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1.
Brief Bioinform ; 25(1)2023 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-38189540

RESUMO

Nanopore sequencers can enrich or deplete the targeted DNA molecules in a library by reversing the voltage across individual nanopores. However, it requires substantial computational resources to achieve rapid operations in parallel at read-time sequencing. We present a deep learning framework, NanoDeep, to overcome these limitations by incorporating convolutional neural network and squeeze and excitation. We first showed that the raw squiggle derived from native DNA sequences determines the origin of microbial and human genomes. Then, we demonstrated that NanoDeep successfully classified bacterial reads from the pooled library with human sequence and showed enrichment for bacterial sequence compared with routine nanopore sequencing setting. Further, we showed that NanoDeep improves the sequencing efficiency and preserves the fidelity of bacterial genomes in the mock sample. In addition, NanoDeep performs well in the enrichment of metagenome sequences of gut samples, showing its potential applications in the enrichment of unknown microbiota. Our toolkit is available at https://github.com/lysovosyl/NanoDeep.


Assuntos
Aprendizado Profundo , Sequenciamento por Nanoporos , Nanoporos , Humanos , Biblioteca Gênica , Genoma Bacteriano
2.
Psychol Med ; 52(13): 2651-2660, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-33298220

RESUMO

BACKGROUND: This study aimed to explore the impacts of COVID-19 outbreak on mental health status in general population in different affected areas in China. METHODS: This was a comparative study including two groups of participants: (1) general population in an online survey in Ya'an and Jingzhou cities during the COVID-19 outbreak from 10-20 February 2020; and (2) matching general population selected from the mental health survey in Ya'an in 2019 (from January to May 2019). General Health Questionnaire (GHQ-12), Self-rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS) were used. RESULTS: There were 1775 participants (Ya'an in 2019 and 2020: 537 respectively; Jingzhou in 2020: 701). Participants in Ya'an had a significantly higher rate of general health problems (GHQ scores ⩾3) in 2020 (14.7%) than in 2019 (5.2%) (p < 0.001). Compared with Ya'an (8.0%), participants in Jingzhou in 2020 had a significantly higher rate of anxiety (SAS scores ⩾50, 24.1%) (p < 0.001). Participants in Ya'an in 2020 had a significantly higher rate of depression (SDS scores ⩾53, 55.3%) than in Jingzhou (16.3%) (p < 0.001). The risk factors of anxiety symptoms included female, number of family members (⩾6 persons), and frequent outdoor activities. The risk factors of depression symptoms included participants in Ya'an and uptake self-protective measures. CONCLUSIONS: The prevalence of psychological symptoms has increased sharply in general population during the COVID-19 outbreak. People in COVID-19 severely affected areas may have higher scores of GHQ and anxiety symptoms. Culture-specific and individual-based psychosocial interventions should be developed for those in need during the COVID-19 outbreak.


Assuntos
COVID-19 , Humanos , Feminino , Saúde Mental , SARS-CoV-2 , Depressão/epidemiologia , Ansiedade/psicologia , Surtos de Doenças , Inquéritos e Questionários , China/epidemiologia
3.
BMC Psychiatry ; 22(1): 273, 2022 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-35439977

RESUMO

OBJECTIVES: This review investigates the efficacy and safety of non-invasive brain stimulation (NIBS) combined with psychosocial intervention on depressive symptoms. MATERIALS AND METHODS: We systematically searched five electronic databases from their inception to June 2021: PubMed, Embase, PsycINFO, Web of Science, and Medline. Randomized or non-randomized clinical trials in which NIBS plus psychosocial intervention was compared to control conditions in people with depressive symptoms were included. RESULTS: A total of 17 eligible studies with 660 participants were included. The meta-analysis results showed that NIBS combined with psychosocial therapy had a positive effect on moderate to severe depression ([SMD = - 0.46, 95%CI (- 0.90, - 0.02), I2 = 73%, p < .01]), but did not significantly improve minimal to mild depression ([SMD = - 0.12, 95%CI (- 0.42, 0.18), I2 = 0%, p = .63]). Compared with NIBS alone, the combination treatment had a significantly greater effect in alleviating depressive symptoms ([SMD = - 0.84, 95%CI (- 1.25, - 0.42), I2 = 0%, p = .93]). However, our results suggested that the pooled effect size of ameliorating depression of NIBS plus psychosocial intervention had no significant difference compared with the combination of sham NIBS [SMD = - 0.12, 95%CI (- 0.31, 0.07), I2 = 0%, p = .60] and psychosocial intervention alone [SMD = - 0.97, 95%CI (- 2.32, 0.38), I2 = 72%, p = .01]. CONCLUSION: NIBS when combined with psychosocial intervention has a significant positive effect in alleviating moderately to severely depressive symptoms. Further well-designed studies of NIBS combined with psychosocial intervention on depression should be carried out to consolidate the conclusions and explore the in-depth underlying mechanism.


