Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 338
Filtrar
1.
iScience ; 27(9): 110648, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39286487

RESUMO

The traditional parameter adjustment design makes it difficult to effectively regulate the acoustic insulation performance of periodic sandwich structures while meeting the lightweight and mechanical stiffness requirements. A dynamic three-field floating projection topology optimization (FPTO) method for periodic structures is proposed to meet the optimization requirements of low-noise and high-stiffness performance of lightweight periodic sandwich structures. The sound transmission loss is taken as the optimization objective, and the lightweight volume and mechanical stiffness performance are taken as the multiple constraints. The results show that a smooth topology configuration with superior sound insulation performance, high stiffness, and a freely customizable number of periodic cores can be obtained via the proposed method. The accuracy and effectiveness of the presented method are verified via 3D printing technology and impedance tube sound insulation experiments, providing an important reference for the optimal design of lightweight composite structures for vibration and noise reduction in transportation equipment.

2.
Nitric Oxide ; 152: 11-18, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39271041

RESUMO

To investigate the protective mechanisms of hydrogen sulfide (H2S) in sepsis-induced acute kidney injury (SAKI), we conducted an in vivo study using a SAKI mouse model induced by intraperitoneal lipopolysaccharide (LPS) injection. Following 6 h of LPS injection, levels of tumor necrosis factor-alpha (TNF-α) and blood urea nitrogen (Bun) were significantly elevated in mouse plasma. In the kidneys of SAKI mice, expression of H2S-generating enzymes cysteinyl-tRNA synthetase (CARS), cystathionine γ-lyase (CSE) and cystathionine ß-synthase (CBS) was markedly downregulated, while glucose-regulated protein 78 (GRP78), activating transcription factor 6 (ATF6), phosphorylated protein kinase R-like endoplasmic reticulum kinase/protein kinase R-like endoplasmic reticulum kinase (p-PERK/PERK), and B-cell lymphoma-2 recombinant protein X/B-cell lymphoma-2 (Bax/Bcl2) expression was significantly upregulated. H2S improved renal function and attenuated renal histopathological changes in SAKI mice, thereby alleviating LPS-induced endoplasmic reticulum stress (ERS). Additionally, it inhibited the expression of p-PERK/PERK and Bax/Bcl2. After inhibiting CSE activity with dl-propargylglycine (PPG i. p.), the renal tissue pathology in LPS-induced AKI mice was further exacerbated, leading to enhanced activation of the PERK/Bax-Bcl2 pathway. Our findings suggest that endogenous H2S influences the pathogenesis of SAKI, while exogenous H2S protects against LPS-induced AKI by inhibiting the PERK/Bax-Bcl2 pathway involved in ERS.

3.
Cancer Immunol Immunother ; 73(11): 233, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39271545

RESUMO

Gastric cancer (GC) is a highly heterogeneous disease with a complex tumor microenvironment (TME) that encompasses multiple cell types including cancer cells, immune cells, stromal cells, and so on. Cancer-associated cells could remodel the TME and influence the progression of GC and therapeutic response. Single-cell RNA sequencing (scRNA-seq), as an emerging technology, has provided unprecedented insights into the complicated biological composition and characteristics of TME at the molecular, cellular, and immunological resolutions, offering a new idea for GC studies. In this review, we discuss the novel findings from scRNA-seq datasets revealing the origin and evolution of GC, and scRNA-seq is a powerful tool for investigating transcriptional dynamics and intratumor heterogeneity (ITH) in GC. Meanwhile, we demonstrate that the vital immune cells within TME, including T cells, B cells, macrophages, and stromal cells, play an important role in the disease progression. Additionally, we also overview that how scRNA-seq facilitates our understanding about the effects on individualized therapy of GC patients. Spatial transcriptomes (ST) have been designed to determine spatial distribution and capture local intercellular communication networks, enabling a further understanding of the relationship between the spatial background of a particular cell and its functions. In summary, scRNA-seq and other single-cell technologies provide a valuable perspective for molecular and pathological disease characteristics and hold promise for advancing basic research and clinical practice in GC.


