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1.
Mol Cell ; 83(7): 1180-1196.e8, 2023 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-37028415

RESUMO

Proper defense against microbial infection depends on the controlled activation of the immune system. This is particularly important for the RIG-I-like receptors (RLRs), which recognize viral dsRNA and initiate antiviral innate immune responses with the potential of triggering systemic inflammation and immunopathology. Here, we show that stress granules (SGs), molecular condensates that form in response to various stresses including viral dsRNA, play key roles in the controlled activation of RLR signaling. Without the SG nucleators G3BP1/2 and UBAP2L, dsRNA triggers excessive inflammation and immune-mediated apoptosis. In addition to exogenous dsRNA, host-derived dsRNA generated in response to ADAR1 deficiency is also controlled by SG biology. Intriguingly, SGs can function beyond immune control by suppressing viral replication independently of the RLR pathway. These observations thus highlight the multi-functional nature of SGs as cellular "shock absorbers" that converge on protecting cell homeostasis by dampening both toxic immune response and viral replication.


Assuntos
DNA Helicases , RNA Helicases , Humanos , DNA Helicases/metabolismo , RNA Helicases/genética , RNA Helicases/metabolismo , Proteínas de Ligação a Poli-ADP-Ribose/metabolismo , Grânulos de Estresse , Proteínas com Motivo de Reconhecimento de RNA/metabolismo , Imunidade Inata , Inflamação/metabolismo , Grânulos Citoplasmáticos/metabolismo , Proteínas de Transporte/metabolismo
2.
Mol Cell ; 66(5): 581-596.e6, 2017 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-28552615

RESUMO

The action of DNA topoisomerase II (Top2) creates transient DNA breaks that are normally concealed inside Top2-DNA covalent complexes. Top2 poisons, including ubiquitously present natural compounds and clinically used anti-cancer drugs, trap Top2-DNA complexes. Here, we show that cells actively prevent Top2 degradation to avoid the exposure of concealed DNA breaks. A genome-wide screen revealed that fission yeast cells lacking Rrp2, an Snf2-family DNA translocase, are strongly sensitive to Top2 poisons. Loss of Rrp2 enhances SUMOylation-dependent ubiquitination and degradation of Top2, which in turn increases DNA damage at sites where Top2-DNA complexes are trapped. Rrp2 possesses SUMO-binding ability and prevents excessive Top2 degradation by competing against the SUMO-targeted ubiquitin ligase (STUbL) for SUMO chain binding and by displacing SUMOylated Top2 from DNA. The budding yeast homolog of Rrp2, Uls1, plays a similar role, indicating that this genome protection mechanism is widely employed, a finding with implications for cancer treatment.


Assuntos
Dano ao DNA , DNA Topoisomerases Tipo II/metabolismo , DNA Fúngico/metabolismo , Proteínas de Ligação a DNA/metabolismo , Genoma Fúngico , Instabilidade Genômica , Proteínas de Schizosaccharomyces pombe/metabolismo , Schizosaccharomyces/enzimologia , Sumoilação , Dano ao DNA/efeitos dos fármacos , DNA Helicases/genética , DNA Helicases/metabolismo , DNA Topoisomerases Tipo II/genética , DNA Fúngico/efeitos dos fármacos , DNA Fúngico/genética , Proteínas de Ligação a DNA/genética , Resistência a Medicamentos , Etoposídeo/farmacologia , Genoma Fúngico/efeitos dos fármacos , Instabilidade Genômica/efeitos dos fármacos , Mutação , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Proteólise , Saccharomyces cerevisiae/enzimologia , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Schizosaccharomyces/efeitos dos fármacos , Schizosaccharomyces/genética , Proteínas de Schizosaccharomyces pombe/genética , Inibidores da Topoisomerase II/farmacologia , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação
3.
BMC Pulm Med ; 24(1): 29, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38212743

RESUMO

BACKGROUND: Some medical conditions may increase the risk of developing pulmonary tuberculosis (PTB); however, no systematic study on PTB-associated comorbidities and comorbidity clusters has been undertaken. METHODS: A nested case-control study was conducted from 2013 to 2017 using multi-source big data. We defined cases as patients with incident PTB, and we matched each case with four event-free controls using propensity score matching (PSM). Comorbidities diagnosed prior to PTB were defined with the International Classification of Diseases-10 (ICD-10). The longitudinal relationships between multimorbidity burden and PTB were analyzed using a generalized estimating equation. The associations between PTB and 30 comorbidities were examined using conditional logistic regression, and the comorbidity clusters were identified using network analysis. RESULTS: A total of 4265 cases and 17,060 controls were enrolled during the study period. A total of 849 (19.91%) cases and 1141 (6.69%) controls were multimorbid before the index date. Having 1, 2, and ≥ 3 comorbidities was associated with an increased risk of PTB (aOR 2.85-5.16). Fourteen out of thirty comorbidities were significantly associated with PTB (aOR 1.28-7.27), and the associations differed by sex and age. Network analysis identified three major clusters, mainly in the respiratory, circulatory, and endocrine/metabolic systems, in PTB cases. CONCLUSIONS: Certain comorbidities involving multiple systems may significantly increase the risk of PTB. Enhanced awareness and surveillance of comorbidity are warranted to ensure early prevention and timely control of PTB.


