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JOURNAL/nrgr/04.03/01300535-202506000-00028/figure1/v/2024-08-05T133530Z/r/image-tiff The pathophysiology of Huntington's disease involves high levels of the neurotoxin quinolinic acid. Quinolinic acid accumulation results in oxidative stress, which leads to neurotoxicity. However, the molecular and cellular mechanisms by which quinolinic acid contributes to Huntington's disease pathology remain unknown. In this study, we established in vitro and in vivo models of Huntington's disease by administering quinolinic acid to the PC12 neuronal cell line and the striatum of mice, respectively. We observed a decrease in the levels of hydrogen sulfide in both PC12 cells and mouse serum, which was accompanied by down-regulation of cystathionine ß-synthase, an enzyme responsible for hydrogen sulfide production. However, treatment with NaHS (a hydrogen sulfide donor) increased hydrogen sulfide levels in the neurons and in mouse serum, as well as cystathionine ß-synthase expression in the neurons and the mouse striatum, while also improving oxidative imbalance and mitochondrial dysfunction in PC12 cells and the mouse striatum. These beneficial effects correlated with upregulation of nuclear factor erythroid 2-related factor 2 expression. Finally, treatment with the nuclear factor erythroid 2-related factor 2 inhibitor ML385 reversed the beneficial impact of exogenous hydrogen sulfide on quinolinic acid-induced oxidative stress. Taken together, our findings show that hydrogen sulfide reduces oxidative stress in Huntington's disease by activating nuclear factor erythroid 2-related factor 2, suggesting that hydrogen sulfide is a novel neuroprotective drug candidate for treating patients with Huntington's disease.
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ETHNOPHARMACOLOGY RELEVANCE: Palm buds are a natural green resource of the forest, which are not only rich in nutrients but contain a large number of phenolic acids and flavonoids, among other components. It has a variety of biological activities such as antioxidant and uterine smooth muscle stimulation. AIM OF THE STUDY: To evaluate the safety of palm buds for use as a nutraceutical product and food by evaluating the toxicity, subacute toxicity and genotoxicity of the young palm buds. Also studied for its immune-enhancing activity. MATERIALS AND METHODS: Acute toxicity tests were performed in mice using the maximum tolerance method, and the manifestations of toxicity and deaths were recorded after administration of 10,000 mg/mL for 14 consecutive d (days) of observations. To assess subacute toxicity, mice were treated with palm buds (750, 1500, or 3000 mg/mL) daily for 28 days. The teratogenicity of palm buds was assessed by the Ames test, the mouse bone marrow cell micronucleus test, and the mouse spermatozoa malformation test. In addition, we evaluated the immune-enhancing ability of palm buds by the mouse carbon profile test, delayed-type metamorphosis reaction, and serum hemolysin assay. RESULTS: In the acute toxicity study, the Median Lethal Dose (LD50) was greater than 10,000 mg/kg bw in both male and female rats. There were also no deaths or serious toxicities in the subacute study. The no-observed-adverse-effect level (NOAEL) was 3000 mg/kg bw. However, the mice's food intake decreased after one week. The medium and high dose groups had a reducing effect on body weight in mice of both sexes. In addition, the changes in organ coefficients of the liver, kidney and stomach in male mice were significantly higher in the high-dose group (3.23 ± 0.35, 0.75 ± 0.05, 0.57 ± 0.05 g) than in the control group (2.94 ± 0.18, 0.58 ± 0.05, 0.50 ± 0.02 g). Hematological analyses showed that all the indices of the rats in each palm sprout dose group were within the normal range. The results of blood biochemical indicators showed that there was a significant reduction in TP in the blood of male mice in the high-dose group (44.6 ± 7.8 g/L) compared to the control group (58.3 ± 15.1 g/L). In histopathological analysis, none of the significant histopathological changes were observed. The results of the immunological experiment in mice showed that the liver coefficient and thymus coefficient of the high-dose group (8400 mg/kg) were significantly lower than the control group. There was no remarkable difference in auricle swelling between each dose palm bud group (1400, 2800, or 8400 mg/kg) and the control group. The anti-volume number of the high-dose group was significantly increased. CONCLUSION: Palm buds have non-toxic effects in vivo and have little effect on non-specific and cellular immunity in the test mice within the dose range of this experiment. The immunoenhancement in mice is mainly achieved through humoral immunity. In conclusion, our results suggest that palm buds are safe for use as healthcare products and food.
