Berberine alleviates inflammation and suppresses PLA2-COX-2-PGE2-EP2 pathway through targeting gut microbiota in DSS-induced ulcerative colitis.

Berberine, isolated from Coptis chinensis and Phellodendron amurense, can attenuate colonic injury and modulate gut microbiota disorders in ulcerative colitis (UC). However, the mechanism and causal relationship between gut microbiota and the efficacy of Berberine on UC are still unclear, which were investigated by pseudo-germ-free (PGF) mice, 16S rRNA gene analysis and transcriptome analysis in this study. The results demonstrated that Berberine improved gut microbiota disorders, colon damage, tight-junction proteins, inflammatory and anti-inflammatory cytokines in DSS-induced colitis mice with intact gut microbiota but not in PGF mice. Besides, immune-related and inflammation-related pathways were closely related to the efficacy that Berberine alleviated colitis by regulating gut microbiota. Furthermore, Berberine reduced PGE2, PLA2, COX-2, Ptges, EP2 and p-Stat3 only in colitis mice with intact gut microbiota. In summary, our study confirms that Berberine inhibits PLA2-COX-2-PGE2-EP2 pathway in UC through gut microbiota, leading to the alleviation of inflammation in colon, which further elucidates the underlying mechanism and promotes the application of Berberine in UC.

Reduction of Backward Scatterings at the Low-Coherence Kunwu Laser Facility.

We report the first experimental observation on the reduction of backward scatterings by an instantaneous broadband laser with 0.6% bandwidth in conditions of interest for inertial confinement fusion at the low-coherence Kunwu laser facility. The backscatter of stimulated Brillouin scattering (SBS) was robustly reduced by half at intensities of 1-5×10^{14} W/cm^{2} with the 0.53-µm broadband laser in comparison with the monochromatic laser. As SBS dominates energy loss of laser-plasma interactions, the reduction of that demonstrates the enhancement of laser-target coupling by the use of broadband laser. The mitigation of filamentation leads to the reduction of stimulated Raman backscattering at low intensities. In addition, the three-halves harmonic emission was reduced with the broadband laser as well.

Identification and Function Analysis of Novel Hypoglycemic and Antioxidant Peptides from Chickpea.

Chickpea is rich in protein and has been demonstrated to possess hypoglycaemic effects. However, the specific bioactive ingredients and mechanisms underlying their hypoglycaemic effects remain unclear. In this study, enzymatic hydrolysis and gel permeation chromatography were used to extract chickpea bioactive peptide (CBP) from chickpea protein. One of the products, CBP-75-3, was found to inhibit α-glucosidase (GAA) activity and significantly increase the viability of insulin resistant (IR) cells. Moreover, CBP-75-3 significantly increased the rate of glucose consumption and glycogen synthesis in IR-HepG2 cells. Moreover, CBP-75-3 decreased the levels of malondialdehyde and increased the levels of superoxide dismutase, glutathione, and glutathione peroxidase. Subsequently, 29 novel bioactive peptides in CBP-75-3 were identified by LC‒MS/MS, and the potential hypoglycaemic targets of these novel bioactive peptides were investigated using molecular docking. Based on the results, the residues of the novel bioactive peptides interact with GAA through hydrogen bonding (especially LLR, FH, RQLPR, KGF and NFQ by binding to the substrate binding pocket or the active centre of GAA), thereby inhibiting GAA activity and laying a foundation for its hypoglycaemic activity. In short, the novel bioactive peptides isolated and identified from chickpea can effectively exert hypoglycaemic effects and increase the antioxidant capacity of IR-HepG2 cells. This study reveals that CBP-75-3, a natural hypoglycaemic ingredient, has potential for applications in functional foods and provides a theoretical basis for the development and application of CBP in the future.

Effect of phosphoric acid additive on the electrolyte of all-vanadium flow batteries.

A phosphoric acid additive with an optimal concentration of 0.1 M can vastly promote the diffusion kinetics of the redox reaction between V(IV) and V(V) without a significant decline in energy efficiency for 300 cycles, and maintain the high-temperature stability (55 °C) of an electrolyte at a high state of charge (SOC) of 70% over the course of 30 days.

A Bivalent Aptamer-Based DNA Agonist for EGFR Signaling Effectively Alleviates Ulcerative Colitis In Vivo.

