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ETHNOPHARMACOLOGICAL RELEVANCE: Tubeimoside-I (TBM) promotes various cancer cell death by increasing the reactive oxygen species (ROS) production. However, the specific molecular mechanisms of TBM and its impact on oxaliplatin-mediated anti-CRC activity are not yet fully understood. AIM OF THE STUDY: To elucidate the therapeutic effect and underlying molecular mechanism of TBM on oxaliplatin-mediated anti-CRC activity. MATERIALS AND METHODS: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, wound healing assays and flow cytometry were conducted to investigate the changes in cell phenotypes and ROS generation. Real-time quantitative PCR (qRT-PCR) and western blotting were performed to detect the expressions of related mRNA and proteins. Finally, mouse xenograft models demonstrated that synergistic anti-tumor effects of combined treatment with TBM and oxaliplatin. RESULTS: The synergistic enhancement of the anti-tumor effects of oxaliplatin in colon cancer cells by TBM involved in the regulation of ROS-mediated endoplasmic reticulum (ER) stress, C-jun-amino-terminal kinase (JNK), and p38 MAPK signaling pathways. Mechanistically, TBM increased ROS generation in colon cancer cells by inhibiting heat shock protein 60 (HSPD1) expression. Knocking down HSPD1 increased TBM-induced antitumor activity and ROS generation in colon cancer cells. The mouse xenograft tumor models further validated that the combination therapy exhibited stronger anti-tumor effects than monotherapy alone. CONCLUSIONS: Combined therapy with TBM and oxaliplatin might be an effective therapeutic strategy for some CRC patients.
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Neoplasias Colorrectales , Sinergismo Farmacológico , Estrés del Retículo Endoplásmico , Oxaliplatino , Especies Reactivas de Oxígeno , Saponinas , Triterpenos , Animales , Humanos , Masculino , Ratones , Antineoplásicos/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Línea Celular Tumoral , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/metabolismo , Estrés del Retículo Endoplásmico/efectos de los fármacos , Células HCT116 , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Ratones Endogámicos BALB C , Ratones Desnudos , Oxaliplatino/farmacología , Especies Reactivas de Oxígeno/metabolismo , Saponinas/farmacología , Triterpenos/farmacología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: Sepsis, which is characterized by acute systemic inflammation and is associated with high rates of morbidity and mortality, presents a significant challenge in health care. Some scholars have found that the sequential organ failure assessment (SOFA) and quick SOFA scores are not ideal for predicting severe sepsis and mortality. Microbial culture takes a long time (2-3 d) and provides no information for early diagnosis and treatment. Therefore, new diagnostic methods for sepsis need to be explored. AIM: To assess cytokine levels in the plasma of sepsis patients and identify potential biomarkers for diagnosing sepsis. METHODS: Ten sepsis patients admitted to the emergency department within 24 h of onset were enrolled as the observation group, whereas ten noninfected patients served as the control group. Of the 10 noninfected patients, 9 hypertension combined with cerebral infarction, 1 patients with vertiginous syndrome. Plasma Cytokines were measured using the Bio-Plex Pro™ Human Chemokine Panel 40-plex. Differentially expressed cytokines in plasma of sepsis and nonsepsis patients were analyzed using Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. RESULTS: Interleukin (IL)-16, granulocyte-macrophage granulocyte-macrophage colony-stimulating factor (GM-CSF), CX3CL1, CXCL9, CXCL16, CCL25, and CCL23 plasma levels were significantly increased in sepsis patients. GO analysis revealed that these cytokines were mainly associated with cellular structures such as intermediates, nuclear plaques, adhesion plaques, lateral plasma membranes, and cell matrix junctions. These genes were involved in various molecular functions, such as cytokine activity, receptor ligand activity, and signal receptor activator activity, contributing to various biological functions, such as leukocyte chemotaxis, migration, and chemotaxis. KEGG analysis indicated involvement in cytokine cytokine receptor interactions, chemokine signaling pathways, virus-protein interactions with cytokines and cytokine receptors, and the tumor necrosis factor signaling pathway. CONCLUSION: Elevated serum levels of IL-16, GM-CSF, CX3CL1, CXCL9, CXCL16, CCL25, and CCL23 in sepsis patients suggest their potential as diagnostic biomarkers for sepsis.
