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1.
Cell ; 184(13): 3438-3451.e10, 2021 06 24.
Artículo en Inglés | MEDLINE | ID: mdl-34139177

RESUMEN

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been spreading worldwide, causing a global pandemic. Bat-origin RaTG13 is currently the most phylogenetically related virus. Here we obtained the complex structure of the RaTG13 receptor binding domain (RBD) with human ACE2 (hACE2) and evaluated binding of RaTG13 RBD to 24 additional ACE2 orthologs. By substituting residues in the RaTG13 RBD with their counterparts in the SARS-CoV-2 RBD, we found that residue 501, the major position found in variants of concern (VOCs) 501Y.V1/V2/V3, plays a key role in determining the potential host range of RaTG13. We also found that SARS-CoV-2 could induce strong cross-reactive antibodies to RaTG13 and identified a SARS-CoV-2 monoclonal antibody (mAb), CB6, that could cross-neutralize RaTG13 pseudovirus. These results elucidate the receptor binding and host adaption mechanisms of RaTG13 and emphasize the importance of continuous surveillance of coronaviruses (CoVs) carried by animal reservoirs to prevent another spillover of CoVs.


Asunto(s)
Enzima Convertidora de Angiotensina 2/metabolismo , Sitios de Unión/fisiología , COVID-19/metabolismo , Quirópteros/virología , SARS-CoV-2/patogenicidad , Secuencia de Aminoácidos , Animales , Anticuerpos Monoclonales/inmunología , COVID-19/inmunología , Quirópteros/inmunología , Quirópteros/metabolismo , Especificidad del Huésped/inmunología , Humanos , Filogenia , Unión Proteica/fisiología , Receptores Virales/metabolismo , SARS-CoV-2/inmunología , Alineación de Secuencia
2.
Immunity ; 55(8): 1501-1514.e3, 2022 08 09.
Artículo en Inglés | MEDLINE | ID: mdl-35777362

RESUMEN

SARS-CoV-2 Omicron variant has presented significant challenges to current antibodies and vaccines. Herein, we systematically compared the efficacy of 50 human monoclonal antibodies (mAbs), covering the seven identified epitope classes of the SARS-CoV-2 RBD, against Omicron sub-variants BA.1, BA.1.1, BA.2, and BA.3. Binding and pseudovirus-based neutralizing assays revealed that 37 of the 50 mAbs lost neutralizing activities, whereas the others displayed variably decreased activities against the four Omicron sub-variants. BA.2 was found to be more sensitive to RBD-5 antibodies than the other sub-variants. Furthermore, a quaternary complex structure of BA.1 RBD with three mAbs showing different neutralizing potencies against Omicron provided a basis for understanding the immune evasion of Omicron sub-variants and revealed the lack of G446S mutation accounting for the sensitivity of BA.2 to RBD-5 mAbs. Our results may guide the application of the available mAbs and facilitate the development of universal therapeutic antibodies and vaccines against COVID-19.


Asunto(s)
Anticuerpos Neutralizantes , COVID-19 , Anticuerpos Monoclonales , Anticuerpos Antivirales , Vacunas contra la COVID-19 , Humanos , Glicoproteínas de Membrana , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Proteínas del Envoltorio Viral
3.
EMBO J ; 42(4): e111737, 2023 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-36519268

RESUMEN

Bat-origin RshSTT182 and RshSTT200 coronaviruses (CoV) from Rhinolophus shameli in Southeast Asia (Cambodia) share 92.6% whole-genome identity with SARS-CoV-2 and show identical receptor-binding domains (RBDs). In this study, we determined the structure of the RshSTT182/200 receptor binding domain (RBD) in complex with human angiotensin-converting enzyme 2 (hACE2) and identified the key residues that influence receptor binding. The binding of the RshSTT182/200 RBD to ACE2 orthologs from 39 animal species, including 18 bat species, was used to evaluate its host range. The RshSTT182/200 RBD broadly recognized 21 of 39 ACE2 orthologs, although its binding affinities for the orthologs were weaker than those of the RBD of SARS-CoV-2. Furthermore, RshSTT182 pseudovirus could utilize human, fox, and Rhinolophus affinis ACE2 receptors for cell entry. Moreover, we found that SARS-CoV-2 induces cross-neutralizing antibodies against RshSTT182 pseudovirus. Taken together, these findings indicate that RshSTT182/200 can potentially infect susceptible animals, but requires further evolution to obtain strong interspecies transmission abilities like SARS-CoV-2.