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Arecaceae , Pruebas de Toxicidad Aguda , Animales , Femenino , Masculino , Arecaceae/química , Ratones , Extractos Vegetales/toxicidad , Extractos Vegetales/farmacología , Extractos Vegetales/administración & dosificación , Factores Inmunológicos/toxicidad , Ratas , Pruebas de Toxicidad Subaguda , Relación Dosis-Respuesta a Droga , Pruebas de Micronúcleos , Pruebas de Mutagenicidad , Proteínas Hemolisinas/toxicidad , Dosificación Letal MedianaRESUMEN
Autophagy is an evolutionarily conserved degradation pathway for maintaining cellular homeostasis and its dysregulation leads to numerous human diseases such as cancer. As a core protein for autophagy, ATG16L1 (autophagy related 16 like 1) is heavily regulated by post-translational modifications, including phosphorylation, ubiquitination, and methylation, which is critical for autophagy regulation. In this study, we identify HDAC1 (histone deacetylase 1) as a regulator of ATG16L1 acetylation and hence autophagy. Specifically, HDAC1 colocalizes and interacts with ATG16L1, and reduces its acetylation, which is highly dependent on its enzymatic activity. By promoting ATG16L1 deacetylation, HDAC1 enhances ATG16L1 interaction with the ATG12-ATG5 conjugate, resulting in the activation of autophagic pathway. Consistently, the induction of basal autophagy by HDAC1 in colorectal cancer cells largely relies on its deacetylase activity as well as ATG16L1. Moreover, HDAC1 enhances the survival, proliferation, and transformation of colorectal cancer cells in an ATG16L-dependent manner, indicating the fundamental roles of autophagy in colorectal cancer. Together, our findings uncover a novel regulatory mechanism of autophagy and suggest both HDAC1 and ATG16L1 as therapeutic targets for colorectal cancer.
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To report the testing signal of an immunochromatographic assay for on-site quantitative detection, a portable and user-friendly smartphone-based biosensing platform is developed in this study. This innovative system is composed of an ambient light sensor inherent smartphone reader and a 3D-printed handhold device, a quantitative tool capable of directly interpreting carbon nanoparticle (CNP)-conjugated immunochromatographic strips. To showcase the platform capability, the smartphone-based immunochromatography system (SPICS) reader and device were successfully used in CNP strips for rapid detection of the early pregnancy marker human chorionic gonadotropin in female urine (HCG; limit of detection [LOD]: 0.30 mIU mL-1), prostate-specific antigen in patient blood (PSA; LOD: 0.28 ng mL-1) and ampicillin residue in animal milk (AMP; LOD: 0.23 ng mL-1). The results were fully correlated with conventional commercial instruments (R2 = 0.99). The SPICS platform exhibits significant advantages, including portability, cost-effectiveness, easy operation, and rapid and quantitative detection, making it a valuable on-site diagnosis tool for use in home and community healthcare facilities.