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Cartilage repair necessitates regenerative medicine because of the unreliable healing mechanism of cartilage. To yield a sufficient number of cells for transplantation, chondrocytes must be expanded in culture. However, in 2D culture, chondrocytes tend to lose their distinctive phenotypes and functionalities after serial passage, thereby limiting their efficacy for tissue engineering purposes. The mechanism of dedifferentiation in 2D culture can be attributed to various factors, including abnormal nuclear strength, stress-induced mitochondrial impairment, chromatin remodeling, ERK-1/2 and the p38/mitogen-activated protein kinase (MAPK) signaling pathway. These mechanisms collectively contribute to the loss of chondrocyte phenotype and reduced production of cartilage-specific extracellular matrix (ECM) components. Chondrocyte 3D culture methods have emerged as promising solutions to prevent dedifferentiation. Techniques, such as scaffold-based culture and scaffold-free approaches, provide chondrocytes with a more physiologically relevant environment, promoting their differentiation and matrix synthesis. These methods have been used in cartilage tissue engineering to create engineered cartilage constructs for transplantation and joint repair. However, chondrocyte 3D culture still has limitations, such as low viability and proliferation rate, and also difficulties in passage under 3D condition. These indicate challenges of obtaining a sufficient number of chondrocytes for large-scale tissue production. To address these issues, ongoing studies of many research groups have been focusing on refining culture conditions, optimizing scaffold materials, and exploring novel cell sources such as stem cells to enhance the quality and quantity of engineered cartilage tissues. Although obstacles remain, continuous endeavors to enhance culture techniques and overcome limitations offer a promising outlook for the advancement of more efficient strategies for cartilage regeneration.
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The dynamics of soil arthropod communities in annual monoculture grasslands is still unclear, which restricts the understanding of the degradation mechanism of cultivated grasslands. We cultivated two annual gramineae species, Lolium multiflorum and Avena sativa, separately in Hongyuan County, located on the eastern edge of the Qinghai-Tibet Plateau, in April 2019. We investigated soil arthropods, plant communities and soil properties in the cultivated grasslands and natural grassland in the late September every year from 2019 to 2022. The results showed that: 1) The taxonomic composition of soil arthropod communities differed significantly among three grasslands and sampling years. 2) There was no significant difference in the density, taxonomic richness, Shannon index and evenness index of soil arthropod communities among three grasslands. 3) The density of soil arthropod communities significantly fluctuated across years in three grasslands, and the taxonomic richness and Shannon index decreased significantly in the L. multiflorum and A. sativa grasslands, with the evenness index declining significantly only in the fourth year. The Shannon index fluctuated significantly and the evenness index varied little in natural grassland. 4) The above- and below-ground biomass, the contents of soil total P, total K and available N were the main factors influencing the taxonomic composition, density and diversity indices of soil arthropod communities. The results suggested that the cultivation of annual gramineae grasslands have significant effects on taxonomic composition, but not on density and diversity of soil arthropod communities, and those variables change significantly across different years.
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Artrópodos , Pradera , Suelo , Animales , Artrópodos/clasificación , Artrópodos/crecimiento & desarrollo , Suelo/química , China , Biodiversidad , Dinámica Poblacional , Lolium/crecimiento & desarrollo , Lolium/clasificación , Poaceae/crecimiento & desarrollo , Poaceae/clasificación , Avena/crecimiento & desarrollo , Avena/clasificación , AltitudRESUMEN
As a medicinal and edible homologous Chinese herb, Polygonatum sibiricum has been used as a primary ingredient in various functional and medicinal products. Damage to the intestinal mucosal barrier can lead to or worsen conditions such as type 2 diabetes and Alzheimer's disease. Traditional Chinese medicine and its bioactive components can help prevent and manage these conditions by restoring the integrity of the intestinal mucosal barrier. This review delves into the mode of action of P. sibiricum polysaccharide in disease prevention and management through the restoration of the intestinal barrier. Polysaccharide from P. sibiricum effectively treats conditions by repairing the intestinal mucosal barrier, offering insights for treating complex diseases and supporting the application of P. sibiricum in clinical settings.