Assuntos
Big Data , Tuberculose Pulmonar , Humanos , Estudos de Casos e Controles , Tuberculose Pulmonar/epidemiologia , Comorbidade , Modelos Logísticos
4.
Semin Cell Dev Biol ; 111: 76-85, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33092958

RESUMO

TRIM (Tripartite motif) and TRIM-like proteins have emerged as an important class of E3 ligases in innate immunity. Their functions range from activation or regulation of innate immune signaling pathway to direct detection and restriction of pathogens. Despite the importance, molecular mechanisms for many TRIM/TRIM-like proteins remain poorly characterized, in part due to challenges of identifying their substrates. In this review, we discuss several TRIM/TRIM-like proteins in RNA sensing pathways and viral restriction functions. We focus on those containing PRY-SPRY, the domain most frequently used for substrate recognition, and discuss emerging mechanisms that are commonly utilized by several TRIM/TRIM-like proteins to tightly control their interaction with the substrates.


Assuntos
Domínio B30.2-SPRY/genética , Proteína DEAD-box 58/genética , Imunidade Inata , Helicase IFIH1 Induzida por Interferon/genética , Receptores Imunológicos/genética , Proteínas com Motivo Tripartido/genética , Ubiquitina-Proteína Ligases/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/imunologia , Proteína DEAD-box 58/imunologia , Regulação da Expressão Gênica , Humanos , Fator Regulador 3 de Interferon/genética , Fator Regulador 3 de Interferon/imunologia , Helicase IFIH1 Induzida por Interferon/imunologia , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/imunologia , Família Multigênica , Receptores Imunológicos/imunologia , Transdução de Sinais , Especificidade por Substrato , Proteínas com Motivo Tripartido/química , Proteínas com Motivo Tripartido/classificação , Proteínas com Motivo Tripartido/imunologia , Ubiquitina-Proteína Ligases/classificação , Ubiquitina-Proteína Ligases/imunologia
5.
Anal Biochem ; 677: 115232, 2023 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-37481195

RESUMO

In view of the superior chemical activity of selenoether bond (-Se-) and the excellent optical properties of naphthimide, a novel fluorescent probe (NapSe) with near-rectangular structure, which contains double naphthimide fluorophores linked by selenoether bond, is designed for specific fluorescence detection of hydrogen sulfide (H2S). NapSe has excellent optical properties: super large Stokes Shift (190 nm) and good stability in a wide pH range. The selectivity of NapSe fluorescence detection of H2S is high, and displays excellent "turn-on" phenomenon and strong anti-interference. And the fluorescence intensity increased obviously, reaching 42 times. The time response of probe NapSe is very rapid (3 min) compared with other fluorescence probes that respond to H2S. It shows high sensitivity by calculating the detection limit (LOD) as low as 5.4 µM. Notably, the identification of H2S by probe NapSe has been successfully applied to the detection of test paper and the detection of exogenous and endogenous fluorescence imaging of MCF-7 breast cancer cells.


Assuntos
Corantes Fluorescentes , Sulfeto de Hidrogênio , Humanos , Corantes Fluorescentes/química , Células MCF-7 , Imagem Óptica , Espectrometria de Fluorescência , Células HeLa
6.
Acta Pharmacol Sin ; 44(3): 499-512, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36229600

RESUMO

Cannabidiol (CBD) reportedly exerts protective effects against many psychiatric disorders and neurodegenerative diseases, but the mechanisms are poorly understood. In this study, we explored the molecular mechanism of CBD against cerebral ischemia. HT-22 cells or primary cortical neurons were subjected to oxygen-glucose deprivation insult followed by reoxygenation (OGD/R). In both HT-22 cells and primary cortical neurons, CBD pretreatment (0.1, 0.3, 1 µM) dose-dependently attenuated OGD/R-induced cell death and mitochondrial dysfunction, ameliorated OGD/R-induced endoplasmic reticulum (ER) stress, and increased the mitofusin-2 (MFN2) protein level in HT-22 cells and primary cortical neurons. Knockdown of MFN2 abolished the protective effects of CBD. CBD pretreatment also suppressed OGD/R-induced binding of Parkin to MFN2 and subsequent ubiquitination of MFN2. Overexpression of Parkin blocked the effects of CBD in reducing MFN2 ubiquitination and reduced cell viability, whereas overexpressing MFN2 abolished Parkin's detrimental effects. In vivo experiments were conducted on male rats subjected to middle cerebral artery occlusion (MCAO) insult, and administration of CBD (2.5, 5 mg · kg-1, i.p.) dose-dependently reduced the infarct volume and ER stress in the brains. Moreover, the level of MFN2 within the ischemic penumbra of rats was increased by CBD treatment, while the binding of Parkin to MFN2 and the ubiquitination of MFN2 was decreased. Finally, short hairpin RNA against MFN2 reversed CBD's protective effects. Together, these results demonstrate that CBD protects brain neurons against cerebral ischemia by reducing MFN2 degradation via disrupting Parkin's binding to MFN2, indicating that MFN2 is a potential target for the treatment of cerebral ischemia.