Assuntos
Encéfalo , Intervenção Psicossocial , Humanos
4.
Med Sci Monit ; 28: e935300, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35288530

RESUMO

BACKGROUND The recurrence of COVID-19 and the continuous escalation of prevention and control policies can lead to an increase in mental health problems. This study aimed to investigate the perceived stress, coping style, resilience, and social support among patients on maintenance hemodialysis (MHD) during the COVID-19 epidemic lockdown in China. MATERIAL AND METHODS This cross-sectional observational study enrolled 197 patients on MHD from the Guangdong Province Traditional Chinese Medical Hospital and the Hedong Hospital of Guangzhou Liwan District People's Hospital during July 2021. AMOS 24.0 and PROCESS Macro 3.1 model 6 were used for analyses of moderating mediating effects. RESULTS Perceived stress was negatively correlated with positive coping style (r=-0.305, P<0.001) and resilience (r=-0.258, P<0.001), whereas resilience (r=0.631, P<0.001) and social support (r=0.300, P<0.001) were positively correlated with positive coping style among patients on MHD. In the moderated mediating model, perceived stress had significant direct predictive effects on positive coping style (95% CI -0.33, -0.07), and perceived stress had significant indirect predictive effects on positive coping styles through resilience (95% CI -0.26, -0.06) or social support (95% CI 0.01, 0.06). Perceived stress had significant indirect predictive effects on positive coping style through both resilience and social support (95% CI -0.04, -0.01). CONCLUSIONS Perceived stress not only predicted coping style directly, but also indirectly predicted coping style through resilience and social support. Coping style was affected by internal and external factors during the COVID-19 pandemic lockdown period.


Assuntos
Adaptação Psicológica/fisiologia , COVID-19/psicologia , Nefropatias/psicologia , Adulto , Povo Asiático/psicologia , COVID-19/complicações , China/epidemiologia , Controle de Doenças Transmissíveis , Estudos Transversais , Feminino , Humanos , Nefropatias/complicações , Nefropatias/virologia , Masculino , Pessoa de Meia-Idade , Pandemias , Diálise Renal , Resiliência Psicológica/fisiologia , SARS-CoV-2/patogenicidade , Apoio Social , Estresse Psicológico/psicologia , Inquéritos e Questionários
5.
BMC Nephrol ; 23(1): 93, 2022 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-35247988

RESUMO

BACKGROUND: Chronic kidney disease (CKD) is a major global health problem. Short-term self-management has been considered to effect some renal and psychological endpoints. However, there are currently very few studies about self-management for CKD that a) have been scientifically designed by a theory-based framework and b) that evaluate the long-term effects and working mechanism. This study presents the rationale and design of a theory-based cohort study to explore how this self-management intervention works and its effectiveness on the Chinese CKD population. METHODS: In this ambispective intervention cohort study,1,200 patients with CKD stages 1-5 will be recruited from July 2015 to July 2024 in 3 branches of Guangdong Provincial Hospital of Chinese Medicine (GPHCM) in Guangdong province, China. The patients in the self-management cohort will choose to receive an intervention that consists of education, nutrition/diet modification, lifestyle change recommendation, medication review, and psychology support based on Social Cognition Theory (SCT). The patients in the control cohort will do regular follow-ups based on the clinic rules. All the patients will be followed up for 5 years, or until the occurrence of a primary outcome. Detailed clinical, laboratory markers, nutritional status, psychological exposures and outcome questionaries will be collected semiannually in CKD stage 1-2 and trimonthly in stage 3-5 patients. The primary outcome is the occurrence of composite clinical endpoints (doubling of serum creatinine level, ESKD, loss of renal function (≥ 40% decline in GFR from baseline), death, major cardiovascular or cerebrovascular events). The main secondary outcomes include the absolute change and slope of eGFR, absolute changes of urinary protein creatinine ratio, 24-h urine proteinuria, intact parathyroid hormone level, and self-management adherence rate and quality of life from baseline to end of the study. The effectiveness of self-management will be analyzed and the association between longitudinal trajectories of self-management and renal outcomes will be evaluated. DISCUSSION: This study aims to provide further evidence for the effectiveness of theory-based self-management in CKD patients and to improve the lives of patients with CKD by slowing progression, improving psychological well-being and overall quality of life. TRIAL REGISTRATION: Chinese Clinical Trial Register (ChiCTR1900024633). 19 July, 2019. http://www.chictr.org.cn/showproj.aspx?proj=38378.


