Combining Gut Microbiota Modulation and Enzymatic-Triggered Colonic Delivery by Prebiotic Nanoparticles Improves Mouse Colitis Therapy.

The efficacy of ulcerative colitis (UC) therapy is closely connected to the composition of gut microbiota in the gastrointestinal tract. Prebiotic-based nanoparticles (NPs) provide a more precise approach to alleviate UC via modulating gut microbiota dysbiosis. The present study develops an efficient prebiotic-based colon-targeted drug delivery system (PCDDS) by using prebiotic pectin (Pcn) and chitosan (Csn) polysaccharides as a prebiotic shell, with the anti-inflammatory drug sulfasalazine (SAS) loaded into a poly(lactic-co-glycolic acid) (PLGA) core to construct SAS@PLGA-Csn-Pcn NPs. Then, we examine its characterization, cellular uptake, and in vivo therapeutic efficacy. The results of our study indicate that the Pcn/Csn shell confers efficient pH-sensitivity properties. The gut microbiota-secreted pectinase serves as the trigger agent for Pcn/Csn shell degradation, and the resulting Pcn oligosaccharides possess a substantial prebiotic property. Meanwhile, the formed PCDDSs exhibit robust biodistribution and accumulation in the colon tissue, rapid cellular uptake, efficient in vivo therapeutic efficacy, and modulation of gut microbiota dysbiosis in a mouse colitis model. Collectively, our synthetic PCDDSs demonstrate a promising and synergistic strategy for UC therapy.

Identification of autophagy-related signatures in nonalcoholic fatty liver disease and correlation with non-parenchymal cells of the liver.

Non-alcoholic fatty liver disease (NAFLD) is a chronic hepatic disease. The incidence and prevalence of NAFLD have increased greatly in recent years, and there is still a lack of effective drugs. Autophagy plays an important role in promoting liver metabolism and maintaining liver homeostasis, and defects in autophagy levels are considered to be related to the development of NAFLD. However, the molecular mechanisms of autophagy in NAFLD still remain unknown. In this study, we identified 6 autophagy-associated hub genes using gene expression profiles obtained from the GSE48452 and GSE89632 datasets. Biomarkers were screened according to gene significance (GS) and module membership (MM) using weighted gene co-expression network analysis (WGCNA), and the immune infiltration landscape of the liver in NAFLD patients was explored using the CIBERSORT algorithm. Subsequently, we analyzed the relationship between liver non-parenchymal cells and autophagy-related hub genes using scRNA-seq data (GSE129516). Finally, we separated the NAFLD patients into two groups based on 6 hub genes by consensus clustering and screened 10 potential autophagy-related small molecules based on the cMAP database.

Stachyose Exerts Anticolitis Efficacy by Re-balancing Treg/Th17 and Activating the Butyrate-Derived PPARγ Signaling Pathway.

Ulcerative colitis (UC) is a complex chronic inflammatory disease closely associated with gut homeostasis dysfunction. The previous studies have shown that stachyose, a functional food additive, has the potential to enhance gut health and alleviate UC symptoms. However, the underlying mechanism of its effects remains unknown. In this study, our findings showed that dietary supplements of stachyose had a significant dose-dependent protective effect on colitis symptoms, regulation of gut microbiota, and restoration of the Treg/Th17 cell balance in dextran sulfate sodium (DSS) induced colitis mice. To further validate these findings, we conducted fecal microbiota transplantation (FMT) to treat DSS-induced colitis in mice. The results showed that microbiota from stachyose-treated mice exhibited a superior therapeutic effect against colitis and effectively regulated the Treg/Th17 cell balance in comparison to the control group. Moreover, both stachyose supplementation and FMT resulted in an increase in butyrate production and the activation of PPARγ. However, this effect was partially attenuated by PPARγ antagonist GW9662. These results suggested that stachyose alleviates UC symptoms by modulating gut microbiota and activating PPARγ. In conclusion, our work offers new insights into the benefical effects of stachyose on UC and its potential role in modulating gut microbiota.

