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1.
Mol Ther ; 2024 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-39217415

RESUMO

As emerging and re-emerging pathogens, filoviruses, especially Ebola virus (EBOV), pose a great threat to public health and require sustained attention and ongoing surveillance. More vaccines and antiviral drugs are imperative to be developed and stockpiled to respond to unpredictable outbreaks. Virus-like vesicles, generated by alphavirus replicons expressing homogeneous or heterogeneous glycoproteins (GPs), have demonstrated the capacity of self-propagation and shown great potential in vaccine development. Here, we describe a novel class of EBOV-like vesicles (eVLVs) incorporating both EBOV GP and VP40. The eVLVs exhibited similar antigenicity as EBOV. In murine models, eVLVs were highly attenuated and elicited robust GP-specific antibodies with neutralizing activities. Importantly, a single dose of eVLVs conferred complete protection in a surrogate EBOV lethal mouse model. Furthermore, our VLVs strategy was also successfully applied to Marburg virus (MARV), the representative member of the genus Marburgvirus. Taken together, our findings indicate the feasibility of an alphavirus-derived VLVs strategy in combating infection of filoviruses represented by EBOV and MARV, which provides further evidence of the potential of this platform for universal live-attenuated vaccine development.

2.
Int J Surg ; 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39316640

RESUMO

BACKGROUND: Hepatoid adenocarcinoma of the stomach (HAS) is a rare subtype of gastric cancer (GC) with a poor prognosis. Furthermore, the current pathological staging system for HAS does not distinguish it from that for common gastric cancer (CGC). METHODS: The clinicopathological data of 251 patients with primary HAS who underwent radical surgery at 14 centers in China from April 2004 to December 2019 and 5082 patients with primary CGC who underwent radical surgery at 2 centers during the same period were retrospectively analyzed. A modified staging system was established based on the differences in survival. RESULTS: After 1:4 propensity score matching (PSM), 228 patients with HAS and 828 patients with CGC were analyzed. Kaplan-Meier (K-M) analysis showed patients with HAS had a poorer prognosis compared with CGC. Multivariate analysis identified pN stage, CEA level, and perineural invasion (PNI) as independent prognostic factors in patients with HAS. A modified pT (mpT) staging was derived using recursive partitioning analysis (RPA) incorporating PNI and pT staging. The modified pathological staging system (mpTNM) integrated the mpT and the 8th American Joint Committee on Cancer (AJCC) pN definitions. Multivariate analysis showed that mpTNM stage outperformed other pathological variables as independent predictors of OS and RFS in patients with HAS. The mpTNM staging system exhibited significantly higher predictive accuracy for 3-year OS in patients with HAS (0.707, 95% CI: 0.650-0.763) compared to that of the 8th AJCC staging system (0.667, 95% CI: 0.610-0.723, P<0.05). Analysis using the Akaike information criterion favored the mpTNM staging system over the 8th AJCC staging system (824.69 vs. 835.94) regarding the goodness of fit. The mpTNM stages showed improved homogeneity in survival prediction (likelihood ratio: 41.51 vs. 27.10). Comparatively the mpTNM staging system outperformed the 8th AJCC staging system in survival prediction, supported by improvements in the net reclassification index (NRI: 47.7%) and integrated discrimination improvement (IDI: 0.083, P<0.05). Time-dependent ROC curve showed that the mpTNM staging system consistently outperformed the 8th AJCC staging system with increasing observation time. CONCLUSION: The mpTNM staging system exhibited superior postoperative prognostic accuracy for patients with HAS compared to the 8th AJCC staging system.