Assuntos
Medicina de Precisão , Análise de Sequência de RNA , Análise de Célula Única , Neoplasias Gástricas , Microambiente Tumoral , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Análise de Célula Única/métodos , Medicina de Precisão/métodos , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Análise de Sequência de RNA/métodos , Heterogeneidade Genética , Carcinogênese/genética , Animais
4.
J Med Chem ; 67(17): 15476-15493, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39190821

RESUMO

Hepatobiliary-specific magnetic resonance imaging contrast agents (MRI CAs) play a crucial role in the early diagnosis of hepatocellular carcinoma (HCC). However, only two acyclic CAs, Gd-BOPTA and Gd-EOB-DTPA, exhibit unfavorable kinetic inertness. Our study focused on the development of superior stable innovative macrocyclic CAs. By introducing a lipophilic benzyloxy group (OBn) into the H4DOTA ring (Gd-L1), we achieved significant enhancement in kinetic inertness. In vivo experiments in mice demonstrated that 40% of the dosage was distributed to the liver at 5 min, providing sustained hepatic enhancement for over 35 min. We also developed an MPO-responsive MRI CA (Gd-L3), which can participate in the "peroxidase cycle" as the substrate, generating oligomers with a 3.8-fold increase in relaxivity, and selectively enhance the lesion in an acute gout mouse model. Overall, our work represents a significant advancement in the field of hepatic and inflammatory MRI, offering promising avenues for early diagnosis and improved imaging outcomes.


Assuntos
Meios de Contraste , Fígado , Imageamento por Ressonância Magnética , Compostos Organometálicos , Meios de Contraste/química , Meios de Contraste/síntese química , Animais , Imageamento por Ressonância Magnética/métodos , Camundongos , Compostos Organometálicos/química , Compostos Organometálicos/síntese química , Fígado/diagnóstico por imagem , Fígado/metabolismo , Desenho de Fármacos , Humanos , Inflamação/diagnóstico por imagem , Masculino , Neoplasias Hepáticas/diagnóstico por imagem , Carcinoma Hepatocelular/diagnóstico por imagem , Compostos Heterocíclicos
5.
Front Immunol ; 15: 1404615, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39185405

RESUMO

Chronic obstructive pulmonary disease (COPD) is a common respiratory disease characterized by irreversible progressive airflow limitation, often manifested by persistent cough, sputum production and other respiratory symptoms that pose a serious threat to human health and affect the quality of life of patients. The disease is associated with chronic inflammation, which is associated with the onset and progression of COPD, but anti-inflammatory therapy is not first-line treatment. Inflammation has multiple manifestations and phenotypes, and this heterogeneity reveals different patterns of inflammation, making treatment difficult. This paper aims to explore the direction of more effective anti-inflammatory treatment by analyzing the nature of inflammation and the molecular mechanism of disease occurrence and development in COPD patients, and to provide new ideas for the treatment of COPD patients.


Assuntos
Inflamação , Doença Pulmonar Obstrutiva Crônica , Doença Pulmonar Obstrutiva Crônica/imunologia , Doença Pulmonar Obstrutiva Crônica/etiologia , Humanos , Inflamação/imunologia , Anti-Inflamatórios/uso terapêutico , Animais
7.
Medicine (Baltimore) ; 103(33): e39290, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39151544

RESUMO

To investigate the association between the visceral adiposity index (VAI) and asthma using data from National Health and Nutrition Examination Survey 2003 to 2018 by a cross-sectional study. We explored the potential relationship between the VAI and asthma incidence via a cross-sectional study of the National Health and Nutrition Examination Survey from 2003 to 2018. Multiple logistic regression analysis, restricted cubic spline analysis and subgroup analysis were performed. Among the 80,312 participants, 1984 had been told by a doctor or other health professional, and 1142 still had asthma. With all confounders controlled, the VAI was positively associated with asthma incidence (odds ratios 1.04, 95% confidence interval: 1.01, 1.08). When comparing the second, third, and fourth VAI quartiles to the lowest quartile, the adjusted odds ratios (95% confidence intervals) for asthma risk were 1.02 (0.86, 1.21), 1.14 (0.96, 1.36), and 1.18 (1, 1.39), respectively (P for trend = .02). Subgroup analysis revealed no significant interaction effect among the subgroups (P > .05). The positive association was stronger in current asthma patients (odds ratios 1.13, 95% confidence interval: 1.03, 1.24). When comparing the second, third, and fourth VAI quartiles to the lowest quartile, the adjusted odds ratios for current asthma risk were 1.15 (0.81, 1.64), 1.29 (0.91, 1.84), and 1.51 (1.01, 2.24), respectively (P for trend .04). The restricted cubic spline regression analysis did not reveal a nonlinear correlation between the VAI and asthma or current asthma. Subgroup analysis revealed a significant interaction effect between age (P for interaction = .03) and diabetes status (P for interaction = .02). Except in the age ≥60 years, Less than high school, normal body mass index subgroup, VAI, and current asthma were positively correlated. A positive relationship between the VAI and asthma incidence was observed. In particular, there was a strong positive correlation between the VAI score and current asthma. According to the subgroup analysis, more attention should be given to individuals aged 40 to 59 years who have diabetes.