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Objective To understand the current situation and influencing factors of kindergarten teachers' participation in training for preschool sex education in Luzhou city,and provide a basis for improving the sex education literacy of kindergarten teachers in the future. Methods A multi-stage stratified cluster sampling method was adopted,and a questionnaire survey was conducted from December 2021 to January 2022 on the knowledge,attitude,and practice of preschool sex education among all the teachers in 24 kindergartens in Luzhou city. Results Among the 461 teachers,43.0% had participated in lectures/courses/training activities related to preschool sex education;99.1% hoped to participate in lectures/courses/training activities related to preschool sex education;82.6% learned about child sexual knowledge through school education;75.5% expressed the hope to learn about child sexual knowledge through expert training.The results of multivariate Logistic regression showed that except private kindergartens as an inhibiting factor (OR=0.57,95%CI=0.37-0.87,P=0.008),high monthly income (OR=3.52,95%CI=1.13-9.30,P=0.011),more ways to know about sex education knowledge (OR=2.87,95%CI=1.76-4.70,P<0.001),and social support (OR=1.58,95%CI=1.04-2.38, P=0.030) were promoting factors for teachers to participate in the training for preschool sex education. Conclusion The kindergarten teachers presented a participation rate but a high demand for the training for preschool sex education.They mainly obtain the sex education knowledge from school education.The nature of kindergarten,monthly income of teachers,social support situation,and ways of understanding sex education knowledge are the key factors influencing the teachers' participation in the training for preschool sex education.
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Maestros , Educación Sexual , Humanos , Encuestas y Cuestionarios , Educación Sexual/métodos , Preescolar , Femenino , Masculino , Adulto , Conocimientos, Actitudes y Práctica en Salud , Formación del Profesorado/métodos , ChinaRESUMEN
Background: Obesity represents a significant risk factor for the development of metabolic abnormalities. However, it is not inevitable that all individuals with obesity will develop these disorders. Selenium has been demonstrated to play a role in maintaining metabolic homeostasis in vivo, with the ability to regulate relevant signaling pathways involved in glucose and lipid metabolism processes. Previous studies have indicated that selenium concentrations in obese individuals are higher than those reported in the general population. These findings the question of whether altered selenium concentrations may act as important triggers for accelerating metabolic imbalances in the obese population. The aim of this study was to examine the potential correlation between serum selenium concentrations and the risk of developing metabolic abnormalities in individuals with obesity. Methods: The present study included 6,125 participants from the 2011-2018 National Health and Nutrition Examination Survey (NHANES) who were aged between 20 and 80 years, with a body mass index (BMI) of 30 kg/m2 or greater, and met the inclusion and exclusion criteria. Weighted generalized linear regression analyses were conducted to evaluate the associations between serum selenium concentrations and the conversion of metabolically healthy obesity (MHO) to metabolically unhealthy obesity (MUO). A generalized additive model (GAM) and a two-piecewise linear regression model were employed to investigate the saturation threshold effect between selenium and MUO. The correlation between different selenium concentration intervals and metabolic diseases was evaluated by categorizing selenium concentrations according to the saturation threshold. Furthermore, this study investigated the correlation between serum selenium and lipid concentrations in obese females and between serum selenium and blood pressure in obese males. Results: The weighted prevalence of MUO in the study population was 48.35%. After rigorous adjustment for sociodemographic, physical, and laboratory test covariates, the weighted odds ratio (OR) of MUO increased by 44% for every 1 µM increase (approximately 78.74 µg) in the serum selenium concentration (weighted OR=1.44; 95% CI=1.09 - 1.91; P=0.018). Second, GAM analysis and saturation threshold analyses revealed an inverted U-shaped relationship between serum selenium and metabolic abnormalities in males, with a corresponding inflection point (K) of 2.82 µM. When the serum selenium concentration was below the K-value, the effects of serum selenium were mainly on blood pressure, especially diastolic blood pressure (DBP) (weighted ß: 3.34; 95% CI= 0.25 - 6.44; P=0.038). Conversely, the correlation between the serum selenium concentrations and metabolic homeostasis imbalance in females was linear. When the selenium concentration exceeded 2.12 µM, the increase in selenium content was accompanied by increases in total cholesterol (TC, weighted ß=0.54, 95% CI=0.32 - 0.76; P=0.000) and triglyceride (TG, weighted ß=0.51, 95% CI=0.27 - 0.75; P=0.000) concentrations. Conclusions: The findings of our study indicate that selenium supplementation strategies for individuals with obesity should be tailored to the sex of the individual. In females, serum selenium concentration above the saturation threshold primarily facilitates the transition from MHO to MUO by influencing alterations in serum lipid metabolism. Maintaining selenium concentrations below the threshold levels is highly important for preventing the conversion of MHO to MUO. In males, serum selenium concentrations above the threshold were found to be effective in preventing an elevation in blood pressure, particularly in improving systolic blood pressure (SBP). Nevertheless, serum selenium concentrations below the threshold are linked to an increased risk of hypertension in obese individuals, particularly those with elevated diastolic blood pressure (DBP). Further research is needed to elucidate the optimal serum selenium concentration that exerts deleterious effects on blood pressure.
