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Many people sustain acute lung injuries in road traffic collisions, but few studies have dealt with such injuries in live models. This study aimed to explore the basic pathophysiological and inflammatory changes in adult rabbits following acute thoracic trauma. We randomly assigned 50 rabbits to control and injury groups. Rabbits in the injury group were subjected to right chest pressure (2600 g) using a Hopkinson bar. Measurements were taken in the control group and 0, 24, 48, and 72 h after injury in the injury group. Injury severity was evaluated in gross view; with haematoxylin and eosin (H&E) staining; and through the serum changes of tumor necrosis factor alpha (TNF-α), surfactant protein D (SP-D), and neutrophils. Secretion changes in SP-D in right lung injured tissues were estimated by western blotting and qPCR. Serum TNF-α levels increased rapidly immediately after injury, gradually recovering after 24, 48, and 72 h (p < 0.01). The percentage of neutrophils in the accompanying blood showed a consistent trend. Gross necropsy and H&E staining indicated different levels of bleeding, alveoli exudation, and inflammatory transformation after impact. ELISA depicted the same trend in circulation (F = 22.902, p < 0.01). Western blotting showed that SP-D protein levels in tissues decreased at 0 h and increased at 24, 48, and 72 h. We demonstrate the feasibility of a model of impact lung injury. Primary impact caused injury without external signs. Inflammation began immediately, and the lungs began recovering at 24, 48, and 72 h, as shown by increased SP-D levels in circulation and tissues.With complaints of ALI and inflammation, SP-D may be a potential biomarker after chest trauma.

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Oxidative stress and its impact on aging are critical areas of research. Natural anti-oxidants, such as saponins found in Polygonatum sibiricum, hold promise as potential clinical interventions against aging. In this study, we utilized the nematode model organism, Caenorhabditis elegans, to investigate the pharmacological effects of Polygonatum sibiricum saponins (PKS) on antioxidation and anti-aging. The results demonstrated a significant anti-aging biological activity associated with PKS. Through experiments involving lifespan and stress, lipofuscin, q-PCR, and ROS measurement, we found that PKS effectively mitigated aging-related processes. Furthermore, the mechanism underlying these anti-aging effects was linked to the SKN-1 signaling pathway. PKS increased the nuclear localization of the SKN-1 transcription factor, leading to the up-regulation of downstream anti-oxidant genes, such as gst-4 and sod-3, and a substantial reduction in intracellular ROS levels within the nematode. In conclusion, our study sheds light on the anti-oxidant and anti-aging properties of PKS in C. elegans. This research not only contributes to understanding the biological mechanisms involved but also highlights the potential therapeutic applications of these natural compounds in combating aging-related processes.

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Objective: Emerging evidence suggests alterations in gut microbiota (GM) composition following thyroid nodules (TNs) development, yet the causal relationship remains unclear. Utilizing Mendelian Randomization (MR), this study aims to elucidate the causal dynamics between GM and TNs. Methods: Employing summary statistics from the MiBioGen consortium (n=18,340) and FinnGen consortium (1,634 TNs cases, 263,704 controls), we conducted univariable and multivariable MR analyses to explore the GM-TNs association. Techniques including inverse variance weighted, MR-Egger regression, weighted median, and MR-PRESSO were utilized for causal inference. Instrumental variable heterogeneity was assessed through Cochran's Q statistic and leave-one-out analysis. Reverse MR was applied for taxa showing significant forward MR associations, with multivariate adjustments for confounders. Results: Our findings suggest that certain microbiota, identified as Ruminococcaceae_NK4A214_group (OR, 1.89; 95%CI, 0.47-7.64; p = 0.040), Senegalimassilia (OR, 1.72; 95%CI, 1.03-2.87; p =0.037), Lachnospiraceae (OR,0.64; 95%CI,0.41-0.99; p =0.045), exhibit a protective influence against TNs' development, indicated by negative causal associations. In contrast, microbiota categorized as Desulfovibrionales (OR, 0.63; 95%CI, 0.41-0.95; p =0.028), Prevotella_7 (OR, 0.79; 95%CI, 0.63-1.00; p =0.049), Faecalibacterium (OR, 0.66; 95%CI, 0.44-1.00; p =0.050), Desulfovibrionaceae (OR, 0.55; 95%CI, 0.35-0.86; p =0.008), Deltaproteobacteria (OR, 0.65; 95%CI, 0.43-0.97; p =0.036) are have a positive correlation with with TNs, suggesting they may serve as risk factors. Reverse MR analyses did not establish significant causal links. After comprehensive adjustment for confounders, taxa Desulfovibrionales (Order), Desulfovibrionaceae (Family), Deltaproteobacteria (Class) remain implicated as potential contributors to TNs' risk. Discussion: This study substantiates a significant causal link between GM composition and TNs development, underscoring the thyroid-gut axis's relevance. The findings advocate for the integration of GM profiles in TNs' prevention and management, offering a foundation for future research in this domain.

