Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 280
Filtrar
1.
Sci Total Environ ; : 172593, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38642765

RESUMO

Wastewater surveillance has evolved into a powerful tool for monitoring public health-relevant analytes. Recent applications in tracking severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection highlight its potential. Beyond humans, it can be extended to livestock settings due to the increasing demand for livestock products. Livestock intensification poses risks of disease emergence. Wastewater surveillance offers non-invasive, cost-effective means to detect potential outbreaks. This approach aligns with the "One Health" paradigm, emphasizing the interconnectedness of human, animal, and ecosystem health. By monitoring viruses in livestock wastewater, early detection, prevention, and control strategies can be employed, safeguarding both animal and human health, economic stability, and international trade. This integrated "One Health" approach enhances collaboration and a comprehensive understanding of disease dynamics, supporting proactive measures in the Anthropocene era where animal and human diseases are on the rise.

2.
Inorg Chem ; 63(16): 7464-7472, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38598182

RESUMO

Uranium accumulation in the kidneys and bones following internal contamination results in severe damage, emphasizing the pressing need for the discovery of actinide decorporation agents with efficient removal of uranium and low toxicity. In this work, cinnamic acid (3-phenyl-2-propenoic acid, CD), a natural aromatic carboxylic acid, is investigated as a potential uranium decorporation ligand. CD demonstrates markedly lower cytotoxicity than that of diethylenetriaminepentaacetic acid (DTPA), an actinide decorporation agent approved by the FDA, and effectively removes approximately 44.5% of uranyl from NRK-52E cells. More importantly, the results of the prompt administration of the CD solution remove 48.2 and 27.3% of uranyl from the kidneys and femurs of mice, respectively. Assessments of serum renal function reveal the potential of CD to ameliorate uranyl-induced renal injury. Furthermore, the single crystal of CD and uranyl compound (C9H7O2)2·UO2 (denoted as UO2-CD) reveals the formation of uranyl dimers as secondary building units. Thermodynamic analysis of the solution shows that CD coordinates with uranyl to form a 2:1 molar ratio complex at a physiological pH of 7.4. Density functional theory (DFT) calculations further show that CD exhibits a significant 7-fold heightened affinity for uranyl binding in comparison to DTPA.


Assuntos
Cinamatos , Urânio , Cinamatos/química , Cinamatos/farmacologia , Animais , Ligantes , Camundongos , Urânio/química , Urânio/metabolismo , Urânio/toxicidade , Rim/efeitos dos fármacos , Rim/metabolismo , Linhagem Celular , Teoria da Densidade Funcional , Ratos , Estrutura Molecular , Sobrevivência Celular/efeitos dos fármacos , Quelantes/química , Quelantes/farmacologia , Quelantes/síntese química
4.
Brain Commun ; 6(2): fcae077, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38529357

RESUMO

To explore the causal relationship between age and brain health (cortical atrophy, white matter integrity, white matter hyperintensities and cerebral microbleeds in various brain regions) related multiparameter imaging features using two-sample Mendelian randomization. Age was determined as chronological age of the subject. Cortical volume, white matter micro-integrity, white matter hyperintensity volume and cerebral microbleeds of each brain region were included as phenotypes for brain health. Age and imaging of brain health related genetic data were analysed to determine the causal relationship using inverse-variance weighted model, validated by heterogeneity and horizontal pleiotropy variables. Age is causally related to increased volumes of white matter hyperintensities (ß = 0.151). For white matter micro-integrity, fibres of the inferior cerebellar peduncle (axial diffusivity ß = -0.128, orientation dispersion index ß = 0.173), cerebral peduncle (axial diffusivity ß = -0.136), superior fronto-occipital fasciculus (isotropic volume fraction ß = 0.163) and fibres within the limbic system were causally deteriorated. We also detected decreased cortical thickness of multiple frontal and temporal regions (P < 0.05). Microbleeds were not related with aging (P > 0.05). Aging is a threat of brain health, leading to cortical atrophy mainly in the frontal lobes, as well as the white matter degeneration especially abnormal hyperintensity and deteriorated white matter integrity around the hippocampus.

