Carboxymethylated Lycium barbarum seed dreg dietary fiber alleviates high fat diet-induced hyperlipidemia in mice via intestinal regulation.

In this study, we investigated the ameliorative gut modulatory effect of carboxymethylated Lycium barbarum seed dreg insoluble dietary fiber (LBSDIDF) on hyperlipidemic mice. After seven weeks of insoluble dietary fiber (IDF) intervention, the results demonstrated that IDFs effectively inhibited body weight gain, with slimming and hypolipidemic effects, and improved liver histopathology by decreasing ALT, AST, TNF-α and IL-6, and increasing short-chain fatty acid (SCFA) levels in hyperlipidemic mice. With the increasing diversity and abundance of intestinal bacteria and decreasing ratio of Firmicutes to Bacteroidetes, intestinal flora facilitated cholesterol lowering effects in hyperlipidemic mice. Our research offers a novel concept for the use of LBSDIDF as a prebiotic to improve intestinal dysbiosis or as a preventive measure against obesity and dyslipidemia.

Dialogue between mitochondria and endoplasmic reticulum-potential therapeutic targets for age-related cardiovascular diseases.

Mitochondria-associated endoplasmic reticulum membranes (MAMs) act as physical membrane contact sites facilitating material exchange and signal transmission between mitochondria and endoplasmic reticulum (ER), thereby regulating processes such as Ca2+/lipid transport, mitochondrial dynamics, autophagy, ER stress, inflammation, and apoptosis, among other pathological mechanisms. Emerging evidence underscores the pivotal role of MAMs in cardiovascular diseases (CVDs), particularly in aging-related pathologies. Aging significantly influences the structure and function of the heart and the arterial system, possibly due to the accumulation of reactive oxygen species (ROS) resulting from reduced antioxidant capacity and the age-related decline in organelle function, including mitochondria. Therefore, this paper begins by describing the composition, structure, and function of MAMs, followed by an exploration of the degenerative changes in MAMs and the cardiovascular system during aging. Subsequently, it discusses the regulatory pathways and approaches targeting MAMs in aging-related CVDs, to provide novel treatment strategies for managing CVDs in aging populations.

Deficiency of SECTM1 impairs corneal wound healing in aging.

The corneal epithelium is the outermost transparent barrier of the eyeball and undergoes continuous self-renewal by limbal stem cells (LSCs) during its lifetime; however, the impact of aging on LSCs remains largely unknown. Here, we showed that the healing ability of the cornea in elderly macaques (Macaca fascicularis) was significantly decreased compared to that of younger macaques. This delayed wound closure accompanied a disordered cell arrangement and corneal opacity. A novel cytokine, Secreted and Transmembrane 1 (SECTM1), was found to facilitate corneal healing and was upregulated in young macaques upon wounding. Mechanistically, SECTM1 is essential for LSC migration and proliferation, and may partially function through Cell Division Cycle Associated 7 (CDCA7). Notably, the topical application of SECTM1 to aged wounded corneas dramatically promoted re-epithelialization and improved corneal transparency in both mice and macaques. Our work suggests that aging may impair the expression of healing response factors and injury repair in non-human primate corneas, and that SECTM1 application could potentially benefit corneal wound healing in clinical treatment.

Effect of κ-carrageenan on the quality of crayfish surimi gels.

The demand for crayfish surimi products has grown recently due to its high protein content. This study examined the effects of varying κ-carrageenan (CAR) and crayfish surimi (CSM) concentrations on the gelling properties of CAR-CSM composite gel and its intrinsic formation process. Our findings demonstrated that with the increasing concentration of carrageenan, the quality of CAR-CSM exhibited rising trend followed by subsequently fall. Based on the textural qualities, the highest quality CAR-CSM was achieved at 0.3% carrageenan addition. With the exception of chewiness, and the cooking loss of the gel system was 1.62%, whiteness was 82.35%, and the percentage of ß-sheets increased to 57.18%. Further increase in CAR (0.4-0.5%) addition resulted in internal build-up of LCAR-CSM, conversion of intermolecular forces into disulfide bonds and gel breakage. This study exudes timely recommendations for extending the CAR application for the continuous development of crayfish surimi and its derivatives and its overall economic worth.

