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Cottonseed protein isolate (CPI) is a valuable agro-industrial waste with potential biotechnological applications. However, inadequate stability in water due to its characteristic hinders its widespread use. Therefore, a new sulfonation modification approach was developed to improve the amphiphilicity and structural flexibility of CPI. Structural characterizations confirmed the successful incorporation of sulfonate groups with structural and conformational changes. This significantly unfolded molecular-chain, and improved amphiphilicity, flexibility, and surface-hydrophobicity while reducing pI (5.1-1.7), and molecular-weight (5745-2089 g/mol). The modified samples exhibited improved emulsification with higher amounts of absorbed proteins on the droplet interface, smaller droplet size, and a higher zeta-potential. Additionally, they possessed good emulsification ability under acidic conditions. The nano-emulsions exhibited long-term stability (≥70 days) under different environmental conditions, with excellent fluidity. This study contributes to understanding sulfonation as a viable approach for improving protein properties, thus, opening up new possibilities for their application and maximizing their economic benefits., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Uranium is a key element in the nuclear industry, whose accidental release causes health and environmental problems. In this paper, a protein-directed fluorescent sensor with aggregation-induced emission characteristics (gold nanoclusters@ovalbumin, AuNCs@OVA) was synthesized for the detection of UO 2 2+ with high sensitivity and selectivity. The sensor exhibited good fluorescence stability, and its fluorescence intensity could be selectively enhanced by UO 2 2+ . Based on FT-IR and XPS analyses, the increase in fluorescence intensity of AuNCs@OVA after the addition of UO 2 2+ was attributed to aggregation induced by the complexation between UO 2 2+ and the amino, carboxyl, hydroxyl, and phosphate groups of ovalbumin. The detection limit was determined to be 34.4 nM, and the sensor showed excellent ion selectivity for UO 2 2+ . In combination with a smartphone program, the sensor could realize the real-time detection of UO 2 2+ in a quantitative and portable way., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

IgA antibodies play an important role in mucosal immunity. However, there is still no effective way to consistently boost mucosal IgA responses, and the factors influencing these responses are not fully understood. We observed that colonization with the murine intestinal symbiotic protozoan Tritrichomonas musculis (T.mu) boosted antigen-specific mucosal IgA responses in wild-type C57BL/6 mice. This enhancement was attributed to the accumulation of free arachidonic acid (ARA) in the intestinal lumen, which served as a signal to stimulate the production of antigen-specific mucosal IgA. When ARA was prevented from undergoing its downstream metabolic transformation using the 5-lipoxygenase inhibitor zileuton or by blocking its downstream biological signaling through genetic deletion of the Leukotriene B 4 receptor 1 (Blt1), the T.mu-mediated enhancement of antigen-specific mucosal IgA production was suppressed. Moreover, both T.mu transfer and dietary supplementation of ARA augmented the efficacy of an oral vaccine against Salmonella infection, with this effect being dependent on Blt1. Our findings elucidate a tripartite circuit linking nutrients from the diet or intestinal microbiota, host lipid metabolism, and the mucosal humoral immune response., (© 2024. The Author(s).)

Background: Current cardiovascular prevention strategies are based on studies that seldom include valvular heart disease (VHD). The role of modifiable lifestyle factors on VHD progression and life expectancy among the elderly with different socioeconomic statuses (SES) remains unknown., Methods: This cohort study included 164,775 UK Biobank participants aged 60 years and older. Lifestyle was determined using a five-factor scoring system covering smoking status, obesity, physical activity, diet, and sleep patterns. Based on this score, participants were then classified into "poor," "moderate," or "ideal" lifestyle groups. SES was classified as high or low based on the Townsend Deprivation Index. The association of lifestyle with major VHD progression was evaluated using a multistate mode. The life table method was employed to determine life expectancy with VHD and without VHD., Results: The UK Biobank documented 5132 incident VHD cases with a mean follow-up of 12.3 years and 1418 deaths following VHD with a mean follow-up of 6.0 years. Compared to those with a poor lifestyle, women and men followed an ideal lifestyle had lower hazard ratios for incident VHD (0.66 with 95% CI, 0.59-0.73 for women and 0.77 with 95% CI, 0.71-0.83 for men) and for post-VHD mortality (0.58 for women, 95% CI 0.46-0.74 and 0.62 for men, 95% CI 0.54-0.73). When lifestyle and SES were combined, the lower risk of incident VHD and mortality were observed among participants with an ideal lifestyle and high SES compared to participants with an unhealthy lifestyle and low SES. There was no significant interaction between lifestyle and SES in their correlation with the incidence and subsequent mortality of VHD. Among low SES populations, 60-year-old women and men with VHD who followed ideal lifestyles lived 4.2 years (95% CI, 3.8-4.7) and 5.1 years (95% CI, 4.5-5.6) longer, respectively, compared to those with poor lifestyles. In contrast, the life expectancy gain for those without VHD was 4.4 years (95% CI, 4.0-4.8) for women and 5.3 years (95% CI, 4.8-5.7) for men when adhering to an ideal lifestyle versus a poor one., Conclusions: Adopting a healthier lifestyle can significantly slow down the progression from free of VHD to incident VHD and further to death and increase life expectancy for both individuals with and without VHD within diverse socioeconomic elderly populations., (© 2024. The Author(s).)

