Expression of hepatic genes involved in bile acid metabolism in dairy cows with fatty liver.

Bile acids are cholesterol-derived molecules that are primarily produced in the liver. In nonruminants with fatty liver, overproduction of bile acids is associated with liver injury. During the transition period, fatty liver is a metabolic disorder that can affect up to 50% of high-producing dairy cows. The purpose of this study was to provide a comprehensive evaluation on hepatic bile acid metabolism in dairy cows with fatty liver by assessing expression changes of genes involved in bile acid synthesis, export and uptake. The serum activities of aspartate aminotransferase, alanine aminotransferase and glutamate dehydrogenase and concentration of total bile acids were all greater, whereas serum concentration of total cholesterol was lower in cows with fatty liver than in healthy cows. Content of total bile acids was higher but total cholesterol was slightly lower in liver tissues from fatty liver cows than from healthy cows. The hepatic mRNA abundance of cholesterol 7a-hydroxylase (CYP7A1), hydroxy-delta-5-steroid dehydrogenase, 3 ß- and steroid delta-isomerase 7 (HSD3B7) and sterol 12α-hydroxylase (CYP8B1), enzymes involved in the classic pathway of bile acid synthesis, was higher in fatty liver cows than in healthy cows. Compared with healthy cows, the hepatic mRNA abundance of alternative bile acid synthesis pathway-related genes sterol 27-hydroxylase (CYP27A1) and oxysterol 7α-hydroxylase (CYP7B1) did not differ in cows with fatty liver. The protein and mRNA abundance of bile acid transporter bile salt efflux pump (BSEP) were lower in the liver of dairy cow with fatty liver. Compared with healthy cows, the hepatic mRNA abundance of bile acid transporters solute carrier family 51 subunit α (SLC51A), ATP binding cassette subfamily C member 1 (ABCC1) and 3 (ABCC3) was greater in cows with fatty liver, whereas the solute carrier family 51 subunit ß (SLC51B) did not differ. The expression of genes involved in bile acid uptake, including solute carrier family 10 member 1 (NTCP), solute carrier organic anion transporter family member 1A2 (SLCO1A2) and 2B1 (SLCO2B1) was upregulated in dairy cows with fatty liver. Furthermore, the hepatic protein and mRNA abundance of bile acid metabolism regulators farnesoid X receptor (FXR) and small heterodimer partner (SHP) were lower in cows with fatty liver than in healthy cows. Overall, these data suggest that inhibition of FXR signaling pathway may lead to the increased bile acid synthesis and uptake and decreased secretion of bile acids from hepatocytes to the bile, which elevates hepatic bile acids content in dairy cows with fatty liver. As the hepatotoxicity of bile acids has been demonstrated on nonruminant hepatocytes, it is likely that the liver injury is induced by increased hepatic bile acids content in dairy cows with fatty liver.

Targeting PHB2 mediated mitophagy alleviates non-esterified fatty acid-induced mitochondrial dysfunction in bovine mammary epithelial cells.

Mitochondrial dysfunction has been reported to occur in the mammary gland of dairy cows suffering from ketosis. Prohibitin 2 (PHB2) plays a crucial role in regulating mitophagy, which clears impaired mitochondria to maintain normal mitochondrial function. Therefore, the current study aimed to investigate how PHB2 mediates mitophagy, thereby influencing mitochondrial function in the bovine mammary epithelial cell MAC-T. First, mammary gland tissue and blood samples were collected from healthy cows (control; n = 15, BHB <0.6 mM) and cows with clinical ketosis (CK; n = 15, BHB >3.0 mM). Compared with the control group, the CK group exhibited lower dry matter intake (DMI), milk production, milk protein, milk lactose, and serum glucose. In contrast, milk fat, serum nonesterified fatty acids (NEFA) and BHB were greater in CK group. The protein abundance of PHB2, peroxisome proliferator activated receptor-γ coactivator-1α (PGC-1α), mitofusin 2 (MFN2) in whole cell lysates (WCL), as well as PHB2, sequestosome-1 (SQSTM1, also called p62), microtubule-associated protein 1 light chain 3-II (LC3-II), and ubiquitinated proteins in mitochondrial fraction were significantly lower in the CK group. ATP content of mammary gland tissue in CK group was lower than that of healthy cows. Second, MAC-T were cultured and treated with NEFA (0, 0.3, 0.6, 1.2 mM). MAC-T treated with 1.2 mM NEFA displayed decreased protein abundance of PHB2, PGC-1α, MFN2 in WCL, as well as protein abundance of PHB2, p62, LC3-II, and ubiquitinated proteins in mitochondrial fraction. The content of ATP and JC-1 aggregates in 1.2 mM NEFA group were lower than in the 0 mM NEFA group. Additionally, 1.2 mM NEFA disrupted the fusion between mitochondria and lysosomes. MAC-T were then pretreated with 100 nM rapamycin, followed by treatment with or without NEFA. Rapamycin alleviated impaired mitophagy and mitochondria dysfunction induced by 1.2 mM NEFA. Third, MAC-T were transfected with small interfering RNA to silence PHB2 or a plasmid for overexpression of PHB2, followed by treatment with or without NEFA. The silencing of PHB2 aggravated 1.2 mM NEFA induced impaired mitophagy and mitochondrial dysfunction, whereas the overexpression of PHB2 alleviated these effects. Overall, this study provides evidence that PHB2, in regulation of mitophagy, is a mechanism for bovine mammary epithelial cells to counteract NEFA-induced mitochondrial dysfunction.