Transgenic expression of artificial microRNA targeting soybean mosaic virus P1 gene confers virus resistance in plant.

RNA silencing is an innate immune mechanism of plants against invasion by viral pathogens. Artificial microRNA (amiRNA) can be engineered to specifically induce RNA silencing against viruses in transgenic plants and has great potential for disease control. Here, we describe the development and application of amiRNA-based technology to induce resistance to soybean mosaic virus (SMV), a plant virus with a positive-sense single-stranded RNA genome. We have shown that the amiRNA targeting the SMV P1 coding region has the highest antiviral activity than those targeting other SMV genes in a transient amiRNA expression assay. We transformed the gene encoding the P1-targeting amiRNA and obtained stable transgenic Nicotiana benthamiana lines (amiR-P1-3-1-2-1 and amiR-P1-4-1-2-1). Our results have demonstrated the efficient suppression of SMV infection in the P1-targeting amiRNA transgenic plants in an expression level-dependent manner. In particular, the amiR-P1-3-1-2-1 transgenic plant showed high expression of amiR-P1 and low SMV accumulation after being challenged with SMV. Thus, a transgenic approach utilizing the amiRNA technology appears to be effective in generating resistance to SMV.

Digital ischemic necrosis in a patient with systematic lupus erythematosus patient after severe acute respiratory syndrome coronavirus 2 infection: a case report.

BACKGROUND: Patients with coronavirus disease 2019 have a high incidence of thrombosis that decreases after recovery. When coronavirus disease 2019 is accompanied by diseases prone to thrombosis, risk of post-infection thrombotic events may increase. CASE PRESENTATION: We report a case of digital ischemic gangrene in a 24-year-old Chinese female with systemic lupus erythematosus after recovery from coronavirus disease 2019. The pathogenesis was related to clinical characteristics of systemic lupus erythematosus, hypercoagulability caused by coronavirus disease 2019, and second-hit due to viral infection. CONCLUSION: Patients with autoimmune diseases should remain alert to autoimmune system disorders induced by severe acute respiratory syndrome coronavirus 2 and other viruses. Treatment for these patients should be strictly standardized, and appropriate anticoagulation methods should be selected to prevent thrombosis.

Development of Indocyanine Green/Methyl-ß-cyclodextrin Complex-Loaded Liposomes for Enhanced Photothermal Cancer Therapy.

Photothermal therapy (PTT) is a promising cancer therapeutic approach due to its spatial selectivity and high potency. Indocyanine green (ICG) has been considered a biocompatible PTT agent. However, ICG has several challenges to hinder its clinical use including rapid blood clearance and instability to heat, light, and solvent, leading to a loss of photoactivation property and PTT efficacy. Herein, we leveraged stabilizing components, methyl-ß-cyclodextrin and liposomes, in one nanoplatform (ICD lipo) to enhance ICG stability and the photothermal therapeutic effect against cancer. Compared to ICG, ICD lipo displayed a 4.8-fold reduction in degradation in PBS solvent after 30 days and a 3.4-fold reduction in photobleaching after near-infrared laser irradiation. Moreover, in tumor-bearing mice, ICD lipo presented a 2.7-fold increase in tumor targetability and inhibited tumor growth 9.6 times more effectively than did ICG without any serious toxicity. We believe that ICD lipo could be a potential PTT agent for cancer therapeutics.

Sandwich-structured continuous ZIF-8/Ti3C2 MXene/ZIF-8 for efficient sterilization: Enhanced photocatalytic activity, photothermal effect, and environmental safety.

The development of effective water purification systems is crucial for controlling and remediating environmental pollution, especially in terms of sterilization. Herein, we demonstrate elaborately designed composite nanosheets with a sandwich structure, composed of two-dimensional (2D) Ti3C2 MXene nanosheet core and conformal ZIF-8 ultrathin outer layers, and their potential applications in photocatalytic sterilization. The study results indicate that the conformal ZIF-8-MXene nanosheet exhibits an expanded light absorption range (826 nm), improved photothermal conversion efficiency (6.2 °C s-1), and photocurrent response, thus boosting photocatalytic sterilization efficiency (6.63 log10 CFU mL-1) against Escherichia coli under simulated sunlight within 90 min. Interestingly, 2D ZIF-8 layers exhibit positive zeta potential (19 mV), good hydrophilicity (40.6°), and local photogenerated-hole accumulation, possessing efficient bacteria-trapping efficiency. Membrane filters fabricated from optimized composite nanosheets exhibit an outstanding bacteria-trapping and sterilization efficiency (almost 100 %) against Escherichia coli under simulated sunlight within 30 min of the flow photocatalytic experiments. This work not only presents a rational structural design of the conformal and ultrathin anchoring of ZIF-8 onto a 2D conductive material for bacteria-trapping and sterilization, but also opens new opportunities for using metal-organic frameworks in photocatalytic disinfection of drinking water.