5.
J Colloid Interface Sci ; 664: 691-703, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38492370

RESUMO

Stretchable flexible thin-film electrodes are extensively explored for developing new wearable energy storage devices. However, traditional carbon-based materials used in such independent electrodes have limited practical applications owing to their low energy storage capacity and energy density. To address this, a unique structure and remarkable mechanical stability thin-film flexible positive electrode comprising CoS1.97 nanoparticles decorated hollow CuS cubes and reduced graphene oxide (rGO), hereinafter referred to as CCSrGO, is prepared. Transition metal sulfide CoS1.97 and CuS shows high energy density owing to the synergistic effects of its active components. The electrode can simultaneously meet the high-energy density and safety requirements of new wearable energy storage devices. The electrode has excellent electrochemical performance (1380 F/g at 1 A/g) and ideal capacitance retention (93.8 % after 10,000 cycles) owing to its unique three-dimensional hollow structure and polymetallic synergies between copper and cobalt elements, which are attributed to their different energy storage mechanisms. Furthermore, a flexible asymmetric supercapacitor (FASC) was constructed using CCSrGO as the positive electrode and rGO as the negative electrode (CCSrGO//rGO), which delivers an energy density of 100 Wh kg-1 and a corresponding power density of 2663 W kg-1 within a voltage window of 0-1.5 V. The resulting FASC can power a light-emitting diode (LED) at different bending and twisting angles, exerting little effect on the capacitance. Therefore, the prepared CCSrGO//rGO FASC devices show great application prospects in energy storage.

6.
Sci Total Environ ; 927: 172008, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38547993

RESUMO

OBJECTIVE: Little has been known on the effect of chronic glyphosate exposure on osteoarthritis (OA). The aim of this study was to investigate the association between glyphosate exposure and OA and to further investigate the different moderating effects of leisure time physical activity (LTPA) and body mass index (BMI) types on the association between glyphosate exposure and OA. METHODS: Cross-sectional data from 2540 participants in the 2015-2018 National Health and Nutrition Examination Survey (NHANES) were used to explore the association between glyphosate exposure and OA. Multivariate logistic regression models and restricted cubic spline models were used to investigate the association between glyphosate exposure and OA, and further analyses were conducted to determine the association between glyphosate exposure and OA under different LTPA and BMI types. RESULTS: Of the 2540 participants, 346 had OA. Participants with the highest glyphosate concentration (Q4) had a higher incidence of OA compared to participants with the lowest glyphosate concentration (Q1) (OR, 1.88; 95 % confidence interval [CI]: 1.13, 3.13), there was no nonlinear association between glyphosate and OA (non-linear P = 0.343). In the no LTPA group, glyphosate concentration in the Q4 group was correlated with OA (OR, 2.65; 95%CI: 1.27, 5.51). In the obese group, glyphosate concentration in the Q4 group was correlated with OA (OR, 2.74; 95 % CI: 1.48, 5.07). Among people with high BMI and inactive in LTPA, glyphosate concentrations in Q4 were associated with OA (OR, 2.19; 95 % CI: 1.07, 4.48). CONCLUSIONS: Glyphosate is associated with OA odd, and physical activity and moderate weight loss can mitigate this association to some degree. This study provides a scientific basis for rational prevention of OA by regulation of LTPA and BMI under glyphosate exposure.


Assuntos
Exercício Físico , Glicina , 60658 , Obesidade , Osteoartrite , Humanos , Glicina/análogos & derivados , Osteoartrite/epidemiologia , Masculino , Feminino , Obesidade/epidemiologia , Estudos Transversais , Pessoa de Meia-Idade , Adulto , Estados Unidos/epidemiologia , Herbicidas , Exposição Ambiental/estatística & dados numéricos , Atividades de Lazer , Índice de Massa Corporal , Inquéritos Nutricionais , Idoso
7.
Sci Data ; 11(1): 265, 2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38431735

