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Perioperative neurocognitive disorders (PND) are intractable, indistinct, and considerably diminish the postoperative quality of life of patients. It has been proved that Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) was involved in neurodegenerative diseases by regulating mitochondrial biogenesis. The underlying mechanisms of PGC-1α and Nod-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome in PND are not well understood. In this study, we constructed a model of laparotomy in aged mice, and then examined the cognition changes with novel object recognition tests and fear condition tests. The protein levels of PGC-1α and NLRP3 in the hippocampus were detect after surgery. Our results showed that NLRP3 and downstream PI3K/AKT pathway expressions were augmented in the hippocampus after surgery, whereas, the expressions of PGC-1α/estrogen-related receptor α (ERRα)/Unc-51-like autophagy activating kinase 1 (ULK1) pathway were diminished after surgery. In addition, we found that NLRP3 was mainly co-localized with neurons in the hippocampus, and synaptic-related proteins were reduced after surgery. At the same time, transmission electron microscopy (TEM) showed that mitochondria were impaired after surgery. Pharmacological treatment of MCC950, a selective NLRP3 inhibitor, effectively alleviated PND. Activation of PGC-1α with ZLN005 significantly ameliorated PND by enhancing the PGC-1α/ERRα/ULK1 signaling pathway, and further suppressing NLRP3 activation. As a result, we conclude that suppression of the PGC-1α/ERRα/ULK1 signaling pathway is the primary mechanism of PND which caused mitochondrial dysfunction, and activated NLRP3 inflammasome and downstream PI3K/AKT pathway, eventually improved cognitive dysfunction.
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Introduction: An intelligent office blood pressure measurement (IOBPM) model for community-based hypertension management was piloted in Shanghai, China, to overcome the conventional blood pressure management (CBPM) model's deficiencies. Methods: We selected adults aged 35-89 years who were being treated and managed for hypertension in two community health centers for the IOBPM and CBPM models. The IOBPM model consisted of two or three consecutive blood pressure (BP) measurements using a pre-programmed and validated automatic device. The BP data for the CBPM model were obtained from the routine follow-up records of hypertensive patients and derived from the Shanghai Non-communicable Diseases Management Information System. Subjects in the IOBPM model were selected by a simple random sampling method, and propensity score matching was used to select a comparable control population from the CBPM model based on important covariables. The BP levels, end-digit preferences, frequency distribution, and BP control were compared between the two models. Results: We selected 2,909 patients for the IOBPM model and 5,744 for the CBPM model. The systolic BP in the CBPM model was 12.3 mmHg lower than in the IOBPM model. In the CBPM model, there were statistically significant end-digit preferences (P < 0.001), with zero being the most reported end-digit (23.3% for systolic BP and 27.7% for diastolic BP). There was no significant end-digit preference in the IOBPM model. Certain BP values below 140/90 mmHg in the CBPM model were more frequent, while the IOBPM model showed a normal distribution. The BP control in the CBPM model was significantly higher than the IOBPM model (P < 0.001). Conclusion: The IOBPM model appears to overcome the deficiencies of the CBPM model, leading to more accurate and reliable BP measurements.