3.
Zhongguo Zhong Yao Za Zhi ; 49(17): 4597-4606, 2024 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-39307798

RESUMO

This study aims to reveal the protective effect and mechanism of Zuogui Jiangtang Jieyu Formula on the damage to hippo-campal synaptic microenvironment in rats with diabetes-related depression(DD) via regulating microglia immune receptor molecule-like family member f(CD300f)/Toll-like receptor 4(TLR4) signal. Firstly, the model of DD rats was established by a two-week high-fat diet+STZ injection+chronic mild and unpredictable stress plus isolation for 28 days. The rats were randomly divided into normal group, model group, CD300f blocker(CLM1, 2 µg·kg~(-1)) group, CD300f agonist(Fcγ, 5 µg·kg~(-1)) group, positive drug(0.18 g·kg~(-1) metformin+1.8 mg·kg~(-1) fluoxetine) group, and high-dose and low-dose(20.52 and 10.26 g·kg~(-1)) Zuogui Jiangtang Jieyu Formula groups. Depression-like behavior of rats was evaluated by open field and forced swimming experiments. The levels of blood glucose and insulin were detected by biochemical analysis. The levels of tumor necrosis factor α(TNF-α), interleukin-1ß(IL-1ß), indoleamine 2, 3-dioxygenase(IDO), 5-hydroxytryptamine(5-HT), and dopamine(DA) in the hippocampus were detected by enzyme-linked immunosorbent assay. The changes in the synaptic ultrastructure in hippocampal neurons of rats were observed by transmission electron microscopy. The protein expressions of CD300f, TLR4, synaptophysin(SYN), and postsynaptic density protein 95(PSD-95) in microglial cells of the hippocampus were detected by immunofluorescence and Western blot. The results indicated that compared with that in the normal group, the total movement distance in open field experiments was reduced in the model group, and the immobility time in forced swimming experiments increased, with an elevated insulin level in serum, as well as TNF-α, IL-1ß, and IDO levels in the hippocampus. The 5-HT and DA levels in the hippocampus were reduced. In addition, the CD300f expression was down-regulated in microglial cells of the hippocampus, and the TLR4 expression was up-regulated. Moreover, the expression of synapse-related proteins SYN and PSD-95 in hippocampal neurons decreased, and the synaptic ultrastructure of hippocampal neurons was significantly damaged. Compared with the model group, the CD300f blocker and agonist aggravated and alleviated the above abnormal changes, respectively. High-dose and low-dose Zuogui Jiangtang Jieyu Formula could significantly improve the above depression-like beha-vior in rats, inhibit the abnormal increase of TNF-α, IL-1ß, and IDO and the decrease of 5-HT and DA, effectively increase the expression of CD300f in microglial cells, and decrease the expression of TLR4. They could up-regulate the protein expression of presyna-ptic membrane SYN and postsynaptic membrane PSD-95 in hippocampal neurons and finally improve the damage to the hippocampal synaptic microenvironment. In conclusion, this research confirmed that Zuogui Jiangtang Jieyu Formula effectively alleviated the depression-like behavior and inhibited inflammatory activation of microglial cells in the hippocampus of rats with DD, and the mechanism might be related to the regulation of CD300f/TLR4 signal to alleviate the damage to hippocampal synaptic microenvironment.


Assuntos
Depressão , Medicamentos de Ervas Chinesas , Hipocampo , Microglia , Neurônios , Ratos Sprague-Dawley , Receptor 4 Toll-Like , Animais , Receptor 4 Toll-Like/metabolismo , Receptor 4 Toll-Like/genética , Ratos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Masculino , Microglia/efeitos dos fármacos , Microglia/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Depressão/tratamento farmacológico , Depressão/metabolismo , Transdução de Sinais/efeitos dos fármacos , Sinapses/efeitos dos fármacos , Humanos , Receptores Imunológicos/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/genética
4.
Food Funct ; 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39264166

RESUMO

Background: Probiotics, prebiotics, and synbiotics have been suggested as a possible therapy for non-alcoholic fatty liver disease (NAFLD). However, their efficacy in improving blood glucose levels in NAFLD patients remains uncertain. Objective: The aim of this study was to assess the effects of supplementation with probiotics, prebiotics, or synbiotics on fasting blood glucose (FBG) levels in NAFLD patients. Methods: We searched PubMed, Web of Science, and Google Scholar for relevant trials published up to March 2024. Out of 3369 identified studies, 24 randomized controlled trials (RCTs) were included. Results: Probiotic, prebiotic, or synbiotic supplementation substantially reduced FBG (n = 23; standard mean difference (SMD) = -0.17; 95% confidence interval (CI): -0.30, -0.03; P = 0.02), fasting insulin levels (n = 12; SMD = -0.28; 95% CI: -0.49, -0.07; P = 0.01), and homeostatic model assessment for insulin resistance (HOMA-IR; n = 14; SMD = -0.28; 95% CI: -0.47, -0.09; P = 0.004). However, glycosylated hemoglobin (HbA1c; n = 3; SMD = -0.17; 95% CI: -0.48, 0.13; P = 0.27) was not significantly affected. The FBG-decreasing effect diminished as the body mass index (BMI) of volunteers increased in the baseline. Additionally, the number of probiotic strains and geographic region were shown to significantly affect FBG levels. Conclusion: This meta-analysis indicates that supplementation with probiotics, prebiotics, or synbiotics may aid in controlling glucose homeostasis in patients with NAFLD.