RESUMO

It is vital to investigate the complex mechanisms underlying tumors to better understand cancer and develop effective treatments. Metabolic abnormalities and clinical phenotypes can serve as essential biomarkers for diagnosing this challenging disease. Additionally, genetic alterations provide profound insights into the fundamental aspects of cancer. This study introduces Cancer-Alterome, a literature-mined dataset that focuses on the regulatory events of an organism's biological processes or clinical phenotypes caused by genetic alterations. By proposing and leveraging a text-mining pipeline, we identify 16,681 thousand of regulatory events records encompassing 21K genes, 157K genetic alterations and 154K downstream bio-concepts, extracted from 4,354K pan-cancer literature. The resulting dataset empowers a multifaceted investigation of cancer pathology, enabling the meticulous tracking of relevant literature support. Its potential applications extend to evidence-based medicine and precision medicine, yielding valuable insights for further advancements in cancer research.


Assuntos
Neoplasias , Medicina de Precisão , Humanos , Mineração de Dados/métodos , Neoplasias/genética , Fenótipo , Medicina de Precisão/métodos
8.
Sci Total Environ ; 908: 167966, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38476760

RESUMO

The lack of standardized methods and large differences in virus concentration and extraction workflows have hampered Severe Acute Respiratory Syndrome (SARS-CoV-2) wastewater surveillance and data reporting practices. Numerous studies have shown that adsorption-extraction (AE) method holds promise, yet several uncertainties remain regarding the optimal AE workflow. Several procedural components may influence the recovered concentrations of target nucleic acid, including membrane types, homogenization instruments, speed and duration, and lysis buffer. In this study, 42 different AE workflows that varied these components were compared to determine the optimal workflow by quantifying endogenous SARS-CoV-2, human adenovirus 40/41 (HAdV 40/41), and a bacterial marker gene of fecal contamination (Bacteroides HF183). Our findings suggest that the workflow chosen had a significant impact on SARS-CoV-2 concentrations, whereas it had minimal impact on HF183 and no effect on HAdV 40/41 concentrations. When comparing individual components in a workflow, such as membrane type (MF-Millipore™ 0.45 µm MCE vs. Isopore™ 0.40 µm), we found that they had no impact on SARS-CoV-2, HAdV 40/41, and HF183 concentrations. This suggests that at least some consumables and equipment are interchangeable. Buffer PM1 + TRIzol-based workflows yielded higher concentrations of SARS-CoV-2 than other workflows. HF183 concentrations were higher in workflows without chloroform. Similarly, higher homogenization speeds (5000-10,000 rpm) led to increased concentrations of SARS-CoV-2 and HF183 but had no effect on HAdV 40/41. Our findings indicate that minor enhancements to the AE workflow can improve the recovery of viruses and bacteria from the wastewater, leading to improved outcomes from wastewater surveillance efforts.


Assuntos
Adenovírus Humanos , Ácidos Nucleicos , Águas Residuárias , Humanos , Adsorção , Vigilância Epidemiológica Baseada em Águas Residuárias , Fluxo de Trabalho , SARS-CoV-2
9.
ACS Pharmacol Transl Sci ; 7(3): 863-877, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38481680

RESUMO

Colon cancer is among the most lethal and prevalent malignant tumors in the world, and the lack of effective therapies highlights the need for novel therapeutic approaches. Schisandrin B (Sch B), a lignan extracted from the fruit ofSchisandra chinensis, has been reported for its anticancer properties. However, to date, no studies have been done to characterize the exact molecular mechanisms underlying the antitumorigenic effects of Sch B in colon cancer. This study aimed to explore the antitumorigenic effects of Sch B in colon cancer and to understand the underlying therapeutic mechanism. A comprehensive analysis of the molecular mechanism underlying the antitumorigenic effects of Sch B on human colon cancer cells was performed using a combination of Raman spectroscopy, RNA-seq, computational docking, and molecular biological experiments. The in vivo efficacy was evaluated by a mouse xenograft model. Sch B reduced cell proliferation and triggered apoptosis in human colon cancer cell lines. Raman spectroscopy, computational, RNA-seq, and molecular and cellular studies revealed that Sch B activated unfolded protein responses by interacting with CHOP and upregulating CHOP, which thereby induced apoptosis. CHOP knockdown alleviated the Sch B-induced reduction in cell viability and apoptosis. Sch B reduced colon tumor growth in vivo. Our findings demonstrated that Sch B induced apoptosis and inhibited cell proliferation and tumor growth in vitro and in vivo. These results provided an essential background for clinical trials examining the effects of Sch B in patients with colon cancer.