Assuntos
Insuficiência Renal Crônica , Autogestão , Biomarcadores , China/epidemiologia , Estudos de Coortes , Feminino , Humanos , Masculino , Qualidade de Vida , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/terapia
6.
Soc Psychiatry Psychiatr Epidemiol ; 57(12): 2433-2444, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35932308

RESUMO

PURPOSE: This study aimed to explore the prevalence and distribution of mental disorders in the elderly population 5 years after the Lushan earthquake in Ya'an, China. METHODS: A multi-stage, group-matching random sampling method was adopted with 2579 elderly participants (≥ 60 years old) who were interviewed from January to May 2019. Preliminary screening was conducted using the scale by trained psychiatric nurses, followed by a diagnostic interview during the second stage using Chinese Version of the 5th edition of the Diagnostic and Statistical Manual of Mental Disorder by trained psychiatrists. RESULTS: A total of 2561 participants were included in this study with complete data. The weighted lifetime prevalence of all mental disorders in the elderly was 16.2% (95% CI 15.3-17.1), and the weighted 12-month prevalence was 15.2% (95% CI 13.4-17.0). Depressive disorders, anxiety disorders, substance-related and addictive disorders were the most common mental disorders. The 12-month prevalence of all mental disorders were significantly higher in the elderly living alone, with chronic somatic disease, and being poor (P < 0.05). The 12-month prevalence of posttraumatic stress disorder (PTSD) was significantly higher in the elderly in extremely severely earthquake-affected areas (P < 0.001). CONCLUSION: The results of this study show that mental health status of the elderly in Ya'an area differ by socio-economic development, geographical location, and natural disasters. The social and economic development characteristics, the impact of major natural disasters (e.g., earthquakes), and population characteristics should be combined to formulate strategies and interventions to promote the mental health of the elderly.


Assuntos
Desastres , Terremotos , Transtornos Mentais , Transtornos de Estresse Pós-Traumáticos , Idoso , Humanos , Pessoa de Meia-Idade , Prevalência , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , China/epidemiologia , Fatores de Risco , Transtornos Mentais/diagnóstico , Transtornos Mentais/epidemiologia
7.
J Cell Mol Med ; 25(14): 6925-6935, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34080300

RESUMO

Long non-coding RNAs (lncRNAs) play critical roles in regulating immune-associated diseases and chronic inflammatory disorders. Here, we found that lncRNAs involve in the pathogenesis of psoriasis through integrative analysis of RNA-seq data sets from a psoriasis cohort. Then, lncRNA-protein-coding genes (PCGs) co-expression network analysis demonstrated that lncRNAs extensively interact with IFN-γ signalling pathway-associated genes. Further, we validated 3 lncRNAs associate with IFN-γ signalling pathway activation upon IFN-γ stimulated in HaCaT cells, and loss of function experiments indicate their functional roles in the activation of inflammatory cytokine genes. Additionally, microRNA target screening analysis showed that lncRNAs may regulate JAK/STAT pathway activity through complete endogenous RNA (ceRNA) mechanism. Further experimental validation of PRKCQ-AS1/STAT1/miR-545-5p regulatory circuitry showed that lncRNAs regulate the expression of JAK/STAT signalling pathway genes through competing for miR-545-5p. In summary, our results demonstrated that dysregulation of lncRNA-JAK/STAT pathway axis promotes the inflammation level in psoriasis and thus provide potential therapeutic targets for psoriasis treatments.


Assuntos
MicroRNAs/metabolismo , Psoríase/genética , RNA Longo não Codificante/metabolismo , Transcriptoma , Redes Reguladoras de Genes , Células HaCaT , Humanos , Interferon gama/genética , Interferon gama/metabolismo , Janus Quinases/genética , Janus Quinases/metabolismo , MicroRNAs/genética , Psoríase/metabolismo , RNA Longo não Codificante/genética , Fator de Transcrição STAT1/genética , Fator de Transcrição STAT1/metabolismo , Transdução de Sinais , Pele/metabolismo
8.
Gynecol Endocrinol ; 37(1): 2-9, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33412963

RESUMO

Estrogens exert rapid, extranuclear effects by their action on the plasma membrane estrogen receptors (mERs). Gα protein associated with the cell membrane is involved in many important processes regulated by estrogens. However, the Gα's role in the mER-mediated signaling and the signaling pathways involved are poorly understood. This review aims to outline the Gα's role in the mER-mediated signaling. Immunoblotting, immunofluorescence, co-immunoprecipitation, and RNA interference were carried out using vascular endothelial cells (ECs) and human breast carcinoma cell lines as experimental models. Electrophysiology and immunocytochemistry were carried out using guinea pigs as animal models. Recent advances suggest that the signaling of mERα through Gα is required for vascular EC migration or endothelial H2S release, while Gα13 is involved in estrogen-induced breast cancer cell invasion. Besides, the Gαq-coupled PLC-PKC-PKA pathway is critical for the neural regulation of energy homeostasis. This review summarizes the contributions of Gα to mER-mediated signaling, including cardiovascular protection, breast cancer metastasis, neural regulation of homeostatic functions, and osteogenesis.