Asunto(s)

Microbioma Gastrointestinal , Análisis de la Aleatorización Mendeliana , Nódulo Tiroideo , Humanos , Nódulo Tiroideo/microbiología , Nódulo Tiroideo/genética , Nódulo Tiroideo/patología , Estudios de Casos y Controles , Factores de Riesgo

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Background: The escalating global burden of diabetes and its associated cognitive impairment underscores the urgency for effective interventions. Bergenin shows promise in regulating glucose metabolism, mitigating inflammation, and improving cognitive function. Zebrafish models offer a unique platform for assessing drug efficacy and exploring pharmacological mechanisms, complemented by subsequent investigations in cell and rat models. Methods: The experimental subjects included zebrafish larvae (CZ98:Tg (mpeg1:EGFP) ihb20Tg/+ ), adult zebrafish (immersed in 2% glucose), BV2 cell line (50 mM glucose + 10 µm Aß1-42), and a streptozotocin (STZ) bilateral intracerebroventricular injection rat model. Bergenin's effects on the toxicity, behavior, and cognitive function of zebrafish larvae and adults were evaluated. The Morris water maze assessed cognitive function in rats. Neuronal histopathological changes were evaluated using HE and Nissl staining. qPCR and Western blot detected the expression of glycolysis enzymes, inflammatory factors, and Bergenin's regulation of PPAR/NF-κB pathway in these three models. Results: 1) In zebrafish larvae, Bergenin interventions significantly reduced glucose levels and increased survival rates while decreasing teratogenicity rates. Microglial cell fluorescence in the brain notably decreased, and altered swimming behavior tended to normalize. 2) In adult zebrafish, Bergenin administration reduced BMI and blood glucose levels, altered swimming behavior to slower speeds and more regular trajectories, enhanced recognition ability, decreased brain glucose and lactate levels, weakened glycolytic enzyme activities, improved pathological changes in the telencephalon and gills, reduced expression of pro-inflammatory cytokines, decreased ins expression and increased expression of irs1, irs2a, and irs2b, suggesting a reduction in insulin resistance. It also altered the expression of pparg and rela. 3) In BV2 cell line, Bergenin significantly reduced the protein expression of glycolytic enzymes (GLUT1, HK2, PKFKB3, and PKM2), lowered IL-1ß, IL-6, and TNF-α mRNA expression, elevated PPAR-γ protein expression, and decreased P-NF-κB-p65 protein expression. 4) In the rat model, Bergenin improves learning and memory abilities in STZ-induced rats, mitigates neuronal damage in the hippocampal region, and reduces the expression of inflammatory factors IL-1ß, IL-6, and TNF-α. Bergenin decreases brain glucose and lactate levels, as well as glycolytic enzyme activity. Furthermore, Bergenin increases PPARγ expression and decreases p-NF-κB p65/NF-κB p65 expression in the hippocampus. Conclusion: Bergenin intervenes through the PPAR-γ/NF-κB pathway, redirecting glucose metabolism, alleviating inflammation, and preventing high glucose-induced neuronal damage.

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Increased fatty acid synthesis benefits glioblastoma malignancy. However, the coordinated regulation of cytosolic acetyl-CoA production, the exclusive substrate for fatty acid synthesis, remains unclear. Here, we show that proto-oncogene tyrosine kinase c-SRC is activated in glioblastoma and remodels cytosolic acetyl-CoA production for fatty acid synthesis. Firstly, acetate is an important substrate for fatty acid synthesis in glioblastoma. c-SRC phosphorylates acetyl-CoA synthetase ACSS2 at Tyr530 and Tyr562 to stimulate the conversion of acetate to acetyl-CoA in cytosol. Secondly, c-SRC inhibits citrate-derived acetyl-CoA synthesis by phosphorylating ATP-citrate lyase ACLY at Tyr682. ACLY phosphorylation shunts citrate to IDH1-catalyzed NADPH production to provide reducing equivalent for fatty acid synthesis. The c-SRC-unresponsive double-mutation of ACSS2 and ACLY significantly reduces fatty acid synthesis and hampers glioblastoma progression. In conclusion, this remodeling fulfills the dual needs of glioblastoma cells for both acetyl-CoA and NADPH in fatty acid synthesis and provides evidence for glioma treatment by c-SRC inhibition.

Asunto(s)

Acetilcoenzima A , Ácidos Grasos , Glioblastoma , Proto-Oncogenes Mas , Glioblastoma/metabolismo , Glioblastoma/genética , Glioblastoma/patología , Humanos , Ácidos Grasos/metabolismo , Ácidos Grasos/biosíntesis , Línea Celular Tumoral , Fosforilación , Acetilcoenzima A/metabolismo , Animales , Proteína Tirosina Quinasa CSK/metabolismo , Proteína Tirosina Quinasa CSK/genética , Familia-src Quinasas/metabolismo , Familia-src Quinasas/genética , Progresión de la Enfermedad , Ratones , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , NADP/metabolismo , Ratones Desnudos , Isocitrato Deshidrogenasa/genética , Isocitrato Deshidrogenasa/metabolismo

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Introduction: Glioblastoma multiforme (GBM), the most common primary malignant brain tumor, is notorious for its aggressive growth and dismal prognosis. This study aimed to elucidate the molecular underpinnings of GBM, particularly focusing on the role of AGBL4 and its connection to inflammatory pathways, to discover viable therapeutic targets. Methods: Single-cell sequencing was utilized to examine the expression levels of AGBL4 and functional assays were performed to assess the effects of AGBL4 modulation. Results: Our findings identified the significant upregulation of AGBL4 in GBM, which correlated with adverse clinical outcomes. Functional assays demonstrated that AGBL4 knockdown inhibited GBM cell proliferation, migration, and invasion and influenced inflammatory response pathways, while AGBL4 overexpression promoted these activities. Further investigation revealed that AGBL4 exerted its oncogenic effects through modulation of MMP-1, establishing a novel regulatory axis critical for GBM progression and inflammation. Discussion: Both AGBL4 and MMP-1 may be pivotal molecular targets, offering new avenues for targeted therapy in GBM management.