Assuntos
Asma , Inquéritos Nutricionais , Humanos , Asma/epidemiologia , Masculino , Estudos Transversais , Feminino , Pessoa de Meia-Idade , Adulto , Obesidade Abdominal/epidemiologia , Obesidade Abdominal/complicações , Incidência , Gordura Intra-Abdominal , Fatores de Risco , Índice de Massa Corporal , Estados Unidos/epidemiologia , Idoso , Adiposidade
8.
Int J Biol Macromol ; 277(Pt 4): 134409, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39097042

RESUMO

Alginate is a linear polysaccharide with a modifiable structure and abundant functional groups, offers immense potential for tailoring diverse alginate-based materials to meet the demands of biomedical applications. Given the advancements in modification techniques, it is significant to analyze and summarize the modification of alginate by physical, chemical and biological methods. These approaches provide plentiful information on the preparation, characterization and application of alginate-based materials. Physical modification generally involves blending and physical crosslinking, while chemical modification relies on chemical reactions, mainly including acylation, sulfation, phosphorylation, carbodiimide coupling, nucleophilic substitution, graft copolymerization, terminal modification, and degradation. Chemical modified alginate contains chemically crosslinked alginate, grafted alginate and oligo-alginate. Biological modification associated with various enzymes to realize the hydrolysis or grafting. These diverse modifications hold great promise in fully harnessing the potential of alginate for its burgeoning biomedical applications in the future. In summary, this review provides a comprehensive discussion and summary of different modification methods applied to improve the properties of alginate while expanding its biomedical potentials.


Assuntos
Alginatos , Materiais Biocompatíveis , Alginatos/química , Materiais Biocompatíveis/química , Humanos , Animais , Hidrólise
9.
Eur Radiol ; 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39214895

RESUMO

OBJECTIVES: This study aimed to evaluate the feasibility, safety, and efficacy of the transjugular mesenteric-caval shunt (TMCS) as a treatment for the cavernous transformation of the portal vein (CTPV) and recurrent variceal bleeding. METHODS: This retrospective case series was conducted with approval from the institutional review board. It involved seven patients diagnosed with CTPV and recurrent variceal bleeding who underwent the TMCS procedure. We analyzed the rate of procedural complications, incidents of rebleeding, stent stenosis, hepatic encephalopathy, and overall survival to assess treatment outcomes. RESULTS: The TMCS was successfully performed in all seven patients without any life-threatening complications. Postoperatively, one patient developed a lung infection and pleural effusion, which resolved with appropriate treatment. Additionally, two patients experienced an increase in total bilirubin levels, but there was no further deterioration in liver function. The median portal pressure gradient significantly decreased from a preoperative value of 27 mmHg (range 20-36 mmHg) to a postoperative value of 6 mmHg (range 4-11 mmHg). A notable improvement was observed in one cirrhotic patient, with liver function progressing from Child-Pugh class B (score 9) to class A (score 6). Over a median follow-up period of 14 months (range 7-18 months), none of the patients encountered rebleeding, stent stenosis, hepatic encephalopathy, or mortality. CONCLUSION: The TMCS appears to be a viable and effective alternative for managing CTPV with recurrent variceal bleeding. Its long-term outcome requires further evaluation. CLINICAL RELEVANCE STATEMENT: TMCS provides a promising treatment for patients with life-threatening CTPV complications when occluded portal vein cannot be recanalized and portal vein recanalization TIPS is not an option. KEY POINTS: Performing TIPS in patients with portal vein cavernoma is complex due to the requirement for recanalization of the occluded portal vein. Creating a mesenteric-caval shunt through a transjugular approach is a feasible technique. Establishing a TMCS provides a means to manage life-threatening complications arising from portal vein cavernoma.