Asunto(s)
Enzima Convertidora de Angiotensina 2 , Betacoronavirus , Quirópteros , Glicoproteína de la Espiga del Coronavirus , Animales , Humanos , Enzima Convertidora de Angiotensina 2/química , Enzima Convertidora de Angiotensina 2/metabolismo , Quirópteros/metabolismo , Quirópteros/virología , Especificidad del Huésped , Unión Proteica , Receptores Virales/química , Receptores Virales/metabolismo , SARS-CoV-2/metabolismo , Betacoronavirus/metabolismo , Betacoronavirus/patogenicidad , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/metabolismo
4.
EMBO J ; 40(16): e107786, 2021 08 16.
Artículo en Inglés | MEDLINE | ID: mdl-34018203

RESUMEN

Pangolins have been suggested as potential reservoir of zoonotic viruses, including SARS-CoV-2 causing the global COVID-19 outbreak. Here, we study the binding of two SARS-CoV-2-like viruses isolated from pangolins, GX/P2V/2017 and GD/1/2019, to human angiotensin-converting enzyme 2 (hACE2), the receptor of SARS-CoV-2. We find that the spike protein receptor-binding domain (RBD) of pangolin CoVs binds to hACE2 as efficiently as the SARS-CoV-2 RBD in vitro. Furthermore, incorporation of pangolin CoV RBDs allows entry of pseudotyped VSV particles into hACE2-expressing cells. A screen for binding of pangolin CoV RBDs to ACE2 orthologs from various species suggests a broader host range than that of SARS-CoV-2. Additionally, cryo-EM structures of GX/P2V/2017 and GD/1/2019 RBDs in complex with hACE2 show their molecular binding in modes similar to SARS-CoV-2 RBD. Introducing the Q498H substitution found in pangolin CoVs into the SARS-CoV-2 RBD expands its binding capacity to ACE2 homologs of mouse, rat, and European hedgehog. These findings suggest that these two pangolin CoVs may infect humans, highlighting the necessity of further surveillance of pangolin CoVs.


Asunto(s)
Enzima Convertidora de Angiotensina 2/metabolismo , Betacoronavirus/fisiología , Pangolines/virología , SARS-CoV-2/fisiología , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/metabolismo , Sustitución de Aminoácidos , Enzima Convertidora de Angiotensina 2/química , Animales , Sitios de Unión , Células HEK293 , Erizos/virología , Especificidad del Huésped , Humanos , Ratones , Modelos Moleculares , Filogenia , Unión Proteica , Conformación Proteica , Ratas , Glicoproteína de la Espiga del Coronavirus/genética , Internalización del Virus
5.
J Org Chem ; 89(2): 835-843, 2024 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-38194354

RESUMEN

A one-pot dehydration cross-coupling reaction between allyl alcohols and sodium sulfinates that provides allyl sulfones in good to excellent yields is presented. Its broad substrate scope includes symmetrical and asymmetrical α,α-diaryl- and α-aryl-substituted allylic alcohols and aryl and alkyl sodium sulfinates. For asymmetrical allylic substrates, the E isomer predominates with examples of excellent stereoselectivity. Control experiments provide the basis for a proposed radical-mediated mechanism. The metal-free procedure applies cheap and commercially available tetrabutylammonium tribromide as the catalyst and H2O as the solvent. Notable features of this simple, efficient, weakly toxic, and environmentally benign strategy include mild and convenient operating conditions and readily accessible starting materials.

6.
Proc Natl Acad Sci U S A ; 118(1)2021 01 05.
Artículo en Inglés | MEDLINE | ID: mdl-33335073

RESUMEN

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as a major threat to global health. Although varied SARS-CoV-2-related coronaviruses have been isolated from bats and SARS-CoV-2 may infect bat, the structural basis for SARS-CoV-2 to utilize the human receptor counterpart bat angiotensin-converting enzyme 2 (bACE2) for virus infection remains less understood. Here, we report that the SARS-CoV-2 spike protein receptor binding domain (RBD) could bind to bACE2 from Rhinolophus macrotis (bACE2-Rm) with substantially lower affinity compared with that to the human ACE2 (hACE2), and its infectivity to host cells expressing bACE2-Rm was confirmed with pseudotyped SARS-CoV-2 virus and SARS-CoV-2 wild virus. The structure of the SARS-CoV-2 RBD with the bACE2-Rm complex was determined, revealing a binding mode similar to that of hACE2. The analysis of binding details between SARS-CoV-2 RBD and bACE2-Rm revealed that the interacting network involving Y41 and E42 of bACE2-Rm showed substantial differences with that to hACE2. Bats have extensive species diversity and the residues for RBD binding in bACE2 receptor varied substantially among different bat species. Notably, the Y41H mutant, which exists in many bats, attenuates the binding capacity of bACE2-Rm, indicating the central roles of Y41 in the interaction network. These findings would benefit our understanding of the potential infection of SARS-CoV-2 in varied species of bats.