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Determinação da Pressão Arterial , Pressão Sanguínea , Hipertensão , Humanos , Pessoa de Meia-Idade , China/epidemiologia , Feminino , Masculino , Idoso , Projetos Piloto , Adulto , Determinação da Pressão Arterial/métodos , Hipertensão/fisiopatologia , Hipertensão/epidemiologia , Hipertensão/diagnóstico , Pressão Sanguínea/fisiologia , Idoso de 80 Anos ou maisRESUMO
Objective: To systematically review studies on the correlation between sleep duration during pregnancy and gestational diabetes mellitus (GDM) and use meta-analysis to explore the correlation between the two to provide a basis for preventing GDM during pregnancy. Methods: The search databases were China Knowledge Network (CNKI), Weipu, Wanfang, China Biomedical Literature Service System (SinoMed), Cochrane Library, Web of Science, Embase, and PubMed, and the search time was from the establishment of the above databases to July 2023. The data were statistically analyzed using STATA/MP17 and RevMan 5.3 software. Publication bias could be accurately assessed using funnel plots and Egger's test. Results: A total of 5,197 papers were searched, and 13 studies were finally included, which included 80,259 individuals, including 3,461 patients with GDM. The comprehensive analysis showed that. Based on pooled data from prospective, cross-sectional, and case-control studies, extreme sleep duration during pregnancy was strongly associated with GDM compared with average sleep duration. The results of the prospective studies showed that both short (OR = 1.50, 95% CI: 1.07-2.10, I2 = 60.9%, p = 0.02) and long (OR = 1.28, 95% CI: 1.13-1.46, I2 = 0.0%, p < 0.0001) sleep duration increased the risk of gestational diabetes mellitus, but the harms were more pronounced with short sleep. In analyzing the association between extreme sleep duration and GDM, publication bias was found in prospective, cross-sectional, and case-control studies with moderate heterogeneity and prospective-only studies with low heterogeneity. Conclusion: Both too short and too long sleep duration during pregnancy are strongly associated with GDM. Either too short or too long sleep duration predicts the risk of developing GDM, but the harms are more pronounced with short sleep. These findings remind us of the importance of controlling sleep duration during pregnancy and help to optimize early strategies to prevent GDM.Systematic review registration: http://www.crd.york.ac.uk/prospero, identifier [CRD42023470925].
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BACKGROUND: Uniparental disomy is the inheritance of a homologous chromosome pair or part of homologous chromosomes from only one parent. However, the clinical significance of uniparental disomy and the difference among the prognosis of involvement of different chromosomes remain unclear. OBJECTIVE: To assess the associated prenatal ultrasound presentations and clinical outcomes of uniparental disomy on different chromosomes and to analyze the relationship between prenatal ultrasound markers and clinical outcomes. STUDY DESIGN: We retrospectively analyzed data from fetuses with uniparental disomy diagnosed using chromosome microarray analysis with the Affymetrix CytoScan HD array at our institution between January 2013 and September 2022. The relationship between prenatal ultrasound findings, the involved chromosome(s), and clinical outcomes was evaluated. RESULTS: During the study period, 36 fetuses with uniparental disomy were diagnosed, and two cases were excluded for non-available postnatal data. Finally, 34 fetuses were included in our study, of which 30 (88.2%) had uniparental disomy occurring on a single chromosome, while four (11.8%) were identified with uniparental disomy on different chromosomes. The most frequently involved chromosomes were chromosomes 16, X and 2, which presented in 8 (23.5%), 5 (14.7%) and 4 (11.8%), respectively. Prenatal ultrasound abnormalities were detected in 21 fetuses, with the most common category being multiple abnormalities (12 (57.1%)). Fetal growth restriction was identified in 14 (41.2%) fetuses, all of which coexisted with other abnormal findings. The rate of adverse perinatal outcomes in patients with uniparental disomy and fetal abnormalities was significantly higher than those without abnormalities (76.2% versus 15.4%, P = 0.002). The incidence of fetal or neonatal death was significantly higher in fetuses with fetal growth restriction than those without (85.7% versus 30.0%, P = 0.004). CONCLUSIONS: The prognosis of fetuses with uniparental disomy combined with fetal abnormalities, especially fetal growth restriction, was much poorer than those without.
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Anormalidades Múltiplas , Dissomia Uniparental , Feminino , Recém-Nascido , Gravidez , Humanos , Dissomia Uniparental/genética , Estudos Retrospectivos , Retardo do Crescimento Fetal/genética , Ultrassonografia Pré-Natal , Diagnóstico Pré-NatalRESUMO
Motivation-driven mating is a basic affair for the maintenance of species. However, the underlying molecular mechanisms that control mating motivation are not fully understood. Here, we report that NRG1-ErbB4 signaling in the medial amygdala (MeA) is pivotal in regulating mating motivation. NRG1 expression in the MeA negatively correlates with the mating motivation levels in adult male mice. Local injection and knockdown of MeA NRG1 reduce and promote mating motivation, respectively. Consistently, knockdown of MeA ErbB4, a major receptor for NRG1, and genetic inactivation of its kinase both promote mating motivation. ErbB4 deletion decreases neuronal excitability, whereas chemogenetic manipulations of ErbB4-positive neuronal activities bidirectionally modulate mating motivation. We also identify that the effects of NRG1-ErbB4 signaling on neuronal excitability and mating motivation rely on hyperpolarization-activated cyclic nucleotide-gated channel 3. This study reveals a critical molecular mechanism for regulating mating motivation in adult male mice.