5.
Chin J Traumatol ; 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39294091

RESUMO

PURPOSE: This study aims to identify the prevalence and risk factors of military training-related abdominal injuries and help plan and conduct training properly. METHODS: This questionnaire survey study was conducted from October 2021 to May 2022 among military personnel from 6 military units and 8 military medical centers and participants' medical records were consulted to identify the training-related abdominal injuries. All the military personnel who ever participated in military training were included. Those who refused to participate in this study or provided an incomplete questionnaire were excluded. The questionnaire collected demographic information, type of abdominal injury, frequency, training subjects, triggers, treatment, and training disturbance. Chi-square test and t-test were used to compare baseline information. Univariate and multivariate regression analyses were used to explore the risk factors associated with military training-related abdominal injuries. RESULTS: A total of 3058 participants were involved in this study, among which 1797 (58.8%) had suffered training-related abdominal injuries (the mean age was 24.3 years and the service time was 5.6 years), while 1261 (41.2%) had no training-related abdominal injuries (the mean age was 23.1 years and the service time was 4.3 years). There were 546 injured patients (30.4%) suspended the training and 84 (4.6%) needed to be referred to higher-level hospitals. The most common triggers included inadequate warm-up, fatigue, and intense training. The training subjects with the most abdominal injuries were long-distance running (589, 32.8%). Civil servants had the highest rate of abdominal trauma (17.1%). Age ≥ 25 years, military service ≥ 3 years, poor sleep status, and previous abdominal history were independent risk factors for training-related abdominal injury. CONCLUSION: More than half of the military personnel have suffered military training-related abdominal injuries. Inadequate warm-up, fatigue, and high training intensity are the most common inducing factors. Scientific and proper training should be conducted according to the factors causing abdominal injuries.

6.
Mol Biol Evol ; 41(9)2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39213378

RESUMO

Polyploidization drives regulatory and phenotypic innovation. How the merger of different genomes contributes to polyploid development is a fundamental issue in evolutionary developmental biology and breeding research. Clarifying this issue is challenging because of genome complexity and the difficulty in tracking stochastic subgenome divergence during development. Recent single-cell sequencing techniques enabled probing subgenome-divergent regulation in the context of cellular differentiation. However, analyzing single-cell data suffers from high error rates due to high dimensionality, noise, and sparsity, and the errors stack up in polyploid analysis due to the increased dimensionality of comparisons between subgenomes of each cell, hindering deeper mechanistic understandings. In this study, we develop a quantitative computational framework, called "pseudo-genome divergence quantification" (pgDQ), for quantifying and tracking subgenome divergence directly at the cellular level. Further comparing with cellular differentiation trajectories derived from single-cell RNA sequencing data allows for an examination of the relationship between subgenome divergence and the progression of development. pgDQ produces robust results and is insensitive to data dropout and noise, avoiding high error rates due to multiple comparisons of genes, cells, and subgenomes. A statistical diagnostic approach is proposed to identify genes that are central to subgenome divergence during development, which facilitates the integration of different data modalities, enabling the identification of factors and pathways that mediate subgenome-divergent activity during development. Case studies have demonstrated that applying pgDQ to single-cell and bulk tissue transcriptomic data promotes a systematic and deeper understanding of how dynamic subgenome divergence contributes to developmental trajectories in polyploid evolution.


Assuntos
Poliploidia , Análise de Célula Única , Análise de Célula Única/métodos , Animais , Biologia Computacional/métodos
7.
Langmuir ; 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39150369

RESUMO

The interlayer strategy has emerged as an effective approach for modulating the interfacial polymerization process and improving the permeability and selectivity of polyamide membranes. However, the underlying mechanisms by which charged interlayers influence the interfacial polymerization process remain inadequately understood. In this study, we utilized two distinct charged cellulose nanofibers, namely, carboxylated cellulose (⊖-CNF) and quaternized cellulose ([Formula: see text]-CNF), as interlayers to regulate the interfacial polymerization process. Through simulation results, isothermal titration calorimetry (ITC) and UV tests, we demonstrated that the [Formula: see text]-CNF interlayer, which possesses stronger hydration capability and better piperazine affinity, enhanced the diffusion of piperazine across the reaction interface compared with the ⊖-CNF interlayer. This led to an acceleration of the interfacial polymerization process and the formation of a denser membrane structure. Further investigation revealed that the charged interlayers significantly influenced the surface charging properties of the resulting nanofiltration membranes within a 30 nm range of electrostatic effects. Specifically, the ⊖-CNF interlayer conferred a higher negative charge to the membrane surface, while the [Formula: see text]-CNF interlayer endowed the membranes with a lower surface negative charge. Leveraging these differences, the ⊖-i-TFC membranes exhibited exceptional separation performance for divalent anions, achieving a SO42-/Cl- selectivity of 136. Conversely, the [Formula: see text]-i-TFC membrane demonstrated an enhanced separation of divalent cations, displaying a Mg2+/Na+ selectivity of 3.5. This study lays the groundwork for regulating the surface charging properties of polyamide membranes, offering potential advancements in nanofiltration applications.