Sucrose and Ca2+ synergistically regulate the rheological properties of apple high-methoxyl pectin.

The thickening and gelling mechanism of high-methoxyl pectins (HMPs) with different degree of esterification (DE) values (60.6 %, 66.1 %, and 72.4 %) synergistically affected by calcium ion (Ca2+) and sucrose was investigated using several technical methods. Rheological measurements, including steady-shear flow, thixotropy and dynamic viscoelasticity tests, texture analysis, water-holding capacity (WHC), thermal analyses (TG), and microstructure observation (TEM), were all systemically conducted. The results showed that the main thickening and gelling mechanism of Ca2+ on different HMPs was complex and the presence of sucrose had a synergistic effect on structure formation in HMP systems. Ca2+ was not always conducive to structure formation, and excessive Ca2+ addition may hinder structure formation. HMP systems with lower DE values had higher gel strengths due to the presence of more binding domains. The results of the texture properties, WHC, and thermal characteristics coincided with those obtained from the rheological measurements, which reflect the variations in HMPs affected by Ca2+ and DE. All of these results showed that Ca2+ addition at an appropriate concentration in the presence of sucrose favors HMP gelation even in the absence of acid. The results obtained here are expected to broaden the application of HMPs in acid-free gel food products.

High internal phase pickering emulsions stabilized by zein/whey protein nanofibril complexes: Preparation and lycopene loading.

High internal phase Pickering emulsions (HIPPEs) prepared from natural polymers have attracted much attention in the food manufactures. However, single zein-stabilized HIPPEs are poorly stable and prone to flocculation near the isoelectric point. To address this issue, in this study, zein and whey protein nanofibrils (WPN) complex nanoparticles (ZWNPs) were successfully prepared using a pH-driven method, and ZWNPs were further used as HIPPEs stabilizers. The results showed that zein and WPN were combined together through hydrogen bonding and hydrophobic interaction to form ZWNPs, and the HIPPEs stabilized by ZWNPs had excellent stability, which could effectively protect the internally encapsulated lycopene and improve the bioaccessibility of lycopene. In conclusion, this study provides a new strategy for the preparation of stable hydrophobic protein-based HIPPEs, represented by zein.

Locality Preservation for Unsupervised Multimodal Change Detection in Remote Sensing Imagery.

Multimodal change detection (MCD) is a topic of increasing interest in remote sensing. Due to different imaging mechanisms, the multimodal images cannot be directly compared to detect the changes. In this article, we explore the topological structure of multimodal images and construct the links between class relationships (same/different) and change labels (changed/unchanged) of pairwise superpixels, which are imaging modality-invariant. With these links, we formulate the MCD problem within a mathematical framework termed the locality-preserving energy model (LPEM), which is used to maintain the local consistency constraints embedded in the links: the structure consistency based on feature similarity and the label consistency based on spatial continuity. Because the foundation of LPEM, i.e., the links, is intuitively explainable and universal, the proposed method is very robust across different MCD situations. Noteworthy, LPEM is built directly on the label of each superpixel, so it is a paradigm that outputs the change map (CM) directly without the need to generate intermediate difference image (DI) as most previous algorithms have done. Experiments on different real datasets demonstrate the effectiveness of the proposed method. Source code of the proposed method is made available at https://github.com/yulisun/LPEM.

Polygenic risk-stratified screening for nasopharyngeal carcinoma in high-risk endemic areas of China: a cost-effectiveness study.