The efficacy and safety of adding PD-1 blockade to induction chemotherapy and concurrent chemoradiotherapy (IC-CCRT) for locoregionally advanced nasopharyngeal carcinoma: an observational, propensity score-matched analysis.

BACKGROUND: Despite the success of PD-1 blockade in recurrent/metastatic nasopharyngeal carcinoma (NPC), its effect for locoregionally advanced NPC (LANPC) remains unclear. This study aimed to evaluate the benefit of adding PD-1 blockade to the current standard treatment (gemcitabine and cisplatin IC  plus cisplatin CCRT ) for LANPC patients. METHODS: From January 2020 to November 2022, 347 patients with non-metastatic high-risk LANPC (stage III-IVA, excluding T3-4N0) were included. Of the 347 patients, 268 patients were treated with standard treatment (IC-CCRT), and 79 received PD-1 blockade plus IC-CCRT (PD-1 group). For the PD-1 group, PD-1 blockade was given intravenously once every 3 weeks for up to 9 cycles (3 induction and 6 adjuvant). The primary endpoint was disease-free survival (DFS) (i.e. freedom from local/regional/distant failure or death). The propensity score matching (PSM) with the ratio of 1:2 was performed to control confounding factors. RESULTS: After PSM analysis, 150 patients receiving standard treatment and 75 patients receiving additional PD-1 blockade remained in the current analysis. After three cycles of IC, the PD-1 group had significantly higher rates of complete response (defined as disappearance of all target lesions; 24% vs. 9%; P = 0.006) and complete biological response (defined as undetectable cell-free Epstein-Barr virus DNA, cfEBV DNA; 79% vs. 65%; P = 0.046) than that in the standard group. And the incidence of grade 3-4 toxicity during IC was 47% in the PD-1 group and 41% in the standard group, with no significant difference (P = 0.396). During follow-up period, additional PD-1 blockade to standard treatment improved 3-year DFS from 84 to 95%, with marginal statistical significance (HR, 0.28; 95%CI, 0.06-1.19; P = 0.064). CONCLUSION: Additiaonl PD-1 blockade to gemcitabine and cisplatin IC and adjuvant treatment results in significant improvement in tumor regression, cfEBV DNA clearance, superior DFS, and comparable toxicity profiles in high-risk LANPC patients.

Age-dependent distribution of IgA and IgG antibody-secreting cells in the pharyngeal tonsil of the Bactrian camel.

The pharyngeal tonsil, located in the nasopharynx, can effectively defend against pathogens invading the body from the upper respiratory tract and play a crucial role in mucosal immunity of the respiratory tract. Immunoglobulin A (IgA) and Immunoglobulin G (IgG) serve as key effector molecules in mucosal immunity, exhibiting multiple immune functions. This study aimed to investigate the distribution patterns and age-related alterations of IgA and IgG antibody-secreting cells (ASCs) in the pharyngeal tonsils of Bactrian camels. Twelve Alashan Bactrian camels were categorized into four age groups: young (1-2 years, n=3), pubertal (3-5 years, n=3), middle-aged (6-16 years, n=3) and old (17-20 years, n=3). The distribution patterns of IgA and IgG ASCs in the pharyngeal tonsils of Bactrian camels of different ages were meticulously observed, analyzed and compared using immunohistochemical and statistical methods. The results revealed that IgA ASCs in the pharyngeal tonsils of all age groups were primarily clustered or diffusely distributed in the reticular epithelium and its subepithelial regions (region A) and around the glands (region C), scattered in the subepithelial regions of non-reticular epithelium (region B), and sporadically distributed in the interfollicular regions (region D). Interestingly, the distribution pattern of IgG ASCs in the pharyngeal tonsils closely mirrored that of IgA ASCs. The distribution densities of IgA and IgG ASCs in these four regions were significantly decreased in turn (P<0.05). However, IgA ASCs exhibited significantly higher densities than IgG ASCs in the same region (P<0.05). Age-related alterations indicated that the distribution densities of IgA and IgG ASCs in each region of the pharyngeal tonsils exhibited a trend of initially increasing and subsequently decreasing from young to old camels, reaching a peak in the pubertal group. As camels age, there was a significant decrease in the densities of IgA and IgG ASCs in all regions of the pharyngeal tonsils (P<0.05). The results demonstrate that the reticular epithelium and its subepithelial regions in the pharyngeal tonsils of Bactrian camels are the primary regions where IgA and IgG ASCs colonize and exert their immune functions. These regions play a pivotal role in inducing immune responses and defending against pathogen invasions in the pharyngeal tonsils. IgA ASCs may be the principal effector cells of the mucosal immune response in the pharyngeal tonsils of Bactrian camels. Aging significantly reduces the densities of IgA and IgG ASCs, while leaving their distribution patterns unaffected. These findings will provide valuable insights for further investigations into the immunomorphology, immunosenescence, and response mechanisms of the pharyngeal tonsils in Bactrian camels.