8.
Nucleic Acids Res ; 2024 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-39180394

RESUMO

Dipicolinic acid is an essential component of bacterial spores for stress resistance, which is released into the environment after spore germination. In a previous study, a dip gene cluster was found to be responsible for the catabolism of dipicolinic acid in Alcaligenes faecalis JQ135. However, the transcriptional regulatory mechanism remains unclear. The present study characterized the new GntR/FadR family transcriptional factor DipR, showing that the dip cluster is transcribed as the six transcriptional units, dipR, dipA, dipBC, dipDEFG, dipH and dipJKLM. The purified DipR protein has six binding sites sharing the 6-bp conserved motif sequence 5'-GWATAC-3'. Site-directed mutations indicated that these motif sequences are essential for DipR binding. Moreover, the four key amino acid residues R63, R67, H196 and H218 of DipR, examined by site-directed mutagenesis, played crucial roles in DipR regulation. Bioinformatics analysis showed that dip clusters including dipR genes are widely distributed in bacteria, are taxon-related, and co-evolved with their hosts. This paper provides new insights into the transcriptional regulatory mechanism of dipicolinic acid degradation by DipR in bacteria.

9.
Am Surg ; : 31348241265143, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39047144

RESUMO

OBJECTIVE: This study aimed to analyze the malignant probability of thyroid nodules diagnosed as indeterminate cytology, including atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS), and investigate the diagnostic value of combining BRAF V600E gene testing within this classification. METHODS: We conducted a retrospective analysis of 126 patients who underwent fine-needle aspiration (FNA) examination of thyroid nodules and subsequent surgical treatment at Beijing Haidian Hospital between October 2021 and November 2022. Among them, there were 22 male and 104 female patients, aged between 18 and 75 years old. Surgical pathology results were considered the gold standard for diagnosing the nature of thyroid nodules, evaluating the malignant incidence of cytological results categorized as AUS/FLUS. Fisher's exact test and diagnostic test evaluation methods were used to analyze the discriminatory diagnostic efficacy of preoperative FNA combined with BRAF V600E gene testing for papillary thyroid carcinoma (PTC). Statistical analysis was performed using SPSS 22.0 software. RESULTS: In PTC patients, the BRAF V600E gene mutation rate was 87.93% (102/116). Within the category of FNA results as AUS/FLUS, the proportion of PTC was 60.00% (15/25). The specificity, sensitivity, positive predictive value, and negative predictive value of the BRAF V600E gene mutation in diagnosing PTC within the AUS/FLUS category were 10/10, 6/15, 6/6, and 10/19, respectively. The BRAF V600E gene mutation significantly increased the detection rate of PTC in patients classified under this cytology (P = 0.028, <0.05). CONCLUSION: Preoperative FNA combined with BRAF V600E gene mutation testing significantly enhances the malignant detection rate of thyroid nodules diagnosed cytologically as AUS/FLUS. This combined approach provides a potent tool to improve diagnostic accuracy in this indeterminate classification.

10.
Nat Commun ; 15(1): 5705, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38977710

RESUMO

In nature, coenzyme-independent oxidases have evolved in selective catalysis using isolated substrate-binding pockets. Single-atom nanozymes (SAzymes), an emerging type of non-protein artificial enzymes, are promising to simulate enzyme active centers, but owing to the lack of recognition sites, realizing substrate specificity is a formidable task. Here we report a metal-ligand dual-site SAzyme (Ni-DAB) that exhibited selectivity in uric acid (UA) oxidation. Ni-DAB mimics the dual-site catalytic mechanism of urate oxidase, in which the Ni metal center and the C atom in the ligand serve as the specific UA and O2 binding sites, respectively, characterized by synchrotron soft X-ray absorption spectroscopy, in situ near ambient pressure X-ray photoelectron spectroscopy, and isotope labeling. The theoretical calculations reveal the high catalytic specificity is derived from not only the delicate interaction between UA and the Ni center but also the complementary oxygen reduction at the beta C site in the ligand. As a potential application, a Ni-DAB-based biofuel cell using human urine is constructed. This work unlocks an approach of enzyme-like isolated dual sites in boosting the selectivity of non-protein artificial enzymes.


