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1.
Microbiol Res ; 285: 127773, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38833830

ABSTRACT

Salmonella is an important foodborne pathogen. Given the ban on the use of antibiotics during the egg-laying period in China, finding safe and effective alternatives to antibiotics to reduce Salmonella enterica subsp. enterica serovar Typhimurium (S. Typhimurium) infections in chickens is essential for the prevention and control of this pathogen and the protection of human health. Numerous studies have shown that unsaturated fatty acids have a positive effect on intestinal inflammation and resistance to infection by intestinal pathogens. Here we investigated the protective effect of α-linolenic acid (ALA) against S. Typhimurium infection in chickens and further explored its mechanism of action. We added different proportions of ALA to the feed and observed the effect of ALA on S. Typhimurium colonization using metagenomic sequencing technology and physiological index measurements. The role of gut flora on S. Typhimurium colonization was subsequently verified by fecal microbiota transplantation (FMT). We found that ALA protects chickens from S. Typhimurium infection by reducing intestinal inflammation through remodeling the gut microbiota, up-regulating the expression of ileocecal barrier-related genes, and maintaining the integrity of the intestinal epithelium. Our data suggest that supplementation of feed with ALA may be an effective strategy to alleviate S. Typhimurium infection in chickens.

2.
Prev Med ; 184: 107999, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38735587

ABSTRACT

BACKGROUND: Limited research explores the impact of body mass index (BMI) change on osteoporosis, regarding the role of lipid metabolism. We aimed to cross-sectionally investigate these relationships in 820 Chinese participants aged 55-65 from the Taizhou Imaging Study. METHODS: We used the baseline data collected between 2013 and 2018. T-score was calculated by standardizing bone mineral density and was used for osteoporosis and osteopenia diagnosis. Multinomial logistic regression was used to examine the effect of BMI change on bone health status. Multivariable linear regression was employed to identify the metabolites corrected with BMI change and T-score. Exploratory factor analysis (EFA) and mediation analysis were conducted to ascertain the involvement of the metabolites. RESULTS: BMI increase served as a protective factor against osteoporosis (OR = 0.79[0.71-0.88], P-value<0.001) and osteopenia (OR = 0.88[0.82-0.95], P-value<0.001). Eighteen serum metabolites were associated with both BMI change and T-score. Specifically, high-density lipoprotein (HDL) substructures demonstrated negative correlations (ß = -0.08 to -0.06 and - 0.12 to -0.08, respectively), while very low-density lipoprotein (VLDL) substructions showed positive correlations (ß = 0.09 to 0.10 and 0.10 to 0.11, respectively). The two lipid factors (HDL and VLDL) extracted by EFA acted as mediators between BMI change and T-score (Prop. Mediated = 8.16% and 10.51%, all P-value<0.01). CONCLUSION: BMI gain among Chinese aged 55-65 is beneficial for reducing the risk of osteoporosis. The metabolism of HDL and VLDL partially mediates the effect of BMI change on bone loss. Our research offers novel insights into the prevention of osteoporosis, approached from the perspective of weight management and lipid metabolomics.


Subject(s)
Body Mass Index , Bone Density , Lipid Metabolism , Osteoporosis , Humans , Female , Male , Bone Density/physiology , Middle Aged , Cross-Sectional Studies , China/epidemiology , Aged , Bone Diseases, Metabolic
4.
Nat Sci Sleep ; 16: 503-515, 2024.
Article in English | MEDLINE | ID: mdl-38803507

