Physiologically based Kinetic Modeling-Facilitated Quantitative In Vitro to In Vivo Extrapolation to Predict the Effects of Aloe-Emodin in Rats and Humans.

Aloe-emodin, a natural hydroxyanthraquinone, exerts both adverse and protective effects. This study aimed at investigating these potential effects of aloe-emodin in humans upon the use of food supplements and herbal medicines using a physiologically based kinetic (PBK) modeling-facilitated quantitative in vitro to in vivo extrapolation (QIVIVE) approach. For this, PBK models in rats and humans were established for aloe-emodin including its active metabolite rhein and used to convert in vitro data on hepatotoxicity, nephrotoxicity, reactive oxidative species (ROS) generation, and Nrf2 induction to corresponding in vivo dose-response curves, from which points of departure (PODs) were derived by BMD analysis. The derived PODs were subsequently compared to the estimated daily intakes (EDIs) resulting from the use of food supplements or herbal medicines. It is concluded that the dose levels of aloe-emodin from food supplements or herbal medicines are unlikely to induce toxicity, ROS generation, or Nrf2 activation in liver and kidney.

Nanozyme-Catalyzed Colorimetric Detection of the Total Antioxidant Capacity in Body Fluids by Paper-Based Microfluidic Chips.

Total antioxidants play a crucial role in human health, and detection of the total antioxidant capacity (TAC) has broad application prospects in fields such as food safety, environmental assessment, and disease diagnosis. However, a long detection time, cumbersome steps, high cost, reliance on professional equipment, and nonportability still remain significant challenges. In this work, an efficient strategy of point-of-care testing (POCT) of the TAC in body fluids by nanozyme-catalyzed colorimetric paper-based microfluidic sensors is proposed. The paper-based microfluidic sensors coupled with a smartphone can reduce testing costs and provide portability. The nanozyme prepared by the solvothermal method presents Michaelis constants of 0.11 and 0.129 mM for H2O2 and TMB, respectively. A method for immobilizing nanozymes and chromogenic agents on a paper-based microfluidic chip is established. Based on smartphone photography and image grayscale extraction, the TAC can be qualitatively detected with a detection limit and linear range of 33.4 and 50-700 µM, respectively. Furthermore, the proposed sensor can realize the one-step quantitative analysis of the TAC in body fluids (blood, saliva, and sweat) within 15 min. The proposed nanozyme-catalyzed colorimetric paper-based microfluidic sensors presented in this study exhibit promising application prospects in the fields of biochemical analysis and POCT.

A ginseng polysaccharide protects intestinal barrier integrity in high-fat diet-fed obese mice.

A novel polysaccharide, GPH1, was extracted and isolated from ginseng. Structural analysis of GPH1 revealed a molecular weight of 7.321 × 105 Da and the presence of glucose and galactose components in a 30.2: 1 molar ratio. Results of methylation and NMR analyses indicated the GPH1 backbone consisted of →1)-α-Glc-(3→ and →1)-α-Glc-(6→. The anti-obesity activity of GPH1 was assessed by HFD-induced obesity mouse model. GPH1 was found to significantly reduced body weight, alleviated liver lipid accumulation and inflammatory damage. Meanwhile, GPH1 treatment increased the expression of tight junction proteins, including zonula occludens-1 (ZO-1) and claudin-1, while also regulating the intestinal microbiota of obese mice by promoting proliferation of beneficial bacteria with known anti-obesity effects, including s_Akkermansia muciniphila, s_Lactobacillus intestinalis, s_Lactobacillus reuteri, s_Streptococcus hyointestinalis, and s_Lactococcus garvieae. Our findings demonstrated that GPH1 is a practical natural dietary supplement with potential therapeutic effects on obesity.

Quantifying the pollution changes and meteorological dependence of airborne trace elements coupling source apportionment and machine learning.