10.
Front Med (Lausanne) ; 11: 1401900, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39076764

RESUMO

Objectives: Nonselective beta blockers (NSBBs) or endoscopic therapies are currently recommended by guidelines for preventing the first variceal bleed in patients with high-risk varices. However, there is a lack of detailed treatment strategies for patients who are intolerant to both NSBBs and endoscopic approaches. Our study aimed to assess the efficacy and safety of variceal embolization as a primary prophylaxis method in cirrhosis patients who are not suitable candidates for NSBBs or endoscopic treatments. Methods: The study included 43 cirrhotic patients with high-risk varices who were candidates for primary prophylaxis against variceal bleeding. These patients underwent variceal embolization at the Xijing Hospital between January 2020 and June 2022. The primary endpoint was the occurrence of bleeding from varices, and the secondary endpoints were the recurrence of varices and the emergence of complications. Results: The procedure of variceal embolization had a success rate of 93.0% (40 out of 43 patients). Over a 2-year follow-up period, the rate of variceal bleeding was 11.6% (5 out of 43 patients), the recurrence rate of varices was 14.0% (6 out of 43 patients), and the rate of severe complications was limited to 2.3% (1 out of 43 patients). Conclusion: Variceal embolization is a viable primary prophylactic intervention for cirrhotic patients who are at risk of variceal bleeding when standard treatments, such as NSBBs or endoscopic therapies, are difficult to perform.

11.
J Virol Methods ; 329: 114971, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38876255

RESUMO

Peste des petis ruminants (PPR) is an acute, highly contagious fatal disease affecting both domestic and wild small ruminants, caused by Morbillivirus caprinae (also known as peste des petis ruminants virus (PPRV)). Herein, a rapid method based on recombinase aided amplification-clustered regularly interspaced short palindromic repeats-Cas12a (RAA-CRISPR Cas12a) to detect PPRV was developed. CRISPR RNAs and RAA primers for PPRV-N (nucleocapsid) and PPRV-M (matrix) fragments were designed. The reaction system was constructed following screening and optimization. Detection could be completed within in 50 minutes at 37°C. Detection of gradient dilutions of plasmids carrying of PPRV N and M gene fragments indicated a minimum limit of detection of 10 copies/µL. There were no cross-reactions with related viruses and all tested lineages of PPRV were detected successfully. The method also showed good repeatability. The detection of clinical samples (previously detected using reverse transcription polymerase chain reaction (RT-PCR)) indicated good consistency between the RAA-CRISPR Cas12a method and RT-PCR. Thus, the RAA-CRISPR Cas12a method for rapid PPRV diagnosis has strong specificity, high sensitivity, and stable repeatability. Moreover, the results can be observed visually under blue or UV light or using lateral flow strips without complex instruments.


Assuntos
Sistemas CRISPR-Cas , Cabras , Peste dos Pequenos Ruminantes , Vírus da Peste dos Pequenos Ruminantes , Sensibilidade e Especificidade , Vírus da Peste dos Pequenos Ruminantes/genética , Vírus da Peste dos Pequenos Ruminantes/isolamento & purificação , Animais , Peste dos Pequenos Ruminantes/diagnóstico , Peste dos Pequenos Ruminantes/virologia , Proteínas do Nucleocapsídeo/genética , Proteínas da Matriz Viral/genética , Doenças das Cabras/diagnóstico , Doenças das Cabras/virologia , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Amplificação de Ácido Nucleico/métodos , RNA Viral/genética , Ovinos , Proteínas de Bactérias , Endodesoxirribonucleases , Proteínas Associadas a CRISPR
12.
Pharmaceuticals (Basel) ; 17(6)2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38931467

RESUMO

Trollius chinensis Bunge (TCB) is a perennial plant of the Ranunculaceae family with medicinal and edible values. It is widely distributed and commonly used in various regions, including Asia, Europe, and North America. The main chemical components of TCB include alkaloids, flavonoids, phenolic acids, and volatile oil compounds. TCB is renowned for its anti-inflammatory, heat-clearing, detoxifying, and eyesight-improving properties. Its dried flowers are commonly used as a traditional Chinese medicine indicated for the treatment of upper respiratory tract infections, chronic tonsillitis, pharyngitis, influenza, and bronchitis. Modern pharmacology has demonstrated the anti-cancer, anti-inflammatory, antihypertensive, and antioxidant effects of TCB. This study presents a comprehensive overview of various aspects of TCB, including herbal textual research, botany, phytochemistry, pharmacology, traditional uses, clinical application, and quality control, aiming to provide new ideas on the scientific application of TCB as well as the integration of modern research with traditional medicinal uses.