ABSTRACT

Purpose: The prevalence of obstructive sleep apnea (OSA) is high worldwide. This study aimed to quantify the relationship between the incidence of OSA and sleep patterns and genetic susceptibility. Methods: A total of 355,133 white British participants enrolled in the UK Biobank between 2006 and 2010 with follow-up data until September 2021 were recruited. We evaluated sleep patterns using a customized sleep scoring method based on the low-risk sleep phenotype, defined as follows: morning chronotype, 7-8 hours of sleep per day, never/rarely experience insomnia, no snoring, no frequent daytime sleepiness, never/rarely nap, and easily getting up early. The polygenic risk score was calculated to assess genetic susceptibility to OSA. Cox proportional hazard models were used to evaluate the associations between OSA and sleep patterns and genetic susceptibility. Results: During a mean follow-up of 12.57 years, 4618 participants were diagnosed with OSA (age: 56.83 ± 7.69 years, women: 31.3%). Compared with those with a poor sleep pattern, participants with a normal (HR: 0.42, 95% CI: 0.38-0.46), ideal (HR: 0.21, 95% CI: 0.19-0.24), or optimal (HR: 0.15, 95% CI: 0.12-0.18) sleep pattern were significantly more likely to have OSA. The genetic susceptibility of 173,239 participants was calculated, and the results showed that poor (HR: 3.67, 95% CI: 2.95-4.57) and normal (HR: 1.89, 95% CI: 1.66-2.16) sleep patterns with high genetic susceptibility can increase the risk for OSA. Conclusion: This large-scale prospective study provides evidence suggesting that sleep patterns across seven low-risk sleep phenotypes may protect against OSA in individuals with varying degrees of genetic susceptibility.

5.
Arch Gerontol Geriatr ; 124: 105477, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38735225

ABSTRACT

BACKGROUND: The biological process of aging plays an important role in nonalcoholic fatty liver disease (NAFLD) development. However, epidemiological evidence about the association of biological aging with mortality risk among people with NAFLD is limited. METHODS: A total of 2199 participants with NAFLD from the National Health and Nutrition Examination Surveys (NHANES) III were included. The outcomes were all-cause and cause-specific (cardiovascular disease [CVD], cancer, and diabetes) mortality. We computed three BA measures, the Klemera-Doubal method (KDM) age, Phenotypic age, and homeostatic dysregulation (HD), by using 18 age-associated clinical biomarkers, and assessed their associations with mortality risk using Cox proportional hazards (CPH) models. RESULTS: After a median follow-up of 16 years, a total of 1077 deaths occurred. People with NAFLD who died during follow-up period exhibited higher baseline biological age (BA) and biological age accelerations (BAAs). The multivariate-adjusted CPH suggested that a one-standard deviation (SD) increase in KDM age acceleration, Phenotypic age acceleration, or HD was associated with a 3 %, 7 %, or 39 % elevated risk of all-cause mortality, respectively. The results of age-varying HRs showed that the associations of KDM age accelerations (AAs) and Phenotypic AAs with all-cause mortality appeared to be stronger in people with NAFLD younger than 45 years. CONCLUSIONS: Biological aging was positively associated with both all-cause and cause-specific mortality among people with NAFLD, particularly among younger individuals.

6.
BMC Geriatr ; 24(1): 303, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38561655

ABSTRACT

BACKGROUND: Gait disturbance is common in older adults with vascular diseases. However, how carotid atherosclerosis affects gait remains poorly understood. The objectives were to investigate the associations between carotid intima-media thickness and specific gait performances and explore the potential role of brain structure in mediating these associations. METHODS: A cross-sectional analysis of data from the Taizhou Imaging Study was conducted, including 707 individuals who underwent both gait and carotid ultrasound examinations. Gait assessments include the Timed-Up-and-Go test, the Tinetti test, and quantitative gait assessment using a wearable device. Quantitative parameters were summarized into independent gait domains with factor analysis. Magnetic resonance images were obtained on a 3.0-Tesla scanner, and the volumes of fifteen brain regions related to motor function (primary motor, sensorimotor), visuospatial attention (inferior posterior parietal lobules, superior posterior parietal lobules), executive control function (dorsolateral prefrontal cortex, anterior cingulate), memory (hippocampus, entorhinal cortex), motor imagery (precuneus, parahippocampus, posterior cingulated cortex), and balance (basal ganglia: pallidum, putamen, caudate, thalamus) were computed using FreeSurfer and the Desikan-Killiany atlas. Mediation analysis was conducted with carotid intima-media thickness as the predictor and mobility-related brain regions as mediators. RESULTS: Carotid intima-media thickness was found to be associated with the Timed-Up-and-Go performance (ß = 0.129, p = 0.010) as well as gait performances related to pace (ß=-0.213, p < 0.001) and symmetry (ß = 0.096, p = 0.045). Besides, gait performances were correlated with mobility-related brain regions responsible for motor, visuospatial attention, executive control, memory, and balance (all FDR < 0.05). Notably, significant regions differed depending on the gait outcomes measured. The primary motor (41.9%), sensorimotor (29.3%), visuospatial attention (inferior posterior parietal lobules, superior posterior parietal lobules) (13.8%), entorhinal cortex (36.4%), and motor imagery (precuneus, parahippocampus, posterior cingulated cortex) (27.3%) mediated the association between increased carotid intima-media thickness and poorer Timed-Up-and-Go performance. For the pace domain, the primary motor (37.5%), sensorimotor (25.8%), visuospatial attention (12.3%), entorhinal cortex (20.7%), motor imagery (24.9%), and balance (basal ganglia: pallidum, putamen, caudate, thalamus) (11.6%) acted as mediators. CONCLUSIONS: Carotid intima-media thickness is associated with gait performances, and mobility-related brain volume mediates these associations. Moreover, the distribution of brain regions regulating mobility varies in the different gait domains. Our study adds value in exploring the underlying mechanisms of gait disturbance in the aging population.


