Punicic acid ameliorates obesity-related hyperlipidemia and fatty liver in mice via regulation of intestinal flora and lipopolysaccharide-related signaling pathways.

Punicic acid (PA), mainly found in pomegranate seed oil (PSO), has attracted increasing attention due to its potential to mitigate obesity. The regulation of intestinal microflora was identified as a crucial factor and an effective strategy to reverse obesity-related hyperlipidemia and non-alcoholic fatty liver disease (NAFLD). To assess the impact of PSO on hyperlipidemia related to obesity, we investigated the hepatic lipid status and gut microbiota regulation in mice over 13 weeks of feeding a high-fructose high-fat diet (HFHFD). Serum lipid markers, including TG, TC and LDL-C, were markedly reduced in hyperlipidemic mice. PSO supplementation reduced hepatic lipid accumulation and steatosis, inhibited the expression of pro-inflammatory mediators (including IL-6 and IL-1ß), and restored the normal levels of the anti-inflammatory cytokine IL-10. In addition, PSO also alleviated oxidative stress and increased T-AOC and SOD activities, as well as GSH levels, while reducing the MDA content in the liver of HFHFD-fed mice. The activation of TLR4/MyD88/NF-κB and TLR4/IL-22/STAT3 signaling pathways in the liver due to the HFHFD was also evidently inhibited by PSO. Furthermore, supplementation of PSO ameliorated the HFHFD-induced dysbiosis of intestinal microflora, resulting in a markedly increased proportion of Muribaculaceae, a decreased ratio of Blautia, and elevated levels of microbiota-derived short-chain fatty acids (SCFAs). Moreover, the expression of tight junction proteins correlated with intestinal barrier function was notably restored in the colon. The collected results indicate that PSO may be an effective nutraceutical ingredient for attenuating lipid metabolic disorders.

Identification and Characterization of a Potential Probiotic, Clostridium butyricum G13, Isolated from the Intestine of the Mud Crab (Scylla paramamosain).

The butyrate-producing bacterium Clostridium butyricum has been proven to be important in improving the growth and health benefits of aquatic animals. In this study, C. butyricum G13 was isolated for the first time from the gut of the mud crab (Scylla paramamosain). The results of this study showed that C. butyricum G13 could produce a high concentration of butyric acid and grow well in a wide range of pHs (4 to 9) and NaCl (1 to 2.5%) and bile salt (0.2 to 1.0%) concentrations. In vitro characterization revealed that C. butyricum G13 is a Gram-positive and gamma-hemolytic bacterium sensitive to most antibiotics and shows hydrophobicity and the capacity to degrade starch. In vitro fermentation using mud crab gut contents showed that C. butyricum G13 alone or in combination with galactooligosaccharides (GOS) and/or resistant starch (RS) significantly increased butyric acid production and beneficially affected the abundance and diversity of intestinal microbiota. In addition, C. butyricum G13 can improve the survival rate of mud crabs and effectively maintain the normal structure of gut morphology after infection with Vibrio parahaemolyticus. In conclusion, C. butyricum G13 can be considered a potential probiotic that improves the immune capacity and confers health benefits on mud crabs. IMPORTANCE With the development of society, more and more aquatic animals are demanded. Intensification in the aquaculture scale is facing problems, such as disease outbreaks, eutrophication of water bodies, and misuse of antibiotics. Among these challenges, disease outbreak is the most important factor directly affecting aquaculture production. It is crucial to explore new approaches effective for the prevention and control of diseases. Probiotics have been widely used in aquaculture and have shown beneficial effects on the host. In this study, the butyrate-producing bacterium Clostridium butyricum G13 was isolated for the first time from the intestine of the mud crab through in vitro fermentation. The bacterium has probiotic properties and changes the gut microbiota to be beneficial to hosts in vitro as well as protecting hosts from Vibrio parahaemolyticus infection in vivo. The outcomes of this study indicate that C. butyricum G13 can be used as a potential probiotic in mud crab aquaculture.

[Quantitative Analysis of Spatio-temporal Evolution Characteristics of Seasonal Average Maximum Temperature and Its Influence by Atmospheric Circulation in China from 1950 to 2019].