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Neoplasias Encefálicas , Glioblastoma , Metaloproteinasa 1 de la Matriz , Glioblastoma/patología , Glioblastoma/metabolismo , Glioblastoma/genética , Humanos , Metaloproteinasa 1 de la Matriz/metabolismo , Metaloproteinasa 1 de la Matriz/genética , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/inmunología , Línea Celular Tumoral , Proliferación Celular , Movimiento Celular/genética , Progresión de la Enfermedad , Inflamación/metabolismo , Regulación Neoplásica de la Expresión Génica , Transducción de Señal , Masculino

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Background: Schisanlactone E, also known as XueTongSu (XTS), is an active compound extracted from the traditional Tujia medicine Kadsura heteroclita ("XueTong"). Recent studies highlight its anti-inflammatory and antioxidant properties, yet the mechanisms of XTS's therapeutic effects on Alzheimer's disease (AD) are unclear. This study aims to elucidate the therapeutic efficacy and mechanisms of XTS in AD. Methods: Ten C57BL/6 mice were assigned to the control group (NC), and twenty APP/PS1 transgenic mice were randomly divided into the model group (M) (10 mice) and the XTS treatment group (Tre) (10 mice). After an acclimatization period of 7 days, intraperitoneal injections were administered over a 60-day treatment period. The NC and M groups received saline, while the Tre group received XTS at 2 mg/kg. Learning and memory abilities were assessed using the Morris Water Maze (MWM) test. Histopathological changes were evaluated using hematoxylin and eosin (HE) and Nissl staining, and immunofluorescence was used to assess pathological products and glial cell activation. Cytokine levels (IL-1ß, IL-6, TNF-α) in the hippocampus were quantified by qPCR. 16S rDNA sequencing analyzed gut microbiota metabolic alterations, and metabolomic analysis was performed on cortical samples. The KEGG database was used to analyze the regulatory mechanisms of XTS in AD treatment. Results: XTS significantly improved learning and spatial memory in APP/PS1 mice and ameliorated histopathological changes, reducing Aß plaque aggregation and glial cell activation. XTS decreased the expression of inflammatory cytokines IL-1ß, IL-6, and TNF-α. It also enhanced gut microbiota diversity, notably increasing Akkermansia species, and modulated levels of metabolites such as isosakuranetin, 5-KETE, 4-methylcatechol, and sphinganine. Pathway analysis indicated that XTS regulated carbohydrate metabolism, neuroactive ligand-receptor interactions, and alanine, aspartate, and glutamate metabolism, mitigating gut microbiota dysbiosis and metabolic disturbances. Conclusion: XTS ameliorates cognitive deficits, pathological changes, and inflammatory responses in APP/PS1 mice. It significantly modulates the gut microbiota, particularly increasing Akkermansia abundance, and influences levels of key metabolites in both the gut and brain. These findings suggest that XTS exerts anti-AD effects through the microbial-gut-brain axis (MGBA).

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This study aims to establish an ELISA method with high specificity for the detection of antibodies against Mycoplasma hyopneumoniae. Firstly, we constructed a recombinant strain Escherichia coli BL21(DE3)-pET-32a(+)-mhp336 to express the recombinant protein Mhp336 and used the purified Mhp336 as the coating antigen. Then, we optimized the ELISA parameters, including antigen concentration, blocking buffer, blocking time, dilution of serum, incubation time with serum, secondary antibody dilution, secondary antibody incubation time, colorimetric reaction time, and cut-off value. Afterwards, reproducibility experiments were conducted, and the cross reactivity of Mhp366 with other antisera of porcine major pathogens and the maximum dilution ratios of the sera were determined. Finally, 226 porcine serum samples were detected using the method established in this study, a commercial ELISA kit for M. hyopneumoniae antibody detection, and a convalescent serum ELISA kit for M. hyopneumoniae antibody detection. The detection results of the three methods were compared to evaluate the sensitivity and specificity of the ELISA method established in this study. For this method, the optimal antigen concentration, blocking buffer, blocking time, dilution of serum, incubation time with serum, secondary antibody dilution, secondary antibody incubation time, and colorimetric reaction time were 0.05 µg/mL, PBS containing 2.5% skim milk, 1 h, 1:500, 0.5 h, 1:10 000, 1 h, and 5 min, respectively. Validation of the ELISA method based on Mhp336 showed a cut-off value of 0.332. The coefficients of variation of both intra-batch and inter-batch kits were below 7%. The detection results of porcine serum samples indicated that the method established in this study outperformed the commercial ELISA kit and the convalescent serum ELISA kit for M. hyopneumoniae antibody detection in terms of sensitivity and specificity. We successfully established an ELISA method for detecting the antibodies against M. hyopneumoniae based on Mhp336 protein. This method demonstrated high sensitivity and specificity, serving as a tool for the prevention of mycoplasmal pneumonia of swine in pig farms.