Airborne trace elements (TEs) present in atmospheric fine particulate matter (PM2.5) exert notable threats to human health and ecosystems. To explore the impact of meteorological conditions on shaping the pollution characteristics of TEs and the associated health risks, we quantified the variations in pollution characteristics and health risks of TEs due to meteorological impacts using weather normalization and health risk assessment models, and analyzed the source-specific contributions and potential sources of primary TEs affecting health risks using source apportionment approaches at four sites in Shandong Province from September to December 2021. Our results indicated that TEs experience dual effects from meteorological conditions, with a tendency towards higher TE concentrations and related health risks during polluted period, while the opposite occurred during clean period. The total non-carcinogenic and carcinogenic risks of TEs during polluted period increased approximately by factors of 0.53-1.74 and 0.44-1.92, respectively. Selenium (Se), manganese (Mn), and lead (Pb) were found to be the most meteorologically influenced TEs, while chromium (Cr) and manganese (Mn) were identified as the dominant TEs posing health risks. Enhanced emissions of multiple sources for Cr and Mn were found during polluted period. Depending on specific wind speeds, industrialized and urbanized centers, as well as nearby road dusts, could be key sources for TEs. This study suggested that attentions should be paid to not only the TEs from primary emissions but also the meteorology impact on TEs especially during pollution episodes to reduce health risks in the future.

Analysis on the minimum structure of harmonic spectra from MgO crystals.

Recent theoretical and experimental findings have demonstrated the minimum characteristic in the harmonic spectrum of bulk MgO crystals subjected to intense laser pulses. However, the dominant mechanism behind this minimum structure is still under debate. This study simulates the harmonic spectrum from a MgO crystal in a linearly polarized laser pulse by solving multi-band semiconductor Bloch equations. The results show that the minimum feature at 20 eV in the MgO harmonic spectra from 1700 and 800 nm laser pulses is due to band dispersion and interference between interband harmonics. Notably, the disappearance of the minimum structure at 14 eV in the harmonic spectrum from the 800 nm laser is attributed to the intensity suppression of higher energy harmonics, caused by decreased electron population at the boundary of the first Brillouin zone in the multi-band case. These findings offer insights into the spectral structure of solid-state harmonics, contributing to the all-optical reconstruction of the crystal band based on its harmonic spectrum.

Study of tree shrew biology and models: A booming and prosperous field for biomedical research.

The tree shrew ( Tupaia belangeri) has long been proposed as a suitable alternative to non-human primates (NHPs) in biomedical and laboratory research due to its close evolutionary relationship with primates. In recent years, significant advances have facilitated tree shrew studies, including the determination of the tree shrew genome, genetic manipulation using spermatogonial stem cells, viral vector-mediated gene delivery, and mapping of the tree shrew brain atlas. However, the limited availability of tree shrews globally remains a substantial challenge in the field. Additionally, determining the key questions best answered using tree shrews constitutes another difficulty. Tree shrew models have historically been used to study hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, myopia, and psychosocial stress-induced depression, with more recent studies focusing on developing animal models for infectious and neurodegenerative diseases. Despite these efforts, the impact of tree shrew models has not yet matched that of rodent or NHP models in biomedical research. This review summarizes the prominent advancements in tree shrew research and reflects on the key biological questions addressed using this model. We emphasize that intensive dedication and robust international collaboration are essential for achieving breakthroughs in tree shrew studies. The use of tree shrews as a unique resource is expected to gain considerable attention with the application of advanced techniques and the development of viable animal models, meeting the increasing demands of life science and biomedical research.

Association between red cell distribution width/serum albumin ratio and diabetic kidney disease.