Global warming and intensified human activities have led to regional climate instability with increasing frequency and the persistence of high-temperature climate events. Eco-environmental protection and socio-economic development have been faced with rigorous threats. Taking the monthly maximum temperatures from 1950 to 2019 as the basic data source, the spatial-temporal evolution characteristics of seasonal average maximum temperature (AMT) were discerned using the Mann-Kendall test and unary linear regression method in China from 1950 to 2019. Combined with linear correlation, partial linear correlation, and wavelet analysis, the correlation between seasonal AMT characteristics and atmospheric circulations was analyzed quantitatively. The results showed that:① the AMT in all seasons had a significant upward trend, with an increase of 1.21, 0.08, 1.81, and 0.25℃ in spring, summer, autumn, and winter, respectively. The abrupt change times of the AMT were concentrated in the 1990s to the early 21st century. ② In terms of spatial distribution, except for in summer, the average trend rates of AMT in other seasons increased gradually from south to north, although the increasing degrees were different. Among them, the AMT change rate in spring-winter was the fastest in northeast and northwest China. ③ There were complex correlations between the AMT of every season and atmospheric circulation factors, and the distribution of the interrelation energy varied significantly in different frequency domains. Specifically, the Pacific Decadal Oscillation had a significant negative correlation with AMT in summer. The North Atlantic Oscillation had an active effect on AMT changes in summer, autumn, and winter. The Arctic Oscillation had a significant positive driving effect on AMT in all seasons, and there were significant positive or negative influences on the short-or long-term changes of AMT in spring and summer due to the different EI Niño-Southern Oscillation years. These results could provide a theoretical basis and technical reference for China to formulate scientific and effective response plans of climate change.

A Catalytically Accessible Polyoxometalate in a Porous Fiber for Degradation of a Mustard Gas Simulant.

Polyoxometalates (POMs) are versatile materials for chemical catalysis due to their tunable acidity and rich redox properties. While POMs have attracted significant attention in homogeneous catalysis, challenges regarding aggregation and instability in solvents often prevent the wide implementation of POMs as heterogeneous catalysts. Therefore, the successful incorporation of a POM into a solid support, such as a polymer, is desirable for practical applications where unique functionalities of the POM combine with the advantages of the polymer. In this work, we showcase how polymers of intrinsic microporosity (PIMs) can serve as matrices for anchoring a pure inorganic Keggin-type POM (H3PW12O40) to fabricate PIM-based composite materials. Specifically, we found that PIMs installed with amidoxime functionalities could successfully attach POMs (PW12@PIM-1-AO) without self-segregation. Furthermore, we fabricated porous fibrous mats via electrospinning of the PIM-POM composites. Comprehensive characterization confirmed the integrity of the POM in the composite material. Following this, we demonstrated that the incorporated POMs in the composite fibers maintained their innate catalytic activity for the oxidative degradation of 2-chloroethyl ethyl sulfide, a sulfur mustard simulant, in the presence of hydrogen peroxide as the oxidant. Ultimately, our work highlights that PIM-based hybrid materials provide a potential route for implementing these reactive fiber mats into protective equipment.

Sponge-like loose and porous SnO2 microspheres with rich oxygen vacancies and their enhanced room-temperature gas-sensing performance.

Structure and surface modification of semiconductor materials are of great importance in gas sensors. In this study, a facile citric acid-assisted solvothermal method via a precise calcination process was leveraged to synthesize sponge-like loose and porous SnO2 microspheres with rich oxygen vacancies (denoted as LP-SnO2-Ov). When this material was used in a gas sensor, it exhibited an extremely high response to 10 ppm hydrogen sulfide gas at room temperature (Ra/Rg = 9688), which was 54 times higher than that of commercial SnO2. Furthermore, the response time of LP-SnO2-Ov was 5 s, while the recovery time was 177 s. Moreover, it displayed such high selectivity and stability for hydrogen sulfide gas that its properties remained almost unchanged after 1 month. This method paves a new way to fabricate materials possessing a sponge-like loose and porous structure with oxygen vacancies, which is promising for many other scientific fields such as lithium-ion batteries and photocatalysis.

Bacterial Genotoxin Accelerates Transient Infection-Driven Murine Colon Tumorigenesis.