Assuntos
Subunidades alfa de Proteínas de Ligação ao GTP/metabolismo , Receptores de Estrogênio/metabolismo , Animais , Membrana Celular/metabolismo , Humanos , Transdução de Sinais
9.
Soc Psychiatry Psychiatr Epidemiol ; 56(7): 1263-1272, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33146858

RESUMO

PURPOSE: This study aimed to (1) explore the prevalence and relevant influencing factors of different mental disorders 5 years after the Lushan earthquake in Ya'an, China. METHODS: An epidemiological mental health survey was conducted to identify the prevalence of mental disorders in general population in Ya'an. A multi-stage, group-matching random sampling method was adopted. Face-to-face interviews were done with a two-stage design by trained interviewers and psychiatrists. The 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) was used for the diagnosis. RESULTS: There were 8876 participants who were interviewed in this study. The total 12-month and lifetime prevalence of all mental disorders were 12.5% and 14.7%, respectively. There was a significant difference between males and females in the prevalence patterns of several mental disorders. Han ethnic group had higher prevalence of anxiety disorders (2.7%), and the Tibetan group had higher prevalence of alcohol-related disorders (5.0%). Logistic regression analysis showed that the areas severely affected by the earthquake had significantly higher prevalence of depressive disorders, and the extremely severe affected areas had significantly higher prevalence of trauma- and stressor-related disorders. CONCLUSION: Our findings show that the prevalence of a range of mental disorders 5 years after the earthquake in Ya'an are high, and the prevalence of depressive and trauma- and stressor-related disorders may be influenced differently by the various severity of earthquake impact. This study may be crucial for the health policy-making, cultural-specific mental health services and long-term mental recovery after the earthquake.


Assuntos
Desastres , Terremotos , Transtornos Mentais , Transtornos de Estresse Pós-Traumáticos , China/epidemiologia , Depressão , Feminino , Humanos , Masculino , Transtornos Mentais/epidemiologia , Prevalência , Fatores de Risco , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Inquéritos e Questionários , Sobreviventes
10.
PLoS Genet ; 14(5): e1007389, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29758020

RESUMO

Polymyxin is the last line of defense against severe infections caused by carbapenem-resistant gram-negative pathogens. The emergence of transferable MCR-1/2 polymyxin resistance greatly challenges the renewed interest in colistin (polymyxin E) for clinical treatments. Recent studies have suggested that Moraxella species are a putative reservoir for MCR-1/2 genetic determinants. Here, we report the functional definition of ICR-Mo from M. osloensis, a chromosomally encoded determinant of colistin resistance, in close relation to current MCR-1/2 family. ICR-Mo transmembrane protein was prepared and purified to homogeneity. Taken along with an in vitro enzymatic detection, MALDI-TOF mass spectrometry of bacterial lipid A pools determined that the ICR-Mo enzyme might exploit a possible "ping-pong" mechanism to accept the phosphoethanolamine (PEA) moiety from its donor phosphatidylethanolamine (PE) and then transfer it to the 1(or 4')-phosphate position of lipid A via an ICR-Mo-bound PEA adduct. Structural decoration of LPS-lipid A by ICR-Mo renders the recipient strain of E. coli resistant to polymyxin. Domain swapping assays indicate that the two domains of ICR-Mo cannot be functionally-exchanged with its counterparts in MCR-1/2 and EptA, validating its phylogenetic position in a distinct set of MCR-like genes. Structure-guided functional mapping of ICR-Mo reveals a PE lipid substrate recognizing cavity having a role in enzymatic catalysis and the resultant conference of antibiotic resistance. Expression of icr-Mo in E. coli significantly prevents the formation of reactive oxygen species (ROS) induced by colistin. Taken together, our results define a member of a group of intrinsic colistin resistance genes phylogenetically close to the MCR-1/2 family, highlighting the evolution of transferable colistin resistance.