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PURPOSE: The prevalence of biliary tract diseases, which are common gastrointestinal disorders, is steadily rising. If it progresses to sepsis or septic shock, it can endanger the patient's life. Therefore, it is crucial to promptly diagnose bacterial infection in individuals suffering from biliary diseases and comprehend the risk factors associated with infection. The objective of this study was to examine the types of bacteria present in the bile of patients with biliary tract diseases, assess any alterations in their susceptibility to antimicrobial agents, and identify the risk factors contributing to the development of infection in these patients. PATIENTS AND METHODS: From June 2019 to November 2022, 317 patients of biliary tract diseases with positive bile culture were included in this hospital-based descriptive analysis. The hospital's computerized medical records were used to collect data on demographic information (including gender, age, and occupation), laboratory, and clinical findings, physical examination results, comorbidities, basic diseases, treatment history, complications, and in-hospital outcomes. The study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) principles. RESULTS: Of the 317 patients with positive biliary tract diseases, 247 had benign diseases and 70 had malignant diseases. Patients with benign disease experienced a higher prevalence of statistically significant symptoms such as abdominal pain (81.4% vs. 57.1%, P = 0.000), nausea (31.2% vs. 14.3%, P = 0.005), vomiting (30.0% vs. 12.9%, P = 0.004), and chills (10.9% vs. 2.9%, P = 0.039), while jaundice (12.6% vs. 37.1%, P = 0.000) was more common in patients with malignant disease. At the species level, Escherichia coli (105; 40.5%), Klebsiella pneumoniae (41; 15.8%), and Pseudomonas aeruginosa (30; 11.6%) were the most commonly found Gram-negative bacterial strains in biliary tract infection. Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa were most susceptible to tigecycline, ertapenem and ceftazidime/avibactam, respectively. CONCLUSION: Gram-negative bacteria are the most commonly isolated biliary bacteria. Clinical doctors should pay attention to patients with malignant diseases with low hemoglobin, high total bilirubin and high alkaline phosphatase. Carbapenems, tigecycline, and minocycline are the recommended antibiotics for Enterobacteriaceae. In recent years, the proportion of enterococcus has gradually increased, and clinical attention should be paid to enterococcus infection. Linezolid and vancomycin were recommended for the treatment of Enterococci infections. Overall, this work can provide reference for clinical diagnosis, treatment and effective interventions.
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Antibacterianos , Bilis , Enfermedades de las Vías Biliares , Centros de Atención Terciaria , Humanos , Masculino , Femenino , Enfermedades de las Vías Biliares/microbiología , Enfermedades de las Vías Biliares/epidemiología , Centros de Atención Terciaria/estadística & datos numéricos , Persona de Mediana Edad , Anciano , Adulto , Bilis/microbiología , Antibacterianos/uso terapéutico , Factores de Riesgo , Anciano de 80 o más Años , Bacterias/aislamiento & purificación , Bacterias/clasificación , Bacterias/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Infecciones Bacterianas/epidemiología , Infecciones Bacterianas/microbiología , Infecciones Bacterianas/tratamiento farmacológico , Prevalencia , Adulto JovenRESUMEN
Ischemic stroke is a devastating disease and one of the leading causes of mortality worldwide. Overproduction of reactive oxygen species and inflammatory response contribute to secondary damage following ischemic insult. Nanozymes with robust anti-oxidative stress properties possess therapeutic possibility for ischemic insult. However, insufficiency of nanozyme accumulation in the neuronal mitochondria hindered their application. Herein, we constructed polydopamine-coated Prussian blue nanoparticles (PB@PDA NPs) to realize the targeting neuronal mitochondria for ischemic stroke, with the properties of antioxidant and anti-inflammation. After administration, much higher accumulation of PB@PDA NPs in the brain was observed compared to that in the PB NP group. Moreover, PB@PDA NPs effectively attenuated brain infarct than that of PB NPs in neonatal mice following hypoxia-ischemia (HI) insult. PB@PDA NPs mainly colocated with neuronal mitochondria in vivo and in vitro. Apart from attenuating oxidative stress, PB@PDA NPs also suppressed neuronal apoptosis and counteracted inflammation, which effectively promote a short- and long-term functional recovery in HI mice. Further, the therapeutic efficacy of PB@PDA NPs was also found in adult ischemic mice via tail vein injection. Collectively, these findings illustrate that PB@PDA NPs via system injection accumulate in neuronal mitochondria and are beneficial for ischemic stroke.
