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1.
Artigo em Inglês | MEDLINE | ID: mdl-39018792

RESUMO

Inhabiting some of the world's most inhospitable climatic regions, the Sunite Mongolian sheep generates average temperatures as low as 4.3 °C and a minimum temperature of -38.8 °C; in these environments, they make essential cold adaptations. In this regard, scapular fat tissues from Mongolian sheep were collected both in winter and summer for transcriptomic and proteomic analyses to identify genes related to adaptive thermogenesis. In the transcriptome analysis, 588 differentially expressed genes were identified to participate in smooth muscle activity and fat metabolism, as well as in nutrient regulation. There were 343 upregulated and 245 downregulated genes. GO and KEGG pathway analyses on these genes revealed their participation in regulating smooth muscle activity, metabolism of fats, and nutrients. Proteomic analysis showed the differential expression of 925 proteins: among them, there are 432 up- and 493 down-expressed proteins. These proteins are mainly involved in oxidative phosphorylation, respiratory chain complex assembly, and ATP production by electron transport. Furthermore, using both sets at a more detailed level of analysis revealed over-representation in gene ontology categories related to hormone signaling, metabolism of lipids, the pentose phosphate pathway, the TCA cycle, and especially the process of oxidative phosphorylation. The identified essential genes and proteins were further validated by quantitative real-time polymerase chain reaction and Western blotting, respectively; key metabolic network constriction was constructed. The present study emphasized the critical role of lipid turnover in scapular fat for thermogenic adaptation in Sunite sheep.

2.
Molecules ; 29(13)2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38999084

RESUMO

Sensitively detecting hazardous and suspected bioaerosols is crucial for safeguarding public health. The potential impact of pollen on identifying bacterial species through fluorescence spectra should not be overlooked. Before the analysis, the spectrum underwent preprocessing steps, including normalization, multivariate scattering correction, and Savitzky-Golay smoothing. Additionally, the spectrum was transformed using difference, standard normal variable, and fast Fourier transform techniques. A random forest algorithm was employed for the classification and identification of 31 different types of samples. The fast Fourier transform improved the classification accuracy of the sample excitation-emission matrix fluorescence spectrum data by 9.2%, resulting in an accuracy of 89.24%. The harmful substances, including Staphylococcus aureus, ricin, beta-bungarotoxin, and Staphylococcal enterotoxin B, were clearly distinguished. The spectral data transformation and classification algorithm effectively eliminated the interference of pollen on other components. Furthermore, a classification and recognition model based on spectral feature transformation was established, demonstrating excellent application potential in detecting hazardous substances and protecting public health. This study provided a solid foundation for the application of rapid detection methods for harmful bioaerosols.


Assuntos
Algoritmos , Pólen , Espectrometria de Fluorescência , Staphylococcus aureus , Pólen/química , Espectrometria de Fluorescência/métodos , Staphylococcus aureus/classificação , Staphylococcus aureus/isolamento & purificação , Substâncias Perigosas/análise , Substâncias Perigosas/classificação , Enterotoxinas/análise , Ricina/análise , Aerossóis/análise , Análise de Fourier
3.
Insects ; 15(6)2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38921132

RESUMO

The invasive pest, Bactrocera tsuneonis (Miyake), has become a significant threat to China's citrus industry. Predicting the area of potentially suitable habitats for B. tsuneonis is essential for optimizing pest control strategies that mitigate its impact on the citrus industry. Here, existing distribution data for B. tsuneonis, as well as current climate data and projections for four future periods (2021-2040, 2041-2060, 2061-2080, and 2081-2100) from the Coupled Model Intercomparison Project Phase 6 (CMIP6) were obtained. The distribution of B. tsuneonis under current and different climate change scenarios in China was predicted using the optimized MaxEnt model, ArcGIS, and the ENMeval data package. Model accuracy was assessed using ROC curves, and the primary environmental factors influencing the distribution of the pest were identified based on the percent contribution. When the regularization multiplier (RM) was set to 1.5 and the feature combination (FC) was set to LQH, a model with lower complexity was obtained. Under these parameter settings, the mean training AUC was 0.9916, and the mean testing AUC was 0.9854, indicating high predictive performance. The most influential environmental variables limiting the distribution of B. tsuneonis were the Precipitation of Warmest Quarter (Bio18) and Temperature Seasonality (standard deviation ×100) (Bio4). Under current climatic conditions, potentially suitable habitat for B. tsuneonis in China covered an area of 215.9 × 104 km2, accounting for 22.49% of the country's land area. Potentially suitable habitat was primarily concentrated in Central China, South China, and East China. However, under future climatic projections, the area of suitable habitat for B. tsuneonis exhibited varying degrees of expansion. Furthermore, the centroid of the total suitable habitat for this pest gradually shifted westward and northward. These findings suggest that B. tsuneonis will spread to northern and western regions of China under future climate changes. The results of our study indicate that climate change will have a major effect on the invasion of B. tsuneonis and have implications for the development of strategies to control the spread of B. tsuneonis in China.