Background: Nasopharyngeal carcinoma (NPC) has an extremely high incidence rate in Southern China, resulting in a severe disease burden for the local population. Current EBV serologic screening is limited by false positives, and there is opportunity to integrate polygenic risk scores for personalized screening which may enhance cost-effectiveness and resource utilization. Methods: A Markov model was developed based on epidemiological and genetic data specific to endemic areas of China, and further compared polygenic risk-stratified screening [subjects with a 10-year absolute risk (AR) greater than a threshold risk underwent EBV serological screening] to age-based screening (EBV serological screening for all subjects). For each initial screening age (30-34, 35-39, 40-44, 45-49, 50-54, 55-59, 60-64, and 65-69 years), a modeled cohort of 100,000 participants was screened until age 69, and then followed until age 79. Results: Among subjects aged 30 to 54 years, polygenic risk-stratified screening strategies were more cost-effective than age-based screening strategies, and almost comprised the cost-effectiveness efficiency frontier. For men, screening strategies with a 1-year frequency and a 10-year absolute risk (AR) threshold of 0.7% or higher were cost-effective, with an incremental cost-effectiveness ratio (ICER) below the willingness to pay (¥203,810, twice the local per capita GDP). Specifically, the strategies with a 10-year AR threshold of 0.7% or 0.8% are the most cost-effective strategies, with an ICER ranging from ¥159,752 to ¥201,738 compared to lower-cost non-dominated strategies on the cost-effectiveness frontiers. The optimal strategies have a higher probability (29.4-35.8%) of being cost-effective compared to other strategies on the frontier. Additionally, they reduce the need for nasopharyngoscopies by 5.1-27.7% compared to optimal age-based strategies. Likewise, for women aged 30-54 years, the optimal strategy with a 0.3% threshold showed similar results. Among subjects aged 55 to 69 years, age-based screening strategies were more cost-effective for men, while no screening may be preferred for women. Conclusion: Our economic evaluation found that the polygenic risk-stratified screening could improve the cost-effectiveness among individuals aged 30-54, providing valuable guidance for NPC prevention and control policies in endemic areas of China.

High-Performance Hard X-Ray Imaging Detector Using Facet-Dependent Bismuth Vanadate.

Bismuth vanadate (BiVO4) exhibits large absorption efficiency for hard X-rays, which endows it with a robust capacity to attenuate X-ray radiation across a broad energy range. The anisotropic properties of BiVO4 allow for the manipulation of their physical and chemical characteristics through crystallographic orientation and exposed facets. In this study, the issue of heavy recombination caused by sluggish electron transport in BiVO4 is successfully addressed by enhancing the abundance of the (040) crystal face ratio using a Co2+ crystal face exposure agent. The facet-dependent modifications exhibit excellent and balanced intrinsic charge transport properties, and finely optimize both the sensitivity and detection limit of BiVO4 X-ray detectors. As a result, ultra-stable BiVO4 metal oxide X-ray detectors demonstrate a high sensitivity of 3164 µC Gyair -1 cm-2 and a low detection limit of 20.76 nGyair s-1 under 110 kVp hard X-rays, establishing a new benchmark for X-ray detectors based on polycrystalline Bi-halides and metal oxides. These findings highlight the significance of crystal orientation in optimizing materials for X-ray detection, setting a new sensitivity record for X-ray detectors based on polycrystalline Bi-halides and metal oxides, which paves the way for the development of advanced, low-dose, and highly stable imaging systems specifically for hard X-rays.

High-Performance Flat-Panel Perovskite X-ray Detectors Enabled by Defect Passivation in Ruddlesden-Popper Perovskites.

Halide perovskites have emerged as promising candidates in X-ray detection due to their strong X-ray absorption and excellent optoelectronic properties. The development of sensitive and stable flat-panel X-ray detectors with high resolution is crucial for practical applications. In this paper, we introduce a novel flat-panel X-ray detector that integrates quasi-two-dimensional (2D) Ruddlesden-Popper (RP) perovskite with a pixeled thin film transistor (TFT) backplane. We incorporate 2,5-dibromopyrimidine (DBPM) as an additive to passivate the Lewis acid defects in the quasi-2D RP perovskite. This modification results in suppressed ion migration, improved optoelectronic performance, and enhanced operational stability of the device. Impressively, the activation energy of the RP perovskite increases from 0.96 to 1.35 eV with the DBPM additive. As a result, X-ray detectors exhibit a high sensitivity of ∼13,600 µC Gyair-1 cm-2, a low detection limit of 6.56 nGyair s-1, and excellent operational stability. Moreover, the flat-panel detectors demonstrate a high spatial resolution of 3.7 line pairs per millimeter and excellent X-ray imaging properties under a remarkably low X-ray dose of ∼50 µGyair, which is just half of the X-ray dose typically used in commercial equipment. This study opens new avenues for the development of flat-panel perovskite X-ray detectors with significant potential for various applications.