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Motivação , Transdução de Sinais , Camundongos , Masculino , Animais , Neurônios/metabolismo , Receptor ErbB-4/metabolismo , Tonsila do Cerebelo/metabolismo , Neuregulina-1/metabolismoRESUMO
Versatile, informative, sensitive, and specific nucleic acid detection plays a crucial role in point-of-care pathogen testing, genotyping, and disease monitoring. In this study, we present a novel one-pot Cas12b-based method coupled with the "Green-Yellow-Red" strategy for multiplex detection. By integrating RT-LAMP amplification and Cas12b cleavage in a single tube, the entire detection process can be completed within 1 h. Our proposed method exhibits high specificity, enabling the discrimination of single-base mutations with detection sensitivity approaching single molecule levels. Additionally, the fluorescent results can be directly observed by the naked eye or automatically analyzed using our custom-designed software Result Analyzer. To realize point-of-care detection, we developed a portable cartridge capable of both heating and fluorescence excitation. In a clinical evaluation involving 20 potentially SARS-CoV-2-infected samples, our method achieved a 100% positive detection rate when compared to standard RT-PCR. Furthermore, the identification of SARS-CoV-2 variants using our method yielded results that were consistent with the sequencing results. Notably, our proposed method demonstrates excellent transferability, allowing for the simultaneous detection of various pathogens and the identification of mutations as low as 0.5% amidst a high background interference. These findings highlight the tremendous potential of our developed method for molecular diagnostics.
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Lithium-sulfur (Li-S) batteries show advantage of high theoretical capacity. However, the shuttle effect of polysulfides and sluggish sulfur redox kinetics seriously reduce their service life. Inspired by the porous structural features of biomass materials, herein, a functional interlayer is fabricated by silkworm excrement-derived three-dimensional porous carbon accommodating nano sized CoS2 particles (SC@CoS2 ). The porous carbon delivers a high specific surface area, which provides adequate adsorption sites, being responsible for suppressing the shuttle effect of polysulfides. Meanwhile, the porous carbon is favorable for hindering the aggregation of CoS2 and maintaining its high activity during extended cycles, which effectively accelerates the polysulfides conversion kinetics. Moreover, the SC@CoS2 functional interlayer effectively limits the formation of Li dendrites and promotes the uniform deposition of Li on the Li electrode surface. As a result, the CMK-3/S cathode achieves a high initial capacity of 1599.1â mAh g-1 at 0.2â C rate assisted by the polypropylene separator coated with the functional interlayer and 1208.3â mAh g-1 is maintained after the long cycling test. This work provides an insight into the designing of long-lasting catalysts for stable functional interlayer, which encourages the application of biomass-derived porous carbon in high-energy Li-S batteries.
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Objective: Microorganisms have been the main cause of refractory and high recurrence of diabetic foot ulcer (DFU). This study attempted to observe the skin bacterial colony in healthy skin, diabetic skin and DFU skin. Methods: Forty-eight diabetes patients were recruited at Panyu Central Hospital from March 2021 to March 2022 and divided into DFU group (T group, n = 22), diabetes without foot ulcer group (TW group, n = 26). Besides, a healthy control group (H group, n = 10) was recruited at the same time. The swab samples of foot skin in the same position in the three groups were collected. The microorganisms obtained from the skin were analyzed by 16S rRNA gene sequencing. The composition of the skin microorganisms was determined, and the species diversity of the skin microbiota was analyzed by α and ß diversity. The species differences in the skin microbiota and the relative abundance of different operational taxonomic units (OUTs) with the most significant abundance were analyzed by linear discriminant analysis effect size (LEfSe). Results: Significant changes were found in the composition of the skin microbiota in the T and TW groups relative to the H group. However, the species diversity of the skin microbiota was significantly reduced in the T and TW groups, with the lowest one in the T group. The composition of microbial diversity in the T group was significantly different from that of the TW and H groups. Among the skin bacterial colonies, the abundance of Staphylococcus, Enhydrobacter, and Corynebacterium_1 was obviously reduced, while that of Escherichia coli and Pseudomonas was significantly increased. Conclusion: Changes in the abundance of Staphylococcus, Enhydrobacter, Corynebacterium_1, Escherichia coli and Pseudomonas in the skin bacterial colonies can be the main causative factors for DFU. This study indicates that altering the microbiota composition of wounds may help the treatment of DFU.
