Fermentation of Pyropia spp. seaweed: a comprehensive review on processing conditions, biological activities and potential applications in the food industry.

Pyropia spp. seaweeds are delicious and nutritious red algae widely consumed for a long history. However, due to the non-digestibility of cell wall components by the human intestinal tract, the bioaccessibility of the intracellular bioactive compounds is low. The current industrial processing of Pyropia spp. food by drying and roasting cannot break down the cell wall; however, studies indicate that fermentation of Pyropia spp. by food-derived microorganisms is an efficient processing method to solve this problem. This paper reviews research on the fermentation of Pyropia spp., including the manufacturing process, alterations in chemical composition, flavor properties, bioactivities, and mechanisms. Furthermore, the limitations and opportunities for developing Pyropia spp. fermentation food are explored. Studies demonstrated that key metabolites of fermented Pyropia spp. were degraded polysaccharides, released phenolic compounds and flavonoids, and formed amino acids, which possessed bioactivities such as antioxidant, anti-glycation, anti-diabetic, lipid metabolism regulation beneficial to human health. The increased bioactivities implied the promoted bioaccessibility of intracellular components. Notably, fermentation positively contributed to the safety of Pyropia spp. food. In conclusion, benefits in nutrition, flavor, bioactivity, and safety suggest that fermentation technology has a promising future for application in Pyropia spp. food industry.

Pre-anoxic electro-stimulation enhanced simultaneous nitrification-denitrification in single-stage electrolysis-integrated sequencing batch biofilm reactor.

Simultaneous nitrification-denitrification (SND) is a promising nitrogen removal process. However, total nitrogen (TN) removal is limited due to unsatisfactory denitrification. This study demonstrated that short-time (1 h) pre-anoxic electro-stimulation significantly enhanced SND efficiency in the aerobic phase by promoting the proliferation of mixotrophic and heterotrophic denitrifiers. SND and TN removal efficiencies at the optimal electric current (EC) (0.02 A) were 85.6 % and 93.9 %, which were 39.1 % and 17.2 % higher than control. Microbial community analysis indicated that the abundance of mixotrophic and heterotrophic denitrifiers significantly increased. H2 generated in the electro-stimulation process induced the proliferation of mixotrophic denitrifiers. The weak EC (0.02 A) promoted the activity and growth of heterotrophic denitrifiers by accelerating electron transfer. They concurrently mediated heterotrophic denitrification to enhance SND efficiency. PICRUSt2 analysis revealed that the abundance of denitrifying genes dramatically surged. This study provides new insights into applying electrolysis to achieve advanced SND while minimizing electricity consumption.

Electrochemical promoted three-component reaction to unsymmetric thiosulfonates.

Compounds comprising S-S bonds serve as significant pharmacological scaffolds in medicinal chemistry and natural products. We have devised an efficient electrochemical method for the construction of asymmetric disulfide bonds, leading to the synthesis of unsymmetric thiosulfonates. Compared with existing synthesis methods, our work not only avoids the use of metals and oxidants, but also realizes the operation of a one-pot three-component method, which makes this strategy extremely attractive.

FGF4 ameliorates the liver inflammation by reducing M1 macrophage polarization in experimental autoimmune hepatitis.

BACKGROUND: The global prevalence of autoimmune hepatitis (AIH) is increasing due in part to the lack of effective pharmacotherapies. Growing evidence suggests that fibroblast growth factor 4 (FGF4) is crucial for diverse aspects of liver pathophysiology. However, its role in AIH remains unknown. Therefore, we investigated whether FGF4 can regulate M1 macrophage and thereby help treat liver inflammation in AIH. METHODS: We obtained transcriptome-sequencing and clinical data for patients with AIH. Mice were injected with concanavalin A to induce experimental autoimmune hepatitis (EAH). The mechanism of action of FGF4 was examined using macrophage cell lines and bone marrow-derived macrophages. RESULTS: We observed higher expression of markers associated with M1 and M2 macrophages in patients with AIH than that in individuals without AIH. EAH mice showed greater M1-macrophage polarization than control mice. The expression of M1-macrophage markers correlated positively with FGF4 expression. The loss of hepatic Fgf4 aggravated hepatic inflammation by increasing the abundance of M1 macrophages. In contrast, the pharmacological administration of FGF4 mitigated hepatic inflammation by reducing M1-macrophage levels. The efficacy of FGF4 treatment was compromised following the in vivo clearance of macrophage populations. Mechanistically, FGF4 treatment activated the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT)-signal pathway in macrophages, which led to reduced M1 macrophages and hepatic inflammation. CONCLUSION: We identified FGF4 as a novel M1/M2 macrophage-phenotype regulator that acts through the PI3K-AKT-signaling pathway, suggesting that FGF4 may represent a novel target for treating inflammation in patients with AIH.