While epidermal growth factor (EGF) shows promise in addressing the clinical manifestations of intestinal ulcerative diseases by activating the EGF receptor (EGFR)-mediated cell signaling, its clinical application is hampered by poor protein hydrolytic stability, low thermostability, and difficulty in modification. The development of a novel EGFR agonist for ulcerative colitis remains an urgent need, necessitating innovative solutions to overcome the limitations of current therapies via recombinant EGF protein. Herein, we introduce a novel DNA agonist for EGFR, Dimer-YL, which employs a bivalent aptamer to induce stable receptor dimerization, thereby activating the EGFR signaling and related cell behaviors. Dimer-YL has been demonstrated to recapitulate the EGF-promoted cellular behaviors, including proliferation and migration, as well as repair the damage of intercellular tight junctions. Furthermore, our findings demonstrate the potent therapeutic function of Dimer-YL in alleviating DSS-induced ulcerative colitis in vivo. Together, the present work has revealed Dimer-YL as an innovative DNA molecule for effective EGFR activation, offering promise for the development of EGFR-agonistic agents for therapeutic purposes.

Insights into the biosynthesis of palladium nanoparticles for oxygen reduction reaction by genetically engineered bacteria of Shewanella oneidensis MR-1.

Owing to the increasing need for green synthesis and environmental protection, the utilization of biological organism-derived carbons as supports for noble-metal electrocatalysts has garnered public interest. Nevertheless, the mechanism by which microorganisms generate nanometals has not been fully understood yet. In the present study, we used genetically engineered bacteria of Shewanella oneidensis MR-1 (∆SO4317, ∆SO4320, ∆SO0618 and ∆SO3745) to explore the effect of surface substances including biofilm-associated protein (bpfA), protein secreted by type I secretion systems (TISS) and type II secretion systems (T2SS), and lipopolysaccharide in microbial synthesis of metal nanoparticles. Results showed Pd/∆SO4317 (the catalyst prepared with the mutant ∆SO4317) shows better performance than other biocatalysts and commercial Pd/C, where the mass activity (MA) and specific activity (SA) of Pd/∆SO4317 are 3.1 and 2.1 times higher than those of commercial Pd/C, reaching 257.49 A g-1 and 6.85 A m-2 respectively. It has been found that the exceptional performance is attributed to the smallest particle size and the presence of abundant functional groups. Additionally, the absence of biofilms has been identified as a crucial factor in the formation of high-quality bio-Pd. Because the absence of biofilm can minimize metal agglomeration, resulting in uniform particle size dispersion. These findings provide valuable mechanical insights into the generation of biogenic metal nanoparticles and show potential industrial and environmental applications, especially in accelerating oxygen reduction reactions.

Rapidly enrichment and detection of per-and polyfluoroalkyl substances in foods using a novel bifunctional covalent organic framework.

Per- and polyfluoroalkyl substances (PFASs) are extensively found in foods, posing potential toxicity to humans. Therefore, rapid analysis and monitoring of PFASs in foods are crucial for public health and also a challenge. To detect trace PFASs in foods, construction of sorbents with multiple interactions could be an effective approach. Herein, a cationic-fluorinated covalent organic framework (CF-COF) was prepared by post-modification and used as a magnetic solid-phase extraction adsorbent for adsorption of PFASs. By combining magnetic solid-phase extraction based on CF-COF with liquid chromatography-tandem mass spectrometry (LC - MS/MS), a novel method was developed for determination of eight long-chain PFASs in foods. Under optimized conditions, the method exhibited low detection limits (0.003-0.019 ng/g) and satisfactory recovery rates (73.5-118%) for PFASs. This study introduces a novel idea for the development of adsorbents targeting PFASs, along with a new analytical method for monitoring of PFASs in foods.

Parabacteroides distasonis-Derived Outer Membrane Vesicles Enhance Antitumor Immunity Against Colon Tumors by Modulating CXCL10 and CD8+ T Cells.

Purpose: Given the potent immunostimulatory effects of bacterial outer membrane vesicles (OMVs) and the significant anti-colon tumor properties of Parabacteroides distasonis (Pd), this study aimed to elucidate the role and potential mechanisms of Pd-derived OMVs (Pd-OMVs) against colon cancer. Methods: This study isolated and purified Pd-OMVs from Pd cultures and assessed their characteristics. The effects of Pd-OMVs on CT26 cell uptake, proliferation, and invasion were investigated in vitro. In vivo, a CT26 colon tumor model was used to investigate the anti-colon tumor effects and underlying mechanisms of Pd-OMVs. Finally, we evaluated the biosafety of Pd-OMVs. Results: Purified Pd-OMVs had a uniform cup-shaped structure with an average size of 165.5 nm and a zeta potential of approximately -9.56 mV, and their proteins were associated with pathways related to immunity and apoptosis. In vitro experiments demonstrated that CT26 cells internalized the Pd-OMVs, resulting in a significant decrease in their proliferation and invasion abilities. Further in vivo studies confirmed the accumulation of Pd-OMVs in tumor tissues, which significantly inhibited the growth of colon tumors. Mechanistically, Pd-OMVs increased the expression of CXCL10, promoting infiltration of CD8+ T cells into tumor tissues and expression of pro-inflammatory factors TNF-α, IL-1ß, and IL-6. Notably, Pd-OMVs demonstrated a high level of biosafety. Conclusion: This paper elucidates that Pd-OMVs can exert significant anti-colon tumor effects by upregulating the expression of the chemokine CXCL10, thereby increasing the infiltration of CD8+ T cells into tumors and enhancing antitumor immune responses. This suggests that Pd-OMVs may be developed as a novel nanoscale potent immunostimulant with great potential for application in tumor immunotherapy. As well as developed as a novel nano-delivery carrier for combination with other antitumor drugs.