Assuntos
Isquemia Encefálica , Canabidiol , GTP Fosfo-Hidrolases , Fármacos Neuroprotetores , Traumatismo por Reperfusão , Animais , Masculino , Ratos , Apoptose , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Canabidiol/farmacologia , Glucose/metabolismo , Infarto da Artéria Cerebral Média/metabolismo , Neuroproteção , Fármacos Neuroprotetores/farmacologia , Oxigênio/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Ubiquitina-Proteína Ligases/metabolismo , GTP Fosfo-Hidrolases/efeitos dos fármacos , GTP Fosfo-Hidrolases/metabolismo , Proteínas Mitocondriais/efeitos dos fármacos , Proteínas Mitocondriais/metabolismo
7.
Acta Pharmacol Sin ; 44(7): 1337-1349, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36697977

RESUMO

Diabetic patients frequently experience neuropathic pain, which currently lacks effective treatments. The mechanisms underlying diabetic neuropathic pain remain unclear. The anterior cingulate cortex (ACC) is well-known to participate in the processing and transformation of pain information derived from internal and external sensory stimulation. Accumulating evidence shows that dysfunction of microglia in the central nervous system contributes to many diseases, including chronic pain and neurodegenerative diseases. In this study, we investigated the role of microglial chemokine CXCL12 and its neuronal receptor CXCR4 in diabetic pain development in a mouse diabetic model established by injection of streptozotocin (STZ). Pain sensitization was assessed by the left hindpaw pain threshold in von Frey filament test. Iba1+ microglia in ACC was examined using combined immunohistochemistry and three-dimensional reconstruction. The activity of glutamatergic neurons in ACC (ACCGlu) was detected by whole-cell recording in ACC slices from STZ mice, in vivo multi-tetrode electrophysiological and fiber photometric recordings. We showed that microglia in ACC was significantly activated and microglial CXCL12 expression was up-regulated at the 7-th week post-injection, resulting in hyperactivity of ACCGlu and pain sensitization. Pharmacological inhibition of microglia or blockade of CXCR4 in ACC by infusing minocycline or AMD3100 significantly alleviated diabetic pain through preventing ACCGlu hyperactivity in STZ mice. In addition, inhibition of microglia by infusing minocycline markedly decreased STZ-induced upregulation of microglial CXCL12. Together, this study demonstrated that microglia-mediated ACCGlu hyperactivity drives the development of diabetic pain via the CXCL12/CXCR4 signaling, thus revealing viable therapeutic targets for the treatment of diabetic pain.


Assuntos
Diabetes Mellitus Experimental , Neuralgia , Camundongos , Animais , Microglia/metabolismo , Regulação para Cima , Hiperalgesia/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/metabolismo , Quimiocina CXCL12/farmacologia , Giro do Cíngulo/metabolismo , Minociclina/farmacologia , Minociclina/uso terapêutico , Medula Espinal/metabolismo , Neuralgia/metabolismo , Modelos Animais de Doenças
8.
BMC Med Imaging ; 23(1): 213, 2023 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-38097964

RESUMO

OBJECTIVE: To investigate the diagnostic value of computed tomography (CT) and magnetic resonance imaging (MRI) in ovarian malignant mesothelioma (OMM). METHODS: The clinical and imaging data of 10 pathologically-confirmed OMM patients were analyzed retrospectively. RESULT: (1) The patients were 27 years to 70 years old, with an average age of 57.2 ± 15.4 years. Seven patients reported abdominal distension and pain, 1 reported lower abdominal discomfort and decreased appetite, and 2 patients had no symptoms. (2) Two cases of localized OMM with incomplete semi-annular "capsule" observed around the localized OMM tumors were reported while 8 cases had diffuse OMM in which the tumor parenchyma showed isointense or slightly hypointense on T1WI, inhomogeneous hyperintense on T2WI, and obviously hyperintense on DWI, with obvious inhomogeneous enhancement after enhancement. Diffuse OMM was not mainly composed of ovarian masses and was mainly characterized by mild ovarian enlargement, nodular and irregular thickening of the peritoneum, cloudy omentum, unclear fat gap, and reticular or irregular thickening, which can fuse into a "cake-shape". (3) All 10 patients underwent surgery, while 9 patients underwent systemic chemotherapy or immunotherapy after surgery. All patients with localized OMM survived. Out of the 8 diffuse-type patients, 5 died, 1 was lost to follow-up, and 2 survived. CONCLUSION: OMM has certain clinical and imaging characteristics. There is no liquefaction, calcification, or partition in the tumor. The ovarian enlargement in the diffuse lesion is not significant. The diffuse thickening of the peritoneum and omentum with early appearance of mural nodules and ascites in the upper abdomen, help the diagnosis of OMM.