Progesterone boosts abiraterone-driven target and NK cell therapies against glioblastoma.

INTRODUCTION: Glioblastoma (GBM) poses a significant challenge in oncology, with median survival times barely extending beyond a year due to resistance to standard therapies like temozolomide (TMZ). This study introduces a novel therapeutic strategy combining progesterone (Prog) and abiraterone (Abi) aimed at enhancing GBM treatment efficacy by modulating the tumor microenvironment and augmenting NK cell-mediated immunity. METHODS: We employed in vitro and in vivo GBM models to assess the effects of Prog and Abi on cell viability, proliferation, apoptosis, and the immune microenvironment. Techniques included cell viability assays, Glo-caspase 3/7 apoptosis assays, RNA-seq and qPCR for gene expression, Seahorse analysis for mitochondrial function, HPLC-MS for metabolomics analysis, and immune analysis by flow cytometry to quantify NK cell infiltration. RESULTS: Prog significantly reduced the IC50 of Abi in TMZ-resistant GBM cell, suggesting the enhanced cytotoxicity. Treatment induced greater apoptosis than either agent alone, suppressed tumor growth, and prolonged survival in mouse models. Notably, there was an increase in CD3-/CD19-/CD56+/NK1.1+ NK cell infiltration in treated tumors, indicating a shift towards an anti-tumor immune microenvironment. The combination therapy also resulted in a reduction of MGMT expression and a suppression of mitochondrial respiration and glycolysis in GBM cells. CONCLUSION: The combination of Prog and Abi represents a promising therapeutic approach for GBM, showing potential in suppressing tumor growth, extending survival, and modulating the immune microenvironment. These findings warrant further exploration into the clinical applicability of this strategy to improve outcomes for GBM patients.

Coupled Ni─Co Dual-Atom Catalyst for Guiding Sulfur and Lithium Evolutions in Lithium-Sulfur Batteries.

The kinetically retarded sulfur evolution reactions and notorious lithium dendrites as the major obstacles hamper the practical implementation of lithium-sulfur batteries (LSBs). Dual metal atom catalysts as a new model are expected to show higher activity by their rational coupling. Herein, the dual-atom catalyst with coupled Ni─Co atom pairs (Ni/Co-DAC) is designed successfully by programmed approaches. The Ni─Co atom pairs alter the local electron structure and optimize the coordination configuration of Ni/Co-DAC, leading to the coupling effect for promoting the interconversion of sulfur and guiding lithium plating/striping. The LSB delivers a remarkable capacity of 818 mA h g-1 at 3.0 C and a low degeneration rate of 0.053% per cycle over 500 cycles. Moreover, the LSB with a high sulfur mass loading of 6.1 mg cm-2 and lean electrolyte dosage of 6.0 µL mgS -1 shows a remarkable areal capacity of 5.7 mA h cm-2.

Direct Identification of O─O Bond Formation Through Three-Step Oxidation During Water Splitting by Operando Soft X-ray Absorption Spectroscopy.

Anionic redox allows the direct formation of O─O bonds from lattice oxygens and provides higher catalytic in the oxygen evolution reaction (OER) than does the conventional metal ion mechanism. While previous theories have predicted and experiments have suggested the possible O─O bond, it has not yet been directly observed in the OER process. In this study, operando soft X-ray absorption spectroscopy (sXAS) at the O K-edge and the operando Raman spectra is performed on layered double CoFe hydroxides (LDHs) after intercalation with [Cr(C2O4)3]3-, and revealed a three-step oxidation process, staring from Co2+ to Co3+, further to Co4+ (3d6L), and ultimately leading to the formation of O─O bonds and O2 evolution above a threshold voltage (1.4 V). In contrast, a gradual oxidation of Fe is observed in CoFe LDHs. The OER activity exhibits a significant enhancement, with the overpotential decreasing from 300 to 248 mV at 10 mA cm-2, following the intercalation of [Cr(C2O4)3]3- into CoFe LDHs, underscoring a crucial role of anionic redox in facilitating water splitting.