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BACKGROUND: Phosphorus-solubilizing bacteria (PSB) are vital in converting insoluble phosphorus into a soluble form that plants can readily absorb and utilize in soil. While previous studies have mainly focused on the extracellular secretion of microorganisms, few have explored the intricate intracellular metabolic processes involved in PSB-mediated phosphorus solubilization. RESULTS: Here, we uncovered that Ca3(PO4)2 could serve as a source of insoluble phosphorus for the PSB, Pseudomonas sp. NK2. High-performance liquid chromatography (HPLC) results indicated higher levels of organic acids released from insoluble phosphorus compared to a soluble phosphorus source (KH2PO4), with acetic acid released exclusively under insoluble phosphorus condition. Moreover, non-target metabolomics was employed to delve into the intracellular metabolic profile. It unveiled that insoluble phosphorus significantly enhanced the tricarboxylic acid cycle, glycolysis, glyoxylic acid metabolism, and other pathways, leading to the production of acetic acid, gluconic acid, oxalic acid, and citric acid for insoluble phosphorus solubilization. In our quest to identify suitable biochar carriers, we assessed seven types of biochar through the conjoint analysis of NBRIP medium culture and application to soil for 30 days, with cotton straw-immobilized NK2 emerging as the most potent phosphorus content provider. Lastly, NK2 after cotton straw immobilization demonstrated the ability to enhance biomass, plant height, and root development of Solanum lycopersicum L. cv. Micro Tom. CONCLUSIONS: Pseudomonas sp. NK2 with cotton straw biochar could enhance phosphorus availability and tomato growth. These findings bear significant implications for the practical application of phosphorus-solubilizing bacteria in agricultural production and the promotion of environmentally sustainable farming practices.
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Carbón Orgánico , Fósforo , Pseudomonas , Solanum lycopersicum , Fósforo/metabolismo , Pseudomonas/metabolismo , Pseudomonas/crecimiento & desarrollo , Solanum lycopersicum/microbiología , Solanum lycopersicum/crecimiento & desarrollo , Solanum lycopersicum/metabolismo , Carbón Orgánico/química , Microbiología del Suelo , Estrés Fisiológico , SolubilidadRESUMEN
Objective: The aim of this study is to investigate the influence of ultrasound and molybdenum target X-ray characteristics in predicting non-mass breast cancer. Methods: A retrospective analysis was conducted on the clinical data of 185 patients presenting with non-mass breast lesions between September 2019 and 2021. The non-mass lesions were categorized into benign and malignant types based on ultrasonographic findings, which included lamellar hypoechoic, ductal alteration, microcalcification, and structural disorder types. Furthermore, an examination was undertaken to discern variances in molybdenum target X-ray parameters, ultrasonographic manifestations, and characteristics among individuals diagnosed with non-mass breast lesions. Results: The ultrasonographic depiction of microcalcified lesions and the identification of suspicious malignancy through molybdenum target X-ray evaluation exhibited independent associations with non-mass breast cancer, yielding statistically significant differences (p < 0.05). Subsequently, the logistic regression model was formulated as follows: Logit (P) =-1.757+2.194* microcalcification type on ultrasound + 1.520* suspicious malignancy on molybdenum target X-ray evaluation. The respective areas under the receiver operating characteristic curves for microcalcification type on ultrasound, suspicious malignancy on molybdenum target X-ray, and the integrated diagnostic model were 0.733, 0.667, and 0.827, respectively, demonstrating discriminative capacities. Conclusion: Using both ultrasound and molybdenum target X-ray diagnostics can increase the accuracy of non-mass breast cancer detection. The findings of this study have the potential to augment the detection rate of non-lumpy breast cancer and provide an imaging basis for enhancing the prognosis of individuals with breast cancer.
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CONTEXT: All types of caloric restriction are preventive against cardiovascular risk factors, but the best restriction method and most affected factors have not been identified. OBJECTIVE: The objective of this study was to explore the effects of different caloric restriction methods on various cardiovascular risk factors by horizontally comparing program advantages and disadvantages via network meta-analysis. DATA SOURCES: The PubMed, Web of Science, Cochrane Library, and Embase literature databases were searched (October 2013 to October 2023). DATA EXTRACTION: Eligible randomized controlled trials involving participants who underwent caloric restriction and systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), and high-density lipoprotein (HDL) cholesterol level measurements were included. DATA ANALYSIS: Thirty-six of 13â208 records (0.27%) were included. Two researchers reviewed the articles, extracted data, and assessed article quality. RESULTS: Alternate-day fasting (ADF) reduced SBP (4.88 mmHg; CI, 2.06-7.15) and DBP (5.10 mmHg; CI, 2.44-7.76). Time-restricted eating reduced SBP (2.46 mmHg; CI, 0.16-4.76) but not DBP. Continuous energy restriction (CER) significantly reduced BMI (1.11 kg/m2; CI = 0.16, 2.06) and waist circumference (3.28 cm; CI, 0.62-5.94). CONCLUSIONS: This meta-analysis confirmed the preventive effect of CER and ADF on various cardiovascular risk factors. Additionally, CER is more likely to reduce obesity, and ADF is more likely to reduce blood pressure (BP). Based on this meta-analysis, CER is recommended to control obesity only for people who are obese and do not have elevated BP or other abnormal indicators. Additionally, ADF for early control or prevention is recommended for patients who have abnormal BP or other cardiovascular risk factors. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42023455889.