Assuntos
Mesotelioma Maligno , Neoplasias Ovarianas , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Mesotelioma Maligno/diagnóstico por imagem , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/cirurgia , Tomografia Computadorizada por Raios X/métodos
9.
BMC Med Imaging ; 23(1): 214, 2023 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-38102549

RESUMO

OBJECTIVE: To discuss the value of computed tomography (CT) iterative reconstruction technique combined with target scanning in the diagnosis of solid pseudopapillary tumor of the pancreas (SPTP). METHODS: The clinical information and CT examination data of 27 patients with SPTP were retrospectively analyzed, and the general condition and CT performance of the patients were observed. The CT image reconstruction algorithm of all patients used iterative reconstruction technique combined with the application of target scanning technique. RESULTS: A total of 27 patients were included in this study, including 6 males and 21 females, aged 14-72 years with a mean age of 39.6 ± 13.6 years. SPTP was more common in young and middle-aged females, with a low level of tumor markers, dominated by cystic-solid tumors. The combination of CT iterative reconstruction technology and targeted scanning revealed the following: the capsule of SPTP was clear and complete, where calcifications were visible, solid components were progressively enhanced, and rare pancreatic and bile duct dilation was seen. Tumors were cystic-solid in 18 of 27 patients with SPTP, of which the solid components showed isodensity or slightly low-density, with calcifications. The solid components and cyst walls were mildly enhanced during the arterial phase, and were progressively enhanced during the parenchymal phase, portal vein phase, and delayed phase, with their enhancement degree lower than that of normal pancreatic parenchyma, and pancreatic and bile duct dilation was rare. There were no statistical differences in tumor location, morphology, growth pattern, integrity of capsule, cystic or solid, calcifications, and enhancement features between the male group and the female group (P > 0.05). CONCLUSION: The iterative reconstruction combined with target scanning clearly displayed the CT features of tumors, helping the diagnosis and clinical treatment of the disease.


Assuntos
Calcinose , Neoplasias Pancreáticas , Pessoa de Meia-Idade , Humanos , Masculino , Feminino , Adulto , Estudos Retrospectivos , Pâncreas/patologia , Neoplasias Pancreáticas/patologia , Tomografia Computadorizada por Raios X/métodos
10.
J Virol ; 95(9)2021 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-33536170

RESUMO

N6-Methyladenosine (m6A) is the most abundant internal RNA modification catalyzed by host RNA methyltransferases. As obligate intracellular parasites, many viruses acquire m6A methylation in their RNAs. However, the biological functions of viral m6A methylation are poorly understood. Here, we found that viral m6A methylation serves as a molecular marker for host innate immunity to discriminate self from nonself RNA and that this novel biological function of viral m6A methylation is universally conserved in several families in nonsegmented negative-sense (NNS) RNA viruses. Using m6A methyltransferase (METTL3) knockout cells, we produced m6A-deficient virion RNAs from the representative members of the families Pneumoviridae, Paramyxoviridae, and Rhabdoviridae and found that these m6A-deficient viral RNAs triggered significantly higher levels of type I interferon compared to the m6A-sufficient viral RNAs, in a RIG-I-dependent manner. Reconstitution of the RIG-I pathway revealed that m6A-deficient virion RNA induced higher expression of RIG-I, bound to RIG-I more efficiently, enhanced RIG-I ubiquitination, and facilitated RIG-I conformational rearrangement and oligomerization. Furthermore, the m6A binding protein YTHDF2 is essential for suppression of the type I interferon signaling pathway, including by virion RNA. Collectively, our results suggest that several families in NNS RNA viruses acquire m6A in viral RNA as a common strategy to evade host innate immunity.IMPORTANCE The nonsegmented negative-sense (NNS) RNA viruses share many common replication and gene expression strategies. There are no vaccines or antiviral drugs for many of these viruses. We found that representative members of the families Pneumoviridae, Paramyxoviridae, and Rhabdoviridae among the NNS RNA viruses acquire m6A methylation in their genome and antigenome as a means to escape recognition by host innate immunity via a RIG-I-dependent signaling pathway. Viral RNA lacking m6A methylation induces a significantly higher type I interferon response than m6A-sufficient viral RNA. In addition to uncovering m6A methylation as a common mechanism for many NNS RNA viruses to evade host innate immunity, this study discovered a novel strategy to enhance type I interferon responses, which may have important applications in vaccine development, as robust innate immunity will likely promote the subsequent adaptive immunity.


Assuntos
Adenosina/análogos & derivados , Interações entre Hospedeiro e Microrganismos/imunologia , Interferon Tipo I/imunologia , Vírus de RNA de Sentido Negativo , Infecções por Vírus de RNA , RNA Viral/genética , Células A549 , Adenosina/genética , Regulação Viral da Expressão Gênica , Técnicas de Inativação de Genes , Humanos , Imunidade Inata , Metiltransferases/genética , Vírus de RNA de Sentido Negativo/genética , Vírus de RNA de Sentido Negativo/imunologia , Vírus de RNA de Sentido Negativo/patogenicidade , Processamento Pós-Transcricional do RNA , Infecções por Vírus de RNA/imunologia , Infecções por Vírus de RNA/virologia
11.
Artigo em Inglês | MEDLINE | ID: mdl-35550242