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Dual-interfacial structure within catalysts is capable of mitigating the detrimentally completive adsorption during the catalysis process, but its construction strategy and mechanism understanding remain vastly lacking. Here, a highly active dual-interfaces of CeO2-x/CoO1-x/Co is constructed using the pronounced interfacial interaction from surrounding small CeO2-x islets, which shows high activity in catalyzing the water-gas shift reaction. Kinetic evidence and in-situ characterization results revealed that CeO2-x modulates the oxidized state of Co species and consequently generates the dual active CeO2-x/CoO1-x/Co interface during the WGS reaction. A synergistic redox mechanism comprised of independent contribution from dual functional interfaces, including CeO2-x/CoO1-x and CoO1-x/Co, is authenticated by experimental and theoretical results, where the CeO2-x/CoO1-x interface alleviates the CO poison effect, and the CoO1-x/Co interface promotes the H2 formation. The results may provide guidance for fabricating dual-interfacial structures within catalysts and shed light on the mechanism over multi-component catalyst systems.
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OBJECTIVE: To investigate the effects of ferulic acid (FA) on proliferation, apoptosis and Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway of human acute myeloid leukemia (AML) U937 cells. METHODS: Different concentrations of FA (0ã10ã25ã50ã100ã200 µmol/L) was used to treat human AML cell lines Kasumi-1, HL-60, and U937 cells respectively for 24 h. The cell survival rate was detected by cell counting kit-8 method, and the 50% inhibitory concentration (IC50) of each cell line was calculated. The U937 cells were divided into control group, FA group (50 µmol/L FA), FA+pcDNA group (50 µmol/L FA+transfected with empty plasmid), FA+pcDNA-TLR4 group (50 µmol/L FA+transfected with TLR4 overexpression plasmid). Flow cytometry was used to detect U937 cell cycle and cell apoptosis; plate clone formation test was used to detect U937 cell clone formation ability; fluorescence quantitative PCR was used to detect the TLR4, NF-κB p65 mRNA levels in U937 cells; Western blot was used to detect the expression levels of CyclinD1, CyclinE, Bcl-2 related X protein (Bax), B cell lymphoma-2 (Bcl-2), Caspase-3, TLR4, and NF-κB p65 protein in U937 cells. RESULTS: With the increase of FA concentration, the survival rates of Kasumi-1, HL-60 and U937 cells gradually decreased(r=-0.919, r=-0.909, r=-0.900), the IC50 of U937 cells was 50.25±2.23 µmol/L. Compared with the control group, after drug treatment of U937 cells, the ratio of G0/G1 phase cells, apoptosis rate, expression levels of Bax and Caspase-3 proteins in FA group were significantly increased (P<0.05), the number of cell clones, the ratios of S phase and G2/M phase cells, expression levels of CyclinD1, CyclinE and Bcl-2 proteins, and TLR4, NF-κB p65 mRNA and protein were significantly decreased (P<0.05); compared with FA group and FA+pcDNA group, the ratio of G0/G1 phase cells, apoptosis rate, expression levels of Bax and Caspase-3 proteins in FA+pcDNA-TLR4 group were significantly decreased (P<0.05), the number of cell clones, the ratios of S phase and G2/M phase cells, expression levels of expression levels of CyclinD1, CyclinE and Bcl-2 proteins, and TLR4, NF-κB p65 mRNA and proteins were significantly increased (P<0.05). CONCLUSION: FA inhibits U937 cell proliferation and promotes cell apoptosis by inhibiting the TLR4/NF-κB signaling pathway.
