ≥4) of RLNs removed groups. After PSM, lung cancer-specific survival (LCSS) and overall survival (OS) were compared. Kaplan-Meier analysis and Cox regression analyses were used to clarify the impact of the factors on the prognosis with hazard ratio (HR) and 95% confidence interval (CI). Results: A total of 11,583 patients at stage IIIA N0 NSCLC were included. Prior PSM, survival indicators including 1-year mortality rate, 5-year mortality rate, median survival time (MDST) and mean survival time (MST) from good to bad were all: ≥4, 1-3 and none RLNs removed group. After PSM, Kaplan-Meier survival analyses and univariate Cox regression analyses on OS and LCSS revealed a statistically significance on survival curve (P<0.001) between each two of the three groups (none, 1-3 and ≥4 RLNs removed group). Multivariable Cox regression analyses on OS and LCSS showed an independent association of RLNs removed with higher OS (HR, 0.275; 95% CI, 0.259-0.291; P<0.001) and LCSS (HR, 0.239; 95% CI, 0.224-0.256; P<0.001) compared with none RLN removed and no statistical difference with OS (HR, 1.118; 95% CI, 0.983-1.271; P=0.088) and LCSS (HR, 1.107; 95% CI, 0.954-1.284; P=0.179) between 1-3 RLNs removed and ≥4 RLNs removed. Conclusions: Removing RLNs was beneficial to survival outcomes of patients at stage IIIA N0 NSCLC. Compared with 1-3 RLNs removed, ≥4 RLNs removed could bring a better survival time but not an independent prognostic factor (P>0.05).

14.
Biotechnol J ; 18(12): e2300201, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37575005

RESUMO

The members of the GRAS gene family play important roles in regulating plant growth and development, but their functions in regulating early plant maturity traits are still unknown. In this study, we used a series of bioinformatics tools to identify GRAS gene family members and investigate the function of the gene family (GhGRAS55) using a genome-wide database of upland cotton samples. A total of 58 members of the GRAS gene family were identified and screened, which were distributed on 21 chromosomes within the whole cotton genome. The results of the phylogenetic analysis showed that the genes of upland cotton, island cotton, African cotton, Raymond cotton, and Arabidopsis were distributed in subfamilies I-VIII, although subfamily II did not contain any upland cotton or Arabidopsis GRAS family members. The structures and other characteristics of the genes in this family were clarified using bioinformatics technology. The transcriptomic sequencing results for early and late maturing cotton species showed that the expression of most GRAS family genes, such as GhGRAS10, GhGRAS5511, and GhGRAS55, was lower in early maturing species than late maturing species. We also found that cotton plants with GhGRAS55 genes that were silenced by virus-induced gene silencing (VIGS) technology showed early bud emergence phenotypes, so it could be speculated that the GhGRAS55 gene has the function of regulating early maturity in cotton.


Assuntos
Arabidopsis , Genoma de Planta , Filogenia , Genoma de Planta/genética , Gossypium/genética , Gossypium/metabolismo , Arabidopsis/genética , Fenótipo , Família Multigênica , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas/genética
15.
Artigo em Inglês | MEDLINE | ID: mdl-35682157

RESUMO

The rational allocation of spatial resources is an important factor to ensure the sustainable development of rural areas, and effective pre-emptive spatial evaluation is the prerequisite for identifying the predicament of rural resource allocation. Multi-criteria decision-making analysis has advantages in solving multi-attribute and multi-objective decision-making problems, and has been used in sustainability evaluation research in various disciplines in recent years. Previous studies have proved the value of spatial evaluation using multi-criteria decision analysis in guiding rural incremental development and inventory updates, but systematic reviews of the previous literature from a multidisciplinary perspective and studies of the implementation steps of the evaluation framework are lacking. In the current paper, the research is reviewed from the two levels of quantitative statistics and research content, and through vertical and horizontal comparisons based on three common operating procedures: standard formulation, weight distribution, and ranking and verification. Through the results, the application status and characteristics of the MCDA method in related research are determined, and five research foci in the future are proposed.