Sulfur vacancy-rich bismuth sulfide nanowire derived from CAU-17 for radioactive iodine capture in complex environments: Performance and intrinsic mechanisms.

Effective capture and immobilization of volatile radioiodine from the off-gas of post-treatment plants is crucial for nuclear safety and public health, considering its long half-life, high toxicity, and environmental mobility. Herein, sulfur vacancy-rich Vs-Bi2S3@C nanocomposites were systematically synthesized via a one-step solvothermal vulcanization of CAU-17 precursor. Batch adsorption experiments demonstrated that the as-synthesized materials exhibited superior iodine adsorption capacity (1505.8 mg g-1 at 200 °C), fast equilibrium time (60 min), and high chemisorption ratio (91.7%), which might benefit from the nanowire structure and abundant sulfur vacancies of Bi2S3. Furthermore, Vs-Bi2S3@C composites exhibited excellent iodine capture performance in complex environments (high temperatures, high humidity and radiation exposure). Mechanistic investigations revealed that the I2 capture by fabricated materials primarily involved the chemical adsorption between Bi2S3 and I2 to form BiI3, and the interaction of I2 with electrons provided by sulfur vacancies to form polyiodide anions (I3-). The post-adsorbed iodine samples were successfully immobilized into commercial glass fractions in a stable form (BixOyI), exhibiting a normalized iodine leaching rate of 3.81 × 10-5 g m-2 d-1. Overall, our work offers a novel strategy for the design of adsorbent materials tailed for efficient capture and immobilization of volatile radioiodine.

G-quadruplex DNA-based colorimetric biosensor for the ultrasensitive visual detection of strontium ions using MnO2 nanorods as oxidase mimetics.

Strontium-90 (90Sr) is a major radioactive component that has attracted great attention, but its detection remains challenging since there are no specific energy rays indicative of its presence. Herein, a biosensor that is capable of rapidly detecting Sr2+ ions is demonstrated. Simple colorimetric method for sensitive detection of Sr2+ with the help of single-stranded DNA was developed by preparing MnO2 nanorods as oxidase mimic catalysis 3,3',5,5'-tetramethylbenzidine (TMB). Under weakly acidic conditions, MnO2 exhibited a strong oxidase-mimicking activity to oxidize colorless TMB into blue oxidation products (oxTMB) with discernible absorbance signals. Nevertheless, the introduction of a guanine-rich DNA aptamer inhibited MnO2-mediated TMB oxidation and reduced oxTMB formation, resulting in blue fading and diminished absorbance. Upon the addition of strontium ions to the system, the aptamers formed a stable G-quadruplex structure with strontium ions, thereby restoring the oxidase-mimicking activity of MnO2. Under the best experimental conditions, the absorbance exhibits a linear relationship with the Sr2+ concentration within the range 0.01-200 µM, with a limit of detection of 0.0028 µM. When the concentration of Sr2+ from 10-8 to 10-6 mol L-1, a distinct color change gradient could be observed in paper-based sensor. We successfully applied this approach to determine Sr2+ in natural water samples, obtaining recoveries ranging from 97.6 to 103% with a relative standard deviation of less than 5%. By providing technical solutions for detection, our work contributed to the effective monitoring of transportation of radioactive Sr in the environment.

Bimetallic mutual-doping magnetic aerogels for iodine reduction capture and immobilization.