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Enfermedades Metabólicas , Encuestas Nutricionales , Selenio , Humanos , Selenio/sangre , Masculino , Femenino , Persona de Mediana Edad , Adulto , Estudios Transversales , Estudios Retrospectivos , Anciano , Estados Unidos/epidemiología , Enfermedades Metabólicas/sangre , Enfermedades Metabólicas/epidemiología , Obesidad Metabólica Benigna/sangre , Adulto Joven , Anciano de 80 o más Años , Obesidad/sangre , Índice de Masa Corporal , Factores de RiesgoRESUMEN
Anticoccidial vaccines comprising living oocysts of Eimeria tenella, Eimeria necatrix, Eimeria maxima, and Eimeria acervulina are used to control coccidiosis. This study explored the potential of IL-1ß to act as a molecular adjuvant for enhancing the immunogenicity of Eimeria necatrix and mucosal immunity. We engineered E. necatrix to express a functional chIL-1ß (EnIL-1ß) and immunized chickens with oocysts of the wild type (EnWT) and tranegenic (EnIL-1ß) strains, respectively. The chickens were then challenged with EnWT oocysts to examine the immunogenicity-enhancing potential of chIL-1ß. As expected, the oocyst output of EnIL-1ß-immunized chickens was significantly reduced compared to those immunized using EnWT. No difference in body weight gain and lesion scores of EnIL-1ß and EnWT groups was observed. The parasite load in the small intestine and caeca showed that the invasion and replication of EnIL-1ß was not affected. However, the markers of immunogenicity and mucosal barrier, Claudin-1 and avian ß-defensin-1, were elevated in EnIL-1ß-infected chickens. Ectopic expression of chIL-1ß in E. necatrix thus appears to improve its immunogenicity and mucosal immunity, without increasing pathogenicity. Our findings support chIL-1ß as a candidate for development of effective live-oocyst-based anticoccidial vaccines.
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Pollos , Coccidiosis , Eimeria , Inmunidad Mucosa , Interleucina-1beta , Enfermedades de las Aves de Corral , Vacunas Antiprotozoos , Animales , Coccidiosis/inmunología , Coccidiosis/veterinaria , Interleucina-1beta/inmunología , Interleucina-1beta/metabolismo , Pollos/inmunología , Eimeria/inmunología , Vacunas Antiprotozoos/inmunología , Enfermedades de las Aves de Corral/inmunología , Enfermedades de las Aves de Corral/parasitología , Enfermedades de las Aves de Corral/prevención & control , Inmunización , Oocistos/inmunología , Microorganismos Modificados GenéticamenteRESUMEN
Inflammatory bowel disease (IBD) is a chronic, debilitating condition with limited therapeutic options. Dietary components like blueberries have emerged as potential modulators of inflammation and tissue repair in gastrointestinal diseases. This study investigated endoplasmic reticulum (ER) stress-mediated apoptosis mediated protective effects of blueberries in ameliorating dextran sulfate sodium (DSS)-induced IBD. Firstly, a total of 86 anthocyanin compounds were identified in blueberry extract by LC-MS spectroscopy, including 35 cyanidin, 9 delphinidin, 14 malvidin, 10 peonidin, and 9 petunidin. Then, the animal study showed that blueberry supplementation notably ameliorated DSS-induced IBD symptoms, as evidenced by improved histopathological scores and a reduced disease activity index (DAI) score. Additionally, blueberries attenuated ER stress by inhibiting the colonic PERK/eIF2α/ATF4/CHOP signaling pathway. Furthermore, blueberries inhibited the expression of the pro-apoptotic protein, caspase-3, and decreased colonic apoptosis, as evidenced by TUNEL assay results. However, it did not affect the expression of anti-apoptotic proteins, bcl-2 and bcl-xl. Finally, blueberries enhanced the intestinal barrier by upregulating ZO-1, claudin-1, occludin, and E-cadherin. In conclusion, blueberries demonstrate therapeutic potential against DSS-induced IBD-like symptoms in mice, possibly by regulating ER stress-mediated apoptosis pathways. These findings suggest that blueberries might be an effective dietary intervention for IBD management.