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To investigate the biological role and mechanism of circ_0084188 in colorectal cancer (CRC). Real-time quantitative polymerase chain reaction and western blot assay were used to detect RNA levels and protein levels in CRC cell lines (HCT116 and SW480), respectively. Cell proliferation was evaluated by Cell Counting Kit-8 assay, 5-ethynyl-2'-deoxyuridine assay, and colony formation assays. Cell apoptosis was determined using flow cytometry. Cell migration and invasion were measured by transwell assay. Sphere formation efficiency was determined by sphere formation assay. The interaction between microRNA-654-3p (miR-654-3p) and circ_0084188 or Kruppel-like factor 12 (KLF12) was confirmed by a dual-luciferase reporter, RNA immunoprecipitation and RNA pull-down assays. Xenograft in CRC mice model was utilized for exploring the role of circ_0084188 in vivo.Circ_0084188 was overexpressed in CRC tissues and cells. Circ_0084188 silencing suppressed cell proliferation, migration, invasion, and stemness and induced apoptosis in CRC cells. Circ_0084188 acted as a sponge for miR-654-3p, and circ_0084188 regulated CRC cell behaviors via sponging miR-654-3p. Moreover, KLF12 was a target of miR-654-3p, and miR-654-3p overexpression inhibited the malignant behaviors of CRC cells by downregulating KLF12. Mechanically, circ_0084188 sponged miR-654-3p to regulate KLF12 expression in CRC cells. In addition, circ_0084188 downregulation inhibited tumor growth in vivo.Circ_0084188 knockdown might repress CRC progression partially via regulating the miR-654-3p/KLF12 axis, providing a novel insight into the pathogenesis of CRC.
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Neoplasias Colorretais , MicroRNAs , Animais , Humanos , Camundongos , Apoptose/genética , Western Blotting , Linhagem Celular Tumoral , Proliferação de Células/genética , Neoplasias Colorretais/genética , Fatores de Transcrição Kruppel-Like/genética , MicroRNAs/genética , RNA Circular/genéticaRESUMO
Biofilms play a significant role in the biogeochemical processing of organic matter and the environmental fate of emerging pollutants. In this study, we investigated the occurrence and distribution of 32 endocrine-disrupting chemicals (EDCs), including 24 environmental corticosteroids (ECs) and 8 environmental estrogens (EEs), in natural biofilms from the Pearl River system. Their association between biofilms and water and environmental risk were assessed. The ECs and EEs ubiquitously occurred in the biofilms, ranging from <0.61-6.57 ng/g and <0.8-2535 ng/g, respectively. Temporally, there was no obvious variance in either ECs or EEs in the biofilms during the winter and summer, and their concentrations exhibited a spatial trend of upward to midstream, descending downstream, and then seaward attenuation at the estuary. For ECs and EEs, the similar levels of field-derived bioconcentration factors (BCFs) (logarithm values: 2.42-2.86 and 2.72-2.98, respectively) and biofilm organic carbon-normalized partitioning coefficients (Kboc) (3.39-3.69 and 3.35-3.95) suggest the comparable potential of accumulation and sorption by biofilms between these two classes of EDCs. In addition, higher values of BCF and Kboc for the EEs were found in winter and were correspondingly comparable to their distribution coefficients (Kd) and Koc derived from suspended particles and sediment, revealing that biofilms are a competitive environmental compartment for capturing EDCs, particularly during the mature period. A positive logKboc-logKow relationship suggests hydrophobic partitioning as a primary interaction mechanism between the biofilm and EEs. Moreover, high risks from biofilm-associated ECs and EEs might have posed to the fluvial ecosystem. This study provides original insights into the occurrence, fate, and risk of ECs in natural biofilms for the first time and demonstrates that biofilms may not only serve as reservoirs but also serve as sentinels for fluvial EDC contamination. These results contribute to the further understanding of the behavior and fate of EDCs in aquatic environments.