RESUMO

Three strains of members of the family Bacillaceae, which can inhibit the growth of some Gram-stain-positive strains, designated M4U3P1T, HD4P25T and RD4P76T, were isolated from Suaeda salsa halophytes in Baotou, Inner Mongolia, PR China. A phylogenetic analysis based on the 16S rRNA gene and the whole genome sequences revealed that HD4P25T clustered with Cytobacillus luteolus YIM 93174T with a similarity of 98.4 %, and RD4P76T shared the highest similarity of 16S rRNA gene with Bacillus mesophilus SA4T (97.5 %). M4U3P1T clustered with strains of genera Salipaludibacillus and Alkalicoccus based on whole-genome sequence analyses, but its 16S rRNA gene had the highest similarity to 'Evansella tamaricis' EGI 80668 (96.1 %). The average nucleotide's identity by blast (ANIb) and digital DNA-DNA hybridization (dDDH) values of the three isolated strains to their close relatives were well below the threshold value for identifying a novel species.On the basis of the phylogenetic, physiological and phenotypic results, Paenalkalicoccus suaedae gen. nov., sp. nov. [type strain M4U3P1T (=CGMCC 1.17076T=JCM 33851T)], Cytobacillus suaedae sp. nov. [type strain HD4P25T (=CGMCC 1.18651T =JCM 34524T)], and Bacillus suaedae sp. nov. [type strain RD4P76T (=CGMCC 1.18659T=JCM 34525T)] were proposed, respectively. All three species are ubiquitous in the bulk saline-alkaline soils, but only the species represented by strain RD4P76T was widely distributed in the rhizosphere soil, the above-ground part and the roots of S. salsa. The species represented by M4U3P1T can be detected in the roots of S. salsa, and rarely detected in the above-ground parts of S. salsa. The species represented by HD4P25T was rarely detected in the interior of S. salsa. The three strains could inhibit some of the Gram-stain-positive bacteria (i.e. members of the genera Planococcus, Zhihengliuella and Sanguibacter) in the saline-alkali soil. A genomic analysis of these three strains revealed that they can synthesize different antagonistic compounds, such as aminobenzoate and bacitracin or subtilisin.


Assuntos
Bacillaceae , Bacillus , Chenopodiaceae , Bacillaceae/genética , Bacillus/genética , Técnicas de Tipagem Bacteriana , Composição de Bases , Chenopodiaceae/microbiologia , DNA Bacteriano/genética , Ácidos Graxos/química , Fosfolipídeos , Filogenia , RNA Ribossômico 16S/genética , Plantas Tolerantes a Sal , Análise de Sequência de DNA , Solo
12.
BMC Infect Dis ; 22(1): 332, 2022 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-35379167

RESUMO

BACKGROUND: The current surveillance system only focuses on notifiable infectious diseases in China. The arrival of the big-data era provides us a chance to elaborate on the full spectrum of infectious diseases. METHODS: In this population-based observational study, we used multiple health-related data extracted from the Shandong Multi-Center Healthcare Big Data Platform from January 2013 to June 2017 to estimate the incidence density and describe the epidemiological characteristics and dynamics of various infectious diseases in a population of 3,987,573 individuals in Shandong province, China. RESULTS: In total, 106,289 cases of 130 infectious diseases were diagnosed among the population, with an incidence density (ID) of 694.86 per 100,000 person-years. Besides 73,801 cases of 35 notifiable infectious diseases, 32,488 cases of 95 non-notifiable infectious diseases were identified. The overall ID continuously increased from 364.81 per 100,000 person-years in 2013 to 1071.80 per 100,000 person-years in 2017 (χ2 test for trend, P < 0.0001). Urban areas had a significantly higher ID than rural areas, with a relative risk of 1.25 (95% CI 1.23-1.27). Adolescents aged 10-19 years had the highest ID of varicella, women aged 20-39 years had significantly higher IDs of syphilis and trichomoniasis, and people aged ≥ 60 years had significantly higher IDs of zoster and viral conjunctivitis (all P < 0.05). CONCLUSIONS: Infectious diseases remain a substantial public health problem, and non-notifiable diseases should not be neglected. Multi-source-based big data are beneficial to better understand the profile and dynamics of infectious diseases.


Assuntos
Doenças Transmissíveis , Sífilis , Adolescente , Adulto , Big Data , Criança , China/epidemiologia , Doenças Transmissíveis/epidemiologia , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Adulto Jovem
13.
Surg Endosc ; 36(12): 9046-9053, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35764836