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Apoptosis , Arándanos Azules (Planta) , Colon , Sulfato de Dextran , Estrés del Retículo Endoplásmico , Enfermedades Inflamatorias del Intestino , Extractos Vegetales , Animales , Arándanos Azules (Planta)/química , Estrés del Retículo Endoplásmico/efectos de los fármacos , Apoptosis/efectos de los fármacos , Ratones , Extractos Vegetales/farmacología , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/inducido químicamente , Sulfato de Dextran/efectos adversos , Masculino , Colon/efectos de los fármacos , Colon/metabolismo , Colon/patología , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , HumanosRESUMEN
The design and synthesis of hybrid borates by the organic ligand modification method are urgent and undeveloped areas of research. It is difficult to directly integrate organoboronic acids within inorganic borate chemistry by adopting the traditional preparation approaches. This work reports a facile synthetic method to synthesize a large family of pyrazole molecule-protected borates in a rapid and precise manner under mild conditions. A unique cyclic eight-membered B4O4-ring has been identified as the cluster core for all these hybrid borates with two different conformations (boat and crown). This strategy can be applied to a system of pyrazolyl molecules to generate such hybrid borates in two independent routes from organoboronic or inorganic boric acids. Furtherly, the mechanism of 'click reaction' between boric acid and pyrazole induced by copper ions has been proposed based on the synthetic conditions and the structure of intermediate. Due to the bimetallic Cu sites and the functional surfaces, these materials can be used as electrocatalysts for CO2 reduction reaction and efficiently enhance the selectivity of HCOOH and C2H4. Our strategy can be regarded as a typical template technique for organic molecule-protected borates.
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PURPOSE: To evaluate the long-term subjective and objective visual quality after implantation of a diffractive trifocal intraocular lens (IOL) in high myopic eyes. METHODS: A total of 53 eyes from 38 patients with high myopia who underwent phacoemulsification and trifocal IOL implantation were investigated. The visual acuity, contrast sensitivity, diopter, defocus curve, and objective visual quality at 1 month, 3 months, 1 year, and 2 years after surgery, as well as the satisfaction questionnaire and VF-14 scale, were statistically analyzed. RESULTS: The average age was 53.14 ± 4.70 years. The average preoperative spherical equivalent was -10.77 ± 3.98 D. Two years after surgery, 94.3% of the patients achieved an uncorrected distance visual acuity of 0.1 (LogMAR), and 84.9% and 94.3% of the patients had SE within ±0.50 D and ±1.0 D, respectively. The defocus curve was smooth and at a high value within the range of 0 D to -2.50 D. In CS or objective visual quality, there was no significant difference at 3 months, 1 year, and 2 years after operation (all P > 0.05). The rate of spectacle independence was 100%. The proportion of patients with moderate or severe glare and halo was 10.5% and 13.2%, respectively. Furthermore, 23.7%, 26.3%, and 18.4% of the patients had difficulties in reading small font, doing delicate tasks, and driving or riding at night, respectively. CONCLUSION: The diffractive trifocal IOL implantation provided good distance, intermediate, and near uncorrected visual acuity for patients with cataracts and high myopia. It was safe, effective, predictable, and stable. It provided long-term good visual quality after surgery, with high spectacle independence and high patient satisfaction.
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Patients with substance use disorders (SUDs) often suffer from cognitive dysfunction (CD), affecting their quality of life and daily functioning. Current treatments, including pharmacotherapy and psychotherapy, have limited efficacy and notable side effects. Transcranial direct current stimulation (tDCS), a non-invasive technique that modulates cortical activity, shows promise in improving cognitive function with minimal side effects and low cost, and could potentially serve as a valuable adjunct to existing therapies. This systematic review aims to evaluate the literature on the effectiveness of tDCS for CD in SUD patients to inform clinical practice and future research. Following PRISMA guidelines, the review includes studies that used tDCS for SUD-related CD. The criteria for inclusion encompassed participants aged 18 and older with a diagnosis of SUD, the use of tDCS (either conventional or high-definition), control groups receiving sham stimulation or no intervention, and cognitive outcome measures for substance-related cognitive function using validated tools. Databases searched were Ovid MEDLINE, PubMed, Web of Science, Embase, Scopus, and PsycINFO, with specific keywords. Twenty-two studies met the criteria, suggesting tDCS can improve cognitive functions in SUD patients, though results varied. Effectiveness may depend on the brain area targeted, stimulation parameters, task requirements, and individual differences. tDCS shows potential in treating SUD-related CD, but further research is needed to optimize stimulation protocols and address study variability. Future studies should use functional magnetic resonance imaging to explore the brain mechanisms by which tDCS improves cognitive function in SUDs and focus on larger, long-term trials to confirm efficacy and refine tDCS treatment parameters.