Adsorption is considered to be one of the most effective methods to remove radioiodine from the solution. However, developing highly efficient adsorbents and the rapid recovery of the used adsorbents is still a challenge. Here, a series of Cu/Fe3O4 bimetallic mutual-doping magnetic aerogels (Cu/Fe3O4-BMMA) were synthesized. Based on the in-situ bimetallic co-gelation process, the high dispersion of Cu in the aerogel was realized, providing conditions for the efficient elimination of I2. The Fe3+ in the initial gel was reduced to magnetic Fe3O4 during the preparation process, allowing for the quick recovery of the adsorbent through the application of a magnetic field. The adsorption experiments showed that Cu/Fe3O4-BMMA has good I2 adsorption capacity (631.3 mg/g) and fast capture kinetics (equilibrium time < 30 min). In addition, Cu/Fe3O4-BMMA was able to effectively remove trace I2 in the solution from ppm level (1.0 ppm) down to ppb level (≤30 ppb). The adsorbed I2 was converted into stable CuI, avoiding secondary pollution due to desorption. Overall, this study provides a potentially efficient iodine capture material for long-term decay storage of radioactive iodine.

The intention of utilization and experience toward traditional Chinese medicine among breast cancer patients in the early and late stages: a qualitative study.

BACKGROUND: In Taiwan, breast cancer patients usually take conventional medicine and traditional Chinese medicine simultaneously. The utilization of traditional Chinese medicine among breast cancer patients at various stages has not been examined. This study aims to compare the intention of utilization and experience toward traditional Chinese medicine among early- and late-stage breast cancer patients. METHOD: This qualitative research collected data from breast cancer patients through focus groups interview by convenience sampling. Conducted in 2 branches of Taipei City Hospital, a public hospital managed by the Taipei City government. Breast cancer patients > 20 years old and had used TCM for breast cancer therapy for at least 3 months were included in the interview. A semi-structured interview guide was adopted in each focus group interview. In the following data analysis, stages I and II were considered early-stage, and stages III and IV were late-stage. For analyzing the data and reporting the results, we used qualitative content analysis as the approach for data analysis, assisted by NVivo 12. Categories and subcategories were identified through content analysis. RESULTS: Twelve and seven early- and late-stage breast cancer patients were included in this study, respectively. The side effects were the main intention of utilizing traditional Chinese medicine. Improving side effects and constitution was the main benefit for patients in both stages. Additionally, early-stage breast cancer patients used traditional Chinese medicine to prevent recurrence or metastasis. Late-stage breast cancer patients responded more frequently to the use of traditional Chinese medicine due to the side effects of western medicine. However, some of their symptoms were not fully relieved. CONCLUSIONS: Breast cancer staging may influence the intention and utilization of traditional Chinese medicine. Health policymakers should consider the results of this research and the evidence-based illustrations to establish guidelines for integrating traditional Chinese medicine among various stages of breast cancer to improve the outcome and quality of care for cancer patients.

Synthesis and characterization of Ag@Cu-based MOFs as efficient adsorbents for iodine anions removal from aqueous solutions.

Due to the critical importance of capturing radioiodine from aquatic environments for human health and ecosystems, developing highly efficient adsorbent materials with rapid kinetics for capturing iodide ions in aqueous solutions is urgently needed. Although extensive research has been conducted on iodine adsorption in gas and organic phases, limited research has been dedicated to adsorption in aqueous solutions. An effective technique for removing iodide was proposed using Ag@Cu-based MOFs synthesized by incorporating Ag into calcined HKUST-1 with varying mass ratios of Ag/Cu-C. Extensive characterization using SEM, XRD, XPS, and nitrogen adsorption-desorption analysis confirmed successful incorporation of Ag in Cu-C. Batch adsorption experiments were conducted, demonstrating that the 5% Ag@Cu-C material exhibited a high adsorption capacity of 247.1 mg g-1 at pH 3. Mechanism investigations revealed that Cu0 and dissolved oxygen in water generate Cu2O and H2O2, while Ag and a small amount of CuO generate Ag2O and Cu2O. Furthermore, iodide ions in the solution are captured by Cu+ and Ag+ adsorption sites. These findings highlighted the potential of Ag@Cu-based MOFs as highly effective adsorbents for iodine anions removal in radioactive wastewater.

Synchronous Interventions of Glucose and Mitochondrial Metabolisms for Antitumor Bioenergetic Therapy.