13.
Sci Rep ; 14(1): 12621, 2024 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-38824201

RESUMO

Anaplasma and Ehrlichia are tick-borne bacterial pathogens that cause anaplasmoses and ehrlichioses in humans and animals. In this study, we examined the prevalence of Anaplasma and Ehrlichia species in ticks and domesticated animals in Suizhou County, Hubei Province in the central China. We used PCR amplification and DNA sequencing of the 16S rRNA, groEL, and gltA genes to analyze. We collected 1900 ticks, including 1981 Haemaphysalis longicornis and 9 Rhipicephalus microplus, 159 blood samples of goats (n = 152), cattle (n = 4), and dogs (n = 3) from May to August of 2023. PCR products demonstrated that Anaplasma bovis, Anaplasma capra, and an Ehrlichia species were detected in the H. longicornis with the minimum infection rates (MIR) of 1.11%, 1.32%, and 0.05%, respectively; A. bovis, A. capra, and unnamed Anaplasma sp. were detected in goats with an infection rate of 26.31%, 1.31% and 1.97%, respectively. Anaplasma and Ehrlichia species were not detected from cattle, dogs and R. microplus ticks. The genetic differences in the groEL gene sequences of the Anaplasma in the current study were large, whereas the 16S rRNA and gltA gene sequences were less disparate. This study shows that ticks and goats in Suizhou County, Hubei Province carry multiple Anaplasma species and an Ehrlichia species, with relatively higher infection rate of A. bovis in goats. Our study indicates that multiple Anaplasma and Ehrlichia species exist in ticks and goats in the central China with potential to cause human infection.


Assuntos
Anaplasma , Anaplasmose , Animais Domésticos , Ehrlichia , Variação Genética , Cabras , RNA Ribossômico 16S , Animais , Anaplasma/genética , Anaplasma/isolamento & purificação , China/epidemiologia , Ehrlichia/genética , Ehrlichia/isolamento & purificação , Cabras/microbiologia , Cães , Bovinos , Anaplasmose/epidemiologia , Anaplasmose/microbiologia , Prevalência , Animais Domésticos/microbiologia , RNA Ribossômico 16S/genética , Carrapatos/microbiologia , Ehrlichiose/epidemiologia , Ehrlichiose/veterinária , Ehrlichiose/microbiologia , Filogenia
14.
BMC Microbiol ; 24(1): 204, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38851673

RESUMO

BACKGROUND: The Gastrodia elata Bl. is an orchid, and its growth demands the presence of Armillaria species. The strong competitiveness of Armillaria species has always been a concern of major threat to other soil organisms, thus disrupting the equilibrium of soil biodiversity. Introducing other species to where G. elata was cultivated, could possibly alleviate the problems associated with the disequilibrium of soil microenvironment; however, their impacts on the soil microbial communities and the underlying mechanisms remain unclear. To reveal the changes of microbial groups associated with soil chemical properties responding to different cultivation species, the chemical property measurements coupled with the next-generation pyrosequencing analyses were applied with soil samples collected from fallow land, cultivation of G. elata and Phallus impudicus, respectively. RESULTS: The cultivation of G. elata induced significant increases (p < 0.05) in soil pH and NO3-N content compared with fallow land, whereas subsequent cultivation of P. impudicus reversed these G. elata-induced increases and was also found to significantly increase (p < 0.05) the content of soil NH4+-N and AP. The alpha diversities of soil microbial communities were significantly increased (p < 0.01) by cultivation of G. elata and P. impudicus as indicated with Chao1 estimator and Shannon index. The structure and composition of soil microbial communities differed responding to different cultivation species. In particular, the relative abundances of Bacillus, norank_o_Gaiellales, Mortierella and unclassified_k_Fungi were significantly increased (p < 0.05), while the abundances of potentially beneficial genera such as Acidibacter, Acidothermus, Cryptococcus, and Penicillium etc., were significantly decreased (p < 0.05) by cultivation of G. elata. It's interesting to find that cultivation of P. impudicus increased the abundances of these genera that G. elata decreased before, which contributed to the difference of composition and structure. The results of CCA and heatmap indicated that the changes of soil microbial communities had strong correlations with soil nutrients. Specifically, among 28 genera presented, 50% and 42.9% demonstrated significant correlations with soil pH and NO3-N in response to cultivation of G. elata and P. impudicus. CONCLUSIONS: Our findings suggested that the cultivation of P. impudicus might have potential benefits as result of affecting soil microorganisms coupled with changes in soil nutrient profile.