The influence of emerging atmospheric organophosphorus flame retardants from land source emissions on the East China Sea.

Organophosphate flame retardants (OPFRs) pose a new challenge to the marine environment due to their toxicity and persistence. This study explores the contributions of OPFR emissions from different land sources and sectors to its contamination of the East China Sea (ECS) using a novel atmospheric transport model（ChnMETOP）for POPs and a marine food web model. The results show that the major land sources causing OPFR pollution in the ECS were situated in Yangtze River Delta (YRD) and middle reach areas of China's Yangtze River, confirming that source proximity made most significant contributions to OPFR pollution in the ECS. Among those OPFR emission sectors, industrial emissions accounted for the highest modeled OPFR levels in the seawaters, followed by the OPFR usage process in textile, plastic, and rubber products. Assessment of bioaccumulation of OPFR in the marine food web of the ECS and the potential risk in commercial fish consumers reveals lower exposure risk via dietary fish ingestion. However, the risk might increase if OPFRs are continuously bioaccumulated in the biotic and released into the abiotic marine environment. This study simultaneously identified both the source locations and emission sectors, thereby providing important policy implications in mitigating OPFR pollution in the ECS marine environment.

Multiple-component covalent organic frameworks for simultaneous extraction and determination of multitarget pollutants in sea foods.

Persistent organic pollutants (POPs), such as perfluoroalkyl and polyfluoroalkyl substances (PFASs), polychlorinated biphenyls (PCBs), and bisphenols (BPs), have been raising global concerns due to their toxic effects on environment and human health. The monitoring of residues of POPs in seafood is crucial for assessing the accumulation of these contaminants in the study area and mitigating potential risks to human health. However, the diversity and complexity of POPs in seafood present significant challenges for their simultaneous detection. Here, a novel multi-component fluoro-functionalized covalent organic framework (OH-F-COF) was designed as SPE adsorbent for simultaneous extraction POPs. On this basis, the recognition and adsorption mechanisms were investigated by molecular simulation. Due to multiple interactions and large specific surface area, OH-F-COF displayed satisfactory coextraction performance for PFASs, PCBs, and BPs. Under optimized conditions, the OH-F-COF sorbent was employed in a strategy of simultaneous extraction and stepwise elution (SESE), in combination with HPLC-MS/MS and GC-MS method, to effectively determined POPs in seafood collected from coastal areas of China. The method obtained low detection limits for BPs (0.0037 -0.0089 ng/g), PFASs (0.0038 -0.0207 ng/g), and PCBs (0.2308 -0.2499 ng/g), respectively. This approach provided new research ideas for analyzing and controlling multitarget POPs in seafood. ENVIRONMENTAL IMPLICATIONS: Persistent organic pollutants (POPs), such as perfluoroalkyl and polyfluoroalkyl substances (PFASs), polychlorinated biphenyls (PCBs), and bisphenols (BPs), have caused serious hazards to human health and ecosystems. Hence, there is a need to develop a quantitative method that can rapidly detect POPs in environmental and food samples. Herein, a novel multi-component fluorine-functionalized covalent organic skeletons (OH-F-COF) were prepared at room temperature, and served as adsorbent for POPs. The SESE-SPE strategy combined with chromatographic techniques was used to achieve a rapid detection of POPs in sea foods from the coastal provinces of China. This method provides a valuable tool for analyzing POPs in environmental and food samples.

Construction of dual-chiral covalent organic frameworks for enantioselective separation.

Developing novel chiral stationary phases (CSPs) with versatility is of great importance in enantiomer separation. This study fabricated a dual-chiral covalent organic framework (PA-CA COF) via successive post-synthetic modifications. The chiral trans-1,2-cyclohexanediamine (CA) and (D)-penicillamine (PA) groups were periodically aligned within nanochannels of the COF, allowing selective recognition of enantiomers through intermolecular interactions. It can be a versatile high-performance liquid chromatography (HPLC) CSP for separating a wide range of enantiomers, including chiral pharmaceutical intermediates and chiral drugs. With separation performance comparable to commercial chiral columns and even greater versatility, the PA-CA COF@SiO2 column held promise for practical applications. Chiral separation results combined with molecular simulation indicated that the mixed mode of PA and CA resulted in the broad separation capability of PA-CA COF. The introduction of the dual-chiral COFs concept opens up a new avenue for chiral recognition and separation, holding great potential for practical enantiomer separation.