RESUMO

BACKGROUND: Postoperative pain treatment for pediatrics is often inadequate and the evidence of pediatric postoperative analgesia is scarce. To our knowledge, no report regarding the comparison among caudal block, transversus abdominis plane (TAP) block and quadratus lumborum (QL) block for children undergoing lower abdominal laparoscopic surgery was found at present. Thus this trial aimed to compare the efficacies of them for children undergoing lower abdominal laparoscopic surgery. METHODS: One hundred and eighty children aged from 1 to 12 years undergoing lower abdominal laparoscopic surgery were included and randomized to receive caudal block, TAP block or QL block. The primary outcome was the Face, Legs, Activity, Cry, and Consolability (FLACC) score at 30 min, 1 h, 4 h, 8 h, 12 h, and 24 h and tramadol consumption during first 24 h postoperatively. Secondary outcomes included the number of children received tramadol, time to first tramadol request, parents' satisfaction and postoperative adverse reactions. RESULTS: The QLB group had lower postoperative FLACC scores at 8 h (median difference - 0.43, P = 0.03) than the Caudal group and at 4 h (median difference - 0.6, P = 0.001) and 8 h (median difference - 0.43, P = 0.03) than the TAPB group. The tramadol consumption was lower in the QLB group (28.43 ± 6.55) than the TAPB group (37.17 ± 6.12, P = 0.023). Although the number of children received tramadol did not differ among the three groups, the time to first tramadol request was longer in the QLB group (7.20 ± 0.79) than the caudal group (8.42 ± 0.61, P = 0.008). No statistical difference was observed concerning other secondary outcomes. CONCLUSIONS: QLB produced more effective postoperative analgesia for children undergoing laparoscopic abdominal surgery compared with the TAPB and caudal block.


Assuntos
Analgesia , Laparoscopia , Tramadol , Criança , Humanos , Tramadol/uso terapêutico , Músculos Abdominais , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/tratamento farmacológico , Ultrassonografia de Intervenção , Anestésicos Locais
14.
Int J Syst Evol Microbiol ; 71(10)2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34617881

RESUMO

A Gram-stain-positive, strictly aerobic, motile, endospore-forming, milk-white, indole acetic acid-producing, rod-shaped bacterial strain, designated as HU2P27T, was isolated from a shoot of Kalidium cuspidatum collected in Tumd Right Banner, Inner Mongolia, PR China. Strain grew at 10-40 °C (optimum, 30 °C), at pH 6.0-9.0 (optimum, pH 7.0) and with 0-14.0 % NaCl (optimum, 5.0-8.0 %). The strain tested positive for oxidase, catalase and nitrate reductase. The phylogenetic trees based on the 16S rRNA gene sequence and the core genome both showed that strain HU2P27T clustered with Aquibacillus koreensis BH30097T, sharing 97.7 % and <97.0 % of 16S rRNA gene similarity with A. koreensis BH30097T and any other type strain. Strain HU2P27T contained MK-7 as the major respiratory quinone. Its major fatty acids were anteiso-C15 : 0 and iso-C15 : 0, and the major polar lipids were phosphatidylglycerol, diphosphatidylglycerol and four unidentified phospholipids. The genomic DNA G+C content was 36.0 mol%. The average nucleotide identity, amino acid identity and digital DNA-DNA hybridization values of strain HU2P27T with A. koreensis BH30097T were 71.7, 69.2 and 19.4%, respectively. The phylogenetic, physiological and phenotypic results allowed the discrimination of strain HU2P27T from its phylogenetic relatives. The name Aquibacillus kalidii sp. nov. is therefore proposed. The type strain is strain HU2P27T (=CGMCC 1.18646T=KCTC 43248T). Based on the results of 16S rRNA gene and genome analyses, we propose the reclassification of Virgibacillus campisalis Lee et al. 2012 as a later heterotypic synonym of Virgibacillus alimentarius Kim et al. 2011.


Assuntos
Bacillaceae/classificação , Chenopodiaceae/microbiologia , Filogenia , Virgibacillus/classificação , Bacillaceae/isolamento & purificação , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Endófitos/classificação , Endófitos/isolamento & purificação , Ácidos Graxos/química , Ácidos Indolacéticos , Mongólia , Hibridização de Ácido Nucleico , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
15.
Acta Pharmacol Sin ; 42(12): 1991-2003, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34531546

RESUMO

We have previously shown that roflupram (ROF) protects against MPP+-induced neuronal damage in models of Parkinson's disease (PD). Since impaired degradation of α-synuclein (α-syn) is one of the key factors that lead to PD, here we investigated whether and how ROF affects the degradation of α-syn in rotenone (ROT)-induced PD models in vivo and in vitro. We showed that pretreatment with ROF (10 µM) significantly attenuated cell apoptosis and reduced the level of α-syn in ROT-treated SH-SY5Y cells. Furthermore, ROF significantly enhanced the lysosomal function, as evidenced by the increased levels of mature cathepsin D (CTSD) and lysosomal-associated membrane protein 1 (LAMP1) through increasing NAD+/NADH and the expression of sirtuin 1 (SIRT1). Pretreatment with an SIRT1 inhibitor selisistat (SELI, 10 µM) attenuated the neuroprotection of ROF, ROF-reduced expression of α-syn, and ROF-increased expression levels of LAMP1 and mature CTSD. Moreover, inhibition of CTSD by pepstatin A (20 µM) attenuated ROF-reduced expression of α-syn. In vivo study was conducted in mice exposed to ROT (10 mg·kg-1·d-1, i.g.) for 6 weeks; then, ROT-treated mice received ROF (0.5, 1, or 2 mg·kg-1·d-1; i.g.) for four weeks. ROF significantly ameliorated motor deficits, which was accompanied by increased expression levels of tyrosine hydroxylase, SIRT1, mature CTSD, and LAMP1, and a reduced level of α-syn in the substantia nigra pars compacta. Taken together, these results demonstrate that ROF exerts a neuroprotective action and reduces the α-syn level in PD models. The mechanisms underlying ROF neuroprotective effects appear to be associated with NAD+/SIRT1-dependent activation of lysosomal function.