4.
Sci Rep ; 14(1): 10576, 2024 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-38719947

RESUMO

Capsaicin derivatives with thiourea structure (CDTS) is highly noteworthy owing to its higher analgesic potency in rodent models and higher agonism in vitro. However, the direct synthesis of CDTS remains t one or more shortcomings. In this study, we present reported a green, facile, and practical synthetic method of capsaicin derivatives with thiourea structure is developed by using an automated synthetic system, leading to a series of capsaicin derivatives with various electronic properties and functionalities in good to excellent yields.


Assuntos
Capsaicina , Tioureia , Tioureia/química , Capsaicina/química , Química Verde/métodos , Estrutura Molecular , Animais
5.
Bioresour Technol ; 400: 130683, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38599352

RESUMO

The productivity and efficiency of two-chamber microbial electrolysis cell and anaerobic digestion integrated system (MEC-AD) were promoted by a complex of anaerobic granular sludge and iron oxides (Fe-AnGS) as inoculum. Results showed that MEC-AD with Fe-AnGS achieved biogas upgrading with a 23%-29% increase in the energy recovery rate of external circuit current and a 26%-31% decrease in volatile fatty acids. The energy recovery rate of MEC-AD remained at 52%-57%, indicating a stable operation performance. The selectively enriched methanogens and electroactive bacteria resulted in dominant hydrogenotrophic and acetoclastic methanogenesis in the cathode and anode chambers. Mechanistic analysis revealed that MEC-AD with Fe-AnGS led to specifically upregulated enzymes related to energy metabolism and electron transfer. Fe-AnGS as inoculum could improve the long-term operation performance of MEC-AD. Consequently, this study provides an efficient strategy for biogas upgrading in MEC-AD.


Assuntos
Biocombustíveis , Eletrólise , Metano , Anaerobiose , Metano/metabolismo , Ácidos Graxos Voláteis/metabolismo , Esgotos/microbiologia , Fontes de Energia Bioelétrica/microbiologia , Reatores Biológicos , Eletrodos , Bactérias/metabolismo
6.
Org Lett ; 26(17): 3569-3574, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38648520

RESUMO

The first catalytic enantioselective construction of chiral THIQUINOL and its derivatives has been accomplished through a chiral phosphoric-acid-catalyzed direct aza-Friedel-Crafts reaction of 3,4-dihydroisoquinolines with 2-naphthols/anthracen-2-ols/phenanthren-9-ol. This method offers a powerful and straightforward synthetic route toward chiral THIQUINOL derivatives with good to excellent yields and enantioselectivities. These structural motifs are crucial chiral components for further transformations into established or potential chiral ligands and catalysis.

7.
Eur J Med Chem ; 271: 116442, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38685143

RESUMO

The pandemic and tremendous impact of severe acute respiratory syndrome coronavirus 2 alert us, despite great achievements in prevention and control of infectious diseases, we still lack universal and powerful antiviral strategies to rapidly respond to the potential threat of serious infectious disease. Various highly contagious and pathogenic viruses, as well as other unknown viruses may appear or reappear in human society at any time, causing a catastrophic epidemic. Developing broad-spectrum antiviral drugs with high security and efficiency is of great significance for timely meeting public health emergency and protecting the lives and health of the people. Hence, in this review, we summarized diverse broad-spectrum antiviral targets and corresponding agents from a medicinal chemistry prospective, compared the pharmacological advantages and disadvantages of different targets, listed representative agents, showed their structures, pharmacodynamics and pharmacokinetics characteristics, and conducted a critical discussion on their development potential, in the hope of providing up-to-date guidance for the development of broad-spectrum antivirals and perspectives for applications of antiviral therapy.