Subject(s)
Carotid Intima-Media Thickness , Postural Balance , Humans , Aged , Cross-Sectional Studies , Time and Motion Studies , Brain/pathology , Gait/physiology
7.
Neurol Sci ; 2024 Apr 20.
Article in English | MEDLINE | ID: mdl-38642322

ABSTRACT

BACKGROUND: Early identification individuals at high risk of mild cognitive impairment (MCI) is essential for prevention and intervention strategies of dementia, such as Alzheimer's disease. MCI prediction considering the interdependence of predictors in longitudinal data needs to be further explored. We aimed to employ machine learning (ML) to develop and verify a prediction model of MCI. METHODS: In a longitudinal population-based cohort of China Health and Retirement Longitudinal Study (CHARLS), 8390 non-MCI participants were enrolled. The diagnosis of MCI was based on the aging-associated cognitive decline (AACD), and 13 factors (gender, education, marital status, residence, diabetes, hypertension, depression, hearing impairment, social isolation, physical activity, drinking status, body mass index and expenditure) were finally selected as predictors. We implemented a long short-term memory (LSTM) to predict the MCI risks in middle-aged and older adults within 7 years. The Receiver Operating Characteristic curve (ROC) and calibration curve were used to evaluate the performance of the model. RESULTS: Through 7 years of follow-up, 1925 participants developed MCI. The model for all incident MCI achieved an AUC of 0.774, and its deployment to the participants followed 2, 4, and 7 years achieved results of 0.739, 0.747, and 0.750, respectively. The model was well-calibrated with predicted probabilities plotted against the observed proportions of cognitive impairment. Education level, gender, marital status, and depression contributed most to the prediction of MCI. CONCLUSIONS: This model could be widely applied to medical institutions, even in the community, to identify middle-aged and older adults at high risk of MCI.

8.
Iran J Basic Med Sci ; 27(6): 740-746, 2024.
Article in English | MEDLINE | ID: mdl-38645501

ABSTRACT

Objectives: Neuroinflammation is considered an important step in the progression of secondary brain injury (SBI) induced by cerebral hemorrhage (ICH). The nucleotide-binding and oligomerization structural domain-like receptor family of pyridine structural domain-containing 3 (NLRP3) inflammasomes play an important role in the immune pathophysiology of SBI. Febuxostat (Feb) is a xanthine oxidase inhibitor that is approved for the treatment of gout and has been found to have potent anti-inflammatory effects. However, it has been less studied after ICH and we aimed to explore its protective role in ICH. Materials and Methods: We established an autologous blood-brain hemorrhage model in C57BL/6 mice. Functions of co-expressed genes were analyzed by trend analysis and bioinformatics analysis. Enzyme-linked immunosorbent assay were used to assess the inflammatory factor levels. Fluoro-Jade B histochemistry and TUNEL staining were used to detect neuronal apoptosis. Immunofluorescence staining and western blotting were used to detect the expression of NLRP3 inflammasomes. Results: Pretreatment with Feb reduced neuronal cell death and degeneration and alleviated neurobehavioral disorders in vivo. Feb was found to modulate inflammation-related pathways by trend analysis and bioinformatics analysis. In addition, Feb inhibited microglia activation and elevated cytokine levels after ICH. Furthermore, double immunofluorescence staining showed that co-localization of NLRP3 with Iba1 positive cells was reduced after treatment with Feb. Finally, we found that Feb inhibited the activation of the NLRP3/ASC/caspase-1 pathway after ICH. Conclusion: By inhibiting the NLRP3 inflammasome, preconditioning Feb attenuates inflammatory injury after ICH. Our findings may provide new insights into the role of Feb in neuroprotection.