Assuntos
Derivados de Benzeno/uso terapêutico , Furanos/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Rotenona/toxicidade , alfa-Sinucleína/metabolismo , Animais , Apoptose/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Derivados de Benzeno/farmacologia , Catepsina D/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Furanos/farmacologia , Humanos , Lisossomos/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Movimento/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Inibidores da Fosfodiesterase 4/farmacologia , Inibidores da Fosfodiesterase 4/uso terapêutico , Sirtuína 1/metabolismo
16.
Yi Chuan ; 43(6): 580-600, 2021 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-34284989

RESUMO

Genetic modification technologies can be used for modifying animal genome to express exogenous genes or affect the function of endogenous genes. In animal breeding, genetic modification technologies allow the rapid generation of germplasms with beneficial traits. It includes traditional genetic modification, virus or sperm carrier-mediated genetic modification and nuclease-mediated genome editing, especially the CRISPR/Cas9, one of the artificial nuclease genome editing technologies, have been applied in genome editing in many domestic animals including sheep (Ovis aries). Compared with conventional strategies used for animal breeding, there is great value for sheep breeding improvement by using genome editing technology, which is more effective and timesaving. In this review, we summarize the approaches of genetic modification in sheep and discuss the possibility of molecular design and breeding of sheep by genome editing technologies. We also identify the potential bottlenecks and challenges of these technologies in sheep breeding.


Assuntos
Sistemas CRISPR-Cas , Edição de Genes , Animais , Sistemas CRISPR-Cas/genética , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Melhoramento Vegetal , Ovinos/genética , Tecnologia
17.
Int J Syst Evol Microbiol ; 70(7): 4139-4144, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32501784

RESUMO

Strains of Echinicola, thought to play vital roles in the environment for their high enzyme production capacity during decomposition of polysaccharides, are ubiquitous in hypersaline environments. A Gram-negative, non-spore forming, gliding, aerobic bacterial strain, designated LN3S3T, was isolated from alkaline saline soil sampled in Tumd Right Banner, Inner Mongolia, northern PR China. Strain LN3S3T grew at 10-40 °C (optimum, 30 °C), pH 5.0-9.0 (optimum, pH 8.0) and with 0-12.5 % NaCl (optimum, 2.0 %). A phylogenetic tree based on the 16S rRNA gene sequences showed that strain LN3S3T clustered with Echinicola rosea JL3085T and Echinicola strongylocentroti MEBiC08714T, sharing 97.0, 96.7 and <96.50 % of 16S rRNA gene sequence similarities to E. rosea JL3085T, E. strongylocentroti MEBiC08714T and all other type strains. MK-7 was the major respiratory quinone, while phosphatidylethanolamine, two unidentified phospholipids, an unidentified aminophospholipid, an unidentified lipid and two unidentified aminolipids were the major polar lipids. Its major cellular fatty acids were iso-C15 : 0, anteiso-C15 : 0 and summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c). The genome consisted of a circular 5 550 304 bp long chromosome with a DNA G+C content of 44.0 mol%. The average nucleotide identity (ANI), average amino acid identity (AAI) and digital DNA-DNA hybridization (dDDH) values of strain LN3S3T to E. rosea JL3085T and E. strongylocentroti MEBiC08714T were 82.5 and 81.5 %, 87.5 and 86.0 %, and 39.1 and 35.1 %, respectively. Based on physiological, genotypic and phylogenetic analyses, strain LN3S3T could be discriminated from its phylogenetic relatives. Echinicola soli sp. nov. is therefore proposed with strain LN3S3T (=CGMCC 1.17081T=KCTC 72458T) as the type strain.


Assuntos
Álcalis , Bacteroidetes/classificação , Filogenia , Salinidade , Microbiologia do Solo , Técnicas de Tipagem Bacteriana , Bacteroidetes/isolamento & purificação , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/química , Hibridização de Ácido Nucleico , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Solo/química , Vitamina K 2/análogos & derivados , Vitamina K 2/química
18.
Int J Syst Evol Microbiol ; 70(6): 3888-3898, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32496180