Asunto(s)
Enzima Convertidora de Angiotensina 2 , COVID-19/genética , COVID-19/metabolismo , Quirópteros , SARS-CoV-2 , Sustitución de Aminoácidos , Enzima Convertidora de Angiotensina 2/química , Enzima Convertidora de Angiotensina 2/genética , Enzima Convertidora de Angiotensina 2/metabolismo , Animales , COVID-19/epidemiología , Quirópteros/genética , Quirópteros/metabolismo , Quirópteros/virología , Células HEK293 , Humanos , Mutación Missense , Pandemias , Unión Proteica , Dominios Proteicos , SARS-CoV-2/química , SARS-CoV-2/genética , SARS-CoV-2/metabolismo , Especificidad de la Especie
7.
Fa Yi Xue Za Zhi ; 40(1): 43-49, 2024 Feb 25.
Artículo en Inglés, Zh | MEDLINE | ID: mdl-38500460

RESUMEN

OBJECTIVES: To analyze the high risk factors of obstetric brachial plexus palsy (OBPP), and to explore how to evaluate the relationship between fault medical behavior and OBPP in the process of medical damage forensic identification. METHODS: A retrospective analysis was carried out on 25 cases of medical damage liability disputes related to OBPP from 2017 to 2021 in Beijing Fayuan Judicial Science Evidence Appraisal Center. The shortcomings of hospitals in birth weight assessment, delivery mode selection, labor process observation and shoulder dystocia management, and the causal relationship between them and the damage consequences of the children were summarized. RESULTS: Fault medical behavior was assessed as the primary cause in 2 cases, equal cause in 10 cases, secondary cause in 8 cases, minor cause in 1 case, no causal relationship in 1 case, and unclear causal force in 3 cases. CONCLUSIONS: In the process of forensic identification of OBPP, whether medical behaviors fulfill diagnosis and treatment obligations should be objectively analyzed from the aspects of prenatal evaluation, delivery mode notification, standardized use of oxytocin, standard operation of shoulder dystocia, etc. Meanwhile, it is necessary to fully consider the objective risk of different risk factors and the difficulty of injury prevention, and comprehensively evaluate the causal force of fault medical behavior in the damage consequences.


Asunto(s)
Neuropatías del Plexo Braquial , Plexo Braquial , Parálisis Obstétrica , Distocia de Hombros , Embarazo , Femenino , Niño , Humanos , Estudios Retrospectivos , Parálisis Obstétrica/etiología , Neuropatías del Plexo Braquial/etiología , Neuropatías del Plexo Braquial/complicaciones , Factores de Riesgo , Parálisis/complicaciones
8.
J Opt Soc Am A Opt Image Sci Vis ; 40(7): 1359-1371, 2023 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-37706737

RESUMEN

Fluorescence molecular tomography (FMT) is a preclinical optical tomographic imaging technique that can trace various physiological and pathological processes at the cellular or even molecular level. Reducing the number of FMT projection views can improve the data acquisition speed, which is significant in applications such as dynamic problems. However, a reduction in the number of projection views will dramatically aggravate the ill-posedness of the FMT inverse problem and lead to significant degradation of the reconstructed images. To deal with this problem, we have proposed a deep-learning-based reconstruction method for sparse-view FMT that only uses four perpendicular projection views and divides the image reconstruction into two stages: image restoration and inverse Radon transform. In the first stage, the projection views of the surface fluorescence are restored to eliminate the blur derived from photon diffusion through a fully convolutional neural network. In the second stage, another convolutional neural network is used to implement the inverse Radon transform between the restored projections from the first stage and the reconstructed transverse slices. Numerical simulation and phantom and mouse experiments are carried out. The results show that the proposed method can effectively deal with the image reconstruction problem of sparse-view FMT.