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Anticuerpos Antibacterianos , Ensayo de Inmunoadsorción Enzimática , Mycoplasma hyopneumoniae , Proteínas Recombinantes , Ensayo de Inmunoadsorción Enzimática/métodos , Mycoplasma hyopneumoniae/inmunología , Animales , Porcinos , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/genética , Anticuerpos Antibacterianos/inmunología , Anticuerpos Antibacterianos/sangre , Escherichia coli/genética , Escherichia coli/metabolismo , Escherichia coli/inmunología , Neumonía Porcina por Mycoplasma/inmunología , Neumonía Porcina por Mycoplasma/diagnóstico , Neumonía Porcina por Mycoplasma/microbiología , Sensibilidad y Especificidad , Proteínas Bacterianas/inmunología , Proteínas Bacterianas/genética

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Temozolomide (TMZ) is widely utilized as the primary chemotherapeutic intervention for glioblastoma. However, the clinical use of TMZ is limited by its various side effects and resistance to chemotherapy. The present study revealed the synergistic inhibition of glioblastoma through the combined administration of TMZ and perifosine. This combination therapy markedly diminished BRCA1 expression, resulting in the suppression of DNA repair mechanisms. Furthermore, the combination of TMZ and perifosine elicited caspase-dependent apoptosis, decreasing glioblastoma cell viability and proliferation. The observed synergistic effect of this combination therapy on glioblastoma was validated in vivo, as evidenced by the substantial reduction in glioblastoma xenograft growth following combined treatment with TMZ and perifosine. In recurrent glioma patients, higher BRCA1 expression is associated with worse prognosis, especially the ones that received TMZ-treated. These findings underscore the potent antitumor activity of the AKT inhibitor perifosine when combined with TMZ and suggest that this approach is a promising strategy for clinical glioblastoma treatment.

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Outdoor jogging is one of the most popular practised exercises worldwide, providing various benefits for health and wellbeing. However, PM2.5 exposure risks of jogging behaviors were rarely explored. This study aims to investigate the association between jogging behavior and PM2.5 exposure with big data. PM2.5 exposure concentration and dose inhalation of individuals were calculated by integrating hourly PM2.5 concentration data and jogging GPS trajectory recorded by a sports app during 2015 in Beijing, after which relationships between jogging behaviors and PM2.5 exposure were unpacked using statistics analysis and structural equation modelling. Experimental results on massive jogging trajectories show that: (1) the average jogging PM2.5 exposure concentration is 60.43 µg/m3, and female joggers inhaled significantly less air pollution dose (19.70 µg) than men (24.91 µg). (2) There exist significant spatiotemporal disparities in jogging exposure to PM2.5. Joggings in the city center, in the morning, on weekdays and in autumn and winter seasons were exposed to higher pollution concentrations. (3) Jogging behavior characteristics, especially distance, activity space size, duration and rotation, were systematically associated with PM2.5 exposure across space and time. (4) The role of gender directly shaped joggers' dose inhalation of PM2.5 pollution and indirectly via duration, timing choice and distance. (5) The effects of weather conditions on joggers' exposure to PM2.5 are mainly via direct effects, whereas the direct impacts of precipitation and wind speed are mitigated by indirect effects stemming from jogging behavior patterns. Our findings provide insights for personal guidance and policy intervention for the sake of promoting physical activity and reducing PM2.5 exposure.

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Contaminantes Atmosféricos , Contaminación del Aire , Trote , Material Particulado , Material Particulado/análisis , Humanos , Beijing , Contaminantes Atmosféricos/análisis , Contaminación del Aire/estadística & datos numéricos , Femenino , Masculino , Sistemas de Información Geográfica , Exposición a Riesgos Ambientales/estadística & datos numéricos , Monitoreo del Ambiente/métodos , Exposición por Inhalación/estadística & datos numéricos

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Sulfur metabolism plays a major role in plant growth and development, environmental adaptation, and material synthesis, and the sulfate transporters are the beginning of sulfur metabolism. We identified 37 potential VcSULTR genes in the blueberry genome, encoding peptides with 534 to 766 amino acids. The genes were grouped into four subfamilies in an evolutionary analysis. The 37 putative VcSULTR proteins ranged in size from 60.03 to 83.87 kDa. These proteins were predicted to be hydrophobic and mostly localize to the plasma membrane. The VcSULTR genes were distributed on 30 chromosomes; VcSULTR3;5b and VcSULTR3;5c were the only tandemly repeated genes. The VcSULTR promoters contained cis-acting elements related to the fungal symbiosis and stress responses. The transcript levels of the VcSULTRs differed among blueberry organs and changed in response to ericoid mycorrhizal fungi and sulfate treatments. A subcellular localization analysis showed that VcSULTR2;1c localized to, and functioned in, the plasma membrane and chloroplast. The virus-induced gene knock-down of VcSULTR2;1c resulted in a significantly decreased endogenous sulfate content, and an up-regulation of genes encoding key enzymes in sulfur metabolism (VcATPS2 and VcSiR1). These findings enhance our understanding of mycorrhizal-fungi-mediated sulfate transport in blueberry, and lay the foundation for further research on blueberry-mycorrhizal symbiosis.