Reactive oxygen species (ROS) production is considered central to triggering the nucleotide-binding domain-like receptor family pyrin domain containing 3 (Nlrp3) inflammasome activation and the subsequent inflammatory responses. Coenzyme Q 10 (CoQ 10 ) plays a critical role in maintaining intracellular ROS homeostasis and inhibiting excessive Nlrp3 inflammasome activation. However, direct supplementation of CoQ 10 showed unsatisfactory clinical improvement due to its limited absorption and bioavailability. Therefore, stimulating endogenous CoQ 10 biosynthesis by supplementing CoQ 10 precursors may provide a more promising therapeutic approach. In this study, we described the role of 4-hydroxybenzoic acid (4-HBA), a precursor of CoQ 10 , in attenuating excessive inflammatory responses. We found that while supplementation of 4-HBA inhibited the priming and activation of Nlrp3 inflammasome, this effect was independent of its metabolic transformation into CoQ 10 . 4-HBA itself exhibits antioxidative activities. Furthermore, 4-HBA can disrupt the binding activity of PU.1 on the promoters of Tlr4 and Md2, thereby directly suppressing Nlrp3 inflammasome priming during LPS-induced inflammatory responses. Therefore, strategically utilizing 4-HBA or increasing 4-HBA intake may represent a potential strategy for reducing excessive inflammation., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yanbo Kou has patent #Application of 4-HBA in anti-inflammation pending to China National Intellectural Property Administration. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Intestinal microbiota contributes to host defense against pathogens while avoiding the induction of inflammation in homeostatic conditions, but the mechanism is not fully understood. To investigate the potential role of the bacterial metabolite desaminotyrosine (DAT) in regulating host defense and inflammation, we pretreated mouse bone marrow-derived macrophages (BMDMs) with DAT for 12 hours and then challenged with bacterial lipopolysaccharide (LPS). We found that DAT priming-enhanced type I interferon response while selectively inhibiting proinflammatory interleukin (IL)-6 production after exposure to LPS. This is related to the fact that DAT is a natural antioxidant determined by radical scavenging assay in a cell-free system. DAT-primed cells had increased levels of the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) upon LPS stimulation. Countering the increased NADPH by supplementing extra oxidized NADP + to cells reversed DAT's effect on LPS-induced Il-6 and interferon-stimulated gene expressions. DAT-primed cells also were more resistant to oxidative stress-induced generation of reactive oxygen species and cell death. DAT promoted the production of antimicrobial effector nitric oxide in a cellular redox-dependent manner, leading to enhanced macrophage antimicrobial activity during Salmonella enterica infection. Our data suggest that DAT acts as a host-microbiota crosstalk signal in shaping host immune defense and inflammatory response., (© 2024 Federation of American Societies for Experimental Biology.)