RESUMO

A Gram-negative, strictly aerobic, gliding motility, none-spore forming, yellow, rods bacterial strain, designated XS-5T, was isolated from rhizosphere soil of Suaeda salsa, in Tumd Right Banner, Inner Mongolia, PR China. A phylogenetic tree based on the 16S rRNA gene sequences and the phylogenomic tree both showed that strain XS-5T clustered with Flavobacterium beibuense F44-8T (shared 97.2 % of 16S rRNA gene similarity) and Flavobacterium rakeshii FCS-5T (97.6 %), and shared <96.0 % of 16S rRNA gene similarities with all other type strains. Strain XS-5T contained MK-6 as the major respiratory quinone. Its major polar lipids were phosphatidylethanolamine, an unidentified aminolipid and an unidentified lipid; and the major fatty acids were iso-C15 : 0, iso-C17 : 0 3-OH, C16 : 0, iso-C15 : 0 3-OH, Summed feature 3 (iso-C15 : 0 2-OH and/or C16 : 1 ω7c), and Summed feature 9 (iso-C17 : 1 ω9c and/or C16 : 0 10-methyl). The genome consisted of a 3 985 855 bp circular chromosome, with a G+C content of 37.9 mol%, predicting 3616 coding sequences genes, 45 tRNA genes and three rRNA operons. The average nucleotide identity, amino acid identity and digital DNA-DNA hybridization values of strain XS-5T to F. beibuense F44-8T and F. rakeshii FCS-5T were 79.2 and 79.2 %, 81.7 and 81.6 %, 22.3 and 22.2 %, respectively. The results of phylogenetic, physiological and biochemical tests allowed the discrimination of strain XS-5T from its phylogenetic relatives. Flavobacterium alkalisoli sp. nov. is therefore proposed with strain XS-5T (=CGMCC 1.17077T=KCTC 72459T) as the type strain.


Assuntos
Chenopodiaceae/microbiologia , Flavobacterium/classificação , Filogenia , Rizosfera , Microbiologia do Solo , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/química , Flavobacterium/isolamento & purificação , Hibridização de Ácido Nucleico , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/química
19.
Pak J Med Sci ; 36(5): 935-940, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32704267

RESUMO

OBJECTIVE: To explore the clinical effect of the application of CT navigation in the treatment of lumbar spondylolisthesis with minimally invasive surgery - transforaminal lumbar interbody fusion (MIS-TLIF). METHODS: A retrospective study was conducted on 30 patients with lumbar spondylolisthesis who were continuously treated in linyi central hospital from May 2018 to March 2019.The patients were divided into two groups,15 patients treated with MIS-TLIF with the aid of CT navigation during the operation were included into an observation group. Another 15 patients were treated with open transforaminal lumbar interbody fusion as the control group. The baseline information, including gender, age and course of disease, perioperative period and imaging conditions, and VAS and ODI scores of patients in the two groups were collected and analyzed. RESULTS: Fifteen patients were included into the observation group, including 9 male and 6 female patients with an average age of 52.60 ± 6.31 and a course of disease of 16.33 ± 6.00 months. The other 15 patients were included into the observation group, including seven male and eight female patients with an average age of 52.87 ± 7.38 and a course of disease of 19.13 ± 9.89 months. The difference in the gender, age and course of disease between the two groups had no statistical significance (P > 0.05). However, the difference in the duration of operation and intraoperative blood loss between the two groups had statistical significance (P< 0.05). There were no statistically significant differences in wound complications, neurological complications, preoperative slippage rate, postoperative slippage rate, slippage reduction rate and screw placement accuracy (P > 0.05). VAS scores of the two groups were statistically significant from six months after surgery (P < 0.01). There was no significant difference in ODI between the two groups at any time point (P >, 0.05). VAS and ODI scores were improved at each time point compared with those before surgery. CONCLUSION: The minimally invasive transforaminal lumbar fusion performed with the aid of CT navigation during the operation shortens the duration of operation and the amount of bleeding, reduces the back pain, is beneficial to the early postoperative functional exercise, and speeds up the postoperative recovery.

20.
Urol Int ; 103(2): 187-194, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31170710

RESUMO

OBJECTIVES: This meta-analysis was to assess solifenacin and tolterodine in patients with overactive bladder. METHODS: We searched PubMed, the Cochrane Library, EMBASE, CNKI, Wanfang, and ClinicalTrials.gov databases for randomized controlled trials (RCTs). The efficacy endpoint was daily micturition frequency, daily urgency episodes, daily incontinence episodes, and micturition volume per voiding. The safety endpoint was the incidence of the rate of major bleeding, intracranial bleeding, and gastrointestinal bleeding. RESULTS: Seven RCTs met the inclusion criteria and 1,318 patients were included. The meta-analysis showed that, compared with tolterodine, solifenacin was associated with similar daily micturition frequency, daily urgency episodes, daily incontinence episode, and micturition volume per voiding at 8 and 12 weeks of follow-up. Moreover, no significant difference was obtained in the incidence of dry mouth between solifenacin and tolterodine at 8 and 12 weeks of follow-up. However, tolterodine decreased the constipation rate at 12 weeks compared with solifenacin. CONCLUSION: Solifenacin and tolterodine yielded similar results on daily micturition frequency, daily urgency episodes, daily incontinence episodes, micturition volume per voiding, and the incidence of dry mouth. However, tolterodine can decrease the constipation rate at 12 weeks compared with solifenacin.


Assuntos
Succinato de Solifenacina/uso terapêutico , Tartarato de Tolterodina/uso terapêutico , Bexiga Urinária Hiperativa/tratamento farmacológico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Succinato de Solifenacina/efeitos adversos , Tartarato de Tolterodina/efeitos adversos , Resultado do Tratamento
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