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Arándanos Azules (Planta) , Regulación de la Expresión Génica de las Plantas , Micorrizas , Filogenia , Proteínas de Plantas , Transportadores de Sulfato , Micorrizas/genética , Arándanos Azules (Planta)/genética , Arándanos Azules (Planta)/microbiología , Arándanos Azules (Planta)/metabolismo , Transportadores de Sulfato/genética , Transportadores de Sulfato/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Familia de Multigenes , Sulfatos/metabolismo , Simbiosis/genética , Genoma de Planta

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Background: Traffic accidents, particularly blunt impacts, cause serious injuries in children. We aimed to assess inflammatory and injury responses in infant rabbits subjected to acute lung injury resulting from blunt impact, with the goal of identifying potential circulatory injury markers. Methods: Forty 4-week-old infant rabbits were subjected to a right chest impact using a Hopkinson bar with 2,600 g. Computed tomography was employed to assess injury severity. Pathological changes were observed using hematoxylin and eosin staining in the control, 0, 24, and 72 h groups, post-injury. Immunohistochemistry was used to examine surfactant protein A (SP-A) changes in right lung tissues and upper main bronchi. Serum levels of interleukin-6 (IL-6), IL-8, and SP-A were measured using ELISA within 24 h post-injury in the control, 0 h, and 24 h groups. Results: Following blunt injury, significant increases were observed in blood white blood cell count (F = 101.556, P < 0.01) and neutrophil percentage (F = 104.228, P < 0.01), which gradually decreased after 24 and 72 h. The lung wet/dry weight ratio indicated significant edema (F = 79.677, P < 0.01), corroborated by hematoxylin and eosin staining showing edema, exudation, and marked granulocyte infiltration in the control, 0 h, 24 h and 72 h groups. SP-A levels decreased rapidly at 0 h, and recovered between 24 and 72 h in the right lung tissues (F = 6.7, P < 0.05), left lung (F = 15.825, P < 0.05) and upper main bronchi (F = 59.552, P < 0.01). The ELISA results showed increasing trends for the control and 0 h groups, while decreasing trends were observed in 24 h group for IL-6 (F = 58.328, P < 0.01) and IL-8 (F = 41.802, P < 0.01). Conversely, SP-A exhibited a decreasing trend in the control and 0 h groups but increased in the serum of 24 h group (F = 52.629, P < 0.01). Discussion: In cases of direct chest trauma in infant rabbits, particularly mild injuries without rib fractures. SP-A levels correlated with pathological changes across all groups and may serve as biomarkers for pediatric blunt lung impact.

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We investigated the association between early sexual debut and HIV infection among adolescents and young adults. Analyzing data from nationally representative Population-Based HIV Impact Assessment (PHIA) surveys in 11 African countries, the research employed a multivariate logistic regression model to assess the relationship between the early sexual debut and new HIV infections in the age group of 10-24 years. The results revealed a significant and robust association, indicating that young individuals who experienced early sexual debut were approximately 2.65 times more likely to contract HIV than those who did not, even after accounting for other variables. These findings align with prior research suggesting that early initiation of sexual activity may increase vulnerability to HIV infection due to factors such as biological susceptibility and risky behaviors like low condom use and multiple sexual partners. The implications of these findings for HIV prevention strategies are substantial, suggesting that interventions aimed at delaying sexual debut could be an effective component in reducing HIV risk for this population. Targeted sex education programs that address the risks of early sexual debut may play a pivotal role in these prevention efforts. By employing a comprehensive approach, there is a possibility to advance efforts towards ending AIDS by 2030.

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Infecciones por VIH , Asunción de Riesgos , Conducta Sexual , Parejas Sexuales , Humanos , Adolescente , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Masculino , Femenino , Conducta Sexual/estadística & datos numéricos , Adulto Joven , África/epidemiología , Modelos Logísticos , Factores de Riesgo , Niño , Condones/estadística & datos numéricos , Factores de Edad , Adulto

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Background: EPs pose significant challenges to individual health and quality of life, attracting attention in public health as a risk factor for diminished quality of life and healthy life expectancy in middle-aged and older adult populations. Therefore, in the context of global aging, meticulous exploration of the factors behind emotional issues becomes paramount. Whether ADL can serve as a potential marker for EPs remains unclear. This study aims to provide new evidence for ADL as an early predictor of EPs through statistical analysis and validation using machine learning algorithms. Methods: Data from the 2018 China Health and Retirement Longitudinal Study (CHARLS) national baseline survey, comprising 9,766 samples aged 45 and above, were utilized. ADL was assessed using the BI, while the presence of EPs was evaluated based on the record of "Diagnosed with Emotional Problems by a Doctor" in CHARLS data. Statistical analyses including independent samples t-test, chi-square test, Pearson correlation analysis, and multiple linear regression were conducted using SPSS 25.0. Machine learning algorithms, including Support Vector Machine (SVM), Decision Tree (DT), and Logistic Regression (LR), were implemented using Python 3.10.2. Results: Population demographic analysis revealed a significantly lower average BI score of 65.044 in the "Diagnosed with Emotional Problems by a Doctor" group compared to 85.128 in the "Not diagnosed with Emotional Problems by a Doctor" group. Pearson correlation analysis indicated a significant negative correlation between ADL and EPs (r = -0.165, p < 0.001). Iterative analysis using stratified multiple linear regression across three different models demonstrated the persistent statistical significance of the negative correlation between ADL and EPs (B = -0.002, ß = -0.186, t = -16.476, 95% CI = -0.002, -0.001, p = 0.000), confirming its stability. Machine learning algorithms validated our findings from statistical analysis, confirming the predictive accuracy of ADL for EPs. The area under the curve (AUC) for the three models were SVM-AUC = 0.700, DT-AUC = 0.742, and LR-AUC = 0.711. In experiments using other covariates and other covariates + BI, the overall prediction level of machine learning algorithms improved after adding BI, emphasizing the positive effect of ADL on EPs prediction. Conclusion: This study, employing various statistical methods, identified a negative correlation between ADL and EPs, with machine learning algorithms confirming this finding. Impaired ADL increases susceptibility to EPs.