Hydrogen sulfide (H2 S)-based mitochondrial bioenergetic intervention is an attractive therapeutic modality. However, its therapeutic efficacy is limited owing to metabolic plasticity, which allows tumors to shift their metabolic phenotype between oxidative phosphorylation and glycolysis for energy compensation. To overcome this flexibility, a glycopolymer containing a caged H2 S and hydrogen peroxide (H2 O2 ) dual-donor (1-thio-ß-D-glucose [thioglucose]) is synthesized to wrap glucose oxidase (GOx) for complete depletion of tumorigenic energy sources. The loaded GOx catalyzes the glutathione-activated thioglucose to generate cytotoxic H2 S/H2 O2 , which further induces synergistic defects in mitochondrial function by suppressing cytochrome c oxidase expression and damaging the mitochondrial membrane potential. GOx also blocks glycolysis by depleting endogenous glucose. This synchronous intervention strategy exhibits good anticancer performance, broadening the horizon of antitumor bioenergetic therapy.

Cu/Al2O3 aerogels for high-efficiency and rapid iodide elimination from water.

Cu-based functional materials are excellent candidates for the elimination of iodine anions. However, the low utilization rate of Cu and its unsatisfactory adsorption performance limit its large-scale practical applications. This paper proposes a co-gelation method to obtain Cu/Al2O3 aerogels with a high specific area (537 m2/g). Cu/Al2O3 aerogels have a hierarchical porous structure and contain a high proportion of Cu (20.5 wt%). The high dispersibility of Cu, which is based on an in-situ gel process, provides conditions for the high-efficiency elimination of iodide anions. We conducted adsorption experiments that demonstrated that the fabricated Cu/Al2O3 aerogel had an ultrahigh adsorption capacity (407.6 mg/g) and a fast adsorption equilibrium time (0.5 h) for iodide anions. Additionally, the Cu/Al2O3 aerogel could selectively capture iodine anions even in the presence of high concentrations of competing ions (NO3-, SO42-, and Cl- at 60 mmol/L). Importantly, the aerogel can operate in a wide pH range of 3-11 without causing secondary pollution. This work demonstrates that low-cost Cu/Al2O3 aerogels exhibit great potential for eliminating radioactive iodine anions.

Identification and exploration of pharmacological pyroptosis-related biomarkers of ulcerative colitis.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD). Its etiology is unclear. Much evidence suggests that the death of abnormal intestinal epithelial cells (IECs) leads to intestinal barrier disruption, and the subsequent inflammatory response plays a vital role in UC. Pyroptosis is a form of programmed inflammatory cell death, and the role of pyroptosis in UC etiology remains to be explored. This study identified 10 hub genes in pyroptosis by gene expression profiles obtained from the GSE87466 dataset. Meanwhile, the biomarkers were screened based on gene significance (GS) and module membership (MM) through the Weighted Gene Co-Expression Network Analysis (WGCNA). The following analysis indicated that hub genes were closely associated with the UC progression and therapeutic drug response. The single-cell RNA (scRNA) sequencing data from UC patients within the GSE162335 dataset indicated that macrophages were most related to pyroptosis. Finally, the expression of hub genes and response to the therapeutic drug [5-aminosalicylic acid (5-ASA)] were verified in dextran sulfate sodium (DSS)-induced colitis mice. Our study identified IL1B as the critical pyroptosis-related biomarker in UC. The crosstalk between macrophage pyroptosis and IEC pyroptosis may play an essential role in UC, deserving further exploration.

Androgen receptor functions in pericentral hepatocytes to decrease gluconeogenesis and avoid hyperglycemia and obesity in male mice.