9.
ACS Synth Biol ; 13(4): 1323-1331, 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38567812

ABSTRACT

Porcine deltacoronavirus (PDCoV) is a major cause of diarrhea and diarrhea-related deaths among piglets and results in massive losses to the overall porcine industry. The clinical manifestations of porcine diarrhea brought on by the porcine epidemic diarrhea virus (PEDV), porcine transmissible gastroenteritis virus (TGEV), and PDCoV are oddly similar to each other. Hence, the identification of different pathogens through molecular diagnosis and serological techniques is crucial. Three novel detection methods for identifying PDCoV have been developed utilizing recombinase-aided amplification (RAA) or reverse transcription recombinase-aided amplification (RT-RAA) in conjunction with Pyrococcus furiosus Argonaute (PfAgo): RAA-PfAgo, one-pot RT-RAA-PfAgo, and one-pot RT-RAA-PfAgo-LFD. The indicated approaches have a detection limit of around 60 copies/µL of PDCoV and do not cross-react with other viruses including PEDV, TGEV, RVA, PRV, PCV2, or PCV3. The applicability of one-pot RT-RAA-PfAgo and one-pot RT-RAA-PfAgo-LFD were examined using clinical samples and showed a positive rate comparable to the qPCR method. These techniques offer cutting-edge technical assistance for identifying, stopping, and managing PDCoV.


Subject(s)
Coronavirus Infections , Deltacoronavirus , Porcine epidemic diarrhea virus , Pyrococcus furiosus , Swine Diseases , Animals , Swine , Coronavirus Infections/diagnosis , Coronavirus Infections/veterinary , Pyrococcus furiosus/genetics , Swine Diseases/diagnosis , Swine Diseases/epidemiology , Sensitivity and Specificity , Diarrhea/diagnosis , Recombinases
10.
J Diabetes ; 16(5): e13564, 2024 May.
Article in English | MEDLINE | ID: mdl-38664879

ABSTRACT

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) and liver cirrhosis are significant clinical concerns, especially among individuals with type 2 diabetes mellitus (T2DM). However, in China, there is a paucity of reliable evidence detailing the characteristics of NAFLD and liver cirrhosis in T2DM. Furthermore, the relationship between blood glucose levels and NAFLD prevalence remains unclear. METHODS: Data from the Shanghai Suburban Adult Cohort and Biobank were analyzed, including 6621 participants with T2DM. NAFLD was diagnosed by ultrasonography and liver cirrhosis was performed according to the health information systems. Logistic regression and restricted cubic spline analysis were used to explore the potential risk factors for NAFLD and liver cirrhosis. RESULTS: The prevalence of NAFLD was 59.36%, and liver cirrhosis was 1.43% among T2DM patients. In these patients, factors like age, being female, marital status, and obesity significantly increased the risk of NAFLD. Specifically, obesity had a strong positive association with NAFLD (odds ratio [OR] = 4.70, 95% confidence interval [CI]: 4.13-5.34). The higher glycated hemoglobin (HbA1c) quartile was associated with a heightened NAFLD risk compared to the lowest quartile (all p < .001). The HbA1c-NAFLD relationship displayed a linear that mimicked an inverted L-shaped pattern. A significant positive association existed between HbA1c levels and NAFLD for HbA1c <8.00% (OR = 1.59, 95% CI: 1.44-1.75), but this was not observed for HbA1c >8.00% (OR = 1.03, 95% CI: 0.92-1.15). CONCLUSION: Systematic screening for NAFLD is essential in T2DM patients, especially with poor glucose control and obesity in female.