To improve the accuracy of modal analysis for a four-stage centrifugal-pump rotor system with a balancing disc based on the concentrated-mass analytical method, a simplified concentrated mass mathematical model and an ANSYS simulation model are established. The results from these two models are compared to determine factors that cause significant differences in the mode shapes. Subsequently, an optimized mathematical model based on the corrected mass moment of an inertia matrix and stiffness correction coefficients is proposed, and the effectiveness of this optimized mathematical model is validated using a four-stage centrifugal pump with back blades. The results show that the natural frequencies obtained from the ANSYS simulations are consistently higher than those obtained using the analytical method. The simplification of the moment of inertia at the impeller and balancing disc contributes primarily to the calculated errors. The optimized mathematical model reduces the errors in the natural frequencies from 12.96%, 12.13%, 9.96%, 5.85%, and 8.74% to 2.45%, 1.56%, 0.65%, 5.34%, and 2.28%, respectively. The optimization of natural frequencies offers better performance at lower-order modes, whereas its effects on higher-order modes are less significant. The optimization method is applicable to centrifugal pumps with back blades and reduces the error in theoretical calculations, based on reductions in the concentrated mass from 13.11%, 12.85%, 9.91%, and 7.2% to 3.7%, 3.86%, 0.57%, and 2.87%, respectively, thus further confirming the feasibility of the optimized model design., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Alcohol use disorder is characterized by compulsive alcohol-seeking behavior, which is associated with dysregulation of afferent projections from the medial prefrontal cortex to the basolateral amygdala (BLA). However, the contribution of the cell type-specific mechanism in this neuronal circuit to alcohol-seeking behavior remains unclear., Methods: Mice were trained with 2-bottle choice and operant alcohol self-administration procedures. Anterograde and retrograde viral methods traced the connection between dopamine type 1 receptor (D1R) neurons and BLA neurons. Electrophysiology and in vivo optogenetic techniques were used to test the function of neural circuits in alcohol-seeking behavior., Results: Chronic alcohol consumption preferentially changed the activity of posterior BLA (pBLA) neurons but not anterior BLA (aBLA) neurons and overexcited D1R neurons in the medial prefrontal cortex. Interestingly, we found that 2 populations of D1R neurons, anterior and posterior (pD1R) neurons, separately targeted the aBLA and pBLA, respectively, and only a few D1R neurons innervated both aBLA and pBLA neurons. Furthermore, pD1R neurons exhibited more excitability than anterior D1R neurons in alcohol-drinking mice. Moreover, we observed enhanced glutamatergic transmission and an increased NMDA/AMPA receptor ratio in the medial prefrontal cortex inputs from pD1R neurons to the pBLA. Optogenetic long-term depression induction of the pD1R-pBLA circuit reduced alcohol-seeking behavior, while optogenetic long-term depression or long-term potentiation induction of the anterior D1R-aBLA circuit produced no change in alcohol intake., Conclusions: The pD1R-pBLA circuit mediates chronic alcohol consumption, which may suggest a cell type-specific neuronal mechanism underlying reward-seeking behavior in alcohol use disorder., (Copyright © 2023 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Toxoplasmosis affects a quarter of the world's population. Toxoplasma gondii (T.gondii) is an intracellular parasitic protozoa. Macrophages are necessary for proliferation and spread of T.gondii by regulating immunity and metabolism. Family with sequence similarity 96A (Fam96a; formally named Ciao2a) is an evolutionarily conserved protein that is highly expressed in macrophages, but whether it play a role in control of T. gondii infection is unknown., Methodology/principal Findings: In this study, we utilized myeloid cell-specific knockout mice to test its role in anti-T. gondii immunity. The results showed that myeloid cell-specific deletion of Fam96a led to exacerbate both acute and chronic toxoplasmosis after exposure to T. gondii. This was related to a defectively reprogrammed polarization in Fam96a-deficient macrophages inhibited the induction of immune effector molecules, including iNOS, by suppressing interferon/STAT1 signaling. Fam96a regulated macrophage polarization process was in part dependent on its ability to fine-tuning intracellular iron (Fe) homeostasis in response to inflammatory stimuli. In addition, Fam96a regulated the mitochondrial oxidative phosphorylation or related events that involved in control of T. gondii., Conclusions/significance: All these findings suggest that Fam96a ablation in macrophages disrupts iron homeostasis and inhibits immune effector