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Disruptores Endócrinos , Poluentes Químicos da Água , Estrogênios , Prevalência , Ecossistema , Poluentes Químicos da Água/análise , Monitoramento Ambiental/métodos , Corticosteroides , Disruptores Endócrinos/análise , Biofilmes , ChinaRESUMO
Optimizing cell substrates by surface modification of neural stem cells (NSCs), for efficient and oriented neurogenesis, represents a promising strategy for treating neurological diseases. However, developing substrates with the advanced surface functionality, conductivity, and biocompatibility required for practical application is still challenging. Here, Ti3 C2 Tx MXene is introduced as a coating nanomaterial for aligned poly(l-lactide) (PLLA) nanofibers (M-ANF) to enhance NSC neurogenesis and simultaneously tailor the cell growth direction. Ti3 C2 Tx MXene treatment provides a superior conductivity substrate with a surface rich in functional groups, hydrophilicity, and roughness, which can provide biochemical and physical cues to support NSC adhesion and proliferation. Moreover, Ti3 C2 Tx MXene coating significantly promotes NSC differentiation into both neurons and astrocytes. Interestingly, Ti3 C2 Tx MXene acts synergistically with the alignment of nanofibers to promote the growth of neurites, indicating enhanced maturation of these neurons. RNA sequencing analysis further reveals the molecular mechanism by which Ti3 C2 Tx MXene modulates the fate of NSCs. Notably, surface modification by Ti3 C2 Tx MXene mitigates the in vivo foreign body response to implanted PLLA nanofibers. This study confirms that Ti3 C2 Tx MXene provides multiple advantages for decorating the aligned PLLA nanofibers to cooperatively improve neural regeneration.
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Nanofibras , Células-Tronco Neurais , Titânio/farmacologia , NeurôniosRESUMO
MORF-RELATED GENE702 (OsMRG702) regulates flowering time genes in rice, but how it controls transcription is not well known. Here, we found that OsMRGBP can directly interact with OsMRG702. Both Osmrg702 and Osmrgbp mutants show the delayed flowering phenotype with the reduction in the transcription of multiple key flowering time genes, including Ehd1 and RFT1. Chromatin immunoprecipitation study showed that both OsMRG702 and OsMRGBP bind to the Ehd1 and RFT1 loci and the absence of either OsMRG702 or OsMRGBP leads to a decrease of H4K5 acetylation at these loci, indicating OsMRG702 and OsMRGBP cooperatively together to promote the H4K5 acetylation. In addition, whilst Ghd7 are upregulated in both Osmrg702 and Osmrgbp mutants, only OsMRG702 binds to the loci, together with the global increased and Ghd7 locus-specific increased H4K5ac levels in Osmrg702 mutants, suggesting an additional negative effect of OsMRG702 on H4K5 acetylation. In summary, OsMRG702 controls flowering gene regulation by altering H4 acetylation in rice; it works either together with OsMRGBP to enhance transcription by promoting H4 acetylation or with other unknown mechanisms to dampen transcription by preventing H4 acetylation.
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Flores , Oryza , Flores/metabolismo , Oryza/metabolismo , Acetilação , Fotoperíodo , Fenótipo , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMO
Suspended particulate matter (SPM) plays an important role in the geochemical behavior and fate of organic micropollutants in aquatic environments. However, the presence of trace emerging endocrine disruptors such as environmental corticosteroids (ECs) in SPM is less well understood. This study focused on the occurrence, distribution, and partitioning of SPM-associated ECs in the Pearl River system, China. Ubiquitous particulate ECs were found in the surface water of the rivers at average concentrations (dry weight) between 0.46 ng/g (flumethasone) and 8.83 ng/g (clobetasone butyrate). The total EC (∑ECs) concentrations of the 24 selected target compounds varied from <1.03 ng/g to 62.3 ng/g, with an average and median of 17.6 ng/g and 13.7 ng/g, respectively. Higher SPM-bound EC levels were commonly observed in winter (dry season), and spatially, their relatively high contamination in urban tributary networks decreased while flowing to mainstreams and then gradually attenuated from upstream to the estuary. Despite the approximately 90 % mass distribution of ∑ECs in the aqueous phase, approximately 50 % of their effect burden was derived from the suspended particulate fractions. For the first time, in situ SPM-water partitioning coefficients (Kp) and their organic carbon-normalized ones (Koc) of ECs were determined in surface waters, and a field-derived preliminary linear equation was proposed to estimate Koc for ECs using basic physicochemical parameters n-octanol/water partitioning coefficient (Kow), which is of importance with regard to the assessment of transport, fate, and risk of these emerging hazardous chemicals. Furthermore, the significant logKoc-logKow relationship for ECs reveals that nonspecific hydrophobic partitioning is a major association mechanism between SPM and ECs. Moreover, hydrogen bonding is suggested to be a prevailing specific binding mechanism and provides more contribution to nonhydrophobic interactions between ECs and particulate organic matter than environmental estrogens.