9.
J Opt Soc Am A Opt Image Sci Vis ; 40(1): 96-107, 2023 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-36607083

RESUMEN

Optical macroscopic imaging techniques have shown great significance in the investigations of biomedical issues by revealing structural or functional information of living bodies through the detection of visible or near-infrared light derived from different mechanisms. However, optical macroscopic imaging techniques suffer from poor spatial resolution due to photon diffusion in biological tissues. This dramatically restricts the application of optical imaging techniques in numerous situations. In this paper, an image restoration method based on deep learning is proposed to eliminate the blur caused by photon diffusion in optical macroscopic imaging. Two blurry images captured at orthogonal angles are used as the additional information to ensure the uniqueness of the solution and restore the small targets at deep locations. Then a fully convolutional neural network is proposed to accomplish the image restoration, which consists of three sectors: V-shaped network for central view, V-shaped network for side views, and synthetical path. The two V-shaped networks are concatenated to the synthetical path with skip connections to generate the output image. Simulations as well as phantom and mouse experiments are implemented. Results indicate the effectiveness of the proposed method.


Asunto(s)
Aprendizaje Profundo , Animales , Ratones , Procesamiento de Imagen Asistido por Computador/métodos , Redes Neurales de la Computación , Fantasmas de Imagen , Imagen Óptica
10.
Ecotoxicol Environ Saf ; 255: 114770, 2023 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-36931089

RESUMEN

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) have been demonstrated to be neurotoxic. OBJECTIVES: To summarize the existing epidemiological studies to quantify the effects of PAHs exposure on child neurodevelopment and adult emotional disorders. DATA SOURCES AND STUDY ELIGIBILITY CRITERIA: We conducted a systematic literature search for studies of child neurodevelopment and adult emotional disorders published in English up to April 2022 in the databases of PubMed, Web of Science and Embase using combinations of MeSH terms and Entry terms, and the articles were filtered out according to data availability. A variety of common PAHs were included in the meta-analysis: 1-hydroxynaphthalene, 2-hydroxynaphthalene, 2-hydroxyfluorene, 3-hydroxyfluorene, 9-hydroxyfluorene, 1-hydroxyphenanthrene, 2-hydroxyphenanthrene, 3-hydroxyphenanthrene, 4-hydroxyphenanthrene, 9-hydroxyphenanthrene, 1-hydroxypyrene and benzoapyrene (BaP). STUDY EVALUATION AND SYNTHESIS METHODS: We extracted the content of each article, summarized its design characteristics and performed quality evaluation. We combined the odds ratio (OR) available in various studies to obtain the risk of PAHs exposure and adaptive, language, social, attention, motor skills and child depression/anxiety in children ≤ 15 years old. In addition, we also conducted a meta-analysis on the relationship between PAHs exposure and the risk of depression in adults. RESULTS: We included a total of 16 epidemiological studies (4 cross-sectional studies and 12 cohort studies). The sample size of all included studies ranged from 110 to 9625. Prenatal exposure to PAHs was found to be associated with increased risk of social behavior (OR = 1.60, 95% CI: 1.00-2.54), attention (OR = 2.99, 95% CI: 1.48-6.02), motor skill problems (OR = 1.91, 95% CI: 1.27-2.86) and any adverse neurodevelopmental outcome in children (OR = 2.10, 95% CI: 1.69-2.62). In addition, we found that PAHs exposure could increase the risk of adult depression, with 2-hydroxyfluorene exposure showing the highest combined OR (OR = 1.48, 95% CI: 1.10-2.00). CONCLUSIONS: The results suggested that PAHs exposure are associated with increased risk of child neurodevelopment and adult depression. The neurotoxic effects of PAHs exposure in human being should be paid more attention. The results suggested that PAHs exposure are associated with increased risk of child neurodevelopment and adult depression. The neurotoxic effects of PAHs exposure in human being should be paid more attention. Steps should be taken to enhance the biomonitoring of PAHs and to reduce the exposure in general population.