Subject(s)
Diabetes Mellitus, Type 2 , Liver Cirrhosis , Non-alcoholic Fatty Liver Disease , Humans , Non-alcoholic Fatty Liver Disease/epidemiology , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/blood , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/blood , Female , Middle Aged , Male , China/epidemiology , Liver Cirrhosis/epidemiology , Liver Cirrhosis/complications , Liver Cirrhosis/blood , Prevalence , Risk Factors , Adult , Glycated Hemoglobin/analysis , Glycated Hemoglobin/metabolism , Aged , Blood Glucose/metabolism , Blood Glucose/analysis , Obesity/complications , Obesity/epidemiology , East Asian People
11.
Sci Rep ; 14(1): 8483, 2024 04 11.
Article in English | MEDLINE | ID: mdl-38605086

ABSTRACT

This mediation analysis aimed to investigate the associations among areal bone mineral density, mobility-related brain atrophy, and specific gait patterns. A total of 595 participants from the Taizhou Imaging Study, who underwent both gait and bone mineral density measurements, were included in this cross-sectional analysis. We used a wearable gait tracking device to collect quantitative gait parameters and then summarized them into independent gait domains with factor analysis. Bone mineral density was measured in the lumbar spine, femoral neck, and total hip using dual-energy X-ray absorptiometry. Magnetic resonance images were obtained on a 3.0-Tesla scanner, and the volumes of brain regions related to mobility were computed using FreeSurfer. Lower bone mineral density was found to be associated with higher gait variability, especially at the site of the lumbar spine (ß = 0.174, FDR = 0.001). Besides, higher gait variability was correlated with mobility-related brain atrophy, like the primary motor cortex (ß = 0.147, FDR = 0.006), sensorimotor cortex (ß = 0.153, FDR = 0.006), and entorhinal cortex (ß = 0.106, FDR = 0.043). Bidirectional mediation analysis revealed that regional brain atrophy contributed to higher gait variability through the low lumbar spine bone mineral density (for the primary motor cortex, P = 0.018; for the sensorimotor cortex, P = 0.010) and the low lumbar spine bone mineral density contributed to higher gait variability through the primary motor and sensorimotor cortices (P = 0.026 and 0.010, respectively).


Subject(s)
Bone Density , Gait , Humans , Cross-Sectional Studies , Absorptiometry, Photon/methods , Lumbar Vertebrae/diagnostic imaging , Brain/diagnostic imaging
12.
Mol Plant ; 17(6): 867-883, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38678365

ABSTRACT

Given the escalating impact of climate change on agriculture and food security, gaining insights into the evolutionary dynamics of climatic adaptation and uncovering climate-adapted variation can empower the breeding of climate-resilient crops to face future climate change. Alfalfa (Medicago sativa subsp. sativa), the queen of forages, shows remarkable adaptability across diverse global environments, making it an excellent model for investigating species responses to climate change. In this study, we performed population genomic analyses using genome resequencing data from 702 accessions of 24 Medicago species to unravel alfalfa's climatic adaptation and genetic susceptibility to future climate change. We found that interspecific genetic exchange has contributed to the gene pool of alfalfa, particularly enriching defense and stress-response genes. Intersubspecific introgression between M. sativa subsp. falcata (subsp. falcata) and alfalfa not only aids alfalfa's climatic adaptation but also introduces genetic burden. A total of 1671 genes were associated with climatic adaptation, and 5.7% of them were introgressions from subsp. falcata. By integrating climate-associated variants and climate data, we identified populations that are vulnerable to future climate change, particularly in higher latitudes of the Northern Hemisphere. These findings serve as a clarion call for targeted conservation initiatives and breeding efforts. We also identified pre-adaptive populations that demonstrate heightened resilience to climate fluctuations, illuminating a pathway for future breeding strategies. Collectively, this study enhances our understanding about the local adaptation mechanisms of alfalfa and facilitates the breeding of climate-resilient alfalfa cultivars, contributing to effective agricultural strategies for facing future climate change.


Subject(s)
Climate Change , Medicago sativa , Medicago sativa/genetics , Medicago sativa/physiology , Adaptation, Physiological/genetics , Genomics , Genome, Plant
13.
Hepatology ; 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38630500