BACKGROUND: Although the impact of hepatic androgen receptor (AR) pathway on liver pathogenesis was documented, its physiological function in normal liver is remained unclear. This study aims to investigate if hepatic AR acts on metabolism, the major liver function, using a hepatic-specific AR-transgenic (H-ARTG) mouse model. METHODS: We established the albumin promoter driven H-ARTG mice and included wild type (WT) and H-ARKO mice for study. The body weight, specific metabolic parameters and results from various tolerance tests were compared in different groups of mice fed a chow diet, from 2 to 18 months of age. Glucose feeding and insulin treatment were used to study the expression and zonal distribution pattern of AR and related genes in liver at different prandial stages. RESULTS: The body weight of H-ARTG mice fed a chow diet was 15 % lower than that of wild-type mice, preceded by lower blood glucose and liver triglyceride levels caused by AR reduced hepatic gluconeogenesis. The opposite phenotypes identified in H-ARKO and castrated H-ARTG mice support the critical role of activated AR in decreasing gluconeogenesis and triglyceride levels in liver. Hepatic AR acting by enhancing the expression of cytosolic glycerol-3-phosphate dehydrogenase (cGPDH), a key of glycerophosphate shuttle, was identified as one mechanism to decrease gluconeogenesis from glycerol. We further found AR normally expressed in zone 3 of hepatic lobules. Its level fluctuates dependent on the demand of glucose, decreased by fasting but increased by glucose uptake or insulin stimulation. CONCLUSION: AR is a newly identified zone 3 hepatic gene with function in reducing blood glucose and body weight in mice. It suggests that stabilization of hepatic AR is a new direction to prevent hyperglycemia, obesity and nonalcoholic fatty liver disease (NAFLD) in males.

Blood brain barrier permeability and immune function of brain in rainbow trout responding to IHNV infection.

Viral infection of the central nervous system (CNS) is often associated with blood-brain barrier (BBB) disruption. Mammals have developed complicated and efficient immune strategies to protect the BBB. However, the immune defense of brain and BBB permeability changes are not well-understood in teleost during virus invading. In this study, we constructed an infectious hematopoietic necrosis virus (IHNV) immersion infected rainbow trout model. After IHNV infection, pathological changes occurred in the brain, and MPO and ROS activities were significantly increased. In addition, the expression levels of BBB permeability-related genes were also changed. Transcriptome analysis showed that immune-related genes and signaling pathways in the brain were activated after IHNV infection. These results showed that the permeability of BBB increased significantly after IHNV infection, thus activating immune related factors and cells to enter the CNS through blood circulation to resist pathogenic infection.

SARS-CoV-2 variants - Evolution, spike protein, and vaccines.

Despite the rising natural and vaccines mediated immunity, several countries have experienced a resurgence of the Coronavirus disease of 2019 (COVID-19) due to the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. From Alpha to Omicron, the variants of concern (VOC) have evolved several spike protein mutations that may have an impact on virus characteristics, such as transmissibility and antigenicity. In this review, we describe the evolution of SARS-CoV-2, summarize current knowledge of epidemiological and clinical features of the variants, and discuss the response strategies in terms of vaccines to reduce the burden of COVID-19.

Application of chitosan/alginate nanoparticle in oral drug delivery systems: prospects and challenges.

Oral drug delivery systems (ODDSs) have various advantages of simple operation and few side effects. ODDSs are highly desirable for colon-targeted therapy (e.g. ulcerative colitis and colorectal cancer), as they improve therapeutic efficiency and reduce systemic toxicity. Chitosan/alginate nanoparticles (CANPs) show strong electrostatic interaction between the carboxyl group of alginates and the amino group of chitosan which leads to shrinkage and gel formation at low pH, thereby protecting the drugs from the gastrointestinal tract (GIT) and aggressive gastric environment. Meanwhile, CANPs as biocompatible polymer, show intestinal mucosal adhesion, which could extend the retention time of drugs on inflammatory sites. Recently, CANPs have attracted increasing interest as colon-targeted oral drug delivery system for intestinal diseases. The purpose of this review is to summarize the application and treatment of CANPs in intestinal diseases and insulin delivery. And then provide a future perspective of the potential and development direction of CANPs as colon-targeted ODDSs.

Efficient and selective adsorption of methylene blue and methyl violet dyes by yellow passion fruit peel.