Efficient organized colorectal cancer screening in Shenzhen: a microsimulation modelling study.

BACKGROUND: Colorectal cancer (CRC) is a global health issue with noticeably high incidence and mortality. Microsimulation models offer a time-efficient method to dynamically analyze multiple screening strategies. The study aimed to identify the efficient organized CRC screening strategies for Shenzhen City. METHODS: A microsimulation model named CMOST was employed to simulate CRC screening among 1 million people without migration in Shenzhen, with two CRC developing pathways and real-world participation rates. Initial screening included the National Colorectal Polyp Care score (NCPCS), fecal immunochemical test (FIT), and risk-stratification model (RS model), followed by diagnostic colonoscopy for positive results. Several start-ages (40, 45, 50 years), stop-ages (70, 75, 80 years), and screening intervals (annual, biennial, triennial) were assessed for each strategy. The efficiency of CRC screening was assessed by number of colonoscopies versus life-years gained (LYG). RESULTS: The screening strategies reduced CRC lifetime incidence by 14-27 cases (30.9-59.0%) and mortality by 7-12 deaths (41.5-71.3%), yielded 83-155 LYG, while requiring 920 to 5901 colonoscopies per 1000 individuals. Out of 81 screening, 23 strategies were estimated efficient. Most of the efficient screening strategies started at age 40 (17 out of 23 strategies) and stopped at age 70 (13 out of 23 strategies). Predominant screening intervals identified were annual for NCPCS, biennial for FIT, and triennial for RS models. The incremental colonoscopies to LYG ratios of efficient screening increased with shorter intervals within the same test category. Compared with no screening, when screening at the same start-to-stop age and interval, the additional colonoscopies per LYG increased progressively for FIT, NCPCS and RS model. CONCLUSION: This study identifies efficient CRC screening strategies for the average-risk population in Shenzhen. Most efficient screening strategies indeed start at age 40, but the optimal starting age depends on the chosen willingness-to-pay threshold. Within insufficient colonoscopy resources, efficient FIT and NCPCS screening strategies might be CRC initial screening strategies. We acknowledged the age-dependency bias of the results with NCPCS and RS.

Cyanuric Acid-Assisted Synthesis of Hierarchical Amorphous Carbon Nitride Assembled by Ultrathin Oxygen-Doped Nanosheets for Excellent Photocatalytic Hydrogen Generation.

Amorphous carbon nitride with typical short-range order arrangement as an effective photocatalyst is worth exploring but remains a great challenge because its disordered structure induces severe recombination of photogenerated charge carriers. Herein, for the first time, we demonstrate that a hierarchical amorphous carbon nitride (HACN) with structural oxygen incorporation can be synthesized via a cyanuric acid-assisted melem hydrothermal process, accompanied by freeze-drying and pyrolysis. The complex composed of melem and cyanuric acid exhibiting a unique 3D self-supporting skeleton and significant phase transformation is responsible for the formation of an interconnected hierarchical framework and amorphous structure for HACN. These features are beneficial to enhance its visible light harvesting by the multiple-reflection effect within the architecture consisting of more exposed porous nanosheets and introducing a long band tail absorption. The well-designed morphology, band tail state, and oxygen doping effectively inhibit rapid band-to-band recombination of the photogenerated electrons and holes and facilitate subsequent separation. Accordingly, the HACN catalyst exhibits exceptional visible light (λ > 420 nm)-driven photoreduction for hydrogen production with a rate of 82.4 µmol h-1, which is 21.7 and 9.5 times higher than those of melem-derived carbon nitride and crystalline nanotube carbon nitride counterparts, respectively, and significantly surpasses those of most reported amorphous carbon nitrides. Our controlling of rearrangement of the in situ supramolecular self-assembly of melem oligomer using cyanuric acid directly instructs the development of highly efficient amorphous photocatalysts for converting solar energy into hydrogen fuel.

Untargeted metabolomic profiling reveals molecular signatures associated with type 2 diabetes in Nigerians.