10.
Biotechnol J ; 19(2): e2300560, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38403459

RESUMO

Tamoxifen (TAM) resistance is finally developed in over 40% of patients with estrogen receptor α-positive breast cancer (ERα+ -BC), documenting that discovering new molecular subtype is needed to confer perception to the heterogeneity of ERα+ -BC. We obtained representative gene sets subtyping ERα+ -BC using gene set variation analysis (GSVA), non-negative matrix factorization (NMF), and COX regression methods on the basis of METABRIC, TCGA, and GEO databases. Furthermore, the risk score of ERα+ -BC subtyping was established using least absolute shrinkage and selection operator (LASSO) regression on the basis of genes in the representative gene sets, thereby generating the two subtypes of ERα+ -BC. We further found that minichromosome maintenance complex component 2 (MCM2) functioned as the hub gene subtyping ERα+ -BC using GO, KEGG, and MCODE. MCM2 expression was capable for specifically predicting 1-year overall survival (OS) of ERα+ -BC and correlated with T stage, AJCC stage, and tamoxifen (TAM) sensitivity of ERα+ -BC. The downregulation of MCM2 expression inhibited proliferation, migration, and invasion of TAM-resistant cells and promoted G0/G1 arrest. Altogether, tamoxifen resistance entails that MCM2 is a hub gene subtyping ERα+ -BC, providing a novel dimension for discovering a potential target of TAM-resistant BC.


Assuntos
Neoplasias da Mama , Receptor alfa de Estrogênio , Componente 2 do Complexo de Manutenção de Minicromossomo , Tamoxifeno , Feminino , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Regulação para Baixo , Resistencia a Medicamentos Antineoplásicos/genética , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Regulação Neoplásica da Expressão Gênica , Células MCF-7 , Componente 2 do Complexo de Manutenção de Minicromossomo/genética , Componente 2 do Complexo de Manutenção de Minicromossomo/metabolismo , Tamoxifeno/farmacologia
11.
Neurochem Res ; 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38305960

RESUMO

In the present study, sulfated polysaccharides were obtained by digestion of Sargassum horneri and preparation with enzyme-assisted extraction using three food-grade enzymes, and their anti- Alzheimer's activities were investigated. The results demonstrated that the crude sulfated polysaccharides extracted using AMGSP, CSP and VSP dose-dependently (25-100 µg·mL- 1) raised the spontaneous alternating manner (%) in the Y maze experiment of mice and reduced the escape latency time in Morris maze test. AMGSP, CSP and VSP also exhibited good anti-AChE and moderate anti-BuChE activities. CSP displayed the best inhibitory efficacy against AChE. with IC50 values of 9.77 µM. And, CSP also exhibited good inhibitory selectivity of AChE over BuChE. Next, CSP of the best active crude extract was separated by the preparation type high performance liquid phase to obtain the sulphated fucooligosaccharide section: SFcup (→3-α-L-fucp(2-SO3-)-1→4-α-L-fucp(2,3-SO3-)-1→section), SFcup showed a best inhibitory efficacy against AChE with IC50 values of 4.03 µM. The kinetic research showed that SFcup inhibited AChE through dual binding sites. Moreover, the molecular docking of SFcup at the AChE active site was in accordance with the acquired pharmacological results.