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Actividades Cotidianas , Envejecimiento , Humanos , Femenino , Masculino , Anciano , Persona de Mediana Edad , Estudios Longitudinales , China , Envejecimiento/psicología , Envejecimiento/fisiología , Aprendizaje Automático , Resiliencia Psicológica , Calidad de Vida , Anciano de 80 o más Años , Salud Mental , Emociones

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Microglia are natural immune cells in the central nervous system, and the activation of microglia is accompanied by a reprogramming of glucose metabolism. In our study, we investigated the role of long non-coding RNA taurine-upregulated gene 1 (TUG1) in regulating microglial glucose metabolism reprogramming and activation. BV2 cells were treated with Lipopolysaccharides (LPS)/Interferon-γ (IFN-γ) to establish a microglial activation model. The glycolysis inhibitor 2-Deoxy-D-glucose (2-DG) was used as a control. The expression levels of TUG1 mRNA and proinflammatory cytokines such as Interleukin-1ß (IL-1ß), Interleukin -6, and Tumor Necrosis Factor-α mRNA and anti-inflammatory cytokines such as IL-4, Arginase 1(Arg1), CD206, and Ym1 were detected by RT-qPCR. TUG1 was silenced using TUG1 siRNA and knocked out using CRISPR/Cas9. The mRNA and protein expression levels of key enzymes involved in glucose metabolism, such as Hexokinase2, Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), Lactate dehydrogenase, Glucose 6 phosphate dehydrogenase, and Pyruvate dehydrogenase (PDH), were determined by RT-qPCR and Western blotting. The glycolytic rate of microglial cells was measured using Seahorse. Differential metabolites were determined by metabolomics, and pathway enrichment was performed using these differential metabolites. Our findings revealed that the expression of TUG1 was elevated in proinflammatory-activated microglia and positively correlated with the levels of inflammatory factors. The expression of anti-inflammatory cytokines such as IL-4, Arg1, CD206, and Ym1 were decreased when induced with LPS/IFN-γ. However, this decrease was reversed by the treatment with 2-DG. Silencing of GAPDH led to an increase in the expression of TUG1 and inflammatory factors. TUG1 knockout (TUG1KO) inhibited the expression of glycolytic key enzymes and promoted the expression of oxidative phosphorylation key enzymes, shifting the metabolic profile of activated microglia from glycolysis to oxidative phosphorylation. Additionally, TUG1KO reduced the accumulation of metabolites, facilitating the restoration of the tricarboxylic acid cycle and enhancing oxidative phosphorylation in microglia. Furthermore, the downregulation of TUG1 was found to reduce the expression of both proinflammatory and anti-inflammatory cytokines under normal conditions. Interestingly, when induced with LPS/IFN-γ, TUG1 downregulation showed a potentially beneficial effect on microglia in terms of inflammation. Downregulation of TUG1 expression inhibits glycolysis and facilitates the shift of microglial glucose metabolism from glycolysis to oxidative phosphorylation, promoting their transformation towards an anti-inflammatory phenotype and exerting anti-inflammatory effects in BV2.

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Glucosa , Glucólisis , Lipopolisacáridos , Microglía , ARN Largo no Codificante , Microglía/metabolismo , Animales , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Glucosa/metabolismo , Ratones , Lipopolisacáridos/farmacología , Citocinas/metabolismo , Inflamación/metabolismo , Inflamación/genética , Interferón gamma/metabolismo , beta-N-Acetilhexosaminidasas/metabolismo , beta-N-Acetilhexosaminidasas/genética , Línea Celular , Receptor de Manosa , Lectinas de Unión a Manosa/metabolismo , Lectinas de Unión a Manosa/genética , Desoxiglucosa/farmacología , Interleucina-4/metabolismo , Interleucina-1beta/metabolismo , Reprogramación Metabólica , Arginasa , Hexoquinasa , Lectinas

RESUMEN

Background: The degeneration and functional decline of paravertebral muscles (PVMs) are reported to be closely linked to the incidence of degenerative lumbar scoliosis (DLS), a spinal deformity of the mature skeleton. However, the functional role and degeneration of PVMs and their relationship to the development of spinal deformities remain controversial. Therefore, the present study analyzed the morphological changes in the PVMs of patients with DLS, and explored the relationship between PVM degeneration and spinal osseous parameters. Methods: In this retrospective case-control study, we evaluated the PVM parameters of patients with DLS (n=120) and compared them with patients free of DLS (control group, n=120). The cross-sectional area (CSA) and computed tomography (CT) values of the PVM at the lumbar vertebra 1-5 levels were measured. Further, the lumbar scoliosis Cobb, lumbar lordotic, and apical vertebral rotation angles were measured on CT and radiographs in the DLS group, and the relationship between PVM changes and these factors was analyzed. Results: In the control group, the PVM CSA and CT values differed insignificantly between the bilateral sides at all levels (P>0.05). In the DLS group, the CSAs of the multifidus (MF) and erector spinae (ES) were larger on the convex side than the concave side (P>0.05), whereas that of the psoas major (PM) was smaller on the convex side than the concave side (P<0.05). The CT value of the PVM was lower on the convex side at all levels (P<0.05). The CSA and CT values on both sides of the patients were lower in the DLS group than the control group at all levels (P<0.05). Further, the degree of PVM asymmetry at the apical vertebral level was positively correlated with the lumbar scoliosis (P<0.01) and apical vertebral rotation angles (P<0.05), but negatively correlated with the lumbar lordotic angle (P<0.05). Conclusions: Asymmetric degeneration of the PVM was observed bilaterally in DLS patients, and the degeneration was more pronounced on the concave side than the convex side. This asymmetrical degeneration was closely associated with the severity of lumbar scoliosis, vertebral rotation, and loss of lumbar lordosis, and a stronger correlation was observed with the MF and ES than with the PM.