BACKGROUND: Type 2 diabetes (T2D) has reached epidemic proportions globally, including in Africa. However, molecular studies to understand the pathophysiology of T2D remain scarce outside Europe and North America. The aims of this study are to use an untargeted metabolomics approach to identify: (a) metabolites that are differentially expressed between individuals with and without T2D and (b) a metabolic signature associated with T2D in a population of Sub-Saharan Africa (SSA). METHODS: A total of 580 adult Nigerians from the Africa America Diabetes Mellitus (AADM) study were studied. The discovery study included 310 individuals (210 without T2D, 100 with T2D). Metabolites in plasma were assessed by reverse phase, ultra-performance liquid chromatography and mass spectrometry (RP)/UPLC-MS/MS methods on the Metabolon Platform. Welch's two-sample t-test was used to identify differentially expressed metabolites (DEMs), followed by the construction of a biomarker panel using a random forest (RF) algorithm. The biomarker panel was evaluated in a replication sample of 270 individuals (110 without T2D and 160 with T2D) from the same study. RESULTS: Untargeted metabolomic analyses revealed 280 DEMs between individuals with and without T2D. The DEMs predominantly belonged to the lipid (51%, 142/280), amino acid (21%, 59/280), xenobiotics (13%, 35/280), carbohydrate (4%, 10/280) and nucleotide (4%, 10/280) super pathways. At the sub-pathway level, glycolysis, free fatty acid, bile metabolism, and branched chain amino acid catabolism were altered in T2D individuals. A 10-metabolite biomarker panel including glucose, gluconate, mannose, mannonate, 1,5-anhydroglucitol, fructose, fructosyl-lysine, 1-carboxylethylleucine, metformin, and methyl-glucopyranoside predicted T2D with an area under the curve (AUC) of 0.924 (95% CI: 0.845-0.966) and a predicted accuracy of 89.3%. The panel was validated with a similar AUC (0.935, 95% CI 0.906-0.958) in the replication cohort. The 10 metabolites in the biomarker panel correlated significantly with several T2D-related glycemic indices, including Hba1C, insulin resistance (HOMA-IR), and diabetes duration. CONCLUSIONS: We demonstrate that metabolomic dysregulation associated with T2D in Nigerians affects multiple processes, including glycolysis, free fatty acid and bile metabolism, and branched chain amino acid catabolism. Our study replicated previous findings in other populations and identified a metabolic signature that could be used as a biomarker panel of T2D risk and glycemic control thus enhancing our knowledge of molecular pathophysiologic changes in T2D. The metabolomics dataset generated in this study represents an invaluable addition to publicly available multi-omics data on understudied African ancestry populations.

Trends of mean systolic and diastolic blood pressure among adults in Shenzhen, China, 1997-2018: findings from three rounds of the population-based survey.

OBJECTIVE: To quantify the trends in systolic and diastolic blood pressure (BP) among adults in Shenzhen from 1997 to 2018. DESIGN: Cross-sectional study. SETTINGS: The data were collected from all districts in Shenzhen, China in the years of 1997, 2009 and 2018 by multistage cluster sampling procedure. PARTICIPANTS: Participants were residents aged 18-69 years in Shenzhen, China. A total of 26 621 people were included: 8266 people in 1997, 8599 people in 2009 and 9756 people in 2018. PRIMARY AND SECONDARY OUTCOME MEASURES: All participants were surveyed about their sociodemographic and lifestyle information. BP was measured by trained physicians using a mercury sphygmomanometer. Hypertension was defined as systolic BP of at least 140 mm Hg and diastolic BP of at least 90 mm Hg, self-reported use of antihypertensive medications or both. Hypertension control was defined as systolic BP values of less than 140 mm Hg and diastolic BP values of less than 90 mm Hg. RESULT: Age-adjusted mean systolic BP increased from 117±16 mm Hg to 123±15 mm Hg (p<0.001) in males, and from 113±18 mm Hg to 115±16 mm Hg (p<0.001) in females from 1997 to 2018. Diastolic BP among males increased from 75 mm Hg (SD=11) to 79 mm Hg (SD=11) and increased from 71 mm Hg (SD=10) to 73 mm Hg (SD=10) among females between 1997 and 2018 (p<0.001). Rate of hypertension rose rapidly from 17.71% (95% CI: 16.60% to 18.90%) in 2009 to 24.01% (95% CI: 22.84% to 25.22%) in 2018 among males (p<0.001), whereas the prevalence among females remained stable at around 13.5% (p=0.98). Both awareness and treatment rates of hypertension among males and females showed a decreased trend between 2009 and 2018, while no significant changes were observed for control rates. CONCLUSIONS: The mean systolic BP and diastolic BP among adults in Shenzhen increased from 1997 to 2018, and no improvements in hypertension awareness, treatment and control rates were found.

Regulating Crystal Orientation in VO2 for Aqueous Zinc Batteries with Enhanced Pseudocapacitance.