Assuntos
Antivirais , Química Farmacêutica , SARS-CoV-2 , Antivirais/química , Antivirais/farmacologia , Humanos , SARS-CoV-2/efeitos dos fármacos , Pandemias , Tratamento Farmacológico da COVID-19 , COVID-19/epidemiologia
8.
Exp Ther Med ; 27(5): 182, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38515646

RESUMO

Human induced pluripotent stem cells (hiPSCs) have been regarded as a potential stem cell source for cell therapy. However, the production of cells with mesenchymal potential from hiPSCs through spontaneous differentiation is time consuming and laborious. In the present study, the combined use of the GSK-3 inhibitor CHIR99021 and TGF-ß was used to obtain mesenchymal stem cell (MSC)-like cells from hiPSCs. During the induction process, the transcription of epithelial-mesenchymal transition (EMT)-related genes N-cadherin and Vimentin in the transformed cells was upregulated, whereas the transcription of E-cadherin and pluripotency-related transcription factors SOX2, OCT4 and NANOG did not change significantly. This indicated that whilst cells were pluripotent, EMT was initiated by the upregulation of transcription of EMT promoting genes. Both SMAD-dependent and independent signalling pathways were significantly activated by the combined induction treatment compared with the single factor induction. The hiPSC-derived MSC-like cells (hiPSC-MSCs) expressed MSC-related markers and acquired osteogenic, chondrogenic and adipogenic differentiation potentials. After being injected into the peritoneal cavity of rats, the hiPSC-MSCs secreted angiogenic and immune-regulatory factors and remained on the colicomentum for 3 weeks. Within an 11-week period, four intraperitoneal hiPSC-MSC injections (1x107 cells/injection) into acute myocardial infarction (AMI) model rats significantly increased the left ventricular ejection fraction, left ventricular fractional shortening and angiogenesis and significantly reduced scar size and the extent of apoptosis in the infarcted area compared with that of the control PBS injection. Symptoms of hiPSC-MSC-induced immune reaction or tumour formation were not observed over the course of the experiment in the hiSPC-MSC treated rats. In conclusion, the CHIR99021 and TGF-ß combined induction was a rapid and effective method to obtain MSC-like cells from hiPSCs and multiple high dose intraperitoneal injections of hiPSC-derived MSCs were safe and effective at restoring cardiac function in an AMI rat model.

9.
Environ Res ; 247: 118230, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38237756

RESUMO

The transport of per- and polyfluoroalkyl substances (PFAS) from landfill leachate to surrounding soil and groundwater poses a threat to human health via the food chain or drinking water. Studies have shown that the transport process of PFAS from the solid to liquid phase in the environment is significantly affected by dissolved organic matter (DOM) adsorption. However, the mechanism of PFAS release from landfill solids into leachate and its transport to the surrounding groundwater remains unclear. In this study, we identified the composition of PFAS and DOM components and analyzed the association between DOM components, physicochemical factors, and PFAS concentrations in landfill leachate and groundwater. This study demonstrated that the frequency of PFAS detection in the samples was 100%, and the PFAS concentrations in leachate were greater than in the groundwater samples. Physicochemical factors, such as ammonium-nitrogen (NH4+-N), sodium (Na), calcium (Ca), DOM components C4 (macromolecular humic acid), SUVA254 (aromatic component content), and A240-400 (humification degree and molecular weight), were strongly correlated with PFAS concentrations. In conclusion, PFAS environmental risk management should be enhanced in landfills, especially in closed landfills, or landfills that are scheduled to close in the near future.


Assuntos
Fluorocarbonos , Água Subterrânea , Eliminação de Resíduos , Poluentes Químicos da Água , Humanos , Matéria Orgânica Dissolvida , Poluentes Químicos da Água/análise , Instalações de Eliminação de Resíduos , Água Subterrânea/química
10.
Cryobiology ; 114: 104791, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37956782