Assuntos
Proteínas de Bactérias/genética , Colistina/farmacologia , Farmacorresistência Bacteriana/genética , Proteínas de Membrana/genética , Moraxella/efeitos dos fármacos , Antibacterianos/farmacologia , Proteínas de Bactérias/classificação , Proteínas de Bactérias/metabolismo , Etanolaminas/metabolismo , Proteínas de Membrana/classificação , Proteínas de Membrana/metabolismo , Simulação de Acoplamento Molecular , Moraxella/enzimologia , Moraxella/genética , Fosfatidiletanolaminas/metabolismo , Filogenia , Ligação Proteica , Especificidade por Substrato
11.
BMC Nephrol ; 21(1): 412, 2020 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-32972378

RESUMO

BACKGROUND: The optimal choice of treatment, with hemodialysis (HD) or peritoneal dialysis (PD), for end-stage renal disease (ESRD) patients, is still controversial. Only a few studies comparing HD and PD have been conducted in China, which has the largest number of dialysis patients in the world. METHODS: A retrospective cohort study was conducted on ESRD patients who began renal replacement treatment from January 1, 2012 to December 31, 2017 in Guangdong Provincial Hospital of Chinese Medicine. Propensity scoring match was applied to balance the baseline conditions and multivariate Cox regression analysis to compare the mortality between HD and PD patients, and evaluated the correlation between mortality and various baseline characteristics. RESULTS: A total of 436 HD patients and 501 PD patients were included in this study, and PD patients had better survival than HD patients, but the difference was not statistically significant. For younger ESRD patients (≤60-year-old), the overall survival of PD was better than that of HD, but HD was associated with a lower risk of death in older patients (> 70-year-old). This difference was still significant after adjustment for a variety of confounding factors. Female gender, age at dialysis initiation, cardiovascular disease, cholesterol, and HD were risk factors of all-cause mortality in the younger subgroup, while PD was risk factor in the older subgroup. CONCLUSION: PD may be a better choice for younger ESRD patients, and HD for the older patients.


Assuntos
Falência Renal Crônica/terapia , Diálise Renal/métodos , Adulto , Fatores Etários , Idoso , China/epidemiologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Falência Renal Crônica/mortalidade , Masculino , Pessoa de Meia-Idade , Diálise Peritoneal/mortalidade , Pontuação de Propensão , Modelos de Riscos Proporcionais , Diálise Renal/mortalidade , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
12.
J Biol Chem ; 293(12): 4350-4365, 2018 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-29462787

RESUMO

Polymyxins such as colistin are antibiotics used as a final line of defense in the management of infections with multidrug-resistant Gram-negative bacteria. Although natural resistance to polymyxins is rare, the discovery of a mobilized colistin resistance gene (mcr-1) in gut bacteria has raised significant concern. As an intramembrane enzyme, MCR-1 catalyzes the transfer of phosphoethanolamine (PEA) to the 1 (or 4')-phosphate group of the lipid A moiety of lipopolysaccharide, thereby conferring colistin resistance. However, the structural and biochemical mechanisms used by this integral membrane enzyme remain poorly understood. Here, we report the modeled structure of the full-length MCR-1 membrane protein. Together with molecular docking, our structural and functional dissection of the complex of MCR-1 with its phosphatidylethanolamine (PE) substrate suggested the presence of a 12 residue-containing cavity for substrate entry, which is critical for both enzymatic activity and its resultant phenotypic resistance to colistin. More importantly, two periplasm-facing helices (PH2 and PH2') of the trans-membrane domain were essential for MCR-1 activity. MALDI-TOF MS and thin-layer chromatography assays provide both in vivo and in vitro evidence that MCR-1 catalyzes the transfer of PEA from the PE donor substrate to its recipient substrate lipid A. Also, the chemical modification of lipid A species was detected in clinical species of bacteria carrying mcr-1 Our results provide mechanistic insights into transferable MCR-1 polymyxin resistance, raising the prospect of rational design of small molecules that reverse bacterial polymyxin resistance, as a last-resort clinical option to combat pathogens with carbapenem resistance.


Assuntos
Antibacterianos/farmacologia , Colistina/farmacologia , Farmacorresistência Bacteriana , Proteínas de Escherichia coli/metabolismo , Escherichia coli/crescimento & desenvolvimento , Trato Gastrointestinal/microbiologia , Polimixinas/farmacologia , Cristalografia por Raios X , Escherichia coli/efeitos dos fármacos , Escherichia coli/isolamento & purificação , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/genética , Etanolaminas/química , Etanolaminas/metabolismo , Lipídeo A/química , Lipídeo A/metabolismo , Simulação de Acoplamento Molecular , Mutagênese Sítio-Dirigida , Mutação , Filogenia
13.
PLoS Pathog ; 12(11): e1005957, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27893854

RESUMO

Polymyxins are the last line of defense against lethal infections caused by multidrug resistant Gram-negative pathogens. Very recently, the use of polymyxins has been greatly challenged by the emergence of the plasmid-borne mobile colistin resistance gene (mcr-1). However, the mechanistic aspects of the MCR-1 colistin resistance are still poorly understood. Here we report the comparative genomics of two new mcr-1-harbouring plasmids isolated from the human gut microbiota, highlighting the diversity in plasmid transfer of the mcr-1 gene. Further genetic dissection delineated that both the trans-membrane region and a substrate-binding motif are required for the MCR-1-mediated colistin resistance. The soluble form of the membrane protein MCR-1 was successfully prepared and verified. Phylogenetic analyses revealed that MCR-1 is highly homologous to its counterpart PEA lipid A transferase in Paenibacili, a known producer of polymyxins. The fact that the plasmid-borne MCR-1 is placed in a subclade neighboring the chromosome-encoded colistin-resistant Neisseria LptA (EptA) potentially implies parallel evolutionary paths for the two genes. In conclusion, our finding provids a first glimpse of mechanism for the MCR-1-mediated colistin resistance.