12.
Phytomedicine ; 125: 155269, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38237510

RESUMO

BACKGROUND: Energy deficiency is the characteristic of chemotherapy-induced cachexia (CIC) which is manifested by muscle wasting. glycolysis, tricarboxylic acid (TCA) cycle, and lipid metabolism are central to muscle bioenergy production, which is vulnerable to chemotherapy during cancer treatment. Recent investigations have spotlighted the potential of Shenqi Fuzheng injection (SQ), a Chinese proprietary medicine comprising Radix Codonopsis and Radix Astragali, in alleviating CIC. However, the specific effects of SQ on muscle energy metabolism remains less explored. PURPOSE AND METHODS: Here, we integrated transcriptomics, spatial metabolomics, gas chromatography-mass spectrometry targeted quantitative analysis, and transmission electron microscopy techniques, combined with Seahorse live-cell metabolic analysis to reveal the changes in genes and pathways related to energy metabolism in the CIC model and SQ's protective effects at molecular and functional levels. RESULTS: Our data showed that chemotherapeutic agents caused glycolysis imbalance, which further leads to metabolic derangements of TCA cycle intermediates. SQ maintained glycolysis balance by facilitating pyruvate fluxing to mitochondria for more efficient bioenergy production, which involved a dual effect on promoting functions of mitochondrial pyruvate dehydrogenase complexes and inhibiting lactate dehydrogenase for lactate production. As a result of the sustained pyruvate level achieved by SQ administration, glycolysis balance was maintained, which further led to the preservation of mitochondrial integrity and function of electron transport chain, thereby, ensuring the normal operation of the TCA cycle and the proper synthesis of adenosine triphosphate (ATP). The above results were further validated using the Seahorse live-cell assay. CONCLUSION: In conclusion, our study highlights SQ as a promising strategy for CIC management, emphasizing its ability to harmonize the homeostasis of the muscle bioenergetic profile. Beyond its therapeutic implications, this study also offers a novel perspective for the development of innovative treatments in the realm of herbal medicine.


Assuntos
Antineoplásicos , Caquexia , Medicamentos de Ervas Chinesas , Camundongos , Animais , Caquexia/induzido quimicamente , Caquexia/tratamento farmacológico , Caquexia/metabolismo , Metabolismo Energético , Músculo Esquelético/metabolismo , Piruvatos/metabolismo
13.
World Neurosurg ; 182: 136-143, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37951461

RESUMO

OBJECTIVES: Timely diagnosis and management of elevated intracranial pressure (ICP) in patients with traumatic brain injury (TBI) can significantly reduce mortality rates. Ultrasound examination of the optic nerve sheath diameter (ONSD) is considered a potential, noninvasive, and effective method for assessing ICP. We conducted a systematic review and meta-analysis of ONSD ultrasound detection and invasive ICP monitoring methods to compare and evaluate the diagnostic accuracy of ONSD ultrasound detection methods for intracranial hypertension (IH) in patients with TBI. METHODS: We searched the Web of Science, PubMed, and Embase databases to assess the diagnostic accuracy of ONSD sonography for predicting increased ICP. The 2 authors independently extracted the collected data. Simultaneously, the QUADAS-2 tool was used to evaluate the bias risk of each study and conducted random-effects meta-analyses for the accuracy and specificity of diagnosis, and calculated pooled estimates. RESULTS: Ten studies with 512 patients were included. The diagnostic accuracy of ONSD sonography for IH was revealed as a pooled sensitivity of 0.85 (95% confidence interval [CI], 0.79-0.89) and specificity of 0.88 (95% CI, 0.80-0.93), compared with the invasive ICP monitoring standard for patients with TBI. CONCLUSIONS: ONSD sonography may be a useful method for predicting increased ICP in adult patients with TBI. Further clinical studies are required to confirm the diagnostic value of ONSD sonography.


Assuntos
Lesões Encefálicas Traumáticas , Hipertensão Intracraniana , Adulto , Humanos , Nervo Óptico/diagnóstico por imagem , Pressão Intracraniana/fisiologia , Ultrassonografia , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Hipertensão Intracraniana/diagnóstico por imagem , Hipertensão Intracraniana/etiologia
14.
Transl Oncol ; 40: 101843, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38101175