Gallic acid attenuates murine ulcerative colitis by promoting group 3 innate lymphocytes, affecting gut microbiota, and bile acid metabolism.

Gallic acid (GA), a plant phenol that is widely distributed in fruits and vegetables, and exhibits a protective role against ulcerative colitis (UC). UC is an inflammatory disease characterized by immune response disorders. However, the role and mechanism of action of GA in gut immunity remain unknown. Here, we observed that GA treatment improved enteritis symptoms, decreased the concentrations of cytokines TNF-α, IFN-γ, IL-6, IL-17A, and IL-23, increased the concentrations of cytokines IL-10, TGF-ß and IL-22, and increased the proportion of group 3 innate lymphoid cells (ILC3) in mesenteric lymph nodes and lamina propria. However, GA did not upregulate ILC3 or impair UC in antibody-treated sterile mice. Notably, transplantation of fecal bacteria derived from GA-treated UC mice, instead of UC mice, increased ILC3 levels. Therefore, we analyzed the gut microbiota and related metabolites to elucidate the mechanism promoting ILC3. We determined that GA treatment altered the diversity of the gut microbiota and activated the bile acid (BA) metabolic pathway. We evaluated three BAs, namely, UDCA, isoalloLCA, and 3-oxoLCA that were significantly upregulated after GA treatment, improved UC symptoms, and elevated the proportion of ILC3 in vivo and in vitro. Collectively, these data indicate that GA attenuates UC by elevating ILC3 proportion, regulating the gut microbiota, and impacting BA metabolism. Additionally, we highlight the modulatory effects of BAs on ILC3 for the first time. Our findings provide novel insights into the multiple roles of GA in alleviating UC and provide a mechanistic explanation that supports the dietary nutrition in UC therapy.

Lactobacillus acidophilus and its metabolite ursodeoxycholic acid ameliorate ulcerative colitis by promoting Treg differentiation and inhibiting M1 macrophage polarization.

Lactobacillus acidophilus (LA) is a common clinical probiotic that improves ulcerative colitis (UC) by restoring intestinal immune balance. However, the interaction of LA with the gut microbiota and its metabolites in the treatment of UC remains unknown. Therefore, this study seeks to elucidate whether the gut microbiota and its metabolites act as pivotal effectors in LA's therapeutic mechanisms and how precisely they modulate intestinal immunity. In this study, we verified that LA can obviously ameliorate the disease severity, and regulate intestinal immune disorders in UC mice. Subsequently, antibiotic (ABX)-mediated depletion of the gut microflora demonstrated that the therapeutic efficiency of LA was closely associated with gut microbiota. In addition, the results of metabolomics revealed that ursodeoxycholic acid (UDCA), a metabolite of intestinal flora, may be a potential effector molecule mediating therapeutic effects of LA. Indeed, we found that UDCA can improve the macro pathological characteristics of UC mice, and through a comprehensive set of in vivo and in vitro experiments, we discovered that UDCA exerts dual effects on immune regulation. Firstly, it promotes the differentiation of Treg cells, resulting in increased secretion of anti-inflammatory cytokines. Secondly, UDCA inhibits the polarization of M1 macrophages, effectively reducing the secretion of pro-inflammatory cytokines. Moreover, we found that UDCA regulation of immune response is directly related to the RapGap/PI3K-AKT/NF-κB signaling pathway. In conclusion, LA and its metabolite, UDCA, may treat UC by activating the RapGap/PI3K-AKT/NF-κB signaling pathway and modulating Treg cells and M1 macrophages. All in all, our findings highlight the potential of microbial metabolites in enhancing probiotic for UC treatment.

Laboratory evidence of Weibel magnetogenesis driven by temperature gradient using three-dimensional synchronous proton radiography.

The origin of the cosmic magnetic field remains an unsolved mystery, relying not only on specific dynamo processes but also on the seed field to be amplified. Recently, the diffuse radio emission and Faraday rotation observations reveal that there has been a microgauss-level magnetic field in intracluster medium in the early universe, which places strong constraints on the strength of the initial field and implies the underlying kinetic effects; the commonly believed Biermann battery can only provide extremely weak seed of 10-21 G. Here, we present evidence for the spontaneous Weibel-type magnetogenesis in laser-produced weakly collisional plasma with the three-dimensional synchronous proton radiography, where the distribution anisotropy directly arises from the temperature gradient, even without the commonly considered interpenetrating plasmas or shear flows. This field can achieve sufficient strength and is sensitive to Coulomb collision. Our results demonstrate the importance of kinetics in magnetogenesis in weakly collisional astrophysical scenarios.