molecules, which may aggravate both acute and chronic toxoplasmosis. It highlights that Fam96a may autonomously act as a critical gatekeeper of T. gondii control in macrophages., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Microbial community and succession of 5-, 20-, and 50-year pit mud (PM) were uncovered in this study. The results showed that Bacteroidetes , Firmicutes and Ascomycota were dominant phyla in these PM samples. Interestingly, most sequences could not be classified into fungal taxa at the genus level by UNITE Database, the diversity and richness of bacteria in these PMs were higher than that of fungi. It was noteworthy that both 20-year and 50-year PMs exhibited higher abundances of Caproiciproducens and Petrimonas when compared with 5-year PM. While higher proportions of Lactobacillus and Acinetobacter were observed in the 5-year PM. Furfermore, these PMs microbiota mainly involved biosynthesis, degradation, and generation of precursor metabolites, which contributed to carbon cycling of Nong-xiang Baijiu anaerobic fermentation. Taken together, lactic acid bacteria depletion and caproic acid bacteria accumulation might be an important succession trend of PM microbiota during the long-term fermentation of Chinese Nong-xiang Baijiu ., Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-024-01558-4., Competing Interests: Conflict of interestThe authors declare no conflict of interest., (© The Korean Society of Food Science and Technology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Chemically synthesized surfactants have promising applications in the treatment of uranium, however, their hazardous environmental effects, non-biodegradability, and numerous drawbacks prevent them from being widely used in practice. Herein, we successfully synthesized a green chelating and foaming integrated surfactant (BTBS) by Mannich reaction and acylation of bayberry tannin for the effective removal of UO 2 2+ from aqueous environments or solid surfaces. The as-prepared surfactant was systematically characterized by FT-IR, showing that the hydrophobic groups were successfully grafted onto tannin. The modified material showed better foaming and emulsifying properties, which proved this method could improve the amphiphilicity of tannin. Moreover, for the first time, a foam fractionation method in conjunction with a tannin-based surfactant was applied for UO 2 2+ removal from water. This surfactant was used as a co-surfactant and could readily remove 90 % of UO 2 2+ (20 mg L -1 ) from water. The removal of UO 2 2+ could be completed in a short time (30 min), and the maximum adsorption capacity was determined as 175.9 mg g -1 . This surfactant can also be used for efficient decontamination of uranium-contaminated cotton cloth with a high removal rate of 94.55 %. In addition, the mechanism studies show that the adsorption of BTBS for UO 2 2+ can be mainly attributed to a chelating mechanism between UO 2 2+ and the adjacent phenolic hydroxyls. The novel biomass-derived BTBS with advantages such as high capture capacity, environmental friendliness, and cost-effectiveness suggests that it plays an important role in the remediation of radionuclide pollution., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: Consumption of a modern Western-type high-fat low-fiber diet increases the risk of obesity. However, how a host responds to such a diet, especially during the early period of dietary transition from a previous low-fat and fiber-rich diet, remains poorly explored., Methods: Wild-type C57BL/6 mice were fed a normal chow diet or a high-fat diet. Enteric glial cell (EGC) activation was detected through quantitative real-time PCR (qRT-PCR), immunoblotting and immunohistology analysis. Fluorocitrate or genetic deletion of glial fibrillary acidic protein (GFAP)-positive glial-intrinsic myeloid differentiation factor 88 (Myd88) was used to inhibit EGC activation, and the effect of a high-fat diet on obesity was further investigated. The role of MYD88-dependent sensing of commensal products in adipocyte was observed to analyze the effect of obesity., Results: A dietary shift from a normal chow diet to a high-fat diet in mice induced a transient early-phase emergence of a GFAP-positive EGC network in the lamina propria of the ileum, accompanied with an increase in glial-derived neurotrophic factor production. Inhibition of glial cell activity blocked this response. GFAP-positive glial Myd88 knockout mice gained less body weight after high-fat diet (HFD) feeding than littermate controls. In contrast, adipocyte deletion of Myd88 in mice had no effect on weight gain but instead exacerbated glucose intolerance. Furthermore, short-term fluorocitrate intervention during HFD feeding attenuated body weight gain., Conclusions: Our findings indicate that EGCs are early responders to intestinal ecosystem changes and the GFAP-positive glial Myd88 signaling participates in regulating obesity.