Assuntos
Oxirredução , Urato Oxidase , Ácido Úrico , Especificidade por Substrato , Urato Oxidase/química , Urato Oxidase/metabolismo , Ácido Úrico/química , Ácido Úrico/metabolismo , Ácido Úrico/urina , Ligantes , Humanos , Níquel/química , Níquel/metabolismo , Sítios de Ligação , Domínio Catalítico , Catálise , Modelos Moleculares , Espectroscopia por Absorção de Raios X
11.
Front Neurol ; 15: 1393022, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38846044

RESUMO

Purpose: The prevalence of comorbid pain and Bipolar Disorder in clinical practice continues to be high, with an increasing number of related publications. However, no study has used bibliometric methods to analyze the research progress and knowledge structure in this field. Our research is dedicated to systematically exploring the global trends and focal points in scientific research on pain comorbidity with bipolar disorder from 2003 to 2023, with the goal of contributing to the field. Methods: Relevant publications in this field were retrieved from the Web of Science core collection database (WOSSCC). And we used VOSviewer, CiteSpace, and the R package "Bibliometrix" for bibliometric analysis. Results: A total of 485 publications (including 360 articles and 125 reviews) from 66 countries, 1019 institutions, were included in this study. Univ Toront and Kings Coll London are the leading research institutions in this field. J Affect Disorders contributed the largest number of articles, and is the most co-cited journal. Of the 2,537 scholars who participated in the study, Stubbs B, Vancampfort D, and Abdin E had the largest number of articles. Stubbs B is the most co-cited author. "chronic pain," "neuropathic pain," "psychological pain" are the keywords in the research. Conclusion: This is the first bibliometric analysis of pain-related bipolar disorder. There is growing interest in the area of pain and comorbid bipolar disorder. Focusing on different types of pain in bipolar disorder and emphasizing pain management in bipolar disorder are research hotspots and future trends. The study of pain related bipolar disorder still has significant potential for development, and we look forward to more high-quality research in the future.

12.
Drug Des Devel Ther ; 18: 2227-2248, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38882046

RESUMO

Purpose: The Baihe Dihuang decoction (BDD) is a representative traditional Chinese medicinal formula that has been used to treat anxiety disorders for thousands of years. This study aimed to reveal mechanisms of anxiolytic effects of BDD with multidimensional omics. Methods: First, 28-day chronic restraint stress (CRS) was used to create a rat model of anxiety, and the open field test and elevated plus maze were used to assess anxiety-like behavior. Enzyme-linked immunosorbent assay (ELISA), hematoxylin-eosin staining, and immunofluorescence staining were used to evaluate inflammatory response. Besides, 16S rRNA gene sequencing assessed fecal microbiota composition and differential microbiota. Non-targeted metabolomics analysis of feces was performed to determine fecal biomarkers, and targeted metabolomics was used to observe the levels of hippocampus neurotransmitters. Finally, Pearson correlation analysis was used to examine relationships among gut microbiota, fecal metabolites, and neurotransmitters. Results: BDD significantly improved anxiety-like behaviors in CRS-induced rats and effectively ameliorated hippocampal neuronal damage and abnormal activation of hippocampal microglia. It also had a profound effect on the diversity of microbiota, as evidenced by significant changes in the abundance of 10 potential microbial biomarkers at the genus level. Additionally, BDD led to significant alterations in 18 fecal metabolites and 12 hippocampal neurotransmitters, with the majority of the metabolites implicated in amino acid metabolism pathways such as D-glutamine and D-glutamate, alanine, arginine and proline, and tryptophan metabolism. Furthermore, Pearson analysis showed a strong link among gut microbiota, metabolites, and neurotransmitters during anxiety and BDD treatment. Conclusion: BDD can effectively improve anxiety-like behaviors by regulating the gut-brain axis, including gut microbiota and metabolite modification, suppression of hippocampal neuronal inflammation, and regulation of neurotransmitters.


Assuntos
Ansiolíticos , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas , Microbioma Gastrointestinal , Metabolômica , Ratos Sprague-Dawley , Animais , Ratos , Ansiolíticos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Masculino , Microbioma Gastrointestinal/efeitos dos fármacos , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/metabolismo , Ansiedade/tratamento farmacológico , Ansiedade/metabolismo , Restrição Física , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo
13.
World J Clin Cases ; 12(17): 2946-2950, 2024 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-38898826

RESUMO

Hypoparathyroidism is one of the main complications after total thyroidectomy, severely affecting patients' quality of life. How to effectively protect parathyroid function after surgery and reduce the incidence of hypoparathyroidism has always been a key research area in thyroid surgery. Therefore, precise localization of parathyroid glands during surgery, effective imaging, and accurate surgical resection have become hot topics of concern for thyroid surgeons. In response to this clinical phenomenon, this study compared several different imaging methods for parathyroid surgery, including nanocarbon, indocyanine green, near-infrared imaging techniques, and technetium-99m methoxyisobutylisonitrile combined with gamma probe imaging technology. The advantages and disadvantages of each method were analyzed, providing scientific recommendations for future parathyroid imaging. In recent years, some related basic and clinical research has also been conducted in thyroid surgery. This article reviewed relevant literature and provided an overview of the practical application progress of various imaging techniques in parathyroid surgery.