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Ischemic stroke is a common cause of mortality and severe disability in human and currently lacks effective treatment. Neuronal activation and neuroinflammation are the major two causes of neuronal damage. However, little is known about the connection of these two phenomena. This study uses middle cerebral artery occlusion mouse model and chemogenetic techniques to study the underlying mechanisms of neuronal excitotoxicity and severe neuroinflammation after ischemic stroke. Chemogenetic inhibition of neuronal activity in ipsilesional M1 alleviates infarct area and neuroinflammation, and improves motor recovery in ischemia mice. This study identifies that ischemic challenge triggers neuron to produce unique small extracellular vesicles (EVs) to aberrantly activate adjacent neurons which enlarge the neuron damage range. Importantly, these EVs also drive microglia activation to exacerbate neuroinflammation. Mechanistically, EVs from ischemia-evoked neuronal activity induce neuronal apoptosis and innate immune responses by transferring higher miR-100-5p to adjacent neuron and microglia. MiR-100-5p can bind to and activate TLR7 through U18U19G20-motif, thereby activating NF-κB pathway. Furthermore, knock-down of miR-100-5p expression improves poststroke outcomes in mice. Taken together, this study suggests that the combination of inhibiting aberrant neuronal activity and the secretion of specific EVs-miRNAs may serve as novel methods for stroke treatment.
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Vesículas Extracelulares , Ratones Endogámicos C57BL , MicroARNs , Microglía , Neuronas , Accidente Cerebrovascular , Animales , Vesículas Extracelulares/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Microglía/metabolismo , Neuronas/metabolismo , Ratones , Masculino , Receptor Toll-Like 7/metabolismo , Receptor Toll-Like 7/genética , Modelos Animales de Enfermedad , FN-kappa B/metabolismo , Enfermedades Neuroinflamatorias/metabolismo , Infarto de la Arteria Cerebral Media , Apoptosis , Inmunidad Innata , Humanos , Glicoproteínas de MembranaRESUMEN
Chemical investigation of the acid hydrolysate of Cynanchum bungei roots led to the isolation of eleven undescribed steroids, namely cynbungenins A-K (1-11), and seven previously described analogues (12-18). The complete structures of these compounds were elucidated using the comprehensive spectroscopic analyses and reference data. Structurally, compounds 1 and 2 represent the first example of androstane-type steroids found in the Cynanchum plants, and compounds 3-6 and 12 are characterized as pregnane-type steroids with a rare 8,14-seco-steroid core. In the cytotoxic activity assay, compound 16 displayed the strongest cytotoxic effect against MCF-7, HCT-116, HeLa, and HepG2 cancer cell lines, with IC50 values of 9.98-16.42 µM, and further research indicated that it induced both apoptosis and cell cycle arrest in the G0/G1 phase in a dose-dependent manner toward HepG2 cells.
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Protein deterioration caused by ice crystals is an important factors affecting the frozen storage of fish. In this study, antifreeze peptides extracted from hydrolysates of sea cucumber intestinal protein with inhibition of protein denaturation were screened and characterized. The peptide Leu-Pro-Glu-Phe-Thr-Glu-Glu-Glu-Lys (LPEFTEEEK), derived from neutral protease hydrolysates of sea cucumber intestinal protein, was investigated for its potential to enhance the quality of salmon fillets during three freeze-thaw cycles. The results showed that the application of LPEFTEEEK effectively maintained the texture of fish fillets, as well as the oxidative and conformation stability of myofibrillar protein during the freezing process. Additionally, molecular dynamics simulations verified that LPEFTEEEK could bind to ice crystals and inhibit their recrystallization, thus preventing organisms from being damaged by freezing. This suggests that LPEFTEEEK holds significant promise as a novel cryoprotective agent for marine-derived antifreeze peptides.