RESUMO

Previous studies have demonstrated that carbohydrate sulfotransferase family proteins (CHSTs) play a crucial role in the extracellular matrix structural constituent and cancer progression, however, the effect of CHSTs on gastric cancer is still superficial. To investigate these, our study seeks to provide a comprehensive understanding of CHSTs' expression, immune infiltration, and prognostic implications in gastric cancer, utilizing data from the TCGA, GEO and GTEx databases. Furthermore, we conducted experimental validation to elucidate the role of CHST14 specifically in gastric cancer. Our findings suggest that most CHSTs were highly expressed in gastric cancer. Gene copy number variations further indicated prevalent CHSTs amplification in gastric cancer, pointing to its potential relevance in disease progression. Intriguingly, we noted strong positive correlations between most CHSTs and immune cell infiltration. Importantly, most members of CHSTs were related to OS and PFI with gastric cancer, with particular emphasis on CHST14 and CHST9. Multifactorial regression analysis indicates that CHST14 is an independent prognostic factor influencing the overall survival of gastric cancer patients. In further experimental validation, our results demonstrate elevated expression of CHST14 in gastric cancer, and knocking down CHST14 inhibits gastric cancer cell proliferation, invasion, migration and EMT. Additionally, CHST14 may exert its function through the regulation of the Wnt pathway. In summary, our study comprehensively analyzes the hitherto undescribed role of CHSTs in gastric cancer through the analysis of multi-omics data. Importantly, we identify CHST14 as a pivotal promoter in the malignant progression of gastric cancer, offering potential targets for gastric cancer therapy.

15.
Chemosphere ; 350: 141066, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38159731

RESUMO

Radionuclide uranium is a great threat to human health, due to its high chemical toxicity and radioactivity. Finding suitable uranium decorporation to reduce damage caused by uranium internal contamination is an important aspect of nuclear emergency response. However, the poor selectivity and/or high toxicity of the only excretory promoter approved by Food and Drug Administration (FDA) is an obvious disadvantage. Herein, we choose an edible natural product, the traditional Chinese medicine called Perilla frutescens (PF), which has wide sources and can be used as an excellent and effective uranyl decorporation. In vivo uranium decorporation assays illustrate the removal efficiency of uranium in kidney were 68.87% and 43.26%, in femur were 56.66% and 54.53%, by the test of prophylactic and immediate administration, respectively. Cell level experiments confirmed that it had better biocompatibility than CaNa3-DTPA (CaNa3-diethylenetriamine pentaacetate, a commercial actinide excretion agent). In vitro static adsorption experiments exhibited that its excellent selectivity sorption for uranyl. All those results findings would provide new research insights about natural product for uranyl decorporation.


Assuntos
Produtos Biológicos , Perilla frutescens , Urânio , Humanos , Urânio/toxicidade , Quelantes/farmacologia , Rim , Produtos Biológicos/farmacologia
16.
Aquat Toxicol ; 264: 106733, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37875383

RESUMO

The present study was undertaken to explore the effects of sulfamethazine (SMZ) dietary exposure on the enrichment of the intestine microbial structure, and antibiotic resistance gene (ARGs) transmission in marine medaka, with respect to antibiotic dose, duration, and sex. In male fish, a dietary exposure of 10 µg/L SMZ led to a heightened SMZ enrichment in the intestine, whereas metabolite (N-SMZ) levels were elevated at a higher exposure concentration (100 µg/L). Conversely, female fish exhibited stable levels of accumulation and metabolic rates across the exposure period. The composition of intestinal microorganisms revealed that exposure duration exerted a greater impact on the abundance and diversity of gut microbes, and microbial responses to SMZ varied across exposure time points. The expansion of Bacteroidetes and Ruegeria likely stimulated SMZ metabolism and contributed to the more balanced level of SMZ and N-SMZ observed in females. In males, short-term SMZ stress resulted in a disruption of intestinal homeostasis, while the rise in the abundance of the Fusobacteria and Propionigeniuma suggested a potential enhancement in intestinal anti-inflammatory capacity over time. Overall, female medaka exhibited greater adaptability to SMZ, and males appear to experience prolonged effects due to SMZ. A total of 11 ARGs and 5 mobile genetic elements (MGEs) were identified. Ruegeria is the main carrier of two types of MGEs (IS1247, ISSm2-Xanthob), and may serve as an indicator of ARG transmission. Therefore, it is rational to consider some fish breeding areas in natural waters as potential "reservoirs" of antibiotic resistance. This research will provide a valuable reference for the transmission of drug resistance along the food chain.