RESUMO

Mongolian sheep are a breed of sheep in China known for their excellent cold and drought resistance. Sperm from Mongolian sheep are often cryopreserved to improve breeding outcomes. However, cryopreservation of sperm often results in issues such as reduced vitality and altered morphology. Therefore, the objective of this study was to investigate the impact of the cryoprotectant resveratrol on frozen sperm from Mongolian sheep, specifically examining its effects on key proteins during cryopreservation. In this study, sperm samples were obtained from three adult Mongolian rams and processed through semen centrifugation. The sperm motility parameters of Fresh Sperm Group (FR), Resveratrol added before freezing group (FF-Res), Resveratrol-free frozen sperm group (FT), and Resveratrol added after freeze-thawing group (FA-Res) were determined. The tandem mass tags (TMT) peptide labeling combined with LC-MS/MS was used for proteomic analysis of the total proteins in FR and FT groups. A total of 2651 proteins were identified, among which 41 proteins were upregulated and 48 proteins were downregulated after freezing. In-depth bioinformatics analysis of differentially abundant proteins (DAPs) revealed their close association with the tricarboxylic acid cycle (TCA) and oxidative phosphorylation pathway. The energy-related protein dihydrolipoamide dehydrogenase (DLD) and the reactive oxygen species (ROS)-related protein NADH dehydrogenase 1 beta subcomplex subunit 9 (NDUFB9) exhibited significant decreases, indicating their potential role as key proteins contributing to reduced sperm vitality. The study demonstrated that the addition of resveratrol (RES) to semen could elevate the expression levels of DLD and NDUFB9 proteins. This study represents the pioneering proteomic analysis of Mongolian ram sperm before and after cryopreservation, establishing the significance of DLD and NDUFB9 as key proteins influencing the decline in vitality following cryopreservation of Mongolian ram sperm. These findings clarify that resveratrol can enhance the levels of DLD and NDUFB9 proteins in cryopreserved Mongolian ram sperm, consequently enhancing their vitality.


Assuntos
Preservação do Sêmen , Sêmen , Masculino , Ovinos , Animais , Resveratrol/farmacologia , Preservação do Sêmen/veterinária , Preservação do Sêmen/métodos , Di-Hidrolipoamida Desidrogenase/farmacologia , Criopreservação/métodos , Proteômica , Cromatografia Líquida , Motilidade dos Espermatozoides , Espectrometria de Massas em Tandem , Espermatozoides , Carneiro Doméstico
11.
Bioresour Technol ; 394: 129980, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38042433

RESUMO

In response to the problem of asynchronous fermentation between lignocellulose and perishable materials in compost, the combined technology of low-temperature hydrochar and compost has been studied. Hydrochar was prepared through low-temperature hydrothermal reactions and applied to aerobic fermentation. The response relationship between lignocellulose content, electron transfer capability, and microbes was explored. The results showed that a pore structure with oxygen-containing functional groups was formed in hydrochar, promoting electron transfer during composting. With the rapid increase in composting temperature, the lignocellulose content decreased by 64.36 mg/g. Oceanobacillus, Cerasibacillus, Marinimicrobium, and Gracilibacillus promoted the degradation of lignocellulose and the carbon/nitrogen cycle during aerobic fermentation, and there was a significant response relationship between electron transfer capability and functional microbes. The combined application of hydrochar and aerobic fermentation accelerated the degradation of lignocellulose. This study provides technical support for the treatment of heterogeneous organic waste.


Assuntos
Compostagem , Elétrons , Lignina , Fermentação , Carbono/química , Solo
12.
Nat Commun ; 14(1): 6469, 2023 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-37833289

RESUMO

Niemann-Pick C1-like 1 (NPC1L1) is essential for intestinal cholesterol absorption. Together with the cholesterol-rich and Flotillin-positive membrane microdomain, NPC1L1 is internalized via clathrin-mediated endocytosis and transported to endocytic recycling compartment (ERC). When ERC cholesterol level decreases, NPC1L1 interacts with LIMA1 and moves back to plasma membrane. However, how cholesterol leaves ERC is unknown. Here, we find that, in male mice, intracellular bile acids facilitate cholesterol transport to other organelles, such as endoplasmic reticulum, in a non-micellar fashion. When cholesterol level in ERC is decreased by bile acids, the NPC1L1 carboxyl terminus that previously interacts with the cholesterol-rich membranes via the A1272LAL residues dissociates from membrane, exposing the Q1277KR motif for LIMA1 recruitment. Then NPC1L1 moves back to plasma membrane. This study demonstrates an intracellular cholesterol transport function of bile acids and explains how the substantial amount of cholesterol in NPC1L1-positive compartments is unloaded in enterocytes during cholesterol absorption.