Asunto(s)
Hidrocarburos Policíclicos Aromáticos , Humanos , Adulto , Niño , Adolescente , Hidrocarburos Policíclicos Aromáticos/toxicidad , Hidrocarburos Policíclicos Aromáticos/análisis , Estudios Transversales , Estudios de Cohortes , Conducta Social
11.
J Med Virol ; 94(5): 2108-2125, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35032057

RESUMEN

Variants of SARS-CoV-2 continue to emerge, posing great challenges in outbreak prevention and control. It is important to understand in advance the impact of possible variants of concern (VOCs) on infectivity and antigenicity. Here, we constructed one or more of the 15 high-frequency naturally occurring amino acid changes in the receptor-binding domain (RBD) of Alpha, Beta, and Gamma variants. A single mutant of A520S, V367F, and S494P in the above three VOCs enhanced infectivity in ACE2-overexpressing 293T cells of different species, LLC-MK2 and Vero cells. Aggregation of multiple RBD mutations significantly reduces the infectivity of the possible three VOCs. Regarding neutralization, it is noteworthy that E484K, N501Y, K417N, and N439K predispose to monoclonal antibodies (mAbs) protection failure in the 15 high-frequency mutations. Most importantly, almost all possible VOCs (single RBD mutation or aggregation of multiple mutations) showed no more than a fourfold decrease in neutralizing activity with convalescent sera, vaccine sera, and immune sera of guinea pigs with different immunogens, and no significant antigenic drift was formed. In conclusion, our pseudovirus results could reduce the concern that the aggregation of multiple high-frequency mutations in the RBD of the spike protein of the three VOCs would lead to severe antigenic drift, and this would provide value for vaccine development strategies.


Asunto(s)
COVID-19 , SARS-CoV-2 , Animales , Anticuerpos Neutralizantes , Deriva y Cambio Antigénico , COVID-19/terapia , Chlorocebus aethiops , Cobayas , Humanos , Inmunización Pasiva , Mutación , SARS-CoV-2/genética , Glicoproteína de la Espiga del Coronavirus , Células Vero , Sueroterapia para COVID-19
12.
Mol Cell Probes ; 61: 101790, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-35051595

RESUMEN

PCV2 is one of the most economically important viral agents in swine worldwide. Recently, PCV3 has been frequently reported, and the co-infection of PCV2 and PCV3 is common in China. In order to explore the distribution, epidemiology and genetic diversity of PCV2 and PCV3, a total of 1,760 clinical tissue samples were randomly collected from 18 different regions in Henan province of China from October 2018 to September 2019 and screened for the presence of PCV2 and PCV3 by a duplex real-time PCR assay. The results showed that the positive rates of PCV2 and PCV3 were 72.90% and 5.17% respectively, and the co-infection rate of the two viruses was 3.64%. PCV2 and PCV3 are prevalent all year round. The prevalence of PCV2 in diseased pigs was 83.98%, higher than that in slaughterhouse pigs, while the prevalence of PCV3 in diseased pigs was 2.16%, slightly lower than that in slaughterhouse pigs. Furthermore, the complete genomes of 14 PCV2 and 3 PCV3 strains were obtained, among which 1 belonged to PCV2a, 5 belonged to PCV2b and 8 belonged to PCV2d. A new variant strain (XX2) might escape the host immune system. The phylogenetic analysis of PCV3 showed high nucleotide identity (>98%) between sequences obtained in this study and reference sequences. The results of this study might enrich the epidemiological data of PCV2 and PCV3 in Henan province and provide reference information for the comprehensive prevention and control of PCVAD.


Asunto(s)
Infecciones por Circoviridae , Circovirus , Coinfección , Enfermedades de los Porcinos , Animales , China/epidemiología , Infecciones por Circoviridae/epidemiología , Infecciones por Circoviridae/veterinaria , Circovirus/genética , Genotipo , Filogenia , Porcinos , Enfermedades de los Porcinos/epidemiología
14.
Hereditas ; 156: 14, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31057347

RESUMEN

BACKGROUND: Grapevine is an important fruit crop grown worldwide, and its cultivars are mostly derived from the European species Vitis vinifera, which has genes for high fruit quality and adaptation to a wide variety of climatic conditions. Disease resistance varies substantially across grapevine species; however, the molecular mechanisms underlying such variation remain uncharacterized. RESULTS: The anatomical structure and disease symptoms of grapevine leaves were analyzed for two grapevine species, and the critical period of resistance of grapevine to pathogenic bacteria was determined to be 12 h post inoculation (hpi). Differentially expressed genes (DEGs) were identified from transcriptome analysis of leaf samples obtained at 12 and 36 hpi, and the transcripts in four pathways (cell wall genes, LRR receptor-like genes, WRKY genes, and pathogenesis-related (PR) genes) were classified into four co-expression groups by using weighted correlation network analysis (WGCNA). The gene VdWRKY53, showing the highest transcript level, was introduced into Arabidopsis plants by using a vector containing the CaMV35S promoter. These procedures allowed identifying the key genes contributing to differences in disease resistance between a strongly resistant accession of a wild grapevine species Vitis davidii (VID) and a susceptible cultivar of V. vinifera, 'Manicure Finger' (VIV). Vitis davidii, but not VIV, showed a typical hypersensitive response after infection with a fungal pathogen (Coniella diplodiella) causing white rot disease. Further, 20 defense-related genes were identified, and their differential expression between the two grapevine species was confirmed using quantitative real-time PCR analysis. VdWRKY53, showing the highest transcript level, was selected for functional analysis and therefore over-expressed in Arabidopsis under the control of the CaMV35S promoter. The transgenic plants showed enhanced resistance to C. diplodiella and to two other pathogens, Pseudomonas syringae pv. tomato DC3000 and Golovinomyces cichoracearum. CONCLUSION: The consistency of the results in VID and transgenic Arabidopsis indicated that VdWRKY53 might be involved in the activation of defense-related genes that enhance the resistance of these plants to pathogens. Thus, the over-expression of VdWRKY53 in transgenic grapevines might improve their resistance to pathogens.