Assuntos
Sulfametazina , Poluentes Químicos da Água , Animais , Feminino , Masculino , Exposição Dietética , Poluentes Químicos da Água/toxicidade , Antibacterianos/farmacologia , Homeostase
17.
Chem Biodivers ; 20(12): e202301271, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37806964

RESUMO

According to the fusion technique create effective multi-target-directed ligands, in this study, we designed and synthesized a series of benzo[d]thiazol-2-yl)-3-(pyrrolidin-1-yl) or 3-(morph- olino-1-yl)propanamide derivatives, and evaluated their inhibitory potency against MAOs, AChE, BuChE by in vitro enzyme effect assays. Based on activity results, we found that derivatives N-(5-methylbenzo[d]thiazol-2-yl)-3-(pyrrolidin-1-yl)propanamide (2 c) and N-(6-bromobenzo[d]thiazol-2-yl)-3-(pyrrolidin-1-yl)propanamide (2 h) showed good inhibitory potency against BuChE with IC50 values of 15.12 µM and 12.33 µM, respectively. Besides, 2 c and 2 h also exhibited selective MAO-B inhibitory effects with inhibition rates of 60.10 % and 66.30 % at 100 µM, respectively. In contrast, all designed derivatives were poor active against AChE and MAO-A at a concentration of 100 µM. The toxicity analysis in vitro by MTT and AO/EB fluorescence staining confirmed that 2 c and 2 h were nontoxic up to 100 µM. Molecular modeling studies showed that 2 c and 2 h could bind to the active site of BuChE. This research paves the way for further study aimed at designing MAO-B and BuChE inhibitors for the treatment of neurodegenerative disorders.


Assuntos
Doença de Alzheimer , Butirilcolinesterase , Humanos , Butirilcolinesterase/metabolismo , Inibidores da Monoaminoxidase/farmacologia , Acetilcolinesterase/metabolismo , Inibidores da Colinesterase/química , Monoaminoxidase , Benzotiazóis/farmacologia , Morfolinas , Relação Estrutura-Atividade , Estrutura Molecular , Simulação de Acoplamento Molecular
18.
Commun Biol ; 6(1): 911, 2023 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-37670137

RESUMO

The immune synapse, a highly organized structure formed at the interface between T lymphocytes and antigen-presenting cells (APCs), is essential for T cell activation and the adaptive immune response. It has been shown that this interface shares similarities with the primary cilium, a sensory organelle in eukaryotic cells, although the roles of ciliary proteins on the immune synapse remain elusive. Here, we find that inositol polyphosphate-5-phosphatase E (INPP5E), a cilium-enriched protein responsible for regulating phosphoinositide localization, is enriched at the immune synapse in Jurkat T-cells during superantigen-mediated conjugation or antibody-mediated crosslinking of TCR complexes, and forms a complex with CD3ζ, ZAP-70, and Lck. Silencing INPP5E in Jurkat T-cells impairs the polarized distribution of CD3ζ at the immune synapse and correlates with a failure of PI(4,5)P2 clearance at the center of the synapse. Moreover, INPP5E silencing decreases proximal TCR signaling, including phosphorylation of CD3ζ and ZAP-70, and ultimately attenuates IL-2 secretion. Our results suggest that INPP5E is a new player in phosphoinositide manipulation at the synapse, controlling the TCR signaling cascade.