BACKGROUND: Previous studies have shown that the red cell distribution width (RDW)/serum albumin ratio (RA) is an integrative and new inflammatory marker. RA is associated with clinical outcomes in a variety of diseases, but the clinical value of RDW/RA in the assessment of diabetic kidney disease (DKD) has not been elucidated. We examined the link between diabetic RA and DKD while controlling for a wide variety of possible confounders. METHODS: Retrospective cohort analysis of the National Health and Nutrition Examination Survey (NHANES: 2009-2018) database from the Second Affiliated Hospital and Yuying Children's Hospital and the Wenzhou Medical University (WMU) database was conducted. Multivariate logistic regression analysis was used to assess the association between RA and DKD. RESULTS: Overall, 4513 diabetic patients from the NHANES database (n = 2839) and the WMU (n = 1412) were included in this study; 974 patients were diagnosed with DKD in NHANES and 462 in WMU. In the NHANES cohort, diabetes mellitus (DM) patients with higher RA level had a higher risk of DKD (odds ratio = 1.461, 95% confidence interval: 1.250-1.707, p < 0.00001). After adjusting for confounders and propensity score-matched (PSM) analysis, both shown RA levels were independently linked to DKD (pAdjust = 0.00994, pPSM = 0.02889). Similar results were also observed in the WMU cohort (p < 0.00001). CONCLUSIONS: The study observes that the RA was an independent predictor of DKD in DM patients. The RA, a biomarker that is cost-effective and easy-to-access, may have potential for risk stratification of DKD.

Hyperspectral imaging for in situ visual assessment of Industrial-Scale ginseng.

In industrial production, the timely assessment of ginseng-derived ingredients is crucial and requires nondestructive techniques for identifying and analyzing composition. Hyperspectral imaging (HSI) effectively visualizes the three-dimensional spatial distribution of phytochemicals in dried ginseng. This study explores the in-situ prediction and visualization of moisture content (MC) and ginsenoside content (GC) in thermally processed ginseng using dual-band HSI. We collected hyperspectral images from 216 raw ginseng samples, which underwent dimensionality reduction, noise reduction, and feature enhancement via Principal Component Analysis (PCA) and Minimum Noise Separation (MNF). Linear regression models were developed following these pretreatments and evaluated using a validation set. The PCA-based models demonstrated superior performance over those based on MNF, especially in predicting GC in the near-infrared (NIR) spectrum. Similarly, models predicting MC in the visible spectrum showed favorable results. HSI enables rapid generation of distribution maps, facilitating real-time imaging for commercial applications. Repeated drying cycles and increased duration primarily affect the textural characteristics and visible color of the ginseng surface, without significantly altering its intrinsic properties. The deployment of this predictive model alongside real-time content inversion using HSI technology holds promise for integrating visual and intelligent quality monitoring in the trade of valuable herbal commodities.

Inflammatory biomarkers mediate the association between polycyclic aromatic hydrocarbon exposure and dyslipidemia: a national population-based study.

Exploring the association between exposure to polycyclic aromatic hydrocarbons (PAHs) and the risk of dyslipidemia and possible mediating effects is essential for conducting epidemiological health studies on related lipid disorders. Therefore, our study aimed to elucidate the potential association between PAH exposure and dyslipidemia risk and further identify the mediating effects based on blood cell-based inflammatory biomarkers. This cross-sectional study was conducted on 8,380 individuals with complete survey data from the National Health and Nutrition Examination Survey (2001-2016). Multiple models (generalized linear regression model, restricted cubic spline model, Bayesian kernel machine regression, weighted quantiles sum regression) were used to assess the relationship between PAH co-exposure and the dyslipidemia risk and further identify potential mediating effects. Among the 8380 subjects, 2886 (34.44 %) had dyslipidemia. After adjusting for the confounding factors, the adjusted OR and 95% CI for dyslipidemia in the highest quartile of subjects were 1.30 (1.11, 1.51), 1. 22 (1.04, 1.43), 1.21 (1.03, 1.42), 1.29 (1.10, 1.52), 1.18 (1.01, 1.37), and 1.04 (0.89, 1.23) for 1-hydroxynaphthalene, 2-hydroxynaphthalene, 3-hydroxyfluorene, 2-hydroxyfluorene (2-FLU), 1-hydroxyphenanthrene, and 1-hydroxypyrene. The Bayesian kernel machine regression model also showed a positive correlation between PAH mixtures and dyslipidemia, and 2-FLU has the highest contribution. Mediation effect analyses showed that white blood cells and neutrophils were statistically significant in the association between PAHs and dyslipidemia. The present study suggests that individual and mixed PAH exposures may increase the risk of dyslipidemia in adults. Inflammatory biomarkers significantly mediated the relationship between PAH exposure and dyslipidemia. Environmental pollutants and their mechanisms should be more intensively monitored and studied.