Assuntos
Bactérias , Biodiversidade , Gastrodia , Microbiota , Microbiologia do Solo , Solo , Solo/química , Gastrodia/microbiologia , Gastrodia/química , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Microbiota/genética , Concentração de Íons de Hidrogênio , Nitrogênio/análise , Nitrogênio/metabolismo , Fungos/classificação , Fungos/genética , Fungos/isolamento & purificação , Armillaria/genética , RNA Ribossômico 16S/genética
15.
Microbiol Spectr ; 12(6): e0379623, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38712963

RESUMO

Cyclic GMP-AMP synthase (cGAS) is an important DNA pattern recognition receptor that senses double-stranded DNA derived from invading pathogens or self DNA in cytoplasm, leading to an antiviral interferon response. A tick-borne Bunyavirus, severe fever with thrombocytopenia syndrome virus (SFTSV), is an RNA virus that causes a severe emerging viral hemorrhagic fever in Asia with a high case fatality rate of up to 30%. However, it is unclear whether cGAS interacts with SFTSV infection. In this study, we found that SFTSV infection upregulated cGAS RNA transcription and protein expression, indicating that cGAS is an important innate immune response against SFTSV infection. The mechanism of cGAS recognizing SFTSV is by cGAS interacting with misplaced mitochondrial DNA in the cytoplasm. Depletion of mitochondrial DNA significantly inhibited cGAS activation under SFTSV infection. Strikingly, we found that SFTSV nucleoprotein (N) induced cGAS degradation in a dose-dependent manner. Mechanically, N interacted with the 161-382 domain of cGAS and linked the cGAS to LC3. The cGAS-N-LC3 trimer was targeted to N-induced autophagy, and the cGAS was degraded in autolysosome. Taken together, our study discovered a novel antagonistic mechanism of RNA viruses, SFTSV is able to suppress the cGAS-dependent antiviral innate immune responses through N-hijacking cGAS into N-induced autophagy. Our results indicated that SFTSV N is an important virulence factor of SFTSV in mediating host antiviral immune responses. IMPORTANCE: Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne RNA virus that is widespread in East and Southeast Asian countries with a high fatality rate of up to 30%. Up to now, many cytoplasmic pattern recognition receptors, such as RIG-I, MDA5, and SAFA, have been reported to recognize SFTSV genomic RNA and trigger interferon-dependent antiviral responses. However, current knowledge is not clear whether SFTSV can be recognized by DNA sensor cyclic GMP-AMP synthase (cGAS). Our study demonstrated that cGAS could recognize SFTSV infection via ectopic mitochondrial DNA, and the activated cGAS-stimulator of interferon genes signaling pathway could significantly inhibit SFTSV replication. Importantly, we further uncovered a novel mechanism of SFTSV to inhibit innate immune responses by the degradation of cGAS. cGAS was degraded in N-induced autophagy. Collectively, this study illustrated a novel virulence factor of SFTSV to suppress innate immune responses through autophagy-dependent cGAS degradation.


Assuntos
Imunidade Inata , Nucleoproteínas , Nucleotidiltransferases , Phlebovirus , Phlebovirus/genética , Phlebovirus/imunologia , Nucleotidiltransferases/metabolismo , Nucleotidiltransferases/genética , Humanos , Nucleoproteínas/metabolismo , Nucleoproteínas/genética , Nucleoproteínas/imunologia , Células HEK293 , Febre Grave com Síndrome de Trombocitopenia/virologia , Febre Grave com Síndrome de Trombocitopenia/imunologia , Febre Grave com Síndrome de Trombocitopenia/metabolismo , Autofagia , Animais , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Interferons/metabolismo , Interferons/imunologia , Interferons/genética , Proteínas Virais/metabolismo , Proteínas Virais/genética
16.
Cardiovasc Diagn Ther ; 14(2): 251-263, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38716313