Assuntos
Colesterol , Proteínas de Membrana Transportadoras , Animais , Masculino , Camundongos , Transporte Biológico , Membrana Celular/metabolismo , Colesterol/metabolismo , Absorção Intestinal , Proteínas de Membrana Transportadoras/metabolismo
13.
Virulence ; 14(1): 2258057, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37743649

RESUMO

Host innate immunity plays a pivotal role in the early detection and neutralization of invading pathogens. Here, we show that pseudokinase mixed lineage kinase-like protein (MLKL) is required for host defence against Streptococcus pluranimalium infection by enhancing NLRP3 inflammasome activation and extracellular trap formation. Notably, Mlkl deficiency leads to increased mortality, increased bacterial colonization, severe destruction of organ architecture, and elevated inflammatory cell infiltration in murine models of S. pluranimalium pulmonary and systemic infection. In vivo and in vitro data provided evidence that potassium efflux-dependent NLRP3 inflammasome signalling downstream of active MLKL confers host protection against S. pluranimalium infection and initiates bacterial killing and clearance. Moreover, Mlkl deficiency results in defects in extracellular trap-mediated bactericidal activity. In summary, this study revealed that MLKL mediates the host defence response to S. pluranimalium, and suggests that MLKL is a potential drug target for preventing and controlling pathogen infection.


Assuntos
Armadilhas Extracelulares , Inflamassomos , Infecções Estreptocócicas , Animais , Camundongos , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteínas Quinases/genética , Infecções Estreptocócicas/genética , Infecções Estreptocócicas/metabolismo
14.
Psychol Res Behav Manag ; 16: 2267-2281, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37366481

RESUMO

Purpose: Time poverty has been shown to adversely affect individuals' development as well as organizations and countries, which is also a widespread problem among teachers, affecting work performance, mental health, and even the development of students and schools. However, the advancement of education research on time poverty has been stymied by the lack of a validated measure. Therefore, to fill the theoretical gap of time poverty in education and to compensate for the absence of an instrument for measuring teachers' time poverty and the challenges of using objective measures, it is necessary to develop and verify a domain-specific measurement instrument among teachers. Patients and Methods: An online questionnaire is designed through a Chinese data collection platform (Questionnaire Star). Study 1 and Study 2 are a cross-sectional study included 713 teachers in China and the descriptive statistics, correlation analysis and analyses of exploratory and confirmatory factors are used to develop the Teachers' Time Poverty Scale. Study 3 and Study 4 are a longitudinal study included 330 teachers, while the Time Confusion Tendency Scale and Life Satisfaction Scale is used to verify the measurement tool. SPSS 26.0 and Mplus 8.3 are used to analyze the data. Results: Teachers' Time Poverty Scale with the single-factor structure exhibits good psychometric properties based on seven items. And teachers' time poverty can negatively and significantly predict life satisfaction and teachers' time poverty can be positively and significantly predicted by time confusion tendency. Conclusion: Teachers' Time Poverty Scale is a useful tool that can be used in actual investigations to provide empirical support for teachers, schools, and education policy makers.

15.
Arterioscler Thromb Vasc Biol ; 43(7): 1219-1233, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37165876

RESUMO

BACKGROUND: Lower plasma levels of LDL (low-density lipoprotein) cholesterol (LDL-C) can reduce the risk of atherosclerotic cardiovascular disease. The loss-of-function mutations in PCSK9 (proprotein convertase subtilisin/kexin type 9) have been known to associate with low LDL-C in many human populations. PCSK9 genetic variants in Chinese Uyghurs who are at high risk of atherosclerotic cardiovascular disease due to their dietary habits have not been reported. METHODS: The study involved the whole-exome and target sequencing of college students from Uyghur and other ethnic groups in Xinjiang, China, for the association of PCSK9 loss-of-function mutations with low plasma levels of LDL-C. The mechanisms by which the identified mutations affect the function of PCSK9 were investigated in cultured cells using biochemical and cell assays. The causal effects of the identified PCSK9 mutations on LDL-C levels were verified in mice injected with adeno-associated virus expressing different forms of PCSK9 and fed a high-cholesterol diet. RESULTS: We identified 2 PCSK9 mutations-E144K and C378W-in Chinese Uyghurs with low plasma levels of LDL-C. The E144K and C378W mutations impaired the maturation and secretion of the PCSK9 protein, respectively. Adeno-associated virus-mediated expression of E144K and C378W mutants in Pcsk9 KO (knockout) mice fed a high-cholesterol diet also hampered PCSK9 secretion into the serum, resulting in elevated levels of LDL receptor in the liver and reduced levels of LDL-C in the serum. CONCLUSIONS: Our study shows that E144K and C378W are PCSK9 loss-of-function mutations causing low LDL-C levels in mice and probably in humans as well.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Hipercolesterolemia , Humanos , Camundongos , Animais , Pró-Proteína Convertase 9/genética , LDL-Colesterol , Serina Endopeptidases/genética , Pró-Proteína Convertases/genética , Pró-Proteína Convertases/metabolismo , Receptores de LDL/genética , Receptores de LDL/metabolismo , Camundongos Knockout , Aterosclerose/genética , Aterosclerose/prevenção & controle , Aterosclerose/metabolismo , Mutação
16.
J Agric Food Chem ; 71(18): 7119-7130, 2023 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-37115810