Assuntos
Anticorpos , Monoéster Fosfórico Hidrolases , Fosfatidilinositóis , Receptores de Antígenos de Linfócitos T
19.
Altern Ther Health Med ; 29(8): 644-649, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37678869

RESUMO

Objective: To retrospectively analyze the clinical characteristics and pregnancy outcomes of patients with the non-obstetric acute abdomen (AAD) during pregnancy. Methods: A total of 124 patients with non-obstetric AAD during pregnancy were selected, including acute gastroenteritis (n = 42), acute appendicitis (n = 24), pedicle torsion of ovarian tumor (n = 21), acute pancreatitis (n = 10), urinary stones (n = 8), acute cholecystitis (n = 5), ruptured ovarian cyst (n = 6), red degeneration of hysteromyoma (n = 4), pedicle torsion of subserosal hysteromyoma (n = 3) and intestinal obstruction (n = 1). The clinical data of included patients were collected, and their clinical manifestations, clinical diagnosis, treatment modalities, and pregnancy outcomes were analyzed. Results: Common clinical manifestations included abdominal pain, nausea, vomiting, fever, elevated leukocytes, and neutrophil count. Clinical diagnosis analysis revealed acute gastroenteritis (n = 42), acute appendicitis (n = 24), pedicle torsion of ovarian tumor (n = 21), acute pancreatitis (n = 10), urinary stones (n = 8), acute cholecystitis (n = 5), ruptured ovarian cyst (n = 6), red degeneration of hysteromyoma (n = 4), pedicle torsion of subserosal hysteromyoma (n = 3) and intestinal obstruction (n = 1) in patients. Surgery was performed for conditions such as acute appendicitis and ovarian tumor torsion, while conservative treatment was preferred for cases of acute gastroenteritis. 65 patients received surgery and 59 patients received conservative treatment. The pregnancy outcomes indicated 113 patients with full-term delivery, 5 with premature delivery, 6 with miscarriage and 1 with fetal death. Pregnancy outcomes varied, with 113 patients achieving full-term delivery, 5 experiencing premature delivery, 6 undergoing miscarriage, and 1 case of fetal death. Conclusion: Non-obstetric AAD during pregnancy manifests clinically as nausea and vomiting, abdominal pain, elevated body temperature, and leukocytes, all of which have pregnancy outcomes. Pregnant patients with non-obstetric AAD should be diagnosed according to their clinical manifestations, physical examinations, and relevant imaging examinations, and appropriate treatment modalities should be selected to achieve a better pregnancy outcome and ensure the safety of the mother and baby during the clinical diagnosis and treatment process. This study underscores the need for prompt and accurate diagnosis in pregnant patients with non-obstetric AAD, to optimize pregnancy outcomes and ensure maternal-fetal safety.


Assuntos
Abdome Agudo , Aborto Espontâneo , Apendicite , Colecistite Aguda , Gastroenterite , Obstrução Intestinal , Cistos Ovarianos , Neoplasias Ovarianas , Pancreatite , Complicações na Gravidez , Cálculos Urinários , Feminino , Gravidez , Humanos , Resultado da Gravidez , Abdome Agudo/diagnóstico , Estudos Retrospectivos , Apendicite/diagnóstico , Apendicite/cirurgia , Doença Aguda , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/terapia , Dor Abdominal , Morte Fetal , Obstrução Intestinal/diagnóstico , Náusea , Vômito
20.
Nat Commun ; 14(1): 5486, 2023 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-37679329

RESUMO

Despite considerable research efforts on photoelectrochemical water splitting over the past decades, practical application faces challenges by the absence of efficient, stable, and scalable photoelectrodes. Herein, we report a metal-halide perovskite-based photoanode for photoelectrochemical water oxidation. With a planar structure using mesoporous carbon as a hole-conducting layer, the precious metal-free FAPbBr3 photovoltaic device achieves 9.2% solar-to-electrical power conversion efficiency and 1.4 V open-circuit voltage. The photovoltaic architecture successfully applies to build a monolithic photoanode with the FAPbBr3 absorber, carbon/graphite conductive protection layers, and NiFe catalyst layers for water oxidation. The photoanode delivers ultralow onset potential below 0 V versus the reversible hydrogen electrode and high applied bias photon-to-current efficiency of 8.5%. Stable operation exceeding 100 h under solar illumination by applying ultraviolet-filter protection. The photothermal investigation verifies the performance boost in perovskite photoanode by photothermal effect. This study is significant in guiding the development of photovoltaic material-based photoelectrodes for solar fuel applications.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...