Injectable Regenerated Silk Fibroin Micro/Nanosphere with Enhanced Permeability and Stability for Osteoarthritis Therapy.

In the therapy of early-stage osteoarthritis, to accomplish full infiltration of subchondral bone and cartilage, and to target osteoclast and chondrocyte simultaneously remain challenges in biomaterials design. Herein, a novel hierarchical drug delivery system is introduced, with micrometer-scale outer layer spheres composed of regenerated silk fibroin, characterized by connected porous structure through the n-butanol and regenerated silk fibroin combined emulsion route and freezing method. The design effectively resists clearance from the joint cavity, ensuring stable delivery and prolonged residence time within the joint space. Additionally, the system incorporates phenylboronic acid-enriched silk fibroin nanoparticles, stabilized through chemical cross-linking, which encapsulate isoliquiritin derived from Glycyrrhiza uralensis. These nanoparticles facilitate complete penetration of the cartilage extracellular matrix, exhibit pH-responsive behavior, neutralize reactive oxygen species, and enable controlled drug release, thereby enhancing therapeutic efficacy. The in vitro and in vivo experiments both demonstrate that the composite micro/nanospheres not only inhibit osteoclastogenesis with bone loss in subchondral bone and osteophyte formation, but also mitigate chondrocytes apoptosis, reduce oxidative stress associated with cartilage degeneration, and ameliorate neuropathic hyperalgesia, with the underlying mechanisms being elucidated. The study indicates that such an injectable strategy combining organic biomaterials with Chinese medicine holds substantial promise for the treatment of early osteoarthritis.

Engineered mouse H1 promoter mutants with superior RNA polymerase III activity.

Vectors incorporating the human H1 (hH1) promoter are being applied for RNA interference (RNAi) experiments and genome editing. Although extensive studies have been conducted on the hH1 promoter, our understanding of the mouse H1 promoter remains limited. In this study, we predicted the 163 bp mouse H1 (mH1) promoter and 84 bp mouse H1 core (mH1 core) promoter through global alignment and detected its RNA polymerase II (Pol II) and III activities through the expression of the EGFP and the abundance of artificial sequence, which were generally slightly weaker than those of the hH1 promoter. Furthermore, to boost its Pol III activity, we engineered various promoter mutants by introducing mutations or systematically swapping elements. Surprisingly, the Pol II activity of mH1 core mut5 with AT stretch was at least 2-fold greater than that of the wild type, making it a potential candidate for target protein expression purposes. Fortunately, the Pol III activities of mH1 mut1 and mH1 core mut5 were at least 1.5 times stronger than those of the parental promoters in human and mouse cell lines on account of AT stretch, as did the mH1 mut4 with AT stretch and proximal sequence element (PSE) and TATA box insertion mutations. We highly recommend these three promoters as valuable supplements to the type 3 Pol III promoter toolbox.

The construction of ofloxacin detection in fish matrix based on a shark-derived single-domain antibody.