Assuntos
Colistina/farmacologia , Farmacorresistência Bacteriana/genética , Proteínas de Escherichia coli/genética , Sequência de Bases , Farmacorresistência Bacteriana/efeitos dos fármacos , Resistência a Múltiplos Medicamentos/fisiologia , Humanos , Testes de Sensibilidade Microbiana , Filogenia , Plasmídeos
14.
Appl Environ Microbiol ; 82(9): 2819-2832, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26944841

RESUMO

UNLABELLED: Recently, our group along with others reported that the Vibrio FadR regulatory protein is unusual in that, unlike the prototypical fadR product of Escherichia coli, which has only one ligand-binding site, Vibrio FadR has two ligand-binding sites and represents a new mechanism for fatty acid sensing. The promoter region of the vc2105 gene, encoding a putative thioesterase, was mapped, and a putative FadR-binding site (AA CTG GTA AGA GCA CTT) was proposed. Different versions of the FadR regulatory proteins were prepared and purified to homogeneity. Both electrophoretic mobility shift assay (EMSA) and surface plasmon resonance (SPR) determined the direct interaction of the vc2105 gene with FadR proteins of various origins. Further, EMSAs illustrated that the addition of long-chain acyl-coenzyme A (CoA) species efficiently dissociates the vc2105 promoter from the FadR regulator. The expression level of the Vibrio cholerae vc2105 gene was elevated 2- to 3-fold in a fadR null mutant strain, validating that FadR is a repressor for the vc2105 gene. The ß-galactosidase activity of a vc2105-lacZ transcriptional fusion was increased over 2-fold upon supplementation of growth medium with oleic acid. Unlike the fadD gene, a member of the Vibrio fad regulon, the VC2105 protein played no role in bacterial growth and virulence-associated gene expression of ctxAB (cholera toxin A/B) and tcpA (toxin coregulated pilus A). Given that the transcriptional regulation of vc2105 fits the criteria for fatty acid degradation (fad) genes, we suggested that it is a new member of the Vibrio fad regulon. IMPORTANCE: The Vibrio FadR regulator is unusual in that it has two ligand-binding sites. Different versions of the FadR regulatory proteins were prepared and characterized in vitro and in vivo. An auxiliary fad gene (vc2105) from Vibrio was proposed that encodes a putative thioesterase and has a predicted FadR-binding site (AAC TGG TA A GAG CAC TT). The function of this putative binding site was proved using both EMSA and SPR. Further in vitro and in vivo experiments revealed that the Vibrio FadR is a repressor for the vc2105 gene. Unlike fadD, a member of the Vibrio fad regulon, VC2105 played no role in bacterial growth and expression of the two virulence-associated genes (ctxAB and tcpA). Therefore, since transcriptional regulation of vc2105 fits the criteria for fad genes, it seems likely that vc2105 acts as a new auxiliary member of the Vibrio fad regulon.


Assuntos
Proteínas de Bactérias/genética , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Vibrio cholerae/genética , Acil Coenzima A/metabolismo , Proteínas de Bactérias/metabolismo , Sítios de Ligação , DNA Bacteriano/genética , DNA Bacteriano/metabolismo , Ensaio de Desvio de Mobilidade Eletroforética/métodos , Escherichia coli/genética , Proteínas de Escherichia coli/genética , Ácidos Graxos/biossíntese , Ácidos Graxos/metabolismo , Proteínas de Fímbrias/genética , Regiões Promotoras Genéticas , Ligação Proteica , Regulon , Ressonância de Plasmônio de Superfície/métodos , Fatores de Transcrição/metabolismo , Transcrição Gênica , Vibrio cholerae/metabolismo , beta-Galactosidase/metabolismo
15.
Comput Struct Biotechnol J ; 23: 700-710, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38292475