Asunto(s)
Arabidopsis/genética , Proteínas de Unión al ADN/genética , Resistencia a la Enfermedad/genética , Expresión Génica Ectópica , Interacciones Huésped-Patógeno/genética , Proteínas de Plantas/genética , Vitis/genética , Clonación Molecular , Biología Computacional/métodos , Regulación de la Expresión Génica de las Plantas , Ontología de Genes , Anotación de Secuencia Molecular , Fenotipo , Filogenia , Enfermedades de las Plantas/genética , Hojas de la Planta/genética , Plantas Modificadas Genéticamente , Análisis de Secuencia de ARN
15.
J Cell Biochem ; 119(7): 5373-5381, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29345340

RESUMEN

Berberine (BBR) is an isoquinoline alkaloid derived from various medicinal herbs. Previous studies have suggested that BBR exerts antimicrobial, antitumor, and antidiabetic effects and can be used to treat Helicobacter pylori-induced chronic gastritis. However, the exact mechanism by which BBR inhibits H. pylori infection is not fully understood. We investigated the anti-inflammatory properties and potential mechanism of BBR in H. pylori-infected mice with chronic gastritis. We found that BBR can suppress the expression of pro-inflammatory genes IL-6, TGF-ß, and IL-1ß and upregulate anti-inflammatory gene IL-10 expression in the mucosa and RAW 264.7 macrophages. Exposure to BBR also reduced the expression and accumulation of IL-17 in the mucosa and CD4+ T cells activated by anti-CD3 and anti-CD28, and it decreased the frequency of IL-17-producing CD4+ T cells. B cell-activating factor (BAFF) production was inhibited by BBR and by cultured dendritic and CD4+ T cells. Furthermore, we demonstrated that BAFF can trigger the Th17 response by promoting the production of pro-Th17 cytokines IL-6, TGF-ß, and IL-1ß, which are strongly associated with the anti-inflammatory role of BBR in chronic gastritis caused by H. pylori. In conclusion, we determined that BBR has anti-inflammatory effects on H. pylori-induced chronic gastritis by attenuating the BAFF-triggered Th17 response.


Asunto(s)
Antiinflamatorios/farmacología , Factor Activador de Células B/metabolismo , Berberina/farmacología , Gastritis/tratamiento farmacológico , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori/efectos de los fármacos , Células Th17/inmunología , Animales , Factor Activador de Células B/genética , Células Cultivadas , Enfermedad Crónica , Citocinas/metabolismo , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/inmunología , Mucosa Gástrica/microbiología , Gastritis/inmunología , Gastritis/microbiología , Infecciones por Helicobacter/inmunología , Infecciones por Helicobacter/microbiología , Interleucina-17/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Macrófagos/microbiología , Masculino , Ratones , Ratones Endogámicos C57BL , Células Th17/efectos de los fármacos , Células Th17/microbiología
16.
Artículo en Inglés | MEDLINE | ID: mdl-36673714