As an important biomass resource, agricultural waste is of great significance to improve the application value. In this study, the yellow passion fruit peel (Y-PFP) was used as a biosorbent to remove cationic dyes (methylene blue (MB) and methyl violet (MV)) by the simple treatment process. And the effects of pH, contact time, initial dye concentration, ionic strength, and temperature on the adsorption performance of Y-PFP were studied. The adsorption process was consistent with the pseudo-second-order kinetic model and Langmuir isotherm. What's more, the maximum adsorption capacity for MB and MV was 324.7 and 485.4 mg·g-1, respectively. And Y-PFP still exhibited high removal efficiency after five desorption-adsorption cycles. Thus, Y-PFP had highly valuable for the removal of cationic dyes from wastewater with a simple preparation process, low cost, excellent adsorption capacity and selectivity.

Solvent-controlled two-step one-pot syntheses of α-X (X = Br or Cl) enamino ketones/esters and 3-(2,5-dioxopyrrolidin-1-yl)acrylate by using terminal carbonyl alkynes.

A new two-step one-pot aminobromination/chlorination of carbonyl alkynes has been achieved via a Michael addition of aliphatic secondary amines and subsequent ß-bromination/chlorination of the obtained enamines to afford various α-X (X = Br or Cl) enamino ketones/esters in moderate to good yields. A solvent-controllable protocol has been developed to produce versatile 3-(2,5-dioxopyrrolidin-1-yl)acrylates in moderate yields by using toluene as the solvent and chain alkyl propiolates as alkynyl substrates.

Super and Selective Adsorption of Cationic Dyes onto Carboxylate-Modified Passion Fruit Peel Biosorbent.

The carboxylate-functionalized passion fruit peel (PFPCS) was an efficient and rapid biosorbent for wastewater treatment. The PFPCS exhibited excellent selectivity to the cationic dyes, where the maximum adsorption capacities for methylene blue (MB) and methyl violet (MV) were 1,775.76 mg g-1 and 3,756.33 mg g-1, respectively. And the adsorption process of MB and MV on PFPCS reached equilibrium within 20 min. Moreover, the adsorption conditions and mechanisms were investigated. The adsorption process was in good agreement with the pseudo-second-order and Langmuir isotherm models. The adsorption mechanism was also proposed to be electrostatic interaction and hydrogen bond. After six cycles of desorption-adsorption, the removal efficient of MB and MV could be kept above 95%. Thus, PFPCS was considered as a highly efficient absorbent for removing cationic dyes from polluted water due to excellent adsorption characteristics, low cost and environmental friendliness.

Molecular characterization and expression analysis of Tf_TLR4 and Tf_TRIL in yellow catfish Tachysurus fulvidraco responding to Edwardsiella ictaluri challenge.

Toll-like receptors play significant roles in defensing against pathogen invasion. In this study, TLR4 and TRIL from Yellow catfish Tachysurus fulvidraco (Tf), were identified and characterized. The open reading frames of the Tf_TLR4 and Tf_TRIL genes were 2466 bp and 1827 bp in length, encoding 821 and 608 amino acids, respectively. The Tf_TLR4 consists of LRRs, a transmembrane domain and a TIR domain, and Tf_TRIL only contains LRRs and TIR domain. Homologous identity revealed that both Tf_TLR4 and Tf_TRIL have high protein sequence similarity with that of channel catfish Ictalurus punctatus. Both the Tf_TLR4 and Tf_TRIL genes were highly expressed in head kidney and brain, respectively. The mRNA expression levels of Tf_TLR4 and Tf_TRIL genes were up-regulated in intestine and immune-related tissues after challenge of Edwardsiella ictaluri. The microscopic observation of the gut showed that the pathological changes in midgut and hindgut are more obvious than that in foregut after challenged with E. ictaluri. These results indicate that these two genes play potential roles in the host defense against E. ictaluri invasion. This study will provide valuable information to better understand the synergistic roles of TLR4 and TRIL in the innate immune system of yellow catfish and other fish.