14.
Front Endocrinol (Lausanne) ; 15: 1410370, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38872963

RESUMO

Background: The involvement of ATP and cAMP in sperm function has been extensively documented, but the understanding of the role of adenosine and adenosine receptors remains incomplete. This study aimed to examine the presence of adenosine A2A receptor (A2AR) and study the functional role of A2AR in human sperm. Methods: The presence and localization of A2AR in human sperm were examined by western blotting and immunofluorescence assays. The functional role of A2AR in sperm was assessed by incubating human sperm with an A2AR agonist (regadenoson) and an A2AR antagonist (SCH58261). The sperm level of A2AR was examined by western blotting in normozoospermic and asthenozoospermic men to evaluate the association of A2AR with sperm motility and in vitro fertilization (IVF) outcomes. Results: A2AR with a molecular weight of 43 kDa was detected in the tail of human sperm. SCH58261 decreased the motility, penetration ability, intracellular Ca2+ concentration, and CatSper current of human sperm. Although regadenoson did not affect these sperm parameters, it alleviated the adverse effects of SCH58261 on these parameters. In addition, the mean level of A2AR in sperm from asthenozoospermic men was lower than that in sperm from normozoospermic men. The sperm level of A2AR was positively correlated with progressive motility. Furthermore, the fertilization rate during IVF was lower in men with decreased sperm level of A2AR than in men with normal sperm level of A2AR. Conclusions: These results indicate that A2AR is important for human sperm motility and is associated with IVF outcome.


Assuntos
Fertilização in vitro , Receptor A2A de Adenosina , Motilidade dos Espermatozoides , Espermatozoides , Adulto , Feminino , Humanos , Masculino , Agonistas do Receptor A2 de Adenosina/farmacologia , Antagonistas do Receptor A2 de Adenosina/farmacologia , Astenozoospermia/metabolismo , Pirazóis/farmacologia , Pirimidinas/farmacologia , Receptor A2A de Adenosina/metabolismo , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Espermatozoides/efeitos dos fármacos , Triazóis/farmacologia
15.
J Hazard Mater ; 476: 135045, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-38944990

RESUMO

Isoprocarb (IPC), a representative monocyclic carbamate insecticide, poses risks of environmental contamination and harm to non-target organisms. However, its degradation mechanism has not been reported. In this study, a newly IPC-degrading strain D-6 was isolated from the genus Rhodococcus, and its degradation characteristics and pathway of IPC were analyzed. A novel hydrolase IpcH, responsible for hydrolyzing IPC to 2-isopropylphenol (IPP), was identified. IpcH exhibited low similarity (< 27 %) with other reported hydrolases, including previously characterized carbamate insecticides hydrolases, indicating its novelty. The Km and kcat values of IpcH towards IPC were 69.99 ± 8.33 µM and 95.96 ± 4.02 s-1, respectively. Also, IpcH exhibited catalytic activity towards various types of carbamate insecticides, including monocyclic carbamates (IPC, fenobucarb and propoxur), bicyclic carbamates (carbaryl and carbofuran), and linear carbamates (oxamyl and aldicarb). The molecular docking and site-directed mutagenesis revealed that His254, His256, His329 and His376 were essential for IpcH activity. Strain D-6 can effectively reduce the toxicity of IPC and IPP towards sensitive organisms through its degradation ability. This study presents the initial report on IPC degradation pathway and molecular mechanism of IPC degradation, and provides a good potential strain for bioremediating IPC and IPP-contaminated environments.


Assuntos
Biodegradação Ambiental , Hidrolases , Inseticidas , Rhodococcus , Rhodococcus/metabolismo , Rhodococcus/genética , Hidrolases/metabolismo , Hidrolases/genética , Inseticidas/metabolismo , Inseticidas/química , Inseticidas/toxicidade , Simulação de Acoplamento Molecular , Uretana/metabolismo , Uretana/química
16.
J Hazard Mater ; 476: 134968, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-38901263

RESUMO

The widely used phenylurea herbicide isoproturon (IPU) and its residues can inhibit the growth of subsequently planted crops. However, reports on bioremediation of IPU-contaminated soil are scarce. In this study, Sphingobium sp. strain YBL2-gfp (a derivative of the IPU-degrading Sphingobium sp. strain YBL2 isolated by our lab) was constructed to bioremediate IPU-contaminated soil. In pot experiments, strain YBL2-gfp colonized the roots of wheat and eliminated IPU residues in the soil within 21 d, effectively alleviating its toxicity and restoring wheat growth. IPU treatment reduced the richness and diversity of soil bacteria, while inoculation YBL2-gfp mainly affected richness with less impact on diversity. The high concentrations of IPU and inoculation of YBL2-gfp alone reduced the soil microbial community connections, while bioaugmentation treatment enhanced the soil microbial community connections. Additionally, strain YBL2-gfp stimulated the metabolic capacity of the indigenous microbes, promoting the degradation of IPU and reducing the negative impact of high concentrations of IPU on microbial community. Taken together, this study offers relatively comprehensive insights into the practical application of bioaugmentation, demonstrating that strain YBL2 has the potential to remediate IPU-contaminated soils.