RESUMEN

The green production behavior of pig farmers is the basis for high-quality development in animal husbandry. In order to solve the problem of poor green production behaviors in small- and medium-sized pig farmers, it is necessary to analyze the influencing factors and how they interact with each other. The Rational Peasant Theory and Prospect Theory were used in this paper to analyze the occurrence motivation of the green production behaviors of small- and medium-sized pig farmers. The Logit model and the ISM analysis method were used to test the influencing factors and their mechanisms. This was conducted using data from a study of 747 small- and medium-sized pig farmers in Henan Province. The results show that the green production behaviors of small- and medium-sized pig farmers are motivated by internal expected return, affected by the monitoring pressure from external stakeholders and limited by their own resource capacity; the influencing factors of different green production behaviors are different, and there are more influencing factors of scientific disease control, standardized management and waste recycling than of rational feeding. The following shows how the influencing factors on pig farmers' green production behavior interact with one another: level of education → external pressure, farming conditions and operating characteristics → cognition of return → green production behavior (i.e., cognition of return is the direct factor; external pressure, farming conditions and operating characteristics are indirect factors; and level of education is the underlying factor). Some measures should be implemented to promote green production behaviors, such as the continuation of the support for green production, the strengthening of supervision and publicity, the increasing of investment in technology and equipment, and the improving of the green production literacy of farmers. In conclusion, this paper deepens the understanding of the mechanism of green production behaviors of small- and medium-sized pig farmers, and provides the theoretical basis and concrete measures for the government and for pig farmers.


Asunto(s)
Agricultura , Agricultores , Porcinos , Animales , Humanos , Encuestas y Cuestionarios , Crianza de Animales Domésticos/métodos , Granjas , China
17.
Sci Total Environ ; 863: 160985, 2023 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-36535484

RESUMEN

Occupational exposure and non-occupational exposure to excessive levels of manganese (Mn) result in neuronal cell damage through mitochondrial dysfunction. The functional integrity of mitochondria is maintained by mitophagy and mitochondrial biogenesis. Although Mn-induced S-nitrosylation of PTEN-induced putative kinase 1 (PINK1) can interfere with mitophagy, its effect on mitochondrial biogenesis remains unclear. In this study, we established a rat model of Mn poisoning or "manganism" to examine the relationship between PINK1 S-nitrosylation and impairment of mitochondrial biogenesis, and found that treatment with 60 mg/kg Mn induced marked neurobehavioral abnormalities in rats and significantly increased the S-nitrosylation level of PINK1. We also found that the nuclear-encoded peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PPARGC1A)-mediated mitochondrial biogenesis was significantly upregulated in rats treated with 15 and 30 mg/kg Mn, and downregulated in rats treated with 60 mg/kg Mn. We further investigated the role of S-nitrosylated PINK1 and its molecular mechanism in the high-dose Mn-mediated impairment of mitochondrial biogenesis in primary cultured neurons treated with the nitric oxide synthase 2 (NOS2) inhibitor 1400 W. Our results revealed that the PPARGC1A-mediated mitochondrial biogenesis was upregulated in neurons treated with 100 µM, but downregulated in neurons treated with 200 µM Mn, which was similar to the in vivo results. However, treatment with 1400W could effectively prevent the 200 µM Mn-mediated impairment of mitochondrial biogenesis by suppressing nitric oxide (NO)-mediated PINK1 S-nitrosylation and rescuing Parkin-interacting substrate (PARIS, ZNF746) degradation, thereby upregulating mitochondrial biogenesis via PPARGC1A. These findings demonstrated that S-nitrosylation of PINK1 and subsequent prevention of ZNF746 degradation were crucial signaling processes involved in the Mn-mediated impairment of mitochondrial biogenesis, which might serve as an underlying mechanism of Mn-induced neurotoxicity. Furthermore, this study provided a reliable target for the prevention and treatment of manganism.


Asunto(s)
Manganeso , Proteínas Quinasas , Animales , Ratas , Manganeso/metabolismo , Neuronas/metabolismo , Biogénesis de Organelos , Proteínas Quinasas/metabolismo , Proteínas Represoras/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo
18.
Sci Total Environ ; 887: 164124, 2023 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-37182777