Investigating the Pharmacological Mechanisms of Total Flavonoids from Eucommia ulmoides Oliver Leaves for Ischemic Stroke Protection.

The aim of this study was to explore how the total flavonoids from Eucommia ulmoides leaves (EULs) regulate ischemia-induced nerve damage, as well as the protective effects mediated by oxidative stress. The cell survival rate was significantly improved compared to the ischemic group (p < 0.05) after treatment with the total flavonoids of EULs. The levels of reactive oxygen species (ROS), lactate dehydrogenase (LDH), and malondialdehyde (MDA) decreased, while catalase (CAT) and glutathione (GSH) increased, indicating that the total flavonoids of EULs can significantly alleviate neurological damage caused by ischemic stroke by inhibiting oxidative stress (p < 0.01). The mRNA expression level of VEGF increased (p < 0.01), which was consistent with the protein expression results. Meanwhile, the protein expression of ERK and CCND1 increased (p < 0.01), suggesting that the total flavonoids of EULs could protect PC12 cells from ischemic injury via VEGF-related pathways. MCAO rat models indicated that the total flavonoids of EULs could reduce brain ischemia-reperfusion injury. In conclusion, this study demonstrates the potential mechanisms of the total flavonoids of EULs in treating ischemic stroke and their potential therapeutic effects in reducing ischemic injury, which provides useful information for ischemic stroke drug discovery.

Linewidth Measurement of a Narrow-Linewidth Laser: Principles, Methods, and Systems.

Narrow-linewidth lasers mainly depend on the development of advanced laser linewidth measurement methods for related technological progress as key devices in satellite laser communications, precision measurements, ultra-high-speed optical communications, and other fields. This manuscript provides a theoretical analysis of linewidth characterization methods based on the beat frequency power spectrum and laser phase noise calculations, and elaborates on existing research of measurement technologies. In addition, to address the technical challenges of complex measurement systems that commonly rely on long optical fibers and significant phase noise jitter in the existing research, a short-delay self-heterodyne method based on coherent envelope spectrum demodulation was discussed in depth to reduce the phase jitter caused by 1/f noise. We assessed the performance parameters and testing conditions of different lasers, as well as the corresponding linewidth characterization methods, and analyzed the measurement accuracy and error sources of various methods.

Advances in Chromatographic and Mass Spectrometric Techniques for Analyzing Reducing Monosaccharides and Their Phosphates in Biological Samples.

Reducing monosaccharides and their phosphates are critical metabolites in the central carbon metabolism pathway of living organisms. Variations in their content can indicate abnormalities in metabolic pathways and the onset of certain diseases, necessitating their analysis and detection. Reducing monosaccharides and their phosphates exhibit significant variations in content within biological samples and are present in many isomers, which makes the accurate quantification of reducing monosaccharides and their phosphates in biological samples a challenging task. Various analytical methods such as spectroscopy, fluorescence detection, colorimetry, nuclear magnetic resonance spectroscopy, sensor-based techniques, chromatography, and mass spectrometry are employed to detect monosaccharides and phosphates. In comparison, chromatography and mass spectrometry are highly favored for their ability to simultaneously analyze multiple components and their high sensitivity and selectivity. This review thoroughly evaluates the current chromatographic and mass spectrometric methods used for detecting reducing monosaccharides and their phosphates from 2013 to 2023, highlighting their efficacy and the advancements in these analytical technologies.

Genome-wide identification and expression analysis of protein arginine methyltransferase and JmjC domain-containing family in apple.