BACKGROUND: Due to the serious issue of ofloxacin (OFL) abuse, there is an increasingly urgent need for accurate and rapid detection of OFL. Immunoassay has become the "golden method" for detecting OFL in complex matrix beneficial to its applicability for a large-scale screening, rapidity, and simplicity. However, traditional antibodies used in immunoassay present challenges such as time-consuming preparation, unstable sensitivity and specificity, and difficulty in directional evolution. In this paper, we successfully developed an OFL detection method based on a shark-derived single-domain antibody (ssdAb) to address these issues. RESULTS: Using phage display technology and a heterologous expression system, OFL-specific clones 1O11, 1O13, 1O17, 1O19, 1O21, and 2O26 were successfully isolated and expressed in soluble form. Among all OFL-specific ssdAbs, the 1O17 ssdAb exhibited the highest binding affinity to OFL in a concentration-dependence manner. The limit of detection (IC10) of 1O17 ssdAb was calculated as 0.34 ng/mL with a detection range of 3.40-1315.00 ng/mL, and its cross reactivity with other analogs was calculated to be less than 5.98 %, indicating high specificity and sensitivity. Molecular docking results revealed that 100Trp and 101Arg located in the CDR3 region of 1O17 ssdAb were crucial for OFL binding. In fish matrix performance tests, the 1O17 ssdAb did not demonstrate severe matrix interference in OFL-negative fish matrix, achieving satisfactory recovery rates ranging from 83.04 % to 108.82 % with high reproducibility. SIGNIFICANCE: This research provides a new and efficient OFL detection recognition element with significant potential in immunoassay applications, broadening the application scenarios of ssdAbs. It offers valuable insights into the structure-activity relationship between ssdAbs and small molecules, laying a theoretical foundation for the further directional modification and maturation of ssdAbs in subsequent applications.

The association between frailty and the risk of mortality in critically ill congestive heart failure patients: findings from the MIMIC-IV database.

Background: Frailty is a severe, common co-morbidity associated with congestive heart failure (CHF). This retrospective cohort study assesses the association between frailty and the risk of mortality in critically ill CHF patients. Methods: Eligible patients with CHF from the Medical Information Base for Intensive Care IV database were retrospectively analyzed. The frailty index based on laboratory tests (FI_Lab) index was calculated using 33 variables to assess frailty status. The primary outcomes were in-hospital mortality and one-year mortality. The secondary outcomes were the incidence of acute kidney injury (AKI) and the administration of renal replacement therapy (RRT) in patients with concurrent AKI. Survival disparities among the FI_Lab subgroups were estimated with Kaplan-Meier survival analysis. The association between the FI_Lab index and mortality was examined with Cox proportional risk modeling. Results: A total of 3273 adult patients aged 18 years and older were enrolled in the study, with 1820 men and 1453 women included. The incidence rates of in-hospital mortality and one-year mortality rate were 0.96 per 1,000 person-days and 263.8 per 1,000 person-years, respectively. Multivariable regression analysis identified baseline FI_Lab > 0.45 as an independent risk factor predicting in-hospital mortality (odds ratio = 3.221, 95% CI 2.341-4.432, p < 0.001) and one-year mortality (hazard ratio=2.152, 95% CI: 1.730-2.678, p < 0.001). In terms of predicting mortality, adding FI_Lab to the six disease severity scores significantly improved the overall performance of the model (all p < 0.001). Conclusions: We established a positive correlation between the baseline FI_Lab and the likelihood of adverse outcomes in critical CHF patients. Given its potential as a reliable prognostic tool for such patients, further validation of FI_Lab across multiple centers is recommended for future research.

Impact of omega-3 fatty acids on hypertriglyceridemia, lipidomics, and gut microbiome in patients with type 2 diabetes.

BACKGROUND: Fish oil (FO), a mixture of omega-3 fatty acids mainly comprising docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), has been recommended for patients with type 2 diabetes (T2D) and hypertriglyceridemia. However, its effects on lipidomic profiles and gut microbiota and the factors influencing triglyceride (TG) reduction remain unclear. METHODS: We conducted a 12-week, randomized, double-blind, placebo-controlled trial in 309 Chinese patients with T2D with hypertriglyceridemia (ClinicalTrials.gov: NCT03120299). Participants were randomly assigned (1:1) to receive either 4 g FO or corn oil for 12 weeks. The primary outcome was changes in serum TGs and the lipidomic profile, and the secondary outcome included changes in the gut microbiome and other metabolic variables. FINDINGS: The FO group had significantly better TG reduction (mean [95% confidence interval (CI)]: -1.51 [-2.01, -1.01] mmol/L) compared to the corn oil group (-0.66 [-1.15, -0.16] mmol/L, p = 0.02). FO significantly altered the serum lipid profile by reducing low-unsaturated TG species and increasing those containing DHA or EPA. FO had minor effects on gut microbiota, while baseline microbial features predicted the TG response to FO better than phenotypic or lipidomic features, potentially mediated by specific lipid metabolites. A total of 9 lipid metabolites significantly mediated the link between 4 baseline microbial variables and the TG response to FO supplementation. CONCLUSIONS: Our findings demonstrate differential impacts of omega-3 fatty acids on lipidomic and microbial profiles in T2D and highlight the importance of baseline gut microbiota characteristics in predicting the TG-lowering efficacy of FO. FUNDING: This study was funded by the National Nature Science Foundation.