RESUMO

Background: The presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in myocardial autopsy tissues has been observed in certain individuals with coronavirus disease 2019 (COVID-19). However, the duration of cardiac involvement remains uncertain among recovered COVID-19 patients. Our study aims to evaluate the long-term persistence of SARS-CoV-2 within cardiac tissue. Methods: We prospectively and consecutively evaluated the patients undergoing mitral valve replacement (MVR) and left atrial (LA) volume reduction surgery from May 25 to June 10, 2023 at our center, who had been approximately 6 months of recovery after Omicron wave. Patients tested positive for SARS-CoV-2 upon admission were excluded. The surgical LA tissue was collected in RNA preservation solution and stored at -80 ℃ immediately. Then SARS-CoV-2, interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) RNA expression in LA tissues were assessed through thrice-repeated reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analyses. Categorical variables were assessed using the Chi-square or Fisher's exact tests, and continuous variables was analyzed using the Mann-Whitney U test. Results: Nine of 41 patients were enrolled, all of whom tested negative for SARS-CoV-2 upon admission (two antigen and PCR tests). In four of nine patients, SARS-CoV-2 RNA was detected in their LA tissue, indicating viral colonization. Among the four positive cases, the IL-6 and IL-1ß relative expression levels in the LA tissue of one patient were increased approximately 55- and 110-fold, respectively, compared to those of SARS-CoV-2 (-) patients. Increased expression of IL-6 and IL-1ß were observed in the myocardium of this patient. Another patient demonstrated a remarkable 7-fold increase in both IL-6 and IL-1ß expression, surpassing that of SARS-CoV-2 (-) patients. Additionally, no other cardiac inflammation-related diseases or conditions were presented in these two patients. The IL-6 and IL-1ß expression levels of the remaining two patients were not significantly different from those of SARS-CoV-2 (-) patients. The relative expression levels of IL-6 and IL-1ß in cardiac tissues of all SARS-CoV-2 (-) patients were relatively low. Interestingly, despite abnormally elevated levels of IL-6 and IL-1ß within their cardiac tissue, two patients did not show a significant increase in serum IL-6 and IL-1ß levels when compared to other patients. Conclusions: Our research suggests that certain COVID-19-recovered patients have persistent colonization of SARS-CoV-2 in their cardiac tissue, accompanied by a local increase in inflammatory factors.

17.
Artigo em Inglês | MEDLINE | ID: mdl-38759828

RESUMO

BACKGROUND & AIMS: The effect of transjugular intrahepatic portosystemic shunt (TIPS) plus variceal embolization for treating gastric varices (GVs) remains controversial. This nationwide multicenter cohort study aimed to evaluate whether adding variceal embolization to a small diameter (8-mm) TIPS could reduce the rebleeding incidence in patients with different types of GVs. METHODS: This retrospective cohort study involved 629 patients who underwent 8-mm TIPS for gastric varices at 7 medical centers. The primary endpoint was all-cause rebleeding, and the secondary endpoints included overt hepatic encephalopathy (OHE) and all-cause mortality. RESULTS: A total of 629 patients were included. Among them, 429 (68.2%) had gastroesophageal varices type 1 (GOV1), 145 (23.1%) had gastroesophageal varices type 2 (GOV2), and 55 (8.7%) had isolated gastric varices type 1 (IGV1). In the entire cohort, adjunctive embolization reduced rebleeding (6.2% vs 13.6%; P = .005) and OHE (31.0% vs 39.4%; P = .02) compared with TIPS alone. However, no significant differences were found in mortality (12.0% vs 9.7%; P = .42). In patients with GOV2 and IGV1, TIPS plus variceal embolization reduced both rebleeding (GOV2: 7.8% vs 25.1%; P = .01; IGV1: 5.6% vs 30.8%; P = .03) and OHE (GOV2: 31.8% vs 51.5%; P = .008; IGV1: 11.6% vs 38.5%; P = .04). However, in patients with GOV1, adjunctive embolization did not reduce rebleeding (5.9% vs 8.7%; P = .37) or OHE (33.1% vs 35.3%; P = .60). CONCLUSIONS: Compared with TIPS alone, 8-mm TIPS plus variceal embolization reduced rebleeding and OHE in patients with GOV2 and IGV1. These findings suggest that patients with GOV2 and IGV1, rather than GOV1, could benefit from embolization with TIPS.