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BACKGROUND: Modern pharmacological studies have confirmed that plant-derived compounds from Puerariae flos (PF) has significant biological activities against liver damage, tumors and inflammation. Kakkatin is an isoflavone polyphenolic compound isolated from PF flower. However, the effect of kakkatin and its derivatives on anti-tumor has not been well explored. AIM: To design and synthesize a kakkatin derivative [6-(hept-6-yn-1-yloxy)-3-(4-hydroxyphenyl)-7-methoxy-4H-chromen-4-one (HK)] to explore its anti-tumor biological activity. METHODS: Hept-6-yn-1-yl ethanesulfonate was introduced to replace hydrogen at the hydroxyl position of kakkatin phenol, and the derivative of kakkatin was prepared; the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide was used to detect cell viability, a clone formation assay was adopted to detect cell proliferation, apoptosis, necrosis, and cell cycles were analyzed by Annexin V/propidium iodide staining and flow cytometry. Cell migration and invasion ability were evaluated by cell scratch assay and transwell assay. The potential mechanism of HK on hepatocellular carcinoma (HCC) SMMC-7721 cells was explored through network pharmacology and molecular docking, and finally real-time PCR assays was used to verify the potential targets and evaluate the biological activity of HK. RESULTS: Compared with kakkatin, the modified HK did not significantly increase the inhibitory activity of gastric cancer MGC803 cells, but the inhibitory activity of HCC SMMC-7721 cells was increased by about 30 times, with an IC50 value of 2.5 µM, and the tumor inhibition effect was better than cisplatin, which could significantly inhibit the cloning, invasion and metastasis of HCC SMMC-7721 cells, and induce apoptosis and G2/M cycle arrest. Its mechanism of action is mainly related to the upregulation of PDE3B and NFKB1 target proteins in the cAMP pathway. CONCLUSION: HK have a significant inhibitory effect on HCC SMMC-7721 cells, and the targets of their action may be PDE3B and NFKB1 proteins in the cAMP pathway, making it a good lead drug for the treatment of HCC.
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Phytochemical investigation on the leaves of Tibetan Leucosceptrum canum, a Chinese medicinal herb, led to the isolation of seven new leucosceptrane sesterterpenoids (1-7) and five known analogs (8-12). Comprehensive spectroscopic analysis (including 1D and 2D NMR, and HRMS), quantum chemistry computations, and single crystal X-ray crystallographic analysis were applied to elucidate their structures. Compounds 1-3 and 6 were the first examples of the leucosceptrane sesterterpenoids with rare C-2 oxidation. Compound 2 exhibited immunosuppressive activities via suppressing the secretion of cytokines IL-6 and TNF-α in LPS-induced macrophages RAW264.7 with IC50 values of 13.39 and 19.34 µM, respectively.
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Background: Previous observational studies have reported a possible association between circulating lipids and lipid-lowering drugs and male infertility (MIF), as well as the mediating role of circulating vitamin D. Then, due to issues such as bias, reverse causality, and residual confounding, inferring causal relationships from these studies may be challenging. Therefore, this study aims to explore the effects of circulating lipids and lipid-lowering drugs on MIF through Mendelian randomization (MR) analysis and evaluate the mediating role of vitamin D. Method: Genetic variations related to lipid traits and the lipid-lowering effect of lipid modification targets are extracted from the Global Alliance for Lipid Genetics Genome-Wide Association Study. The summary statistics for MIF are from the FinnGen 9th edition. Using quantitative expression feature loci data from relevant organizations to obtain genetic variations related to gene expression level, further to explore the relationship between these target gene expression levels and MIF risk. Two-step MR analysis is used to explore the mediating role of vitamin D. Multiple sensitivity analysis methods (co-localization analysis, Egger intercept test, Cochrane's Q test, pleiotropy residuals and outliers (MR-PRESSO), and the leave-one-out method) are used to demonstrate the reliability of our results. Result: In our study, we observed that lipid modification of four lipid-lowering drug targets was associated with MIF risk, the LDLR activator (equivalent to a 1-SD decrease in LDL-C) (OR=1.94, 95% CI 1.14-3.28, FDR=0.040), LPL activator (equivalent to a 1-SD decrease in TG) (OR=1.86, 95% CI 1.25-2.76, FDR=0.022), and CETP inhibitor (equivalent to a 1-SD increase in HDL-C) (OR=1.28, 95% CI 1.07-1.53, FDR=0.035) were associated with a higher risk of MIF. The HMGCR inhibitor (equivalent to a 1-SD decrease in LDL-C) was associated with a lower risk of MIF (OR=0.38, 95% CI 0.17-0.83, FDR=0.39). Lipid-modifying effects of three targets were partially mediated by serum vitamin D levels. Mediation was 0.035 (LDLR activator), 0.012 (LPL activator), and 0.030 (CETP inhibitor), with mediation ratios of 5.34% (LDLR activator), 1.94% (LPL activator), and 12.2% (CETP inhibitor), respectively. In addition, there was no evidence that lipid properties and lipid modification effects of six other lipid-lowering drug targets were associated with MIF risk. Multiple sensitivity analysis methods revealed insignificant evidence of bias arising from pleiotropy or genetic confounding. Conclusion: This study did not support lipid traits (LDL-C, HDL-C, TG, Apo-A1, and Apo-B) as pathogenic risk factors for MIF. It emphasized that LPL, LDLR, CETP, and HMGCR were promising drug targets for improving male fertility.