Assuntos
Biodegradação Ambiental , Herbicidas , Compostos de Fenilureia , Microbiologia do Solo , Poluentes do Solo , Sphingomonadaceae , Poluentes do Solo/metabolismo , Sphingomonadaceae/metabolismo , Sphingomonadaceae/genética , Sphingomonadaceae/crescimento & desenvolvimento , Herbicidas/metabolismo , Compostos de Fenilureia/metabolismo , Triticum/metabolismo , Triticum/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Raízes de Plantas/crescimento & desenvolvimento
17.
PLoS One ; 19(5): e0302068, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38758945

RESUMO

The electric power sector is the primary contributor to carbon emissions in China. Considering the context of dual carbon goals, this paper examines carbon emissions within China's electricity sector. The research utilizes the LMDI approach for methodological rigor. The results show that the cumulative contribution of economies scale, power consumption factors and energy structure are 114.91%, 85.17% and 0.94%, which contribute to the increase of carbon emissions, the cumulative contribution of power generation efficiency and ratio of power dissipation to generation factor are -19.15% and -0.01%, which promotes the carbon reduction. The decomposition analysis highlights the significant influence of economic scale on carbon emissions in the electricity industry, among the seven factors investigated. Meanwhile, STIRPAT model, Logistic model and GM(1,1) model are used to predict carbon emissions, the average relative error between actual carbon emissions and the predicted values are 0.23%, 8.72% and 7.05%, which indicates that STIRPAT model is more suitable for medium- to long-term predictions. Based on these findings, the paper proposes practical suggestions to reduce carbon emissions and achieve the dual carbon goals of the power industry.


Assuntos
Carbono , Eletricidade , China , Carbono/análise , Indústrias , Centrais Elétricas , Modelos Teóricos
18.
Zhongguo Zhong Yao Za Zhi ; 49(9): 2489-2500, 2024 May.
Artigo em Chinês | MEDLINE | ID: mdl-38812153

RESUMO

This study aims to reveal the molecular mechanism of Chaijin Jieyu Anshen Tablets(CJJYAS) in regulating the abnormal anterior cingulate cortex(ACC)-ventral hippocampus(vHPC) glutaminergic neural circuit to alleviate synaptic remodeling of ventral hippocampal neurons in depressed rats. Firstly, the study used chemogenetics to localize glutaminergic adeno-associated virus(AAV) into the ACC brain region of rats. The model of depressed rats was established by chronic unpredictable mild stress(CUMS) combined with independent feeding. The rats were randomly divided into control group, model group, AAV empty group, AAV group, AAV+ glucocorticoid receptors(GR) blocker group, AAV+chemokine receptor 1(CX3CR1) blocker group, and AAV+CJJYAS group. Depressive-like behaviors of rats were evaluated by open-field, forced-swimming, and Morris water maze tests, combined with an animal behavior analysis system. The morphological and structural changes of ACC and vHPC neurons in rats were observed by hematoxylin-eosin(HE) staining. Immunofluorescence and nuclear phosphoprotein(c-Fos) were used to detect glutaminergic neural circuit activation of ACC-vHPC in rats. The changes in dendrites, synaptic spines, and synaptic submicrostructure of vHPC neurons were observed by Golgi staining and transmission electron microscopy, respectively. The expressions of synaptic remodeling-related proteins N-methyl-D-asprtate receptor 2A(GRIN2A), N-methyl-D-asprtate receptor 2B(GRIN2B), Ca~(2+)/calmodulin-dependent protein kinase Ⅱ(CaMKⅡ), mitogen-activated protein kinase-activated protein kinase 2(MK2), and a ubiquitous actin-binding protein(cofilin) in vHPC glutaminergic neurons of rats were detected by immunofluorescence and Western blot, respectively. The results indicated that the activated glutaminergic AAV aggravated the depressive-like behaviors phenotype of rats in the model group and deteriorated the damage of morphology and structure of ACC and vHPC neurons and synaptic ultrastructure. However, both GR and CX3CR1 bloc-kers could reverse the abnormal changes to varying degrees, suggesting that the abnormal activation of ACC-vHPC glutaminergic neural circuit mediated by GR/CX3CR1 signals in gliocytes in the ACC brain region may be closely related to the occurrence and development of depression. Interestingly, CJJYAS significantly inhibited the activation of the ACC-vHPC glutaminergic neural circuit induced by AAV and the elevated Glu level. Furthermore, CJJYAS could also effectively reverse the aggravation of depressive-like behaviors and synaptic remodeling of vHPC neurons of rats in the model group induced by the activated AAV. Additionally, the findings suggested that the molecular mechanism of CJJYAS in improving synaptic damage of vHPC neurons might be related to the regulation of synaptic remodeling-related signals such as NR/CaMKⅡ and MK2/cofilin. In conclusion, this research confirms that CJJYAS effectively regulates the abnormal ACC-vHPC glutaminergic neural circuit and alleviates the synaptic remodeling of vHPC glutaminergic neurons in depressed rats, and the molecular mechanism might be associated with the regulation of synapse-related NR/CaMKⅡ and MK2/cofilin signaling pathways, which may be the crucial mechanism of its antidepressant effect.