Chronic and low-grade inflammation associated with persistent bacterial infections has been linked to colon tumor development; however, the impact of transient and self-limited infections in bacterially driven colon tumorigenesis has remained enigmatic. Here we report that UshA is a novel genotoxin in attaching/effacing (A/E) pathogens, which include the human pathogens enteropathogenic Escherichia coli, enterohemorrhagic E. coli, and their murine equivalent Citrobacter rodentium (CR). UshA harbors direct DNA digestion activity with a catalytic histidine-aspartic acid dyad. Injected via the type III secretion system (T3SS) into host cells, UshA triggers DNA damage and initiates tumorigenic transformation during infections in vitro and in vivo. Moreover, UshA plays an indispensable role in CR infection-accelerated colon tumorigenesis in genetically susceptible Apc MinΔ716/+ mice. Collectively, our results reveal that UshA, functioning as a bacterial T3SS-dependent genotoxin, plays a critical role in prompting transient and noninvasive bacterial infection-accelerated colon tumorigenesis in mice. SIGNIFICANCE: We identified UshA, a novel T3SS-dependent genotoxin in A/E pathogens that possesses direct DNA digestion activity and confers bacterially accelerated colon tumorigenesis in mice. Our results demonstrate that acute and noninvasive infection with A/E pathogens harbors a far-reaching impact on the development of colon cancer.This article is highlighted in the In This Issue feature, p. 1.

Simultaneous shaping and confinement of metal-organic polyhedra in alginate-SiO2 spheres.

The simultaneous shaping and confinement of Cu-based MOP in alginate-SiO2 spheres significantly enhance the mechanical strength and leaching resistance of Cu-MOP. The resulting MOP-alginate-SiO2 is shown through chemical fixation of CO2 to exhibit improved product yield over the parent Cu-MOP and Cu-alginate-SiO2.

Catalytic hydrolysis of ß-lactam antibiotics via MOF-derived MgO nanoparticles embedded on nanocast silica.

The antibiotics abuse and the proliferation of antibiotic-resistant bacteria in the environment have a severe impact on both human health and ecosystem. In this study, a silica-nanocasting method was applied in Mg-MOF-74 template to generate a series of MgO/SiO2 catalysts for the hydrolysis of ß-lactam antibiotics. The Mg-based subunits in MOF-74 were converted to highly dispersed MgO nanoparticles with controllable particle size. MgO/SiO2-80 with the smallest MgO particle size exhibits the best catalytic performance in the hydrolysis of four ß-lactam antibiotics. The kinetics study reveals the higher degradation rate and lower activation energy of MgO/SiO2-80 than other benchmark solid base catalysts. The proposed mechanism suggests that small MgO particle size provides more accessible oxygen anions with high proton affinity for the cleavage of the ß-lactam ring, so that all hydrolytic products lose antimicrobial activity. The MgO/SiO2-80 serves as the potential high-performance solid base catalyst for the real-world antibiotic wastewater treatment.

Limited Cross-Linking of 4-1BB by 4-1BB Ligand and the Agonist Monoclonal Antibody Utomilumab.

Monoclonal antibodies (mAbs) targeting the co-stimulatory molecule 4-1BB are of interest for tumor immunotherapy. We determined the complex structures of human 4-1BB with 4-1BB ligand (4-1BBL) or utomilumab to elucidate the structural basis of 4-1BB activation. The 4-1BB/4-1BBL complex displays a typical TNF/TNFR family binding mode. The structure of utomilumab/4-1BB complex shows that utomilumab binds to dimeric 4-1BB with a distinct but partially overlapping binding area with 4-1BBL. Competitive binding analysis demonstrates that utomilumab blocks the 4-1BB/4-1BBL interaction, indicating the interruption of ligand-mediated signaling. The binding profiles of 4-1BBL and utomilumab to monomeric or dimeric 4-1BB indicate limited cross-linking of 4-1BB molecules. These findings provide mechanistic insight into the binding of 4-1BB with its ligand and its agonist mAb, which may facilitate the future development of anti-4-1BB biologics for tumor immunotherapy.

Co(OAc)2-Catalyzed Trifluoromethylation and C(3)-Selective Arylation of 2-(Propargylamino)pyridines via a 6-Endo-Dig Cyclization.

A Co(OAc)2-catalyzed trifluoromethylation and subsequent C(3)-selective arylation of 2-(propargylamino)pyridines has been developed. A new 6-endo-dig cyclization involving an unprecedented C(3) selective arylation of the pyridines instead of a commonly observed 5-exo-dig cyclization with "N" is realized. Moreover, the study presents the first case of the installation of a trifluoromethyl group into electron-deficient azaarenes. The process delivers an efficient cascade approach to new trifluoromethylated 1,8-naphthyridine structures with a broad substrate scope.