ABSTRACT

BACKGROUND AND AIMS: The complications of liver cirrhosis occur after long asymptomatic stages of progressive fibrosis and are generally diagnosed late. We aimed to develop a plasma metabolomic-based score tool to predict these events. APPROACH AND RESULTS: We enrolled 64,005 UK biobank participants with metabolomic profiles. Participants were randomly divided into the training (n=43,734) and validation cohorts (n=20,271). Liver cirrhosis complications were defined as hospitalization for liver cirrhosis or presentation with HCC. An interpretable machine-learning framework was applied to learn the metabolomic states extracted from 168 circulating metabolites in the training cohort. An integrated nomogram was developed and compared to conventional and genetic risk scores. We created 3 groups: low-risk, middle-risk, and high-risk through selected cutoffs of the nomogram. The predictive performance was validated through the area under a time-dependent receiver operating characteristic curve (time-dependent AUC), calibration curves, and decision curve analysis. The metabolomic state model could accurately predict the 10-year risk of liver cirrhosis complications in the training cohort (time-dependent AUC: 0.84 [95% CI: 0.82-0.86]), and outperform the fibrosis-4 index (time-dependent AUC difference: 0.06 [0.03-0.10]) and polygenic risk score (0.25 [0.21-0.29]). The nomogram, integrating metabolomic state, aspartate aminotransferase, platelet count, waist/hip ratio, and smoking status showed a time-dependent AUC of 0.930 at 3 years, 0.889 at 5 years, and 0.861 at 10 years in the validation cohort, respectively. The HR in the high-risk group was 43.58 (95% CI: 27.08-70.12) compared with the low-risk group. CONCLUSIONS: We developed a metabolomic state-integrated nomogram, which enables risk stratification and personalized administration of liver-related events.

14.
J Ethnopharmacol ; 330: 118217, 2024 Aug 10.
Article in English | MEDLINE | ID: mdl-38641072

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: The natural anodyne Ligustilide (Lig), derived from Angelica sinensis (Oliv.) Diels and Ligusticum chuanxiong Hort., has been traditionally employed for its analgesic properties in the treatment of dysmenorrhea and migraine, and rheumatoid arthritis pain. Despite the existing reports on the correlation between TRP channels and the analgesic effects of Lig, a comprehensive understanding of their underlying mechanisms of action remains elusive. AIM OF THE STUDY: The objective of this study is to elucidate the mechanism of action of Lig on the analgesic target TRPA1 channel. METHODS: The therapeutic effect of Lig was evaluated in a rat acute soft tissue injury model. The analgesic target was identified through competitive inhibition of TRP channel agonists at the animal level, followed by Fluo-4/Ca2+ imaging on live cells overexpressing TRP proteins. The potential target was verified through in-gel imaging, colocalization using a Lig-derived molecular probe, and a drug affinity response target stability assay. The binding site of Lig was identified through protein spectrometry and further analyzed using molecular docking, site-specific mutation, and multidisciplinary approaches. RESULTS: The administration of Lig effectively ameliorated pain and attenuated oxidative stress and inflammatory responses in rats with soft tissue injuries. Moreover, the analgesic effects of Lig were specifically attributed to TRPA1. Mechanistic studies have revealed that Lig directly activates TRPA1 by interacting with the linker domain in the pre-S1 region of TRPA1. Through metabolic transformation, 6,7-epoxyligustilide (EM-Lig) forms a covalent bond with Cys703 of TRPA1 at high concentrations and prolonged exposure time. This irreversible binding prevents endogenous electrophilic products from entering the cysteine active center of ligand-binding pocket of TRPA1, thereby inhibiting Ca2+ influx through the channel opening and ultimately relieving pain. CONCLUSIONS: Lig selectively modulates the TRPA1 channel in a bimodal manner via non-electrophilic/electrophilic metabolic conversion. The epoxidized metabolic intermediate EM-Lig exerts analgesic effects by irreversibly inhibiting the activation of TRPA1 on sensory neurons. These findings not only highlight the analgesic mechanism of Lig but also offer a novel nucleophilic attack site for the development of TRPA1 antagonists in the pre-S1 region.