Assuntos
Tomada de Decisões , Técnicas de Apoio para a Decisão , Projetos de Pesquisa
16.
Comput Struct Biotechnol J ; 19: 161-167, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33343834

RESUMO

The SARS-CoV-2 virus and its homolog SARS-CoV penetrate human cells by binding of viral spike protein and human angiotensin converting enzyme II (ACE2). SARS-CoV causes high fever in almost all patients, while SARS-CoV-2 does not. Moreover, analysis of the clinical data revealed that the higher body temperature is a protective factor in COVID-19 patients, making us to hypothesize a temperature-dependent binding affinity of SARS-CoV-2 to human ACE2 receptor. In this study, our molecular dynamics simulation and protein surface plasmon resonance cohesively proved the SARS-CoV-2-ACE2 binding was less affinitive and stable under 40 °C (~18 nM) than the optimum temperature 37 °C (6.2 nM), while SARS-CoV-ACE2 binding was not (6.4 nM vs. 8.5 nM), which evidenced the temperature-dependent affinity and explained that higher temperature is related to better clinical outcome. The decreased infection at higher temperature was also validated by pseudovirus entry assay using Vero and Caco-2 cells. We also demonstrated the structural basis of the distinct temperature-dependence of the two coronaviruses. Furthermore, the meta-analysis revealed a milder inflammatory response happened in the early stage of COVID-19, which explained the low fever tendency of COVID-19 and indicated the co-evolution of the viral protein structure and the inflammatory response. The temperature dependence of the binding affinity also indicated that higher body temperature at early stages might be beneficial to the COVID-19 patients.

17.
Medicine (Baltimore) ; 100(17): e25612, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33907113

RESUMO

BACKGROUND: Metastatic prostate carcinoma has poor prognoses with a median survival period ranging from 2 to 5 years with existing therapeutic challenges. Currently, peptide receptor radionuclide therapy is permitted as a treatment method for metastatic prostate carcinoma patients. Therefore, it is crucial to comprehend the efficiency and safety of peptide receptor radionuclide therapy among this patient population. This study aims to analyse the efficacy of peptide receptor radionuclide therapy when used to treat metastatic prostate carcinoma patients. METHODS: This research will perform a methodological search in the following electronic databases to find related randomized controlled trials: Cochrane Library, EMBASE, PubMed, Web of Science, Scopus, China National Knowledge Infrastructure (CNKI), WanFang database, and Chinese BioMedical Literature. All the databases are searched from their inauguration till November 2020. Two independent authors will screen and select literature for review. The two authors will independently utilize the Cochrane Risk of Bias tool to assess the bias risk in studies. This study also plans to conduct subgroup and sensitivity analyses to evaluate the robustness in the results. Statistical analyses will be conducted with the RevMan 5.3 software. RESULTS: A high-quality synthesis of existing evidence related to peptide receptor radionuclide therapy in the treatment of metastatic prostate carcinoma will be presented in this study. CONCLUSION: Our findings will provide evidence to judge whether peptide receptor radionuclide treatment is efficient for metastatic prostate carcinoma patients. ETHICS AND DISSEMINATION: An ethics approval is not required because the data of the present study are primarily obtained from published studies.OSF registration number: December 1, 2020.osf.io/3psx7. (https://osf.io/3psx7/).