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We propose a simple strategy to fabricate a composite material consisting of amino-functionalized carbon nanotubes (NCNTs) grafted with a covalently bonded Ni(II)-based covalent organic framework (COF) for electrocatalytic water splitting. The resulting electrocatalyst demonstrates remarkable catalytic efficiency in both the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) under alkaline conditions.
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Climate change is exerting unprecedented impacts on marine habitats, and many sessile invertebrate species, such as the endangered giant clam Tridacna maxima, are particularly sensitive to climate driven changes in their environment. Understanding its spatial distribution and conservation requirements is of crucial significance in formulating effective protection strategies. However, the species has been extensively harvested and depleted in many regions, leading to its listing as endangered species by the International Union for Conservation of Nature (IUCN). While marine protected areas (MPAs) are considered effective conservation tools, it remains uncertain whether existing MPAs adequately protect these vulnerable giant clams. To enhance the management and conservation of this species, we employed a Species Distribution Models (SDMs) approach, integrating occurrence records of T. maxima with environmental variables, to predict its potential distribution based on habitat suitability and capture spatiotemporal changes. Based on geographical and genetic variations, the T. maxima in the Indo-Pacific core region is primarily divided into two populations: the East Indian Ocean-South China Sea population (EIOS) and the West Pacific-Indonesia population (WPI). We first quantified realized niche to reveal significant differences in ecological niche space among different populations. Subsequently, SDMs were constructed at both species and population levels, demonstrating that population-level SDMs provide more reliable predictions of population distributions due to differential responses to climatic predictor variables. Finally, we conducted an assessment to identify conservation gaps for T. maxima beyond the existing MPAs and proposed recommendations for future establishment of MPAs within the current framework. Based on these findings, appropriate conservation policies have been proposed to effectively protect the habitat of different geographical populations of T. maxima. Additionally, spatiotemporal predictions of habitat suitability provide crucial information for developing adaptive management strategies for T. maxima in response to climate change, including designing new protected areas and adjusting the location and extent of existing protected areas based on their geographical distribution.
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The grey wolf optimizer is a widely used parametric optimization algorithm. It is affected by the structure and rank of grey wolves and is prone to falling into the local optimum. In this study, we propose a grey wolf optimizer for fusion cell-like P systems. Cell-like P systems can parallelize computation and communicate from cell membrane to cell membrane, which can help the grey wolf optimizer jump out of the local optimum. Design new convergence factors and use different convergence factors in other cell membranes to balance the overall exploration and utilization capabilities of the algorithm. At the same time, dynamic weights are introduced to accelerate the convergence speed of the algorithm. Experiments are performed on 24 test functions to verify their global optimization performance. Meanwhile, a support vector machine model optimized by the grey wolf optimizer for fusion cell-like P systems has been developed and tested on six benchmark datasets. Finally, the optimizing ability of grey wolf optimizer for fusion cell-like P systems on constrained optimization problems is verified on three real engineering design problems. Compared with other algorithms, grey wolf optimizer for fusion cell-like P systems obtains higher accuracy and faster convergence speed on the test function, and at the same time, it can find a better parameter set stably for the optimization of support vector machine parameters, in addition to being more competitive on constrained engineering design problems. The results show that grey wolf optimizer for fusion cell-like P systems improves the searching ability of the population, has a better ability to jump out of the local optimum, has a faster convergence speed, and has better stability.