Subject(s)
4-Butyrolactone , Analgesics , TRPA1 Cation Channel , Animals , Female , Humans , Male , Rats , 4-Butyrolactone/analogs & derivatives , 4-Butyrolactone/pharmacology , 4-Butyrolactone/chemistry , Analgesics/pharmacology , Analgesics/chemistry , Binding Sites , Cysteine/pharmacology , Cysteine/chemistry , HEK293 Cells , Molecular Docking Simulation , Pain/drug therapy , Rats, Sprague-Dawley , TRPA1 Cation Channel/metabolism
15.
Biomed Pharmacother ; 173: 116309, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38479180

ABSTRACT

As the leading killer of life and health, stroke leads to limb paralysis, speech disorder, dysphagia, cognitive impairment, mental depression and other symptoms, which entail a significant financial burden to society and families. At present, physiology, clinical medicine, engineering, and materials science, advanced biomaterials standing on the foothold of these interdisciplinary disciplines provide new opportunities and possibilities for the cure of stroke. Among them, hydrogels have been endowed with more possibilities. It is well-known that hydrogels can be employed as potential biosensors, medication delivery vectors, and cell transporters or matrices in tissue engineering in tissue engineering, and outperform many traditional therapeutic drugs, surgery, and materials. Therefore, hydrogels become a popular scaffolding treatment option for stroke. Diverse synthetic hydrogels were designed according to different pathophysiological mechanisms from the recently reported literature will be thoroughly explored. The biological uses of several types of hydrogels will be highlighted, including pro-angiogenesis, pro-neurogenesis, anti-oxidation, anti-inflammation and anti-apoptosis. Finally, considerations and challenges of using hydrogels in the treatment of stroke are summarized.


Subject(s)
Biosensing Techniques , Stroke , Humans , Hydrogels/therapeutic use , Biocompatible Materials , Tissue Engineering , Stroke/drug therapy
16.
Int Immunopharmacol ; 130: 111801, 2024 Mar 30.
Article in English | MEDLINE | ID: mdl-38442578

ABSTRACT

The mechanism underlying allodynia/hyperalgesia caused by dental pulpitis has remained enigmatic. This investigation endeavored to characterize the influence of the purinergic receptor P2X3 on pain caused by experimental pulpitis and the mechanism involved. An experimental model of irreversible pulpitis was produced by the drilling and exposure of the dental pulp of the left upper first and second molars in rats, followed by measuring nociceptive responses in the oral and maxillofacial regions. Subsequently, neuronal activity and the expression of P2X3 and pertinent cytokines in the trigeminal ganglion (TG) were meticulously examined and analyzed. Histological evidence corroborated that significant pulpitis was produced in this model, which led to a distinct escalation in nociceptive responses in rats. The activation of neurons, coupled with the upregulated expression of c-fos, P2X3, p-p38, TNF-α and IL-1ß, was identified subsequent to the pulpitis surgery within the TG. The selective inhibition of P2X3 with A-317491 effectively restrained the abnormal allodynia/hyperalgesia following the pulpitis surgery and concurrently inhibited the upregulation of p-p38, TNF-α and IL-1ß within the TG. These findings suggest that the P2X3 signaling pathway plays a pivotal role in instigating and perpetuating pain subsequent to the induction of pulpitis in rats, implicating its association with the p38 MAPK signaling pathway and inflammatory factors.


Subject(s)
Hyperalgesia , Pulpitis , Rats , Animals , Hyperalgesia/metabolism , Rats, Sprague-Dawley , Cytokines/metabolism , Tumor Necrosis Factor-alpha/metabolism , Trigeminal Ganglion , Neurons/metabolism , Facial Pain/metabolism , Facial Pain/pathology , Receptors, Purinergic
17.
Arch Microbiol ; 206(4): 141, 2024 Mar 05.
Article in English | MEDLINE | ID: mdl-38441685

ABSTRACT

A strictly anaerobic, motile bacterium, designated as strain Ai-910T, was isolated from the sludge of an anaerobic digestion tank in China. Cells were Gram-stain-negative rods. Optimal growth was observed at 38 °C (growth range 25-42 °C), pH 8.5 (growth range 5.5-10.5), and under a NaCl concentration of 0.06% (w/v) (range 0-2.0%). Major cellular fatty acids were iso-C15 : 0 and anteiso-C15 : 0. The respiratory quinone was MK-7. Using xylose as the growth substrate, succinate was produced as the fermentation product. Phylogenetic analysis based on the 16 S rRNA gene sequences indicated that strain Ai-910T formed a distinct phylogenetic lineage that reflects a new genus in the family Marinilabiliaceae, sharing high similarities to Alkaliflexus imshenetskii Z-7010T (92.78%), Alkalitalea saponilacus SC/BZ-SP2T (92.51%), and Geofilum rubicundum JAM-BA0501T (92.36%). Genomic similarity (average nucleotide identity and digital DNA-DNA hybridization) values between strain Ai-910T and its phylogenetic neighbors were below 65.27 and 16.90%, respectively, indicating that strain Ai-910T represented a novel species. The average amino acid identity between strain Ai-910T and other related members of the family Marinilabiliaceae were below 69.41%, supporting that strain Ai-910T was a member of a new genus within the family Marinilabiliaceae. Phylogenetic, genomic, and phenotypic analysis revealed that strain Ai-910T was distinguished from other phylogenetic relatives within the family Marinilabiliaceae. The genome size was 3.10 Mbp, and the DNA G + C content of the isolate was 42.8 mol%. Collectively, differences of the phenotypic and phylogenetic features of strain Ai-910T from its close relatives suggest that strain Ai-910T represented a novel species in a new genus of the family Marinilabiliaceae, for which the name Xiashengella succiniciproducens gen. nov., sp. nov. was proposed. The type strain of Xiashengella succiniciproducens is Ai-910T (= CGMCC 1.17893T = KCTC 25,304T).