Assuntos
Depressão , Medicamentos de Ervas Chinesas , Giro do Cíngulo , Hipocampo , Neurônios , Ratos Sprague-Dawley , Animais , Ratos , Masculino , Neurônios/metabolismo , Hipocampo/metabolismo , Depressão/metabolismo , Depressão/fisiopatologia , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/administração & dosagem , Giro do Cíngulo/metabolismo , Giro do Cíngulo/fisiopatologia , Sinapses/metabolismo , Plasticidade Neuronal , Humanos
19.
Theor Appl Genet ; 137(6): 128, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38733405

RESUMO

KEY MESSAGE: Discovery of Rht27, a dwarf gene in wheat, showed potential in enhancing grain yield by reducing plant height. Plant height plays a crucial role in crop architecture and grain yield, and semi-dwarf Reduced Height (Rht) alleles contribute to lodging resistance and were important in "Green Revolution." However, the use of these alleles is associated with some negative side effects in some environments, such as reduced coleoptile length, low nitrogen use efficiency, and reduced yield. Therefore, novel dwarf gene resources are needed to pave an alternative route to overcome these side effects. In this study, a super-dwarf mutant rht27 was obtained by the mutagenesis of G1812 (Triticum urartu, the progenitor of the A sub-genome of common wheat). Genetic analysis revealed that the dwarf phenotype was regulated by a single recessive genetic factor. The candidate region for Rht27 was narrowed to a 1.55 Mb region on chromosome 3, within which we found two potential candidate genes that showed polymorphisms between the mutant and non-mutagenized G1812. Furthermore, the natural variants and elite haplotypes of the two candidates were investigated in a natural population of common wheat. The results showed that the natural variants affect grain yield components, and the dwarf haplotypes show the potential in improving agronomic traits and grain yield. Although the mutation in Rht27 results in severe dwarf phenotype in T. urartu, the natural variants in common wheat showed desirable phenotype, which suggests that Rht27 has the potential to improve wheat yield by utilizing its weak allelic mutation or fine-tuning its expression level.


Assuntos
Genes de Plantas , Triticum , Alelos , Mapeamento Cromossômico , Haplótipos , Fenótipo , Triticum/genética , Triticum/crescimento & desenvolvimento
20.
Research (Wash D C) ; 7: 0359, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38694199

RESUMO

Porous substrates act as open "interfacial reactors" during the synthesis of polyamide composite membranes via interfacial polymerization. However, achieving a thin and dense polyamide nanofilm with high permeance and selectivity is challenging when using a conventional substrate with uniform wettability. To overcome this limitation, we propose the use of Janus porous substrates as confined interfacial reactors to decouple the local monomer concentration from the total monomer amount during interfacial polymerization. By manipulating the location of the hydrophilic/hydrophobic interface in a Janus porous substrate, we can precisely control the monomer solution confined within the hydrophilic layer without compromising its concentration. The hydrophilic surface ensures the uniform distribution of monomers, preventing the formation of defects. By employing Janus substrates fabricated through single-sided deposition of polydopamine/polyethyleneimine, we significantly reduce the thickness of the polyamide nanofilms from 88.4 to 3.8 nm by decreasing the thickness of the hydrophilic layer. This reduction leads to a remarkable enhancement in water permeance from 7.2 to 52.0 l/m2·h·bar while still maintaining ~96% Na2SO4 rejection. The overall performance of this membrane surpasses that of most reported membranes, including state-of-the-art commercial products. The presented strategy is both simple and effective, bringing ultrapermeable polyamide nanofilms one step closer to practical separation applications.

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