RESUMO

Clostridium perfringens is a major cause of infectious foodborne disease, frequently associated with the consumption of raw and undercooked food. Despite intensive studies on clarifying C. perfringens pathogenesis, the molecular mechanisms of host-pathogen interactions remain poorly understood. In soft tissue and mucosal infection models, Gpr120-/- mice, G protein-coupled receptor 120 (GPR120), are more susceptible to C. perfringens infection. Gpr120 deficiency leads to a low survival rate (30 and 10%, p < 0.01), more bacterial loads in the muscle (2.26 × 108 ± 2.08 × 108 CFUs/g, p < 0.01), duodenum (2.80 × 107 ± 1.61 × 107 CFUs/g, p < 0.01), cecum (2.50 × 108 ± 2.05 × 108 CFUs/g, p < 0.01), and MLN (1.23 × 106 ± 8.06 × 105 CFUs/g, p < 0.01), less IL-18 production in the muscle (8.54 × 103 ± 1.20 × 103 pg/g, p < 0.01), duodenum (3.34 × 103 ± 2.46 × 102 pg/g, p < 0.01), and cecum (3.81 × 103 ± 5.29 × 102 pg/g, p < 0.01), and severe organ injury. Obviously, GPR120 facilitates IL-18 production and pathogen control via potassium efflux-dependent NOD-like receptor family pyrin domain-containing 3 (NLRP3) signaling. Mechanistically, GPR120 interaction with NLRP3 potentiates the NLRP3 inflammasome assembly. Thus, this study uncovers a novel role of GPR120 in host protection and reveals that GPR120 may be a potential therapeutic target for limiting pathogen infection.


Assuntos
Infecções por Clostridium , Inflamassomos , Animais , Camundongos , Inflamassomos/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteínas NLR , Domínio Pirina , Interleucina-18 , Receptores Acoplados a Proteínas G/genética , Infecções por Clostridium/genética , Interleucina-1beta
17.
Medicina (Kaunas) ; 59(2)2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36837392

RESUMO

Background and Objectives: Sevoflurane is a commonly used inhalational anaesthetic in clinics. Prolonged exposure to sevoflurane can induce significant changes in lipid metabolism and neuronal damage in the developing brain. However, the effect of exposure of pregnant rats to clinical doses of sevoflurane remains unclear. Materials and Methods: Twenty-eight pregnant rats were randomly and equally divided into sevoflurane exposure (S) group, control (C) and a blank group at gestational day (G) 18; Rats in S group received 2% sevoflurane with 98% oxygen for 6 h in an anesthetizing chamber, while C group received 100% oxygen at an identical flow rate for 6 h in an identical chamber. Partial least squares discriminant analysis (PLS-DA), ultra performance liquid chromatography/time-of-flight mass spectrometry(UPLC/TOF-MS) and MetaboAnalyst were used to analysis acquire metabolomics profiles, and immunohistochemical changes of neuronalapoptosis in hippocampus and cortex of neonatal rats were also analyzed. Results: This study aimed to explore lipidomics and transcriptomics changes related to 2% sevoflurane exposure for 6 h in the developing brains of newborn offspring rats. Ultra-performance liquid chromatography/time-of-flight mass spectrometry (UPLC/TOF-MS) and RNA sequencing (RNA-seq) analyses were used to acquire metabolomics and transcriptomics profiles. We used RNA-seq to analyse the expression of the coding and non-coding transcripts in neural cells of the cerebral cortex. No significant differences in arterial oxygen tension (PaO2), arterial carbon dioxide tension (PaCO2), or arterial blood gas were found between the groups. The relative standard deviation (RSD) of retention times was <1.53%, and the RSDs of peak areas ranged from 2.13% to 8.51%. Base peak chromatogram (BPC) profiles showed no differences between the groups. We evaluated the partial least square-discriminant analysis (PLS-DA) model. In negative ion mode, R2X was over 70%, R2Y was over 93%, and Q2 (cum) was over 80%. Cell apoptosis was not remarkably enhanced by TUNEL and haematoxylin and eosin (HE) staining in the sevoflurane-exposed group compared to the control group (p > 0.05). Glycerophospholipid (GP) and sphingolipid metabolism disturbances might adversely influence neurodevelopment in offspring. The expression of mRNAs (Vcan gene, related to neuronal development, function and repair) of the sevoflurane group was significantly increased in the differential genes by qRT-PCR verification. Conclusions: GP and sphingolipid metabolism homeostasis may be potential therapeutic approaches against inhalational anaesthetic-induced neurodegenerative disorders. Meanwhile, sevoflurane-induced Vcan changes indicated some lipidomic and transcriptomic changes, even if neural cell apoptosis was not significantly changed in the usual clinical dose of sevoflurane exposure.