Although aqueous zinc batteries have attracted extensive interest, they are limited by relatively low rate capabilities and poor cyclic stability of cathodes. The crystal orientation of the cathode is one important factor influencing electrochemical properties. However, it has rarely been investigated. Herein, VO2 cathodes with different crystal orientations are developed via tuning the number of hydroxyl groups in polyol, such as using glycerol, erythritol, xylitol, or mannitol. The polyols serve as a reductant as well as a structure-directing agent through a hydrothermal reaction. Xylitol-derived VO2 shows a (110)-orientated crystalline structure and ultrathin nanosheet morphology. Such features greatly enhance the pseudocapacitance to 76.1% at a scan rate of 1.0 mV s-1, which is significantly larger than that (61.6%) of the (001)-oriented VO2 derived from glycerol. The corresponding aqueous zinc batteries exhibit a high energy storage performance with a reversible specific capacity of 317 mAh g-1 at 0.5 A g-1, rate ability of 220 mAh g-1 at 10 A g-1, and capacity retention of 81.0% at 10 A g-1 over 2000 cycles. This work demonstrates a facile method for tailoring VO2 crystal orientations, offers an understanding of the Zn2+ storage mechanism upon different VO2 facets, and provides a novel method to develop cathode materials toward advanced aqueous zinc batteries.

In vitro digestion and fecal fermentation of selenocompounds: impact on gut microbiota, antioxidant activity, and short-chain fatty acids.

Selenium bioavailability is critically influenced by gut microbiota, yet the interaction dynamics with selenocompounds remain unexplored. Our study found that L-Selenomethionine (SeMet) and Se-(Methyl)seleno-L-cysteine (MeSeCys) maintained stability during in vitro gastrointestinal digestion. In contrast, Selenite and L-Selenocystine (SeCys2) were degraded by approximately 13% and 35%. Intriguingly, gut microflora transformed MeSeCys, SeCys2, and Selenite into SeMet. Moreover, when SeCys2 and Selenite incubated with gut microbiota, they produced red selenium nanoparticles with diameters ranging between 100 and 400 nm and boosted glutathione peroxidase activity. These changes were positively associated with an increased relative abundance of unclassified_g__Blautia (Family Lachnospiraceae), Erysipelotrichaceae_UCG-003 (Family Erysipelatoclostridiaceae), and uncultured_bacterium_g__Subdoligranulum (Family Ruminococcaceae). Our findings implied that differential microbial sensitivities to selenocompounds, potentially attributable to their distinct mechanisms governing selenium uptake, storage, utilization, and excretion.

A new Cd(II) Complex: Fluorescence Performances, Loading with Budesonide-hydrogels on Pediatric Asthma and Molecular Docking.

By applying the phosphonic acid ligand to the solvothermal reaction of nitrobenzylphosphonic acid (H2L) with Cd(NO3)2·4H2O in a mixed solvent of water and DMF, a novel Cd(II)-based coordination polymer, {[Cd(L)(H2O)2](H2O)}n (1), was successfully synthesized in this study. The excellent fluorescence performance of complex 1 was confirmed through fluorescence spectroscopy testing, and the obtained CIE standard coordinates (0.1599, 0.0786) positioned it in the blue fluorescence region. Transparent hyaluronic acid/carboxymethyl chitosan hydrogels were prepared using chemical synthesis, and their internal microstructure was observed. Using budesonide as a drug model, a new budesonide metal gel was prepared, and its therapeutic efficacy in treating pediatric asthma was evaluated. Molecular docking simulations indicated that the Cd complex formed three hydrogen bonding interactions with the target protein through its nitro group, revealing the potential origin of its biological activity.

Bidirectional modification effects on nonlinear associations of summer temperature and air pollution with first-ever stroke morbidity.

High temperature and air pollution may induce stroke morbidity. However, whether associations between high temperature and air pollution with stroke morbidity are modified by each other is still unclear. Data on 23,578 first-ever stroke patients in Shenzhen, China, during the summers of 2014-2018 were collected. Distributed lag nonlinear models were used to assess the modifying effects of air pollution stratified by the median for the associations between summer temperature and stroke morbidity at 0-3 lag days; modifying effects of temperature stratified by the minimum morbidity temperature on the associations between air pollution and stroke morbidity at the same lags were also estimated. The attributable risks of high temperature and high pollution on stroke morbidity were quantified. Stratified analyses of gender, age, migration type, and complication type were conducted to assess vulnerable population characteristics. Summer high temperature may induce stroke morbidity at high-level PM2.5, PM10, O3, SO2, and NO2 conditions, with attributable fraction (AF) of 2.982% (95% empirical confidence interval [eCI]: 0.943, 4.929), 3.113% (0.948, 5.200), 2.841% (0.943, 4.620), 3.617% (1.539, 5.470), and 2.048% (0.279, 3.637), respectively. High-temperature effects were statistically insignificant at corresponding low-level air pollution conditions. High-level PM2.5, PM10, and O3 may induce stroke morbidity at high-temperature conditions, with AF of 3.664% (0.036, 7.196), 4.129% (0.076, 7.963), and 4.574% (1.009, 7.762), respectively. High-level PM2.5, PM10, and O3 were not associated with stroke morbidity at low-temperature conditions. The effects of high temperature and high pollution on stroke morbidity were statistically significant among immigrants and patients with hypertension, dyslipidemia, or diabetes but insignificant among natives and patients without complications. The associations of summer temperature and air pollution with first-ever stroke morbidity may be enhanced bidirectionally. Publicity on the health risks of combined high temperature and high pollution events should be strengthened to raise protection awareness of relevant vulnerable populations.