Dry environment on the expression of lacrimal gland S100A9, Anxa1, and Clu in rats via proteomics.

AIM: To investigate the underlying mechanism of dry environment (autumn dryness) affecting the lacrimal glands in rats. METHODS: Twenty Sprague-Dawley rats were randomly divided into two groups. The rats were fed in specific pathogen free environment as the control group (n=10), and the rats fed in dry environment as the dryness group (n=10). After 24d, lacrimal glands were collected from the rats. The tissues morphology was observed by hematoxylin-eosin (HE) staining. Tandem mass tags (TMT) quantitative proteomics analysis technology was used to screen the differential expressed proteins of lacrimal glands between the two groups, then bioinformatics analysis was performed. Further, the immunohistochemical (IHC) method was used to verify the target proteins. RESULTS: In dryness group, the lacrimal glands lobule atrophied, the glandular cavities enlarged, the sparse nuclear distribution and scattered inflammatory infiltration between the acinus were observed. The proteomics exhibited that a total of 195 up-regulated and 236 down-regulated differential expressed proteins screened from the lacrimal glands of rats. It was indicated that the biological processes (BP) of differential expressed proteins mainly included cell processes and single BP. The cellular compositions of differential expressed proteins mainly located in cells, organelles. The molecular functions of differential expressed proteins mainly included binding, catalytic activity. Moreover, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the differential expressed proteins mainly involved lysosome, complement and coagulation cascade, and ribosome pathway. The IHC result verified that the up-regulated expression proteins of Protein S100A9 (S100A9), Annexin A1 (Anxa1), and Clusterin (Clu) in lacrimal glands of rats in dryness group were higher than control group. CONCLUSION: The up-regulated expression proteins of S100A9, Anxa1, and Clu may be the potential mechanisms of dry eye symptoms caused by dry environment. This study provides clues of dry environments causing eye-related diseases for further studies.

Linear Electro-Optic Effect in 2D Ferroelectric for Electrically Tunable Metalens.

The advent of 2D ferroelectrics, characterized by their spontaneous polarization states in layer-by-layer domains without the limitation of a finite size effect, brings enormous promise for applications in integrated optoelectronic devices. Comparing with semiconductor/insulator devices, ferroelectric devices show natural advantages such as non-volatility, low energy consumption and high response speed. Several 2D ferroelectric materials have been reported, however, the device implementation particularly for optoelectronic application remains largely hypothetical. Here, the linear electro-optic effect in 2D ferroelectrics is discovered and electrically tunable 2D ferroelectric metalens is demonstrated. The linear electric-field modulation of light is verified in 2D ferroelectric CuInP2S6. The in-plane phase retardation can be continuously tuned by a transverse DC electric field, yielding an effective electro-optic coefficient rc of 20.28 pm V-1. The CuInP2S6 crystal exhibits birefringence with the fast axis oriented along its (010) plane. The 2D ferroelectric Fresnel metalens shows efficacious focusing ability with an electrical modulation efficiency of the focusing exceeding 34%. The theoretical analysis uncovers the origin of the birefringence and unveil its ultralow light absorption across a wide wavelength range in this non-excitonic system. The van der Waals ferroelectrics enable room-temperature electrical modulation of light and offer the freedom of heterogeneous integration with silicon and another material system for highly compact and tunable photonics and metaoptics.