RESUMO

Introduction: The disconnected-interacting protein 2 homolog A (DIP2A), a member of disconnected-interacting 2 protein family, has been shown to be involved in human nervous system-related mental illness. This protein is highly expressed in the nervous system of mouse. Mutation of mouse DIP2A causes defects in spine morphology and synaptic transmission, autism-like behaviors, and defective social novelty [5], [27], indicating that DIP2A is critical to the maintenance of neural development. However, the role of DIP2A in neural differentiation has yet to be investigated. Objective: To determine the role of DIP2A in neural differentiation, a neural differentiation model was established using mouse embryonic stem cells (mESCs) and studied by using gene-knockout technology and RNA-sequencing-based transcriptome analysis. Results: We found that DIP2A is not required for mESCs pluripotency maintenance, but loss of DIP2A causes the neural differentiation abnormalities in both N2B27 and KSR medium. Functional knockout of Dip2a gene also decreased proliferation of mESCs by perturbation of the cell cycle and profoundly inhibited the expression of a large number of neural development-associated genes which mainly enriched in spinal cord development and postsynapse assembly. Conclusions: The results of this report demonstrate that DIP2A plays an essential role in regulating differentiation of mESCs towards the neural fate.

16.
Front Pharmacol ; 14: 1094844, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36909189

RESUMO

Background: Ovarian cancer is one of the deadliest gynecological cancers, with the most advanced disease and poor survival. Although BRCA genes play a key role in maintaining genomic stability and providing the possibility of clinically individualized treatments, with the emergence of new and more appropriate treatment options, new treatment-related adverse events are challenging and difficult for clinicians. Case presentation: An 80-year-old Chinese woman was diagnosed with stage IIIC ovarian high-grade serous adenocarcinoma (CT3cN1MX) with BRCA2 as the causative gene. She underwent three courses of neoadjuvant chemotherapy with nab-paclitaxel 400 mg and carboplatin 450 mg before surgery. Chest HRCT prior to chemotherapy demonstrated bilateral interstitial pneumonia. During chemotherapy, there were four episodes of dry cough, shortness of breath, dyspnea, and three episodes of bone marrow suppression. The symptoms became intermittent and progressively worse, and after three sessions of empirical cough and phlegm relief, oxygen inhalation, corticosteroids, anti-infectives, and leukopenia therapy, the symptoms became intermittent and progressively worse. The diagnosis of idiopathic pulmonary fibrosis came a week after the third round of chemotherapy. After a strong dose of corticosteroids and nintedanib anti-fibrosis therapy, the pulmonary symptoms abated, and intermediate tumor starvation was performed. The combination therapy was subsequently discontinued, and the patient experienced significant relief from pulmonary symptoms. Treatment response was positive following single-agent nab-paclitaxel 400 mg chemotherapy in combination with nintedanib 150 mg anti-fibrosis therapy. Conclusion: In this report, we describe a rare case of idiopathic pulmonary fibrosis associated with the use of nab-paclitaxel and carboplatin in ovarian cancer. During treatment, it is necessary to maintain a high level of vigilance for patients with interstitial pneumonia and engage the attention of clinicians to improve medication safety. Early diagnosis and anti-fibrosis therapy can reverse lung damage.

17.
J Psychosom Obstet Gynaecol ; 44(1): 2132930, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-36240050

RESUMO

Purpose: There is a rising prevalence in undetected perinatal depression in many countries, more effort in screening and early identification of perinatal depression is needed. While the Whooley questionnaire is the recommended case-finding strategy for perinatal depression, there is no validated Chinese version. The aim was to evaluate the diagnostic accuracy and stability of the translated Chinese Whooley questionnaire against gold standard measurement during and early after pregnancy.Materials and Methods: This observational study recruited 131 pregnant women from an antenatal clinic in Hong Kong from September 2019 to May 2020. We translated the Whooley questionnaire in Chinese and evaluated self-reported responses against an interviewer-assessed diagnostic standard (DSM-IV criteria) in 107 women at 26-28 gestational weeks. We calculated sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio, with DSM-IV diagnosis as the gold standard.Results: The Chinese Whooley questions had a sensitivity of 79% (95% CI 54.4-93.9), a specificity of 97% (95% CI 90.4-99.3), a positive likelihood ratio of 23.2 (95% CI 7.4-72.1) and a negative likelihood ratio of 0.2 (95% CI 0.1-0.5) in identifying perinatal depression.Conclusion: The translated Chinese Whooley questionnaire has an acceptable diagnostic accuracy in identifying perinatal depression. It can be implemented in health services among Cantonesespeaking Chinese population.