Bifidobacterium and Lactobacillus are known to be common members of the human intestinal microbiota, which play important roles in maintaining the homeostasis of host gut microenvironment. Several bifidobacterial and lactobacilli strains have been used as probiotics for health benefits. The exopolysaccharides (EPSs) produced by strains from Bifidobacterium and Lactobacillus are considered as beneficial traits mediating these beneficial effects. In this study, 21 strains belonging to Bifidobacterium and Lactobacillus were isolated from healthy infants' stool and were screened for EPS-producing ability. Among these strains, Bifidobacterium longum XZM1 showed the highest EPS productivity, which was further confirmed and characterized. The complete genome of strain XZM1 was sequenced, which revealed the presence of a gene cluster for EPS production. Furthermore, comparative genome analysis was performed among XZM1 and other strains from B. longum species. Following purification, the molecular weight (Mw) of EPS from XZM1 was determined as 4023 Da (Mw) through gel permeation chromatography. Analysis of the EPS hydrolysates revealed that the EPS was composed of mannose, glucose, galactose, arabinose, and fucose. Additionally, the EPS exhibited higher scavenging abilities toward hydroxyl than 1,1-diphenyl-2-picrylhydrazyl free radical. Overall, these results suggest that XZM1 from B. longum species may be a promising probiotic candidate., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

By-product cottonseed proteins are excellent options for numerous applications due to their superior properties and lower cost. However, its complex folded structure and large molecular weight lead to lower reactivity and insufficient amphiphilicity. Cottonseed protein isolate (CPI) is less-soluble in water. Therefore, we improved the amphiphilicity of CPI with associated hydrolysis, molecular structure unfolding, and activation by alkaline-induced deamidation (at 24, 36, and 72 h) and produced three cottonseed protein hydrolysates CPH 24, 36, and 72. FTIR/UV-CD measurements confirmed the conformational changes and conversion of the structural content. Particle size decreased 2503.4-771.8 nm, while surface hydrophobicity (133.5-326.7), carboxyl content (1.13 × 10־ 3 -2.09 × 10־ 3 ), and flexibility increased, signifying hydrolysis, unfolding, and amphiphilicity improvement. Longer deamidation (CPH 72) exhibited the best properties, its prepared emulsions were long-term stable under all the environmental stresses without visible phase separation after at least 40 days of storage except at pH 4. Compared to CPI, it had smaller droplets (939.3-264.9 nm) and larger absolute ζ-potential (-26.5 to -58.0 mV). From the in-vitro cytotoxicity test, deamidated CPI is extremely safer than commonly used synthetic surfactants. This research provides a new method for producing multifunctional emulsifiers from CPI, which could be utilized in the development of functional foods/non-foods., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Textile dye wastewater has the characteristics of high concentration, complex composition and changeable color degree and pH, which is difficult to be effectively and completely treated, and easy to cause environmental pollution. Here, a strategy of secondary bond interface assembly of polyethyleneimine on zein microparticles (PEI) (PEI@zein) was constructed to achieve rapid and efficient removal of Reactive Black 5 (RB5), which is one of the most widely used reactive dyes in the textile industry. Structural analysis indicated that the as-prepared PEI layer immobilized on zein microparticles was constructed based on the interface assembly dominated by hydrophobic interactions and electrostatic attraction between PEI molecules and zein chains. The novel interface showed excellent absorption performance for RB5 with an absorption capacity of 631.0 mg·g -1 , rapid adsorption in 2 min, wide pH range of 4-10. Mechanism analysis suggested the effective adsorption of RB5 by PEI@zein microparticles was mainly attributed to secondary bond interface such as electrostatic interaction and hydrogen bond between RB5 and PEI immobilized on the surface of zein microparticles. Moreover, due to the presence of secondary bond interface, RB5 adsorbed on microparticles can be easily desorbed by using 0.01 M NaOH. Therefore, the strategy of secondary bond interface assembly with polyethyleneimine on zein microparticles has high potential for practical application in the treatment of dye-containing wastewater., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background and Objective: Propofol is the most commonly used sedative in gastrointestinal endoscopic procedures, but is associated with cardiorespiratory suppression, particularly in elderly patients. Remimazolam is a new short-acting GABA(A) receptor agonist with minimal impact on cardiorespiratory suppression, and may be a viable alternative in elderly patients undergoing endoscopic procedures., Methods: This multicenter, randomized controlled trial was conducted between September 2020 and September 2021. Elderly patients (65-85 years of age) scheduled to undergo upper gastrointestinal endoscopy were randomized in 1:1 ratio to receive remimazolam tosilate (300 mg/h) or propofol (3 g/h) in addition to 50-μg fentanyl, until the Modified Observer's Assessment of Alertness/Sedation Scale (MOAA/S) reached ≤1. MOAA/S was maintained at 0 or 1 throughout the procedure using 2.5 mg remimazolam or 0.5 mg/kg propofol boluses in the two groups, respectively. The primary outcome was the rate of hypotension (defined as systolic blood pressure at ≤90 mmHg or > 30% decline vs. the baseline). Bradycardia was defined as heart rate ≤50 per minute; respiratory depression was defined as respiratory rate <8 per minute and/or SpO 2  < 90%., Results: A total of 400 patients (161 men and 239 women; 70.4 ± 4.6 years of age) were enrolled (200 patients per group). Average body mass index was 22.2 ± 2.4 kg/m 2 . The rate of hypotension was 36.5% in the remimazolam group and 69.6% in the propofol group (p < 0.001). The remimazolam group also had a lower rate of bradycardia (1.5% vs. 8.5%, p < 0.001), respiratory depression (4.5% vs. 10.0%, p < 0.05) and pain at the injection site (0% vs. 12.0%, p < 0.001)., Conclusion: Remimazolam was associated with a lower rate of hypotension in elderly patients undergoing upper gastrointestinal endoscopy under deep sedation/anaesthesia than propofol., (© 2022 The Authors. Journal of Clinical Pharmacy and Therapeutics published by John Wiley & Sons Ltd.)