Assuntos
Carcinoma/radioterapia , Neoplasias da Próstata/radioterapia , Compostos Radiofarmacêuticos/administração & dosagem , Receptores de Peptídeos/administração & dosagem , Carcinoma/patologia , Humanos , Masculino , Metanálise como Assunto , Metástase Neoplásica/radioterapia , Neoplasias da Próstata/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Revisões Sistemáticas como Assunto , Resultado do Tratamento
18.
Sci Rep ; 11(1): 2805, 2021 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-33531594

RESUMO

Most of the cotton bollworm-resistant genes applied in cotton are more than 20 years and they all belong to Cry1Ab/c family, but the insect-resistant effects of Cry5Aa on cotton were rarely reported. The possible risk of resistance is increasing. The study synthesized a novel bollworm-resistant gene Cry5Aa artificially based on preferences of cotton codon. The new gene was transferred to cotton through the method of pollen tube pathway. The transgenic strains were identified by kanamycin test in field and laboratory PCR analysis. Meanwhile, an insect resistance test was conducted by artificial bollworm feeding with transgenic leaves and GK19 was used as a control in this study. Results showed that rate of positive transgenic strains with kanamycin resistance in the first generation (T1), the second generation (T2) and the third generation (T3) respectively were 7.76%, 73.1% and 95.5%. However, PCR analysis showed that the positive strain rate in T1, T2 and T3 were 2.35%, 55.8% and 94.5%, respectively. The resistant assay of cotton bollworm showed that the mortality rate of the second, third and fourth instar larva feed by the transgenic cotton leaves, were 85.42%, 73.35% and 62.79%, respectively. There was a significant difference between transgenic plant of Cry5Aa and GK19 in insect resistance. Finally, we also conducted the further analysis of gene expression patterns, gene flow and the effect on non-target pest in the study. The results showed that Cry5Aa gene had less environmental impact, and Cry5Aa has been transferred successfully and expressed stably in cotton. Therefore, the novel bollworm resistance gene can partially replace the current insect-resistance gene of Lepidoptera insects.

19.
Amino Acids ; 38(5): 1333-42, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-19730979

RESUMO

Protein expression profiles in the fat bodies of larval, pupal, and moth stages of silkworm were determined using shotgun proteomics and MS sequencing. We identified 138, 217, and 86 proteins from the larval, pupal and moth stages, respectively, of which 12 were shared by the 3 stages. There were 92, 150, and 45 specific proteins identified in the larval, pupal and moth stages, respectively, of which 17, 68, and 9 had functional annotations. Among the specific proteins identified in moth fat body, sex-specific storage-protein 1 precursor and chorion protein B8 were unique to the moth stage, indicating that the moth stage fat body is more important for adult sexual characteristics. Many ribosomal proteins (L23, L4, L5, P2, S10, S11, S15A and S3) were found in pupal fat bodies, whereas only three (L14, S20, and S7) and none were identified in larval and moth fat bodies, respectively. Twenty-three metabolic enzymes were identified in the pupal stage, while only four and two were identified in the larval and moth stages, respectively. In addition, an important protein, gloverin2, was only identified in larval fat bodies. Gene ontology (GO) analysis of the proteins specific to the three stages linked them to the cellular component, molecular function, and biological process categories. The most diverse GO functional classes were involved by the relatively less specific proteins identified in larva. GO analysis of the proteins shared among the three stages showed that the pupa and moth stages shared the most similar protein functions in the fat body.


Assuntos
Bombyx/metabolismo , Corpo Adiposo/metabolismo , Metamorfose Biológica , Proteômica , Animais , Bombyx/crescimento & desenvolvimento , Cromatografia Líquida , Eletroforese em Gel de Poliacrilamida , Espectrometria de Massas em Tandem
20.
Acta Biochim Biophys Sin (Shanghai) ; 40(7): 601-11, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18604451

RESUMO

As the only truly domesticated insect, the silkworm not only has great economic value, but it also has value as a model for genetics and molecular biology research. Genomics and proteomics have recently shown vast potential to be essential tools in domesticated silkworm research, especially after the completion of the Bombyx mori genome sequence. This paper reviews the progress of the domesticated silkworm genome, particularly focusing on its genetic map, physical map and functional genome. This review also presents proteomics, the proteomic technique and its application in silkworm research.


Assuntos
Bombyx/genética , Mapeamento Cromossômico , Genoma/genética , Proteínas de Insetos/genética , Proteoma/genética , Animais
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