RESUMEN

This study aims to explore the molecular regulatory mechanism of the differential accumulation of flavonoids between 'Xianglei' and the wild type of Lonicera macranthoides. The flowers, stems, and leaves of the two varieties of L. macranthoides were collected. Ultra-performance liquid chromatography-mass spectrometry(UPLC-MS) and high-throughput sequencing(RNA-seq) were employed to screen out the differential flavonoids, key differentially expressed genes(DEGs) and transcription factors(TFs). Fourteen DEGs were randomly selected for verification by qRT-PCR. The results showed that a total of 17 differential flavonoids were obtained, including naringin chalcone, apigenin, and quercetin. The transcriptomic analysis predicted 19 DEGs associated with flavonoids, including 2 genes encoding chitin synthase(CHS) and 3 genes encoding chalcone isomerase(CHI). The regulatory network analysis and weighted gene co-expression network analysis(WGCNA) screen out the key enzyme genes CHS1, FLS1, and HCT regulating the accumulation of flavonoids. MYB12 and LBD4 may be involved in the biosynthesis of flavonoids by regulating the expression of key enzyme genes CHS1, FLS1, and HCT. The qRT-PCR and RNA-seq results were similar regarding the expression patterns of the 14 randomly selected DEGs. This study preliminarily analyzed the transcriptional regulatory mechanism for the differential accumulation of flavonoids in the two varieties of L. macranthoides and laid a foundation for further elucidating the regulatory effects of key enzyme genes and TFs on the accumulation of flavonoids.

Asunto(s)

Flavonoides , Regulación de la Expresión Génica de las Plantas , Lonicera , Metabolómica , Transcriptoma , Lonicera/genética , Lonicera/metabolismo , Lonicera/química , Flavonoides/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Perfilación de la Expresión Génica , Factores de Transcripción/genética , Factores de Transcripción/metabolismo

RESUMEN

BACKGROUND: Shunt obstruction is a type of ventriculoperitoneal shunt (VPS) failure. Whether changes in cerebrospinal fluid (CSF) parameters can influence shunt outcomes or not is debatable. METHODS: In this study, we retrospectively included adult hydrocephalus patients who received VPS from 6 general hospitals in different provinces of China from November 2013 to September 2021. The inclusion criteria: Patients with hydrocephalus of all etiologies underwent shunt surgery from 6 general hospitals in different provinces of China were included in the study. The exclusion criteria: 1.Patients under the age of 18; 2.Patients who had previous shunt surgery; 3. Shunt failure from other factors; 4.Patients died from other causes; 5. Patients with incomplete data. The CSF of shunt patients had been analyzed at the time of shunt insertion. The CSF samples were collected and analyzed when the shunt was implanted. The relationship between CSF parameters and the incidence rate of shunt obstruction in one year was analyzed. RESULTS: A total of 717 eligible patients from 6 hospitals were included, of whom 59(8.23%) experienced obstruction. Multivariate logistic regression analysis identified that protein level(odds ratio [OR] 1.161, 95% CI 1.005 ~ 1.341, p = 0.043), decreased glucose level(< 2.5 mmol/L)(odds ratio 3.784, 95% confidence interval 1.872 ~ 7.652, p = 0.001) and protein level increase(> 0.45 g/L) (odds ratio 3.653, 95% confidence interval 1.931 ~ 6.910, p = 0.001)were independent risk factors of shunt obstruction. CONCLUSION: This study suggested that increased protein level (> 0.45 g/L) and decreased glucose level (< 2.5 mmol/L) in CSF indicated an increased risk of shunt obstruction in a patient with hydrocephalus. Thus, shunt surgery should be more carefully considered when the CSF glucose and protein were abnormal.

Asunto(s)

Hidrocefalia , Derivación Ventriculoperitoneal , Humanos , Derivación Ventriculoperitoneal/efectos adversos , Femenino , Masculino , Hidrocefalia/cirugía , Hidrocefalia/líquido cefalorraquídeo , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , China/epidemiología , Adulto , Falla de Equipo