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Estudio de Asociación del Genoma Completo , Infertilidad Masculina , Análisis de la Aleatorización Mendeliana , Humanos , Masculino , Infertilidad Masculina/genética , Lípidos/sangre , Vitamina D/sangre , Polimorfismo de Nucleótido Simple , Proteínas de Transferencia de Ésteres de Colesterol/genética , Hipolipemiantes/uso terapéutico , Receptores de LDL/genética , Hidroximetilglutaril-CoA Reductasas/genéticaRESUMEN
Objective: To develop an artificial intelligence model to predict an antimicrobial susceptibility pattern in patients with urinary tract infection (UTI). Materials and methods: 26â087 adult patients with culture-proven UTI during 2015-2020 from a university teaching hospital and three community hospitals in Hong Kong were included. Cases with asymptomatic bacteriuria (absence of diagnosis code of UTI, or absence of leucocytes in urine microscopy) were excluded. Patients from 2015 to 2019 were included in the training set, while patients from the year 2020 were included as the test set.Three first-line antibiotics were chosen for prediction of susceptibility in the bacterial isolates causing UTI: namely nitrofurantoin, ciprofloxacin and amoxicillin-clavulanate. Baseline epidemiological factors, previous antimicrobial consumption, medical history and previous culture results were included as features. Logistic regression and random forest were applied to the dataset. Models were evaluated by F1-score and area under the curve-receiver operating characteristic (AUC-ROC). Results: Random forest was the best algorithm in predicting susceptibility of the three antibiotics (nitrofurantoin, amoxicillin-clavulanate and ciprofloxacin). The AUC-ROC values were 0.941, 0.939 and 0.937, respectively. The F1 scores were 0.938, 0.928 and 0.906 respectively. Conclusions: Random forest model may aid judicious empirical antibiotics use in UTI. Given the reasonable performance and accuracy, these accurate models may aid clinicians in choosing between different first-line antibiotics for UTI.
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Nitrogen addition is commonly used to remediate total petroleum hydrocarbons (TPH) in petroleum-contaminated soils. However, acceptable exogenous nitrogen dosages and their utilization efficiency for the degradation of hydrocarbons in oil-polluted soils are not well understood. This study compared the hydrocarbon bioremediation capacity by applying different doses of NH4Cl as a stimulant in soils contaminated with TPH at 8553 and 17090 mg/kg. The results showed acceptable exogenous nitrogen levels ranging from 60 to 360 mg N/kg soil, and the optimal nitrogen dosage for TPH remediation was 136 mg N/kg in soils with different TPH concentrations. The nitrogen availability efficiency (NAE) and nitrogen polarization factor availability (NPFA) in the 136 mg N/kg addition treatments were 6.69 and 20.47 mg/mg in 8533 mg/kg TPH-polluted soil, and 6.03 and 31.11 mg/mg in 17090 mg/kg TPH-polluted soil, respectively. Metagenomic analysis revealed that the application of 136 mg/kg nitrogen facilitated ammonia oxidation and nitrite reduction to nitric oxide, and induced soil microorganisms to undergo regulatory or adaptive changes in energy supply and metabolic state, which could aid in restoring the ecological functions of petroleum-contaminated soils. These findings underscore that 136 mg/kg of nitrogen dosage application is optimal for remediation of petroleum-contaminated soils irrespective of the TPH concentrations. This exogenous nitrogen application dosage for TPH remediation aligns with the nitrogen requirements for crop growth in agriculture.