Histone methylation is an important type of histone modification that regulates gene expression in plants. In this study, we identified 14 arginine methylation-related genes (Protein Arginine Methyltransferase, MdPRMT) and 32 demethylation-related genes (JmjC Domain-Containing Family, MdJMJ) in apple. Furthermore, we investigated the phylogenetic relationship, chromosome distribution, gene structure, motif analysis, promoter sequence analysis, and expression patterns of MdPRMT and MdJMJ genes. Homology analysis showed a high degree of conservation and homology between PRMT and JMJ genes in Arabidopsis and apple. We identified the types of duplicated genes in the MdJMJ and MdPRMT gene families, found a large number of whole-genome duplicates (WGD) gene pairs and a small number of tandem duplicates (TD) pairs, transposed duplication (TRD) gene pairs as well as proximal duplicates (PD) pairs, and discussed the possible evolutionary pathways of the gene families from the perspective of duplicated genes. Homology analysis showed a high degree of conservation and homology between PRMT and JMJ genes in Arabidopsis and apple. In addition, the promoter regions of MdPRMT and MdJMJ contain numerous cis-acting elements involved in plant growth and development, hormone response, and stress responses. Based on the transcriptional profiles of MdPRMT and MdJMJ in different tissues and developmental stages, it was found that MdPRMT and MdJMJ may play multiple roles in apple growth and development, for example, MdJMJ21 may be involved in the regulation of apple endosperm formation. MdPRMT and MdJMJ exhibit different expression patterns in response to hormone signaling in apple, MdJMJ3, MdJMJ18, MdJMJ30, MdPRMT2, MdPRMT13, and MdPRMT14 may play roles in apple response to drought stress, while the expression of MdJMJ13, MdPRMT3, MdPRMT4, and MdPRMT6 is affected by cold stress. Our study provides a foundation for determining the functional roles of MdPRMT and MdJMJ genes in apple.

Study on an Automatic Classification Method for Determining the Malignancy Grade of Glioma Pathological Sections Based on Hyperspectral Multi-Scale Spatial-Spectral Fusion Features.

This study describes a novel method for grading pathological sections of gliomas. Our own integrated hyperspectral imaging system was employed to characterize 270 bands of cancerous tissue samples from microarray slides of gliomas. These samples were then classified according to the guidelines developed by the World Health Organization, which define the subtypes and grades of diffuse gliomas. We explored a hyperspectral feature extraction model called SMLMER-ResNet using microscopic hyperspectral images of brain gliomas of different malignancy grades. The model combines the channel attention mechanism and multi-scale image features to automatically learn the pathological organization of gliomas and obtain hierarchical feature representations, effectively removing the interference of redundant information. It also completes multi-modal, multi-scale spatial-spectral feature extraction to improve the automatic classification of glioma subtypes. The proposed classification method demonstrated high average classification accuracy (>97.3%) and a Kappa coefficient (0.954), indicating its effectiveness in improving the automatic classification of hyperspectral gliomas. The method is readily applicable in a wide range of clinical settings, offering valuable assistance in alleviating the workload of clinical pathologists. Furthermore, the study contributes to the development of more personalized and refined treatment plans, as well as subsequent follow-up and treatment adjustment, by providing physicians with insights into the underlying pathological organization of gliomas.

AKI-Pro score for predicting progression to severe acute kidney injury or death in patients with early acute kidney injury after cardiac surgery.