Subject(s)
Bacteria , Succinic Acid , Anaerobiosis , Phylogeny , Succinates , DNA
19.
Sci Rep ; 14(1): 5635, 2024 Mar 07.
Article in English | MEDLINE | ID: mdl-38453999

ABSTRACT

Melting of ice in porous media widely exists in energy and environment applications as well as extraterrestrial water resource utilization. In order to characterize the ice-water phase transition within complicated opaque porous media, we employ the nuclear magnetic resonance (NMR) and imaging (MRI) approaches. Transient distributions of transverse relaxation time T2 from NMR enable us to reveal the substantial role of inherent throat and pore confinements in ice melting among porous media. More importantly, the increase in minimum T2 provides new findings on how the confinement between ice crystal and particle surface evolves inside the pore. For porous media with negligible gravity effect, both the changes in NMR-determined melting rate and our theoretical analysis of melting front confirm that conduction is the dominant heat transfer mode. The evolution of mushy melting front and 3D spatial distribution of water content are directly visualized by a stack of temporal cross-section images from MRI, in consistency with the corresponding NMR results. For heterogeneous porous media like lunar regolith simulant, the T2 distribution shows two distinct pore size distributions with different pore-scale melting dynamics, and its maximum T2 keeps increasing till the end of melting process instead of reaching steady in homogeneous porous media.

20.
Int J Food Microbiol ; 415: 110634, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38401379

ABSTRACT

Escherichia coli is one of the important reservoirs of antimicrobial resistance genes (ARG), which often causes food-borne diseases and clinical infections. Contamination with E. coli carrying clinically important antimicrobial resistance genes in retail meat products can be transmitted to humans through the food chain, posing a serious threat to public health. In this study, a total of 330 E. coli strains were isolated from 464 fresh meat samples from 17 food markets in China, two of which were identified as enterotoxigenic and enteropathogenic E. coli. Whole genome sequencing revealed the presence of 146 different sequence types (STs) including 20 new STs, and 315 different clones based on the phylogenetic analysis, indicating the high genetic diversity of E. coli from retail meat products. Antimicrobial resistance profiles showed that 82.42 % E. coli were multidrug-resistant strains. A total of 89 antimicrobial resistance genes were detected and 12 E. coli strains carried clinically important antimicrobial resistance genes blaNDM-1, blaNDM-5, mcr-1, mcr-10 and tet(X4), respectively. Nanopore sequencing revealed that these resistance genes are located on different plasmids with the ability of horizontal transfer, and their genetic structure and environment are closely related to plasmids isolated from humans. Importantly, we reported for the first time the presence of plasmid-mediated mcr-10 in E. coli from retail meat. This study revealed the high genetic diversity of food-borne E. coli in retail meat and emphasized their risk of spreading clinically important antimicrobial resistance genes.


Subject(s)
Enteropathogenic Escherichia coli , Escherichia coli Infections , Escherichia coli Proteins , Humans , Anti-Bacterial Agents/pharmacology , Escherichia coli Proteins/genetics , Phylogeny , beta-Lactamases/genetics , Drug Resistance, Bacterial/genetics , Meat/analysis , Enteropathogenic Escherichia coli/genetics , Whole Genome Sequencing , Plasmids , Microbial Sensitivity Tests
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