Tailoring the composition, antioxidant activity, and prebiotic potential of apple peel by Aspergillus oryzae fermentation.

Apple peel is a typical lignocellulosic food by-product rich in functional components. In this work, apple peel was solid-state fermented with Aspergillus oryzae with an aim to modulate its composition and bioactivity. The results showed that A. oryzae fermentation substantially tailored the composition, improved the antioxidant activity and prebiotic potential of apple peel. Upon the fermentation, 1) free phenolics increased and antioxidant activity improved; 2) the pectin substances degraded significantly, along with a decrease in soluble dietary fiber while an increase in insoluble dietary fiber; 3) the in vitro fermentability increased as indicated by the increase in total acid production. The gut microbiota was shaped with more health-promoting potentials, such as higher abundances of Lactobacillus, Bifidobacterium, Megamonas and Prevotella-9 as well as lower abundances of Enterobacter and Echerichia-Shigella. This work is conducive to the modification of apple peel as a potential ingredient in food formulations.

Thioredoxin-2 suppresses hydrogen peroxide-activated nuclear factor kappa B signaling via alleviating oxidative stress in bovine adipocytes.

During the periparturient period, both oxidative stress, and inflammation of adipose tissue are considered high risk factors for metabolic disorder of dairy cows. Oxidative stress can activate transcription factor nuclear factor kappa B (NF-κB), which lead to the upregulation of genes involved in inflammatory pathways. Thioredoxin-2 (TXN2) is a mitochondrial protein that regulates cellular redox by suppressing mitochondrial reactive oxygen species (ROS) generation in nonruminant, whereas the function of TXN2 in bovine adipocytes was unclear. Thus, the objective of this study was to evaluate how or by which mechanisms TXN2 regulates oxidative stress and NF-κB signaling pathway in bovine adipocytes. Bovine pre-adipocytes isolated from 5 healthy Holstein cows were differentiated and used for (1) treatment with different concentrations of hydrogen peroxide (H2O2; 0, 25, 50, 100, 200, or 400 µM) for 2 h; (2) transfection with or without TXN2 small interfering RNA (si-TXN2) for 48 h and then treated with or without 200 µM H2O2 for 2 h; (3) transfection with scrambled negative control siRNA (si-control) or si-TXN2 for 48 h, and then treatment with or without 10 mM N-acetylcysteine (NAC) for 2 h; (4) transfection with or without TXN2-overexpressing plasmid for 48 h and then treatment with or without 200 µM H2O2 for 2 h. High concentrations of H2O2 (200 and 400 µM) decreased protein and mRNA abundance of TXN2, reduced total antioxidant capacity (T-AOC) and ATP content in adipocytes. Moreover, 200 and 400 µM H2O2 reduced protein abundance of inhibitor of kappa B α (IκBα), increased phosphorylation of NF-κB and upregulated mRNA abundance of tumor necrosis factor-α (TNFA) and interleukin-1B (IL-1B), suggesting that H2O2-induced oxidative stress and activated NF-κB signaling pathway. Silencing of TXN2 increased intracellular ROS content, phosphorylation of NF-κB and mRNA abundance of TNFA and IL-1B, decreased ATP content and protein abundance of IκBα in bovine adipocytes. Knockdown of TXN2 aggravated H2O2-induced oxidative stress and inflammation. In addition, treatment with antioxidant NAC ameliorated oxidative stress and inhibited NF-κB signaling pathway in adipocytes transfected with si-TXN2. In bovine adipocytes treated with H2O2, overexpression of TXN2 reduced the content of ROS and elevated the content of ATP and T-AOC. Overexpression of TXN2 alleviated H2O2-induced inflammatory response in adipocytes, as demonstrated by decreased expression of phosphorylated NF-κB, TNFA, IL-1B, as well as increased expression of IκBα. Furthermore, the protein and mRNA abundance of TXN2 was lower in adipose tissue of dairy cows with clinical ketosis. Overall, our studies contribute to the understanding of the role of TXN2 in adipocyte oxidative stress and inflammatory response.