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BACKGROUND: Aedes albopictus is an important vector for pathogens such as dengue, Zika, and chikungunya viruses. While insecticides is the mainstay for mosquito control, their widespread and excessive use has led to the increased resistance in Ae. albopictus globally. Gut symbiotic bacteria are believed to play a potential role in insect physiology, potentially linking to mosquitoes' metabolic resistance against insecticides. METHODS: We investigated the role of symbiotic bacteria in the development of resistance in Ae. albopictus by comparing gut symbiotic bacteria between deltamethrin-sensitive and deltamethrin-resistant populations. Adults were reared from field-collected larvae. Sensitive and resistant mosquitoes were screened using 0.03% and 0.09% deltamethrin, respectively, on the basis of the World Health Organization (WHO) tube bioassay. Sensitive and resistant field-collected larvae were screened using 5 × LC50 (lethal concentration at 50% mortality) and 20 × LC50 concentration of deltamethrin, respectively. Laboratory strain deltamethrin-sensitive adults and larvae were used as controls. The DNA of gut samples from these mosquitoes were extracted using the magnetic bead method. Bacterial 16S rDNA was sequenced using BGISEQ method. We isolated and cultured gut microorganisms from adult and larvae mosquitoes using four different media: Luria Bertani (LB), brain heart infusion (BHI), nutrient agar (NA), and salmonella shigella (SS). RESULTS: Sequencing revealed significantly higher gut microbial diversity in field-resistant larvae compared with field-sensitive and laboratory-sensitive larvae (P < 0.01). Conversely, gut microorganism diversity in field-resistant and field-sensitive adults was significantly lower compared with laboratory-sensitive adults (P < 0.01). At the species level, 25 and 12 bacterial species were isolated from the gut of field resistant larvae and adults, respectively. The abundance of Flavobacterium spp., Gemmobacter spp., and Dysgonomonas spp. was significantly higher in the gut of field-resistant larvae compared with sensitive larvae (all P < 0.05). Furthermore, the abundance of Flavobacterium spp., Pantoea spp., and Aeromonas spp. was significantly higher in the gut of field-resistant adults compared with sensitive adults (all P < 0.05). The dominant and differentially occurring microorganisms were also different between resistant larval and adult mosquitoes. These findings suggest that the gut commensal bacteria of Ae. albopictus adults and larvae may play distinct roles in their deltamethrin resistance. CONCLUSIONS: This study provides an empirical basis for further exploration of the mechanisms underlying the role of gut microbial in insecticide resistance, potentially opening a new prospect for mosquito control strategies.
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Aedes , Bacterias , Resistencia a los Insecticidas , Insecticidas , Larva , Nitrilos , Piretrinas , ARN Ribosómico 16S , Simbiosis , Animales , Piretrinas/farmacología , Nitrilos/farmacología , Aedes/microbiología , Aedes/efectos de los fármacos , Insecticidas/farmacología , Larva/microbiología , Larva/efectos de los fármacos , ARN Ribosómico 16S/genética , Bacterias/efectos de los fármacos , Bacterias/genética , Bacterias/aislamiento & purificación , Bacterias/clasificación , Microbioma Gastrointestinal/efectos de los fármacos , Mosquitos Vectores/microbiología , Mosquitos Vectores/efectos de los fármacos , ADN Ribosómico/genética , Femenino , ADN Bacteriano/genética , Tracto Gastrointestinal/microbiologíaRESUMEN
Human herpesvirus 8 (HHV-8) infection shows obvious regional and ethnic differences. Although studies have shown that these differences may be associated with lipid metabolism, to date, no large-scale studies have explored this. This study explored the seropositivity rate of HHV-8 among 2516 residents from 10 regions of northwest China and then the correlates of HHV-8 infection with lipid profile. The HHV-8 serological positivity rate was 15.6% among all residents. The HHV-8 seroprevalence ranged 11.2-27.6% among different ethnicities. Across different BMI levels, the positive rates of HHV-8 were 27.6%, 16.9%, and 13.6% for a BMI < 18.5, 18.5-24.9, and ≥25, respectively. HHV-8 seropositivity rate was lower for hypertensive people (12.6%) than for non-hypertensive people (16.7%). Univariate logistic regression analyses revealed that age, hypertension, systolic blood pressure, BMI, total cholesterol, and high-density lipoprotein cholesterol (HDL-C) significantly correlated with HHV-8 seropositivity (p < 0.05). Multivariate logistic regression analysis after adjusting for confounding factors showed that HDL-C (odds ratio [OR]: 0.132, 95% confidence interval [CI], 0.082-0.212; p < 0.001) and BMI (OR: 0.959, 95% CI 0.933-0.986; p = 0.003) were associated with HHV-8 seropositivity. Subgroup analyses concerning ethnicity, sex, or age demonstrated a consistent relationship with HDL-C. The results of HHV-8 seropositivity and BMI were inconsistent in the subgroups. However, Spearman's correlation analysis between HHV-8 serum antibody titer and HDL-C levels showed no linear relationship among HHV-8 seropositive individuals (ρ = -0.080, p = 0.058). HHV-8 serum antibody titers were also not significantly correlated with BMI (ρ = -0.015, p = 0.381). Low HDL-C levels may be an independent risk factor for HHV-8 infection, but there is no significant correlation between HDL-C levels and HHV-8 antibody titers.