Astragaloside IV Ameliorates Colonic Adenomatous Polyps Development by Orchestrating Gut Bifidobacterium and Serum Metabolome.

Astragaloside IV (AS-IV), a natural triterpenoid isolated from Astragalus membranaceus, has been used traditionally in Chinese medicine. Previous studies have highlighted its benefits against carcinoma, but its interaction with the gut microbiota and effects on adenomatous polyps are not well understood. This present study investigates the effects of AS-IV on colonic adenomatous polyp (CAP) development in high-fat-diet (HFD) fed [Formula: see text] mice. [Formula: see text] mice were fed an HFD with or without AS-IV or Naringin for 8 weeks. The study assessed CAP proliferation and employed 16S DNA-sequencing and untargeted metabolomics to explore correlations between microbiome and metabolome in CAP development. AS-IV was more effective than Naringin in reducing CAP development, inhibiting colonic proinflammatory cytokines (IL-1[Formula: see text], IL-6, and TNF-[Formula: see text]), tumor associated biomarkers (c-Myc, Cyclin D1), and Wnt/[Formula: see text]-catenin pathway proteins (Wnt3a, [Formula: see text]-catenin). AS-IV also inhibited the proliferative capabilities of human colon cancer cells (HT29, HCT116, and SW620). Multiomics analysis revealed AS-IV increased the abundance of beneficial genera such as Bifidobacterium pseudolongum and significantly modulated serum levels of certain metabolites including linoleate and 2-trans,6-trans-farnesal, which were significantly correlated with the number of CAP. Finally, the anti-adenoma efficacy of AS-IV alone was significantly suppressed post pseudoaseptic intervention in HFD-fed [Formula: see text] mice but could be reinstated following a combined with Bifidobacterium pseudolongum transplant. AS-IV attenuates CAP development in HFD-fed [Formula: see text] mice by regulating gut microbiota and metabolomics, impacting the Wnt3a/[Formula: see text]-catenin signaling pathway. This suggests a potential new strategy for the prevention of colorectal cancer, emphasizing the role of gut microbiota in AS-IV's antitumor effects.

Multi-resonance thermally activated delayed fluorescence polymers for high-efficiency and narrowband solution-processed green OLEDs.

A series of green multi-resonance thermally activated delayed fluorescence polymeric emitters featuring conjugation-interrupted main chains were facilely prepared via metal-free superacid-catalyzed Friedel-Crafts polyhydroxyalkylation. These emitters exhibited photoluminescence quantum yields of up to 76% and small full-widths at half maximum of 35-38 nm in toluene. The corresponding solution-processed OLEDs achieved an excellent maximum external quantum efficiency of 19.4%, with CIE coordinates of (0.20, 0.62).

[Clinical Significance of the Levels of Peripheral Blood Tregs and Cytokines IL-35, TGF-ß and IL-10 in Hemophilia A Patients with Fâ § Inhibitor].