BACKGROUND: No reliable clinical tools exist to predict acute kidney injury (AKI) progression. We aim to explore a scoring system for predicting the composite outcome of progression to severe AKI or death within seven days among early AKI patients after cardiac surgery. METHODS: In this study, we used two independent cohorts, and patients who experienced mild/moderate AKI within 48 h after cardiac surgery were enrolled. Eventually, 3188 patients from the MIMIC-IV database were used as the derivation cohort, while 499 patients from the Zhongshan cohort were used as external validation. The primary outcome was defined by the composite outcome of progression to severe AKI or death within seven days after enrollment. The variables identified by LASSO regression analysis were entered into logistic regression models and were used to construct the risk score. RESULTS: The composite outcome accounted for 3.7% (n = 119) and 7.6% (n = 38) of the derivation and validation cohorts, respectively. Six predictors were assembled into a risk score (AKI-Pro score), including female, baseline eGFR, aortic surgery, modified furosemide responsiveness index (mFRI), SOFA, and AKI stage. And we stratified the risk score into four groups: low, moderate, high, and very high risk. The risk score displayed satisfied predictive discrimination and calibration in the derivation and validation cohort. The AKI-Pro score discriminated the composite outcome better than CRATE score, Cleveland score, AKICS score, Simplified renal index, and SRI risk score (all P < 0.05). CONCLUSIONS: The AKI-Pro score is a new clinical tool that could assist clinicians to identify early AKI patients at high risk for AKI progression or death.

Porcine deltacoronavirus nonstructural protein 2 inhibits type I and III IFN production by targeting STING for degradation.

Porcine deltacoronavirus (PDCoV) is an enteropathogenic coronavirus that has been reported to use various strategies to counter the host antiviral innate immune response. The cGAS-STING signalling pathway plays an important role in antiviral innate immunity. However, it remains unclear whether PDCoV achieves immune evasion by regulating the cGAS-STING pathway. Here, we demonstrated that the nonstructural protein 2 (nsp2) encoded by PDCoV inhibits cGAS-STING-mediated type I and III interferon (IFN) responses via the regulation of porcine STING (pSTING) stability. Mechanistically, ectopically expressed PDCoV nsp2 was found to interact with the N-terminal region of pSTING. Consequently, pSTING was degraded through K48-linked ubiquitination and the proteasomal pathway, leading to the disruption of cGAS-STING signalling. Furthermore, K150 and K236 of pSTING were identified as crucial residues for nsp2-mediated ubiquitination and degradation. In summary, our findings provide a basis for elucidating the immune evasion mechanism of PDCoV and will contribute to the development of targets for anti-coronavirus drugs.

Floating on groundwater: Insight of multi-source remote sensing for Qaidam basin.

Situated in the north of the Qinghai-Tibet Plateau, the Qaidam Basin experiences limited precipitation and significant evaporation. Despite these conditions, it stands out as one of the most densely distributed lakes in China. The formation of these lakes is controversial: whether the lake water primarily originates from local precipitation or external water sources. To address this issue, this paper explores the recharge sources of lakes in the Qaidam Basin and the circulation patterns of groundwater from a remote sensing perspective. Based on deep learning networks, we optimized the soft object regions of the Object-Contextual Representations Network (OCRNet) and proposed the Remote·Sensing Adaptive-Improved OCRNet (RSA-IOCRNet). Compared with seven other networks, RSA-IOCRNet obtained better experimental results and was used to construct an area sequence of 16 major lakes in the Qaidam Basin. Combined with multi-source data, the comprehensive analysis indicates no significant correlation between climatic factors and lake changes, while an obvious correlation between lakes and groundwater changes in the eastern Qaidam, consisting with the results of the field survey. Deep-circulating groundwater recharges numerous Qaidam lakes through upwelling from fault zones, such as Gasikule Lake and Xiaochaidan Lake. Groundwater in the Qaidam Basin is more depleted in hydrogen-oxygen isotope characteristics than surface water in the basin, but similar to some river water in the endorheic Tibetan Plateau. This indicates that Tibetan seepage water, estimated at approximately 540 billion m3/a, is transported through the Qaidam Basin via deep circulation. Moreover, it rises to recharge the groundwater and lakes within this basin through fracture zones, extending to various arid and semi-arid regions such as Taitema Lake. This work provides a new perspective on the impact of deep groundwater on lakes and water circulation in these areas.

Mitochondrial endogenous substance transport-inspired nanomaterials for mitochondria-targeted gene delivery.