Assuntos
Anestésicos Inalatórios , Sevoflurano , Animais , Feminino , Gravidez , Ratos , Anestésicos Inalatórios/administração & dosagem , Anestésicos Inalatórios/efeitos adversos , Oxigênio , Sevoflurano/administração & dosagem , Sevoflurano/efeitos adversos , Esfingolipídeos
18.
Molecules ; 28(3)2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36770675

RESUMO

Linaclotide is a 14-amino acid residue peptide approved by the FDA for the treatment of irritable bowel syndrome with constipation (IBS-C), which activates guanylate cyclase C to accelerate intestinal transit. Here we show a new method for the synthesis of linaclotide through the completely selective formation of three disulfide bonds in satisfactory overall yields via mild oxidation reactions of the solid phase and liquid phase, using 4-methoxytrityl (Mmt), diphenylmethyl (Dpm) and 2-nitrobenzyl (O-NBn) protecting groups of cysteine as substrate, respectively.


Assuntos
Constipação Intestinal , Síndrome do Intestino Irritável , Humanos , Cisteína , Síndrome do Intestino Irritável/tratamento farmacológico , Peptídeos , Resultado do Tratamento
20.
Front Plant Sci ; 13: 1008198, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36212350

RESUMO

Sorghum [Sorghum bicolor (L.) Moench] is an important crop for food security in semiarid and arid regions due to its high tolerance to abiotic and biotic stresses and its good performance in marginal lands with relatively low fertility. To deeply understand the interrelationship among sorghum genotype, environment, sowing dates, and densities in the spring sowing early maturing (SSEM) areas of China, and to provide a basis for specifying scientific and reasonable cultural practices, a two-year field experiment was conducted with six popular varieties at six locations. Combined ANOVA showed that the yield difference between years was significant (P<0.05); the yield differences among locations, varieties, sowing dates, and densities were all highly significant (P<0.01). The variety effect was mainly influenced by location, year, sowing dates and their interactions. The sowing effect was mainly influenced by the location, year, variety and their interactions The plant density effect was significantly influenced by location and location-year interaction. Of the contributions of various test factors to yield variance, the location was the largest one (38.18%), followed by variety (12.31%), sowing date (1.53%), density (0.54%), and year (0.09%), with all these single factors accounting for 52.65%. The total contribution of all two-factor interactions accounted for 14.24%, among which the greatest contributor was location-hybrid interaction (8.07%). The total contribution of all three-factor interactions accounted for 14.58%, of which year-location-hybrid interaction was the largest contributor (9.02%). Sowing dates significantly affected model of sorghum growth and development, especially during the late period. The key climatic factors affecting yield were different among the six locations. Weather factors during the grain filling stages contributed much more than those during the early stage to grain yield. Mid-maturing varieties are recommended other than early maturing varieties for the SSEM areas even when late sowing occurs. Sowing as early as possible is recommended for areas with very short frost-free period (Harbin, Tongliao, and Datong). Proper delayed sowing is recommended for areas with a relative long frost-free period (Gongzhuling, Baicheng and Zhangjiakou). This research will provide a conducive reference for sorghum production in similar areas.

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