RESUMEN

A total of 334 Salmonella isolates were recovered from 6,223 pet rectal samples collected at 50 pet clinics, 42 pet shops, 7 residential areas, and 4 plazas. Forty serovars were identified that included all strains except for one isolate that did not cluster via self-agglutination, with Salmonella Typhimurium monophasic variant, Salmonella Kentucky, Salmonella Enteritidis, Salmonella Pomona, and Salmonella Give being the predominant serovars. Fifty-one sequence types were identified among the isolates, and ST198, ST11, ST19, ST451, ST34, and ST155 were the most common. The top four dominant antimicrobials to which isolates were resistant were sulfisoxazole, ampicillin, doxycycline, and tetracycline, and 217 isolates exhibited multidrug resistance. The prevalence of ß-lactamase genes in Salmonella isolates was 59.6%, and among these isolates, 185 harbored blaTEM, followed by blaCTX-M (66) and blaOXA (10). Moreover, six PMQR genes, namely, including qnrA (4.8%), qnrB (4.2%), qnrD (0.9%), qnrS (18.9%), aac(6')-Ib-cr (16.5%), and oqxB (1.5%), were detected. QRDR mutations (76.6%) were very common in Salmonella isolates, with the most frequent mutation in parC (T57S) (47.3%). Furthermore, we detected six tetracycline resistance genes in 176 isolates, namely, tet(A) (39.5%), tet(B) (8.1%), tet(M) (7.7%), tet(D) (5.4%), tet(J) (3.3%), and tet(C) (1.8%), and three sulfonamide resistance genes in 303 isolates, namely, sul1 (84.4%), sul2 (31.1%), and sul3 (4.2%). Finally, we found 86 isolates simultaneously harboring four types of resistance genes that cotransferred 2-7 resistance genes to recipient bacteria. The frequent occurrence of antimicrobial resistance, particularly in dogs and cats, suggests that antibiotic misuse may be driving multidrug-resistant Salmonella among pets.IMPORTANCEPet-associated human salmonellosis has been reported for many years, and antimicrobial resistance in pet-associated Salmonella has become a serious public health problem and has attracted increasing attention. There are no reports of Salmonella from pets and their antimicrobial resistance in Chongqing, China. In this study, we investigated the prevalence, serovar diversity, sequence types, and antimicrobial resistance of Salmonella strains isolated from pet fecal samples in Chongqing. In addition, ß-lactamase, QRDR, PMQR, tetracycline and sulfonamide resistance genes, and mutations in QRDRs in Salmonella isolates were examined. Our findings demonstrated the diversity of serovars and sequence types of Salmonella isolates. The isolates were widely resistant to antimicrobials, notably with a high proportion of multidrug-resistant strains, which highlights the potential direct or indirect transmission of multidrug-resistant Salmonella from pets to humans. Furthermore, resistance genes were widely prevalent in the isolates, and most of the resistance genes were spread horizontally between strains.

Asunto(s)

Antibacterianos , Farmacorresistencia Bacteriana Múltiple , Pruebas de Sensibilidad Microbiana , Mascotas , Salmonelosis Animal , Salmonella , Serogrupo , China/epidemiología , Animales , Antibacterianos/farmacología , Farmacorresistencia Bacteriana Múltiple/genética , Salmonella/genética , Salmonella/efectos de los fármacos , Salmonella/clasificación , Salmonella/aislamiento & purificación , Mascotas/microbiología , Salmonelosis Animal/microbiología , Salmonelosis Animal/epidemiología , Genotipo , beta-Lactamasas/genética , Fenotipo , Proteínas Bacterianas/genética

RESUMEN

Numerous studies have suggested that intra-articular administration of antibiotics following primary revision surgery may be one of the methods for treating prosthetic joint infection (PJI). Vancomycin and meropenem are the two most commonly used antibiotics for local application. Determining the concentrations of vancomycin and meropenem in the serum and synovial fluid of patients with PJI plays a significant role in further optimizing local medication schemes and effectively eradicating biofilm infections. This study aimed to establish a rapid, sensitive, and accurate ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for determining the concentrations of vancomycin and meropenem in human serum and synovial fluid. Serum samples were processed using acetonitrile precipitation of proteins and dichloromethane extraction, while synovial fluid samples were diluted before analysis. Chromatographic separation was achieved in 6 min on a Waters Acquity UPLC BEH C18 column, with the mobile phase consisting of 0.1% formic acid in water (solvent A) and acetonitrile (solvent B). Quantification was carried out using a Waters XEVO TQD triple quadrupole mass spectrometer with an electrospray ionization (ESI) source in positive ion mode. The multiple reaction monitoring (MRM) mode was employed to detect the following quantifier ion transitions: 717.95-99.97 (norvancomycin), 725.90-100.04 (vancomycin), 384.16-67.99 (meropenem). The method validation conformed to the guidelines of the FDA and the Chinese Pharmacopoeia. The method demonstrated good linearity within the range of 0.5-50 µg/ml for serum and 0.5-100 µg/ml for synovial fluid. Selectivity, intra-day and inter-day precision and accuracy, extraction recovery, matrix effect, and stability validation results all met the required standards. This method has been successfully applied in the pharmacokinetic/pharmacodynamic (PK/PD) studies of patients with PJI.

Asunto(s)

Antibacterianos , Meropenem , Infecciones Relacionadas con Prótesis , Líquido Sinovial , Espectrometría de Masas en Tándem , Vancomicina , Humanos , Espectrometría de Masas en Tándem/métodos , Vancomicina/sangre , Vancomicina/análisis , Vancomicina/farmacocinética , Líquido Sinovial/química , Meropenem/análisis , Meropenem/sangre , Meropenem/farmacocinética , Cromatografía Líquida de Alta Presión/métodos , Infecciones Relacionadas con Prótesis/tratamiento farmacológico , Infecciones Relacionadas con Prótesis/sangre , Antibacterianos/sangre , Antibacterianos/análisis , Antibacterianos/farmacocinética , Antibacterianos/uso terapéutico , Reproducibilidad de los Resultados , Masculino , Límite de Detección , Persona de Mediana Edad , Cromatografía Líquida con Espectrometría de Masas