RESUMEN

Overexposure to manganese (Mn) is conducive to neurodegenerative diseases and neuronal injury. Persistent activation of the integrated stress response (ISR) has a substantial impact on the etiology of neurodegenerative disorders by interfering with intracellular homeostasis. Nevertheless, the precise mechanism through which ISR engages in Mn-related neurotoxicity remains unclear. Sirtuin 1 (SIRT1), a typical NAD+-dependent protein deacetylase, which is known to participate in Mn-induced neuronal damage. Therefore, the aim of our study was to clarify how SIRT1 regulates persistent ISR activation in mouse hippocampal neuronal cells (HT-22 cells) exposed to various concentrations of Mn. We discovered that persistent ISR activation was engaged in Mn-triggered mitochondrial and exogenous apoptotic signaling pathways, which was attributed to the excessive phosphorylation of eukaryotic translation initiation factor 2α (eIF2α). Growth arrest and DNA damage-inducible protein 34 (GADD34) is known to be responsible for down-regulating the phosphorylation of eIF2α. However, Mn promoted GADD34 protein expression and its acetylation level. We further investigated the effect of SIRT1 on the acetylation of GADD34 by overexpressing and silencing SIRT1. We discovered that SIRT1 activation significantly declined the acetylation level of GADD34, thus alleviating persistent ISR activation-mediated neuronal apoptosis in HT-22 cells-treated with Mn. In summary, these results suggested that Mn induced persistent activation of the ISR by inhibition of SIRT1 on deacetylation of GADD34.


Asunto(s)
Manganeso , Sirtuina 1 , Ratones , Animales , Sirtuina 1/metabolismo , Manganeso/farmacología , Fosforilación , Proteínas/metabolismo , Transducción de Señal
19.
SSM Popul Health ; 24: 101542, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37954014

RESUMEN

Background: Shift work is a potential risk factor for women's reproductive health. Evidence suggests that shift work is associated with menstrual disorders, reproductive disturbances, and adverse pregnancy outcomes. However, previous studies did not systematically examine the results of menstrual irregularities, dysmenorrhea, and early menopause at the same time. Objective: To determine the relationship between shift work and women's menstrual characteristics (e.g., irregular menstruation, dysmenorrhea, and early menopause). Methods: Four databases (PubMed, Embase, Cochrane, and Web of Science) were searched up to December 2022. The study characteristics and risk assessment values of the literature were extracted from 21 studies that met the criteria. Odds ratios (ORs), relative risks (RRs), hazard ratios (HRs), and 95% confidence intervals (CIs) were calculated to assess the relationship between shift work exposure and menstruation. The included studies were evaluated for heterogeneity, publication bias, sensitivity analysis, and subgroup analysis. Results: A total of 21 studies with 195,538 female participants, including 16 cross-sectional studies and 5 cohort studies, were included in this meta-analysis. According to the quality evaluation, the included research had high methodological quality. The overall ORs of shift work for the likelihood of irregular menstruation and dysmenorrhea were 1.30 (95% CI, 1.23-1.36) (I2 = 41.9%, P < 0.05) and 1.35 (95% CI, 1.04-1.75) (I2 = 73.0%, P < 0.05), respectively. There was a significant positive association between shift work and the risk of early menopause (HR = 1.09, 95% CI, 1.04-1.14), without significant heterogeneity (I2 = 0.0%, P > 0.05). Conclusions: This meta-analysis indicated that shift workers have significantly higher odds of menstrual disorders, dysmenorrhea, and early menopause. This study focuses on female reproductive health and has broad implications for adjusting optimal working hours and shift schedules for female workers.

20.
Artículo en Inglés | MEDLINE | ID: mdl-35805258

RESUMEN

Given the rural revitalization strategy in the new era, agricultural development is faced with the dual constraints of resources and the environment. Promoting the green development of agriculture is one of the important missions to solve major social issues in the new era. The implementation goal of the carbon emission trading system is to achieve a win-win situation between carbon emission reduction and green development. To evaluate the effectiveness of the carbon emission trading system on agricultural enterprises, this paper uses a double-difference model to analyze the policy effect and mechanism research path of the impact of the carbon emission trading system on the total factor productivity of agricultural enterprises. The results based on the panel data of listed agricultural companies from 2010 to 2020 show that (1) carbon emission trading rights have significantly improved the total factor productivity of agricultural enterprises; (2) green innovation in carbon emission trading rights have an impact on the total factor productivity of agricultural enterprises; and (3) heterogeneity analysis shows that the effect of carbon emission trading rights on the total factor productivity of agricultural enterprises mainly exists in large-scale, nonstate-owned, high-debt enterprises, enterprises in the eastern region, and enterprises with government subsidies. Therefore, in the future, China should continue to implement the current carbon emission trading rights system in air pollution control, and at the same time, it needs to be supplemented by government intervention and other means for long-term governance. In conclusion, the study provides a reference value for promoting the realization of the long-term goal of "low carbon" and "high quality" green development of agricultural economy and for making reasonable and effective behavioral decisions for the survival and development of enterprises.


Asunto(s)
Agricultura , Carbono , Carbono/análisis , China , Conservación de los Recursos Naturales , Eficiencia , Políticas
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