In Vitro Stability and Pharmacokinetic Study of Pedunculoside and Its Beta-CD Polymer Inclusion Complex.

Pedunculoside, a triterpene saponin derived from various Ilex species, holds potential as a treatment for cardiovascular diseases. However, its clinical application is hindered by poor bioavailability, rapid elimination, and extensive intestinal metabolism to rotundic acid. To address these issues, a water-soluble inclusion complex of pedunculoside, namely, the beta-CD polymer inclusion complex of pedunculoside (pedunculoside-ßCDP), was prepared in this study, and a comparative in vitro stability and pharmacokinetic behavior study was performed between pedunculoside and pedunculoside-ßCDP. Both pedunculoside and pedunculoside-ßCDP exhibited the highest stability in simulated gastric fluid and simulated intestinal fluid but were readily metabolized when co-incubated with Bifidobacterium adolescentis and Bifidobacterium breve. An LC-MS/MS analytical method for the simultaneous determination of pedunculoside and rotundic acid in rat plasma was successfully established, validated, and applied to investigate the pharmacokinetic behavior after rats were intravenously administered with pedunculoside or pedunculoside-ßCDP. The results indicated that pedunculoside-ßCDP could significantly improve the pharmacokinetic profile of pedunculoside by increasing plasma exposure, retarding elimination, and reducing intestinal metabolism. This study enhances our understanding of pedunculoside-ßCDP's metabolic fate and pharmacokinetic properties and potentially advances its further research, development, and clinical application.

Ultrawide Spectra Camouflage Coatings from Metallic Flake Powder.

Ultrawide-spectra-compatible camouflage materials are imperative for military science and national security due to the continuous advancement of various sophisticated multispectral detectors. However, ultrawide spectra camouflage still has challenges, as the spectral requirements for different bands are disparate and even conflicting. This work demonstrates an ultrawide spectra camouflage material compatible with visible (VIS, 400-800 nm), infrared (IR, 3-5 and 8-14 µm), and microwave (S-Ku bands, 2-12 GHz). The carbon nanotubes adsorbed on porous anodic alumina/aluminum flake powder (CNTs@PAA/AFP) material for ultrawide spectra camouflage is composed of bioinspired porous alumina surface layers for low visible reflection and aluminum flake powder substrate for low infrared emissivity, while the surface of the porous alumina layers is loaded with carbon nanotubes for microwave absorption. Compared with previous low-emissivity materials, CNTs@PAA/AFP has omnidirectional low reflectance (Ravg = 0.29) and high gray scale (72%) in the visible band. Further, it exhibits low emissivity (ε3-5µm = 0.15 and ε8-14µm = 0.18) in the dual infrared atmospheric window, which reduces the infrared lock-on range by 59.6%/49.8% in the mid/far-infrared band at high temperatures (573 K). The infrared camouflage performance calculated from the radiation temperature of CNTs@PAA/AFP coatings is enhanced to over 65%, which is at least 4 times greater than that of its substrate. In addition, the CNTs@PAA/AFP coating achieves high microwave absorption (RLmin = -42.46 dB) and an effective absorption bandwidth (EAB = 7.43 GHz) in the microwave band (S-Ku bands) due to the enhancement of interfacial polarization and conductive losses. This study may introduce new insight and feasible methods for multispectral manipulation, electromagnetic signal processing, and thermal management via bioinspired structural design and fabrication.

Enhanced hyaline cartilage formation and continuous osteochondral regeneration via 3D-Printed heterogeneous hydrogel with multi-crosslinking inks.