OBJECTIVE: To explore the levels of regulatory T cells (Tregs) and cytokines IL-35, TGF-ß and IL-10 in peripheral blood of hemophilia A(HA) patients with FⅧ inhibitor and their clinical significance. METHODS: 43 HA patients admitted to the Hematology Department of the Affiliated Hospital of North China University of Science and Technology from October 2019 to December 2020 were selected, including 6 cases with FⅧ inhibitor and 37 cases without FⅧ inhibitor. In addition, 20 healthy males who underwent physical examinations were selected as healthy controls. Flow cytometry was used to detect the levels of CD4 + CD25 + CD127 - Tregs in peripheral blood of the HA patients and healthy controls, and ELISA assay was used to detect the expression levels of IL-35, TGF-ß and IL-10 in serum, and their differences between different groups were compared. RESULTS: Compared with the healthy control group, the level of Tregs in HA patients was decreased, and the level of Tregs in the FⅧ inhibitor positive group was the lowest, the difference was statistically significant (P <0.05). There was no significant difference in the expression level of Tregs in HA patients of different severity levels. The serum IL-35, TGF-ß, and IL-10 levels in both FⅧ inhibitor negative and positive groups were significantly lower than those in healthy control group, and those in FⅧ inhibitor positive group were significantly lower than those in FⅧ inhibitor negative group (all P <0.05). CONCLUSION: The decrease of Tregs, IL-35, TGF-ß, and IL-10 levels in HA patients may be related to the formation of FⅧ inhibitors.

Impact of 25 Years of Mobile Health Tools for Pain Management in Patients With Chronic Musculoskeletal Pain: Systematic Review.

BACKGROUND: Mobile technologies are increasingly being used in health care and public health practice for patient communication, monitoring, and education. Mobile health (mHealth) tools have also been used to facilitate adherence to chronic musculoskeletal pain (CMP) management, which is critical to achieving improved pain outcomes, quality of life, and cost-effective health care. OBJECTIVE: The aim of this systematic review was to evaluate the 25-year trend of the literature on the adherence, usability, feasibility, and acceptability of mHealth interventions in CMP management among patients and health care providers. METHODS: We searched the PubMed, Cochrane CENTRAL, MEDLINE, EMBASE, and Web of Science databases for studies assessing the role of mHealth in CMP management from January 1999 to December 2023. Outcomes of interest included the effect of mHealth interventions on patient adherence; pain-specific clinical outcomes after the intervention; and the usability, feasibility, and acceptability of mHealth tools and platforms in chronic pain management among target end users. RESULTS: A total of 89 articles (26,429 participants) were included in the systematic review. Mobile apps were the most commonly used mHealth tools (78/89, 88%) among the included studies, followed by mobile app plus monitor (5/89, 6%), mobile app plus wearable sensor (4/89, 4%), and web-based mobile app plus monitor (1/89, 1%). Usability, feasibility, and acceptability or patient preferences for mHealth interventions were assessed in 26% (23/89) of the studies and observed to be generally high. Overall, 30% (27/89) of the studies used a randomized controlled trial (RCT), cohort, or pilot design to assess the impact of the mHealth intervention on patients' adherence, with significant improvements (all P<.05) observed in 93% (25/27) of these studies. Significant (judged at P<.05) between-group differences were reported in 27 of the 29 (93%) RCTs that measured the effect of mHealth on CMP-specific clinical outcomes. CONCLUSIONS: There is great potential for mHealth tools to better facilitate adherence to CMP management, and the current evidence supporting their effectiveness is generally high. Further research should focus on the cost-effectiveness of mHealth interventions for better incorporating these tools into health care practices. TRIAL REGISTRATION: International Prospective Register of Systematic Reviews (PROSPERO) CRD42024524634; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=524634.

An artificially evolved gene for herbicide-resistant rice breeding.

Discovering and engineering herbicide-resistant genes is a crucial challenge in crop breeding. This study focuses on the 4-hydroxyphenylpyruvate dioxygenase Inhibitor Sensitive 1-Like (HSL) protein, prevalent in higher plants and exhibiting weak catalytic activity against many ß-triketone herbicides (ß-THs). The crystal structures of maize HSL1A complexed with ß-THs were elucidated, identifying four essential herbicide-binding residues and explaining the weak activity of HSL1A against the herbicides. Utilizing an artificial evolution approach, we developed a series of rice HSL1 mutants targeting the four residues. Then, these mutants were systematically evaluated, identifying the M10 variant as the most effective in modifying ß-THs. The initial active conformation of substrate binding in HSL1 was also revealed from these mutants. Furthermore, overexpression of M10 in rice significantly enhanced resistance to ß-THs, resulting in a notable 32-fold increase in resistance to methyl-benquitrione. In conclusion, the artificially evolved M10 gene shows great potential for the development of herbicide-resistant crops.