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Rios , Poluentes Químicos da Água , Rios/química , Poluentes Químicos da Água/análise , Material Particulado/análise , Corticosteroides , Água , China , Poeira , Monitoramento Ambiental , Sedimentos Geológicos/químicaRESUMO
AIMS: The main purpose of this study was to study the therapeutical effect of oroxylin A glucuronide (OAG) on methicillin-resistant Staphylococcus aureus (MRSA). METHODS AND RESULTS: By substrate peptide reaction-based fluorescence resonance energy transfer (FRET) screening, we identified that OAG was an efficient inhibitor of Sortase A (SrtA) with an IC50 of 45.61 µg mL-1, and achieved efficacy in the treatment of Staphylococcus aureus (S. aureus) infections. We further demonstrated that OAG inhibited the adhesion of the S. aureus to fibrinogen, the surface protein A anchoring and diminished biofilm formation. Results obtained from fluorescence quenching assay elucidated a direct interaction between OAG and SrtA. Employing molecular dynamics simulations, we proved that OAG binds to the binding sites of R197, G192, E105, and V168 in the SrtA. Notably, OAG exhibited a robust therapeutic effect in a MRSA-induced pneumonia model. CONCLUSIONS: We identified that OAG as a novel class of reversible inhibitors of SrtA, combats MRSA-induced Infections.
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Staphylococcus aureus Resistente à Meticilina , Staphylococcus aureus Resistente à Meticilina/metabolismo , Staphylococcus aureus , Glucuronídeos/farmacologia , Proteínas de Bactérias/metabolismoRESUMO
Objective: To analyze the screening value of osteoporosis self-screening tool for Asia (OSTA) and body mass index (BMI) for osteoporosis (OP) in middle-aged and elderly Tibetan population in the Tibetan region. Methods: Data on demographic information, bone mineral density (BMD), and other information of 627 middle-aged and elderly people were collected. Analysis of the correlation between OSTA index, BMI and BMD, and receiver operating characteristic (ROC) curve was performed to evaluate the OP screening effects. Results: OSTA index and BMI were correlated with BMD in both female and male populations ( P<0.05). In both male and female populations, OSTA index screening results for OP yielded higher area under the curve ( AUC) than BMI did, with the AUC for female OSTA index being 0.886 and that for female BMI being 0.785, while that for male OSTA index being 0.957 and that for male BMI being 0.834. When comparing the different age groups, the AUC of OSTA index and BMI of the middle-age group was higher than those of the quasi-elderly group and the elderly group, with the AUC of OSTA index and BMI of the middle-age being 0.939 and 0.858, those of the quasi-elderly group being 0.860 and 0.813, and those of the elderly group being 0.750 and 0.650, respectively. When the optimal cut-off value of diagnosis with OSTA index was ï¼2.20, the sensitivity and specificity were both 100%. When the optimal cut-off value for diagnosis with BMI was 17.512 kg/m2, the sensitivity and specificity were both 100%. Conclusion: OSTA index and BMI have different OP screening effects in different middle-aged and elderly Tibetan populations, and OSTA index shows better effects for OP screening than BMI does.
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Osteoporose , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Absorciometria de Fóton/métodos , Índice de Massa Corporal , Densidade Óssea , Programas de Rastreamento/métodos , Osteoporose/diagnóstico , Osteoporose/epidemiologia , Medição de Risco/métodos , Autoavaliação (Psicologia) , Tibet , População do Leste AsiáticoRESUMO
Chronic pain can cause both hyperalgesia and anxiety symptoms. However, how the two components are encoded in the brain remains unclear. The prelimbic cortex (PrL), a critical brain region for both nociceptive and emotional modulations, serves as an ideal medium for comparing how the two components are encoded. We report that PrL neurons projecting to the basolateral amygdala (PrLBLA) and those projecting to the ventrolateral periaqueductal gray (PrLl/vlPAG) were segregated and displayed elevated and reduced neuronal activity, respectively, during pain chronicity. Consistently, optogenetic suppression of the PrL-BLA circuit reversed anxiety-like behaviors, whereas activation of the PrL-l/vlPAG circuit attenuated hyperalgesia in mice with chronic pain. Moreover, mechanistic studies indicated that elevated TNF-α/TNFR1 signaling in the PrL caused increased insertion of GluA1 receptors into PrLBLA neurons and contributed to anxiety-like behaviors in mice with chronic pain. Together, these results provide insights into the circuit and molecular mechanisms in the PrL for controlling pain-related hyperalgesia and anxiety-like behaviors.
