Association between biological aging and the risk of mortality in individuals with non-alcoholic fatty liver disease: A prospective cohort study.

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.

Lipid metabolism mediates the association between body mass index change and bone mineral density: The Taizhou imaging study.

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.

Bidirectional mediation of bone mineral density and brain atrophy on their associations with gait variability.

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).

Evolutionary genomics of climatic adaptation and resilience to climate change in alfalfa.

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 empower the breeding of climate-resilience crops to face future climate change. Alfalfa (Medicago sativa subsp. sativa), the queen of forages with remarkable adaptability across diverse global environments, is an excellent model for investigating species' responses to climate change. We conducted population genomic analyses to unravel alfalfa's climatic adaptation and genetic susceptibility to future climate change, utilizing genome resequencing data from 702 accessions of 24 Medicago species. We found that interspecific genetic exchange has fueled the gene pool of alfalfa, particularly enriching defense and stress response genes. Inter-subspecific introgression between Medicago 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 introgression from subsp. falcata. Integrating climate-associated variants and climate data, we identified vulnerable populations to future climate change, particularly in higher latitudes of the northern hemisphere, serving as a clarion call for targeted conservation initiatives and breeding efforts. Moreover, we unveil pre-adaptive populations demonstrating heightened resilience to climate fluctuations, illuminating a pathway for future breeding strategies. This study enhances our understanding of alfalfa's local adaptation and facilitates breeding of climate-resilient cultivars, contributing to effective agricultural strategies facing future climate change.

Prevalence of nonalcoholic fatty liver disease and liver cirrhosis in Chinese adults with type 2 diabetes mellitus.

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.

Febuxostat attenuates secondary brain injury caused by cerebral hemorrhage through inhibiting inflammatory pathways.

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.

Establishment of a mild cognitive impairment risk model in middle-aged and older adults: a longitudinal study.

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.

Pyrococcus furiosus Argonaute Based Detection Assays for Porcine Deltacoronavirus.

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.

Machine learning-based plasma metabolomic profiles for predicting long-term complications of cirrhosis.

BACKGROUND AND AIMS: The liver cirrhosis complications 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 profile. 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 hepatocellular carcinoma. 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 three groups: low-risk, middle-risk, and high-risk through selected cut-offs of the nomogram. The predictive performance was validated through area under time-dependent receiver operating characteristic curve (time-dependent AUC), calibration curves, and decision curve analysis. The metabolomic state model could accurately predict 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 hazard ratio 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.

Mobility-related brain regions linking carotid intima-media thickness to specific gait performances in old age.

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.

Ligustilide covalently binds to Cys703 in the pre-S1 helix of TRPA1, blocking the opening of channel and relieving pain in rats with acute soft tissue injury.

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.

The purinergic receptor P2X3 promotes facial pain by activating neurons and cytokines in the trigeminal ganglion.

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.

Perspective insights into versatile hydrogels for stroke: From molecular mechanisms to functional applications.

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.

Xiashengella succiniciproducens gen. nov., sp. nov., a succinate-producing bacterium isolated from an anaerobic digestion tank in the family Marinilabiliaceae of the order Bacteroidales.

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).

Pore-scale physics of ice melting within unconsolidated porous media revealed by non-destructive magnetic resonance characterization.

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.

Whole-genome sequencing of Escherichia coli from retail meat in China reveals the dissemination of clinically important antimicrobial resistance genes.

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.

Unraveling the role of serum metabolites in the relationship between plant-based diets and bone health in community-dwelling older adults.

The potential adverse effects of the plant-based dietary pattern on bone health have received widespread attention. However, the biological mechanisms underlying the adverse effects of plant-based diets on bone health remain incompletely understood. The objective of this study was to identify potential biomarkers between plant-based diets and bone loss utilizing metabolomic techniques in the Taizhou Imaging Study (TIS) (N = 788). Plant-based diet indexes (overall plant-based diet index (PDI), healthy plant-based diet index (hPDI), and unhealthy plant-based diet index (uPDI)) were calculated using the food frequency questionnaire, and bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry. A multinomial logistic regression was used to explore the associations of plant-based diet indexes with bone loss. Furthermore, mediation analysis and exploratory factor analysis (EFA) were performed to explore the mediated effects of metabolites on the association of plant-based diets with BMD T-score. Our results showed that higher hPDI and uPDI were positively associated with bone loss. Moreover, nineteen metabolites were significantly associated with BMD T-score, among them, seven metabolites were associated with uPDI. Except for cholesterol esters in VLDL-1, the remaining six metabolites significantly mediated the negative association between uPDI and BMD T-score. Interestingly, we observed that the same six metabolites mediated the positive association between fresh fruit and BMD T-score. Collectively, our results support the deleterious effects of plant-based diets on bone health and discover the potential mediation effect of metabolites on the association of plant-based diets with bone loss. The findings offer valuable insights that could optimize dietary recommendations and interventions, contributing to alleviate the potential adverse effects associated with plant-based diets.

Low thyroid function is associated with metabolic dysfunction-associated steatotic liver disease.

Background and Aim: Metabolic dysfunction-associated steatotic liver disease (MASLD) is recently introduced to better highlight the pathogenic significance of cardiometabolic dysfunction, as compared with non-alcoholic fatty liver disease. This study aimed to investigate the association between low thyroid function and MASLD in the new context. Methods: We recruited 2901 participants for our retrospective cohort study from 2016 to 2021. Participants were divided into strict-normal thyroid function and low thyroid function groups (low-normal thyroid function, subclinical hypothyroidism) based on initial thyroid stimulating hormone (TSH) levels, respectively. Cox regression models were used to estimate the hazard ratios (HRs) and 95% CI. Results: During a median follow-up of 15.6 months, 165 (8.9%) strict-normal thyroid function subjects and 141 (13.4%) low thyroid function subjects developed MASLD; this result was statistically relevant (P < 0.05). Univariate regression analysis showed that low thyroid function and subclinical hypothyroidism were statistically significantly associated with MASLD (low thyroid function: HR1.53; 95% CI 1.22-1.92; subclinical hypothyroidism: HR1.95; 95% CI 1.47-2.60). Conclusions: MASLD is associated with low thyroid function and the relationship between MASLD and low thyroid function is independent.