Nuciferine protects bovine hepatocytes against free fatty acid-induced oxidative damage by activating the transcription factor EB/peroxisome proliferator-activated receptor γ coactivator 1 alpha pathway.

Excessive free fatty acid (FFA) oxidation and related metabolism are the major cause of oxidative stress and liver injury in dairy cows during the early postpartum period. In nonruminants, activation of transcription factor EB (TFEB) can improve cell damage and reduce the overproduction of mitochondrial reactive oxygen species. As a downstream target of TFEB, peroxisome proliferator-activated receptor γ coactivator 1 α (PGC-1α, gene name PPARGC1A) is a critical regulator of oxidative metabolism. Nuciferine (Nuc), a major bioactive compound isolated from the lotus leaf, has been reported to possess hepatoprotective activity. Therefore, the objective of this study was to investigate whether Nuc could protect bovine hepatocytes from FFA-induced lipotoxicity and the underlying mechanisms. A mixture of FFA was diluted in RPMI-1640 basic medium containing 2% low fatty acid bovine serum albumin to treat hepatocytes. Bovine hepatocytes were isolated from newborn calves and treated with various concentrations of FFA mixture (0, 0.3, 0.6, or 1.2 mM) or Nuc (0, 25, 50, or 100 µM), as well as co-treated with 1.2 mM FFA and different concentrations of Nuc. For the experiments of gene silencing, bovine hepatocytes were transfected with small interfering RNA targeted against TFEB or PPARGC1A for 36 h followed by treatment with 1.2 mM FFA for 12 h in presence or absence of 100 µΜ Nuc. The results revealed that FFA treatment decreased protein abundance of nuclear TFEB, cytosolic TFEB, total (t)-TFEB, lysosome-associated membrane protein 1 (LAMP1) and PGC-1α and mRNA abundance of LAMP1, but increased phosphorylated (p)-TFEB. In addition, FFA treatment increased the content of malondialdehyde (MDA) and hydrogen peroxide (H2O2) and decreased the activities of catalase (CAT) and glutathione peroxidase (GSH-Px) in bovine hepatocytes. Moreover, FFA administration enhanced the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactose dehydrogenase (LDH) in the medium of FFA-treated hepatocytes, but reduced the content of urea. In FFA-treated bovine hepatocytes, Nuc administration increased TFEB nuclear localization and the protein abundance of t-TFEB, LAMP1, and PGC-1α and mRNA abundance of LAMP1, decreased the contents of MDA and H2O2 and the protein abundance of p-TFEB, and enhanced the activities of CAT and GSH-Px in a dose-dependent manner. Consistently, Nuc administration reduced the activities of ALT, AST, and LDH and increased the content of urea in the medium of FFA-treated hepatocytes. Importantly, knockdown of TFEB reduced the protein abundance of p-TFEB, t-TFEB, LAMP1, and PGC-1α and mRNA abundance of LAMP1, and impeded the beneficial effects of Nuc on FFA-induced oxidative damage in bovine hepatocytes. In addition, PPARGC1A silencing did not alter Nuc-induced nuclear translocation of TFEB, increase of the protein abundance of t-TFEB, LAMP1, and PGC-1α and mRNA abundance of LAMP1, or decrease of the protein abundance of p-TFEB, whereas it partially reduced the beneficial effects of Nuc on FFA-caused oxidative injury. Taken together, Nuc exerts protective effects against FFA-induced oxidative damage in bovine hepatocytes through activation of the TFEB/PGC-1α signaling pathway.

Oscillatory rheometry for elucidating the influence of non-network biopolymer aggregation on pectin-gelatin composite gels.

Gel networks formed from biopolymers have intrigued rheological interest, especially in the food industry. Despite ubiquitous non-network biopolymer aggregation in real gel food systems, its fundamental rheological implications remain less understood. This study addresses this by preparing pectin-gelatin composite gels with dispersed or aggregated biopolymers and comparatively analyzing viscoelastic responses using rheometry. Subtle discrepancies in non-network biopolymer states were revealed through oscillatory shearing at different frequencies and amplitudes. Biopolymer aggregation in the network notably influenced loss tangent frequency dependency, particularly at high frequencies, elevating I3/I1 values and sensitizing the yield point. Non-network biopolymers weakened Payne effects and gel non-linearity. A combination of strain stiffening and shear thinning nonlinear responses characterized prepared gel systems. Aggregation of pectin and gelatin enhanced shear thinning, while strain stiffening was notable in highly aggregated pectin cases. This study enhances understanding of the link between non-network structural complexity and viscoelastic properties in oscillatory rheometry of food gels.