Assuntos
População do Leste Asiático , Gravidez , Feminino , Humanos , Hong Kong/epidemiologia
18.
Sci Rep ; 13(1): 19094, 2023 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-37925535

RESUMO

Psychosocial and behavioral interventions have been shown to significantly reduce depressive and anxiety symptoms in different populations. Recent evidence suggests that the mental health of the general population has deteriorated significantly since the start of Coronavirus Disease 2019 (COVID-19) pandemic. We conducted a systematic review and meta-analysis of studies on the therapeutic effects of psychosocial and behavioral interventions on depression and anxiety during the COVID-19 pandemic. We systematically searched six electronic databases between December 2019 and February 2022 including PubMed, PsycINFO, Scopus, Web of Science, CNKI, and Wanfang Data. We included randomized clinical trials of psychosocial and behavioral interventions in individuals with depressive or anxiety symptoms during the COVID-19 outbreak compared to various control conditions. A total of 35 eligible studies with 5457 participants were included. The meta-analysis results showed that psychosocial and behavioral interventions had statistically significant moderate effects on depression [SMD = - 0.73, 95% CI (- 1.01, - 0.45), I2 = 90%] and large effects on anxiety [SMD = - 0.90, 95% CI (- 1.19, - 0.60), I2 = 92%], especially in the general population and COVID-19 survivors. Exercise and cognitive behavioral therapy were found to be the most effective treatments with moderate-to-large effect size for depression and anxiety during the outbreak of COVID-19. We also found the internet-based approach could also achieve almost equally significant effects on depression and anxiety compared with face-to-face traditional approach. Our findings suggest that cognitive behavioral therapy and physical exercise intervention are significantly effective for depression and anxiety related to the COVID-19 pandemic regardless of the delivery modes, and gender differences should be taken into consideration for better implementation of interventions in clinical and community practice.


Assuntos
COVID-19 , Pandemias , Humanos , COVID-19/epidemiologia , Ansiedade/epidemiologia , Ansiedade/terapia , Terapia Comportamental , Transtornos de Ansiedade/terapia , Depressão/epidemiologia , Depressão/terapia
19.
Neurosci Biobehav Rev ; 137: 104625, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35339482

RESUMO

BACKGROUND: Social cognition is significantly associated with daily functioning in patients with schizophrenia. Its neural basis remains unknown. METHODS: A systematic literature search was performed. Studies using imaging to measure theory of mind (ToM) in schizophrenia were identified. Imaging data were synthesized using the seed-based d mapping approach. Potential neuropathways were hypothesized based on the identified brain regions activated during ToM tasks. RESULTS: A total of 25 studies were included in the present study. Compared with healthy people, patients with schizophrenia showed hyperactivations in superior longitudinal fasciculus II and hypoactivations in superior frontal gyrus, precuneus and cuneus, and precentral gyrus during ToM tasks. The primary brain regions involved in the potential neuropathways in schizophrenia were the middle temporal gyrus, superior and inferior frontal gyrus, and supplementary motor areas. CONCLUSION: Deactivated brain regions in schizophrenia overlapped with the default mode and salience networks. Our findings shed light on how to develop a diagnostic tool for deficits in social cognition using neuroimaging techniques and effective therapeutic interventions to rectify dysfunction in schizophrenia.


Assuntos
Esquizofrenia , Teoria da Mente , Encéfalo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodos , Neuroimagem
20.
World J Psychiatry ; 12(1): 169-186, 2022 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-35111587

RESUMO

BACKGROUND: Depression is recognized as a major public health problem with a substantial impact on individuals and society. Complementary therapies such as acupressure may be considered a safe and cost-effective treatment for people with depression. An increasing body of research has been undertaken to assess the effectiveness of acupressure in various populations with depression, but the evidence thus far is inconclusive. AIM: To examine the efficacy of acupressure on depression. METHODS: A systematic literature search was performed on PubMed, PsycINFO, Scopus, Embase, MEDLINE, and China National Knowledge (CNKI). Randomized clinical trials (RCTs) or single-group trials in which acupressure was compared with control methods or baseline in people with depression were included. Data were synthesized using a random-effects or a fixed-effects model to analyze the impacts of acupressure treatment on depression and anxiety in people with depression. The primary outcome measures were set for depression symptoms. Subgroups were created, and meta-regression analyses were performed to explore which factors are relevant to the greater or lesser effects of treating symptoms. RESULTS: A total of 14 RCTs (1439 participants) were identified. Analysis of the between-group showed that acupressure was effective in reducing depression [Standardized mean differences (SMDs) = -0.58, 95%CI: -0.85 to -0.32, P < 0.0001] and anxiety (SMD = -0.67, 95%CI: -0.99 to -0.36, P < 0.0001) in participants with mild-to-moderate primary and secondary depression. Subgroup analyses suggested that acupressure significantly reduced depressive symptoms compared with different controlled conditions and in participants with different ages, clinical conditions, and duration of intervention. Adverse events, including hypotension, dizziness, palpitation, and headache, were reported in one study. CONCLUSION: The evidence of acupressure for mild-to-moderate depressive symptoms was significant. Importantly, the findings should be interpreted with caution due to study limitations. Future research with a well-designed mixed method is required to consolidate the conclusion and provide an in-depth understanding of potential mechanisms underlying the effects.

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