Mitochondrial genome (mtDNA) independent of nuclear gene is a set of double-stranded circular DNA that encodes 13 proteins, 2 ribosomal RNAs and 22 mitochondrial transfer RNAs, all of which play vital roles in functions as well as behaviors of mitochondria. Mutations in mtDNA result in various mitochondrial disorders without available cures. However, the manipulation of mtDNA via the mitochondria-targeted gene delivery faces formidable barriers, particularly owing to the mitochondrial double membrane. Given the fact that there are various transport channels on the mitochondrial membrane used to transfer a variety of endogenous substances to maintain the normal functions of mitochondria, mitochondrial endogenous substance transport-inspired nanomaterials have been proposed for mitochondria-targeted gene delivery. In this review, we summarize mitochondria-targeted gene delivery systems based on different mitochondrial endogenous substance transport pathways. These are categorized into mitochondrial steroid hormones import pathways-inspired nanomaterials, protein import pathways-inspired nanomaterials and other mitochondria-targeted gene delivery nanomaterials. We also review the applications and challenges involved in current mitochondrial gene editing systems. This review delves into the approaches of mitochondria-targeted gene delivery, providing details on the design of mitochondria-targeted delivery systems and the limitations regarding the various technologies. Despite the progress in this field is currently slow, the ongoing exploration of mitochondrial endogenous substance transport and mitochondrial biological phenomena may act as a crucial breakthrough in the targeted delivery of gene into mitochondria and even the manipulation of mtDNA.

Armillariella tabescens-derived polysaccharides alleviated â±°-Gal-induced neuroinflammation and cognitive injury through enterocerebral axis and activation of keap-1/Nrf2 pathway.

The early symptoms of neurodegenerative diseases include oxidative stress disorder and accelerated inflammation levels. Edible fungi polysaccharides play essential roles in anti-neuroinflammation. We analyzed the regulatory mechanisms of polysaccharides from extracellular Armillariella tabescens (ATEP) in alleviating neuroinflammation in mice. Mice were induced with d-galactose and aluminum chloride to establish an animal model of Alzheimer's disease, then intragastrically treated with ATEP, which had been previously analyzed for its physicochemical properties. We assessed the critical characteristics of mice treated for neuroinflammation, including cognitive behavior, the anti-inflammatory potential of ATEP in hippocampal pathology and critical protein expression, and changes in fecal microbial composition and metabolites. ATEP intervened in oxidative stress by enhancing antioxidant enzyme activities and suppressing the Keap-1/Nrf2 signaling pathway. Changing the Nrf2 content in the nucleus led to changes in the downstream oxidation-related enzymes, HO-1, NQO-1, iNOS, and COX-2, and the neuronal morphology in CA3 region of the hippocampus. Microbiome analysis revealed that ATEP remodeled the gut microbiotas and regulated the short-chain fatty acids-producing bacteria. Early intervention with ATEP via active dietary supplementation may promote neuroprotection.

Nationwide trends and features of human salmonellosis outbreaks in China.

Salmonellosis is one of the most common causes of diarrhea, affecting 1/10 of the global population. Salmonellosis outbreaks (SO) pose a severe threat to the healthcare systems of developing regions. To elucidate the patterns of SO in China, we conducted a systematic review and meta-analysis encompassing 1,134 reports across 74 years, involving 89,050 patients and 270 deaths. A rising trend of SO reports has been observed since the 1970s, with most outbreaks occurring east of the Hu line, especially in coastal and populated regions. It is estimated to have an overall attack rate of 36.66% (95% CI, 33.88-39.45%), and antimicrobial resistance towards quinolone (49.51%) and beta-lactam (73.76%) remains high. Furthermore, we developed an online website, the Chinese Salmonellosis Outbreak Database (CSOD), for visual presentation and data-sharing purposes. This study indicated that healthcare-associated SO required further attention, and our study served as a foundational step in pursuing outbreak intervention and prediction.