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Biodegradación Ambiental , Nitrógeno , Petróleo , Microbiología del Suelo , Contaminantes del Suelo , Contaminantes del Suelo/metabolismo , Petróleo/metabolismo , Nitrógeno/metabolismo , Hidrocarburos/metabolismo , MetagenómicaRESUMEN
In moiré crystals resulting from the stacking of twisted two-dimensional (2D) layered materials, a subtle adjustment in the twist angle surprisingly gives rise to a wide range of correlated optical and electrical properties. Herein, we report the synthesis of supertwisted WS2 spirals and the observation of giant second harmonic generation (SHG) in these spirals. Supertwisted WS2 spirals featuring different twist angles are synthesized on a Euclidean or step-edge particle-induced non-Euclidean surface using carefully designed water-assisted chemical vapor deposition. We observed an oscillatory dependence of SHG intensity on layer number, attributed to atomically phase-matched nonlinear dipoles within layers of supertwisted spiral crystals where inversion symmetry is restored. Through an investigation into the twist angle evolution of SHG intensity, we discovered that the stacking model between layers plays a crucial role in determining the nonlinearity, and the SHG signals in supertwisted spirals exhibit enhancements by a factor of 2 to 136 when compared with the SHG of the single-layer structure. These findings provide helpful perspectives on the rational growth of 2D twisted structures and the implementation of twist angle adjustable endowing them great potential for exploring strong coupling correlation physics and applications in the field of twistronics.
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Cataracts are the world's number one blinding eye disease. Cataracts can only be effectively treated surgically, although there is a chance of surgical complications. One of the pathogenic processes of cataracts is oxidative stress, which closely correlated with pyroptosis. SIRT1 is essential for the regulation of pyroptosis. Nevertheless, the role of SIRT1 in formation of cataracts is unclear. In this work, we developed an in vitro model of shortwave blue light (SWBL)-induced scotomization in human lens epithelial cells (HLECs) and an in vivo model of SWBL-induced cataracts in rats. The study aimed to understand how the SIRT1/NF-κB/NLRP3 pathway functions. Additionally, the evaluation included cell death and the release of lactate dehydrogenase (LDH), a cytotoxicity marker, from injured cells. First, we discovered that SWBL exposure resulted in lens clouding in Sprague- Dawley (SD) rats and that the degree of clouding was positively linked to the duration of irradiation. Second, we discovered that SIRT1 exhibited antioxidant properties and was connected to the NF-κB/NLRP3 pathway. SWBL irradiation inhibited SIRT1 expression, exacerbated oxidative stress, and promoted nuclear translocation of NF-κB and the activation of the NLRP3 inflammasome, which caused LEC pyroptosis and ultimately led to cataract formation. Transient transfection to increase the expression of SIRT1 decreased the protein expression levels of NF-κB, NLRP3, caspase-1, and GSDMD, inhibited HLEC pyroptosis, and reduced the release of LDH, providing a potential method for cataract prevention and treatment.
Asunto(s)
Catarata , Células Epiteliales , Cristalino , FN-kappa B , Proteína con Dominio Pirina 3 de la Familia NLR , Piroptosis , Sirtuina 1 , Animales , Humanos , Ratas , Western Blotting , Luz Azul/efectos adversos , Catarata/metabolismo , Catarata/patología , Catarata/etiología , Células Cultivadas , Modelos Animales de Enfermedad , Células Epiteliales/metabolismo , Células Epiteliales/efectos de la radiación , Cristalino/efectos de la radiación , Cristalino/metabolismo , FN-kappa B/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Estrés Oxidativo , Piroptosis/fisiología , Piroptosis/efectos de la radiación , Ratas Sprague-Dawley , Transducción de Señal/fisiología , Sirtuina 1/metabolismoRESUMEN
RATIONALE: This study reports the first case of congenital hypothyroidism (CH) and alpha thalassemia in a child in China, with anemia and muscle damage as the main manifestations. Analyzing and studying this case is of great significance in reducing missed and misdiagnosed CH and will provide a clinical strategy for treating these patients. PATIENT CONCERNS: Child, female, 2 years and 7 months old, the child appeared dispirited, had poor appetite, shallow complexion, reduced activities with anemia, elevated muscle enzymes, height, and growth retardation. DIAGNOSES: The child was diagnosed with CH with alpha thalassemia. INTERVENTIONS: The patient was treated with levothyroxine sodium and anemia correction. OUTCOMES: The children's current spirit, appetite, red face, normal limb activity, physical development, and intelligence were significantly better than those of normal children of the same age. CONCLUSIONS: CH with alpha thalassemia, especially anemia and muscle damage as the main manifestations, has not been reported. Administration of levothyroxine sodium is effective in correcting anemia in patients with CH and alpha thalassemia. LESSON: Due to CH and alpha thalassemia, there are no specific symptoms and they are prone to missed diagnosis and misdiagnosis. Therefore, patients with anemia and elevated muscle enzyme levels should be routinely tested for thyroid function to diagnose them early and provide proper treatment to avoid negative consequences.