The unique gradient structure and complex composition of osteochondral tissue pose significant challenges in defect regeneration. Restoration of tissue heterogeneity while maintaining hyaline cartilage components has been a difficulty of an osteochondral tissue graft. A novel class of multi-crosslinked polysaccharide-based three-dimensional (3D) printing inks, including decellularized natural cartilage (dNC) and nano-hydroxyapatite, was designed to create a gradient scaffold with a robust interface-binding force. Herein, we report combining a dual-nozzle cross-printing technology and a gradient crosslinking method to create the scaffolds, demonstrating stable mechanical properties and heterogeneous bilayer structures. Biofunctional assessments revealed the remarkable regenerative effects of the scaffold, manifesting three orders of magnitude of mRNA upregulation during chondrogenesis and the formation of pure hyaline cartilage. Transcriptomics of the regeneration site in vivo and scaffold cell interaction tests in vitro showed that printed porous multilayer scaffolds could form the correct tissue structure for cell migration. More importantly, polysaccharides with dNC provided a hydrophilic microenvironment. The microenvironment is crucial in osteochondral regeneration because it could guide the regenerated cartilage to ensure the hyaline phenotype.

The Effectiveness of Polyhexanide in Treating Wound Infections Due to Methicillin-Resistant Staphylococcus Aureus: A Prospective Analysis.

Purpose: Polyhexanide is a safe and effective wound care antiseptic commonly used in clinics as wound rinsing solution and gel. However, the efficacy of Polyhexanide in treatment of wound infected with MRSA (methicillin-resistant Staphylococcus aureus) is unknown. The aim of this study is to assess the effectiveness of polyhexanide with povidone iodine in treating wound infected with MRSA. Patients and Methods: A prospective analysis of 62 patients with wound infections, who were admitted to our department from 2016 to 2020, was conducted in order to assess the efficacy of different treatment approaches. The patients were divided into two groups: the experimental group and the control group. In the experimental group, 30 patients underwent treatment with a combination of diluted povidone iodine and polyhexanide immersion. Conversely, in the control group, 32 patients received treatment with diluted povidone iodine along with systemic antibiotic therapy. The time required for dressing changes, bacterial clearance rates, and the Bates-Jasen wound assessment tool (BWAT) scores were utilized as indicators to evaluate the effectiveness of the treatments. Results: In our study, the findings indicated that the experimental group exhibited a lesser number of days for the bacteria culture to turn negative compared to the control group, with statistical significance (p<0.05). Furthermore, the decline in the BWAT score was significantly greater in the experimental group than in the control group (p<0.05). However, no significant differences were observed in terms of dressing times and wound coverage between the two groups (p>0.05). Conclusion: Polyhexanide combined with povidone iodine can effectively remove MRSA infection in wounds and reduce antibiotic dosages.

Construction of an Axial Charge Transfer Channel Between Single-Atom Fe Sites and Nitrogen-Doped Carbon Supports for Boosting Oxygen Reduction.

The introduction of axial-coordinated heteroatoms in Fe─N─C single-atom catalysts enables the significant enhancement of their oxygen reduction reaction (ORR) performance. However, the interaction relationship between the axial-coordinated heteroatoms and their carbon supports is still unclear. In this work, a gas phase surface treatment method is proposed to prepare a series of X─Fe─N─C (X = O, P, and S) single-atom catalysts with axial X-coordination on graphitic-N-rich carbon supports. Synchrotron-based X-ray absorption near-edge structure spectra and X-ray photoelectron spectroscopy indicate the formation of an axial charge transfer channel between the graphitic-N-rich carbon supports and single-atom Fe sites by axial O atoms in O─Fe─N─C. As a result, the O─Fe─N─C exhibits excellent ORR performance with a half-wave potential of 0.905 V versus RHE and a high specific capacity of 884 mAh g-1 for zinc-air battery, which is superior to other X─Fe─N─C catalysts without axial charge transfer and the commercial Pt/C catalyst. This work not only demonstrates a general synthesis strategy for the preparation of single-atom catalysts with axial-coordinated heteroatoms, but also presents insights into the interaction between single-atom active sites and doped carbon supports.

Efficacy and safety of dabigatran and rivaroxaban in atrial fibrillation patients with impaired liver function: a multicenter retrospective cohort study.