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Complexo Nuclear Basolateral da Amígdala , Dor Crônica , Camundongos , Animais , Dor Crônica/genética , Hiperalgesia , Ansiedade/genética , Córtex CerebralRESUMO
BACKGROUND: Extracellular vesicles (EVs) released by helminths play an important role in parasite-host communication. However, little is known about the characteristics and contents of the EVs of Fasciola gigantica, a parasitic flatworm that causes tropical fascioliasis. A better understanding of EVs released by F. gigantica will help elucidate the mechanism of F. gigantica-host interaction and facilitate the search for new vaccine candidates for the control and treatment of fascioliasis. METHODS: Two different populations of EVs (15k EVs and 100k EVs) were purified from adult F. gigantica culture media by ultracentrifugation. The morphology and size of the purified EVs were determined by transmission electron microscopy (TEM) and by the Zetasizer Nano ZSP high performance particle characterization system. With the aim of identifying diagnostic markers or potential vaccine candidates, proteins within the isolated 100k EVs were analyzed using mass spectrometry-based proteomics (LC-MS/MS). Mice were then vaccinated with excretory/secretory products (ESPs; depleted of EVs), 15k EVs, 100k EVs and recombinant F. gigantica heat shock protein 70 (rFg-HSP70) combined with alum adjuvant followed by challenge infection with F. gigantica metacercariae. Fluke recovery and antibody levels were used as measures of vaccine protection. RESULTS: TEM analysis and nanoparticle tracking analysis indicated the successful isolation of two subpopulations of EVs (15k EVs and 100k EVs) from adult F. gigantica culture supernatants using differential centrifugation. A total of 755 proteins were identified in the 100k EVs. Exosome biogenesis or vesicle trafficking proteins, ESCRT (endosomal sorting complex required for transport) pathway proteins and exosome markers, heat shock proteins and 14-3-3 proteins were identified in the 100k EVs. These results indicate that the isolated 100k EVs were exosome-like vesicles. The functions of the identified proteins may be associated with immune regulation, immune evasion and virulence. Mice immunized with F. gigantica ESPs, 15k EVs, 100k EVs and rFg-HSP70 exhibited a reduction in fluke burden of 67.90%, 60.38%, 37.73% and 56.6%, respectively, compared with the adjuvant control group. The vaccination of mice with F. gigantica 100k EVs, 15k EVs, ESP and rFg-HSP70 induced significant production of specific immunoglobulins in sera, namely IgG, IgG1 and IgG2a. CONCLUSION: The results of this study suggest that proteins within the exosome-like vesicles of F. gigantica have immunomodulatory, immune evasion and virulence functions. This knowledge may lead to new strategies for immunotherapy, vaccination and the diagnosis of fascioliasis.
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Exossomos , Fasciola , Fasciolíase , Vacinas , Camundongos , Animais , Fasciolíase/parasitologia , Proteômica , Cromatografia Líquida , Espectrometria de Massas em Tandem , Imunoglobulina GRESUMO
Qingpi, the dried immature pericarp of Citrus reticulata Blanco, is a commonly used medicinal food with some health-promoting benefits. In general, it is essential that Qingpi be stored for a period of time, but there are no reports about the number of storage years needed to obtain the best quality of Qingpi. Our aim was to determine the best storage time of Qingpi by studying the physicochemical properties and metabolite changes in product stored from 1 to 5 years. As a result, the color of Qingpi became darker during storage. Both the levels of three flavonoids (hesperidin, nobiletin, and tangeretin) and total flavonoids (TFs) and the antioxidant activity decreased during storage and the total phenolics (TPs) content fluctuated during storage. Cluster analysis was performed on the color parameters measured using a color difference meter, revealing that the color of Qingpi differed before and after 3 years of storage. A total of 9 special differential metabolites were identified that could be used to distinguish the storage years of Qingpi. This is the first study to report the quality changes of Qingpi during storage. The optimized results of the quality evaluation indicated that Qingpi should be stored for no more than 3 years.