18.
Heliyon ; 10(7): e28045, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38590863

RESUMO

HD-Zip (Homeodomain-Leucine Zipper) is a family of transcription factors unique to higher plants and plays a vital role in plant growth and development. Increasing research results show that HD-Zip transcription factors are widely involved in many life processes in plants. However, the HD-Zip transcription factor for cannabis, a valuable crop, has not yet been identified. The sequence characteristics, chromosome localization, system evolution, conservative motif, gene structure, and gene expression of the HD-Zip transcription factor in the cannabis genome were systematically studied. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to verify its function. The results showed that cannabis contained 33 HD-Zip gene members. The number of amino acids is 136-849aa, the isoelectric point is 4.54-9.04, and the molecular weight is 23264.32-93147.87Da. Many cis-acting elements are corresponding to hormone and abiotic stress in the HD-Zip family promoter area of cannabis. Sequencing of the transcriptome at 5 tissue sites of hemp, stems, leaves, bracts, and seeds showed similar levels of expression of 33 members of the HD-Zip gene family at 5 tissue sites. Bioinformatics results show that HD-Zip expression is tissue-specific and may be influenced by hormones and environmental factors. This lays a foundation for further research on the gene function of HD-Zip.

19.
Inorg Chem ; 63(18): 8462-8475, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38642052

RESUMO

In recent years, pyclen-based complexes have attracted a great deal of interest as magnetic resonance imaging (MRI) contrast agents (CAs) and luminescent materials, as well as radiopharmaceuticals. Remarkably, gadopiclenol, a Gd(III) bishydrated complex featuring a pyclen-based heptadentate ligand, received approval as a novel contrast agent for clinical MRI application in 2022. To maximize stability and efficiency, two novel chiral pyclen-based chelators and their complexes were developed in this study. Gd-X-PCTA-2 showed significant enhancements in both thermodynamic and kinetic stabilities compared to those of the achiral parent derivative Gd-PCTA. 1H NMRD profiles reveal that both chiral gadolinium complexes (Gd-X-PCTA-1 and Gd-X-PCTA-2) have a higher relaxivity than Gd-PCTA, while variable-temperature 17O NMR studies show that the two inner-sphere water molecules have distinct residence times τMa and τMb. Furthermore, in vivo imaging demonstrates that Gd-X-PCTA-2 enhances the signal in the heart and kidneys of the mice, and the chiral Gd complexes exhibit the ability to distinguish between tumors and normal tissues in a 4T1 mouse model more efficiently than that of the clinical agent gadobutrol. Biodistribution studies show that Gd-PCTA and Gd-X-PCTA-2 are primarily cleared by a renal pathway, with 24 h residues of Gd-X-PCTA-2 in the liver and kidney being lower than those of Gd-PCTA.


Assuntos
Compostos Azabicíclicos , Quelantes , Meios de Contraste , Gadolínio , Imageamento por Ressonância Magnética , Meios de Contraste/química , Animais , Camundongos , Quelantes/química , Quelantes/síntese química , Gadolínio/química , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Estrutura Molecular , Estereoisomerismo , Humanos , Feminino
20.
J Hazard Mater ; 470: 134166, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38554511

RESUMO

UV/peracetic acid (PAA) treatment presents a promising approach for antibiotic removal, but its effects on microbial community and proliferation of antibiotic resistance genes (ARGs) during the subsequent bio-treatment remain unclear. Thus, we evaluated the effects of the UV/PAA on tetracycline (TTC) degradation, followed by introduction of the treated wastewater into the bio-treatment system to monitor changes in ARG expression and biodegradability. Results demonstrated effective TTC elimination by the UV/PAA system, with carbon-centered radicals playing a significant role. Crucially, the UV/PAA system not only eliminated antibacterial activity but also inhibited potential ARG host growth, thereby minimizing the emergence and dissemination of ARGs during subsequent bio-treatment. Additionally, the UV/PAA system efficiently removed multi-antibiotic resistant bacteria and ARGs from the bio-treatment effluent, preventing ARGs from being released into the environment. Hence, we propose a multi-barrier strategy for treating antibiotic-containing wastewater, integrating UV/PAA pre-treatment and post-disinfection with bio-treatment. The inhibition of ARGs transmission by the integrated system was verified through actual soil testing, confirming its effectiveness in preventing ARGs dissemination in the surrounding natural ecosystem. Overall, the UV/PAA treatment system offers a promising solution for tackling ARGs challenges by controlling ARGs proliferation at the source and minimizing their release at the end of the treatment process.


Assuntos
Antibacterianos , Ácido Peracético , Raios Ultravioleta , Águas Residuárias , Antibacterianos/farmacologia , Antibacterianos/química , Ácido Peracético/farmacologia , Tetraciclina/farmacologia , Resistência Microbiana a Medicamentos/genética , Genes Bacterianos/efeitos dos fármacos , Purificação da Água/métodos , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água/toxicidade , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/efeitos da radiação , Desinfecção/métodos , Biodegradação Ambiental
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...