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Infecciones por Herpesviridae , Herpesvirus Humano 8 , Lípidos , Humanos , Herpesvirus Humano 8/inmunología , China/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Estudios Transversales , Infecciones por Herpesviridae/epidemiología , Infecciones por Herpesviridae/sangre , Infecciones por Herpesviridae/virología , Adulto , Estudios Seroepidemiológicos , Anciano , Lípidos/sangre , Adulto Joven , Adolescente , Anticuerpos Antivirales/sangre , Factores de Riesgo , Anciano de 80 o más Años , Índice de Masa CorporalRESUMEN
BACKGROUND: This study investigated the use of urinary exosomal mRNA as a potential biomarker for the early detection of prostate cancer (PCa). METHODS: Next-generation sequencing was utilized to analyze exosomal RNA from 10 individuals with confirmed PCa and 10 individuals without cancer. Subsequent validation through qRT-PCR in a larger sample of 43 PCa patients and 92 healthy controls revealed distinct mRNA signatures associated with PCa. RESULTS: Notably, mRNAs for RAB5B, WWP1, HIST2H2BF, ZFY, MARK2, PASK, RBM10, and NRSN2 showed promise as diagnostic markers, with AUC values between 0.799 and 0.906 and significance p values. Combining RAB5B and WWP1 in an exoRNA diagnostic model outperformed traditional PSA tests, achieving an AUC of 0.923, 81.4% sensitivity, and 89.1% specificity. CONCLUSIONS: These findings highlight the potential of urinary exosomal mRNA profiling, particularly focusing on RAB5B and WWP1, as a valuable strategy for improving the early detection of PCa.
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Biomarcadores de Tumor , Detección Precoz del Cáncer , Exosomas , Neoplasias de la Próstata , ARN Mensajero , Humanos , Masculino , Neoplasias de la Próstata/orina , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/diagnóstico , Exosomas/genética , ARN Mensajero/orina , Biomarcadores de Tumor/orina , Biomarcadores de Tumor/genética , Detección Precoz del Cáncer/métodos , Anciano , Persona de Mediana EdadRESUMEN
Lactate dehydrogenase A (LDHA) is highly expressed in many tumor cells and promotes the conversion of pyruvate to lactic acid in the glucose pathway, providing energy and synthetic precursors for rapid proliferation of tumor cells. Therefore, inhibition of LDHA has become a widely concerned tumor treatment strategy. However, the research and development of highly efficient and low toxic LDHA small molecule inhibitors still faces challenges. To discover potential inhibitors against LDHA, virtual screening based on molecular docking techniques was performed from Specs database of more than 260,000 compounds and Chemdiv-smart database of more than 1,000 compounds. Through molecular dynamics (MD) simulation studies, we identified 12 potential LDHA inhibitors, all of which can stably bind to human LDHA protein and form multiple interactions with its active central residues. In order to verify the inhibitory activities of these compounds, we established an enzyme activity assay system and measured their inhibitory effects on recombinant human LDHA. The results showed that Compound 6 could inhibit the catalytic effect of LDHA on pyruvate in a dose-dependent manner with an EC50 value of 14.54 ± 0.83 µM. Further in vitro experiments showed that Compound 6 could significantly inhibit the proliferation of various tumor cell lines such as pancreatic cancer cells and lung cancer cells, reduce intracellular lactic acid content and increase intracellular reactive oxygen species (ROS) level. In summary, through virtual screening and in vitro validation, we found that Compound 6 is a small molecule inhibitor for LDHA, providing a good lead compound for the research and development of LDHA related targeted anti-tumor drugs.