BACKGROUND: The efficacy and safety of direct oral anticoagulants (DOACs) in atrial fibrillation (AF) patients with impaired liver function (ILF) have not been sufficiently studied. The aim of this study was to evaluate the efficacy and safety of DOACs for stroke prevention in patients with AF and ILF. METHOD: This study was based on data from 15 centers in China, including 4,982 AF patients. The patients were divided into 2 subgroups based on their liver function status: patients with normal liver function (NLF)(n = 4213) and patients with ILF (n = 769). Logistic regression analysis was used to investigate the risk of total bleeding, major bleeding, thromboembolism, and all-cause deaths in AF patients with NLF and ILF after taking dabigatran or rivaroxaban, respectively. RESULTS: Among AF patients treated with dabigatran or rivaroxaban, patients with ILF were associated with significantly higher major bleeding, compared with NLF patients (aOR: 4.797; 95% CI: 2.224-10.256; P < 0.001). In patients with NLF, dabigatran (n = 2011) had considerably lower risk of total bleeding than rivaroxaban (n = 2202) (aOR: 1.23; 95% CI: 1.002-1.513; P = 0.049). In patients with ILF, dabigatran (n = 321) significantly favored lower risks of major bleeding compared with rivaroxaban(n = 448) (aOR: 5.484; 95% CI: 1.508-35.269; P = 0.026). CONCLUSION: After using dabigatran or rivaroxaban, patients with ILF had remarkably increased risk of major bleeding compared with patients with NLF. In AF patients with NLF, dabigatran had the distinct strength of significantly reduced risk of total bleeding compared with rivaroxaban. In patients with AF and ILF, dabigatran use was associated with lower risk for major bleeding compared with rivaroxaban.

Metabolomics and HS-SPME-GC-MS-based analysis of quality succession patterns and flavor characteristics changes during the fermentation of Lycium barbarum and Polygonatum cyrtonema compound wine.

This work set out to investigate how the physicochemical markers, volatiles, and metabolomic characteristics of mixed fermented the fermentation of Lycium barbarum and Polygonatum cyrtonema compound wine (LPCW) from S. cerevisine RW and D. hansenii AS2.45 changed over the course of fermentation. HS-SPME-GC-MS combined with non-targeted metabolomics was used to follow up and monitor the fermentation process of LPCW. In total, 43 volatile chemical substances, mostly alcohols, esters, acids, carbonyl compounds, etc., were discovered in LPCW. After 30 days of fermentation, phenylethyl alcohol had increased to 3045.83 g/mL, giving off a rose-like fresh scent. The biosynthesis of valine, leucine, and isoleucine as well as the metabolism of alanine, aspartic acid, and glutamic acid were the major routes that led to the identification of 1385 non-volatile components in total. This study offers a theoretical foundation for industrial development and advances our knowledge of the fundamental mechanism underlying flavor generation during LPCW fermentation.

Riboflavin ameliorates intestinal inflammation via immune modulation and alterations of gut microbiota homeostasis in DSS-colitis C57BL/6 mice.

While there have been advancements in understanding the direct and indirect impact of riboflavin (B2) on intestinal inflammation, the precise mechanisms are still unknown. This study focuses on evaluating the effects of riboflavin (B2) supplementation on a colitis mouse model induced with 3% dextran sodium sulphate (DSS). We administered three different doses of oral B2 (VB2L, VB2M, and VB2H) and assessed its impact on various physiological and biochemical parameters associated with colitis. Mice given any of the three doses exhibited relative improvement in the symptoms and intestinal damage. This was evidenced by the inhibition of the pro-inflammatory cytokines TNF-α, IL-1ß, and CALP, along with an increase in the anti-inflammatory cytokine IL-10. B2 supplementation also led to a restoration of oxidative homeostasis, as indicated by a decrease in myeloperoxidase (MPO) and malondialdehyde (MDA) levels and an increase in reduced glutathione (GSH) and catalase (CAT) activities. B2 intervention showed positive effects on intestinal barrier function, confirmed by increased expression of tight junction proteins (occludin and ZO-1). B2 was linked to an elevated relative abundance of Actinobacteriota, Desulfobacterota, and Verrucomicrobiota. Notably, Verrucomicrobiota showed a significant increase in the VB2H group, reaching 15.03% relative abundance. Akkermansia exhibited a negative correlation with colitis and might be linked to anti-inflammatory function. Additionally, a remarkable increase in n-butyric acid, i-butyric acid, and i-valeric acid was reported in the VB2H group. The ameliorating role of B2 in gut inflammation can be attributed to immune system modulation as well as alterations in the gut microbiota composition, along with elevated levels of fecal SCFAs.