Myeloid-derived suppressor cells (MDSCs) comprise heterogeneous myeloid cell populations with immunosuppressive capacity that contribute to immune regulation and tolerance induction. We previously reported impaired MDSC function in patients with primary Sjögren's syndrome (pSS) and mice with experimental SS (ESS). However, the molecular mechanisms underlying MDSC dysfunction remain largely unclear. In this study, we first found that aryl hydrocarbon receptor (AhR) was highly expressed by human and murine polymorphonuclear MDSCs (PMN-MDSCs). Indole-3-propionic acid (IPA), a natural AhR ligand produced from dietary tryptophan, significantly promoted PMN-MDSC differentiation and suppressive function on CD4 + T cells. In contrast, feeding a tryptophan-free diet resulted in a decreased PMN-MDSC response, a phenotype that could be reversed by IPA supplementation. The functional importance of PMN-MDSCs was demonstrated in ESS mice by using a cell-depletion approach. Notably, AhR expression was reduced in PMN-MDSCs during ESS development, while AhR antagonism resulted in exacerbated ESS pathology and dysregulated T effector cells, which could be phenocopied by a tryptophan-free diet. Interferon regulatory factor 4 (IRF4), a repressive transcription factor, was upregulated in PMN-MDSCs during ESS progression. Chromatin immunoprecipitation analysis revealed that IRF4 could bind to the promoter region of AhR, while IRF4 deficiency markedly enhanced AhR-mediated PMN-MDSC responses. Furthermore, dietary supplementation with IPA markedly ameliorated salivary glandular pathology in ESS mice with restored MDSC immunosuppressive function. Together, our results identify a novel function of AhR in modulating the PMN-MDSC response and demonstrate the therapeutic potential of targeting AhR for the treatment of pSS., (© 2022. The Author(s), under exclusive licence to CSI and USTC.)

Evidence for transcatheter aortic valve implantation (TAVI) is scarce among patients with non-calcific aortic stenosis, and it is not known whether aortic valve calcification is associated with new cerebral ischemic lesions (CILs) that are detected by diffusion-weighted magnetic resonance imaging. So, our study enrolled 328 patients who underwent transfemoral TAVI using a self-expanding valve between December 2016 and June 2021 from the TORCH registry (NCT02803294). A total of 34 patients were finally confirmed as non-calcific AS and the remaining 294 patients were included in the calcific AS group. Incidence of new CILs (70.6% vs. 85.7%, p = 0.022), number of lesions (2.0 vs. 3.0, p = 0.010), and lesions volume (105.0 mm 3 vs. 200.0 mm 3 , p = 0.047) was significantly lower in the non-calcific AS group. However, the maximum and average lesion volumes were comparable between two groups. Non-calcific AS was associated with lower risk for developing new CILs by univariate logistic regression analysis [Odds ratio (OR): 0.040, 95% confident interval (CI): 0.18-0.90, p = 0.026] and multivariate analysis (OR: 0.031, 95% CI: 0.13-0.76, p = 0.010). In summary, non-calcific AS patients had a lower risk of developing new cerebral ischemic infarction after TAVI compared to calcific AS patients. However, new ischemic lesions were still found in over 70% of patients.

The iron (Fe) metabolism plays important role in regulating systemic metabolism and obesity development. The Fe inside cells can form iron-sulfur (Fe-S) clusters, which are usually assembled into target proteins with the help of a conserved cluster assembly machinery. Family with sequence similarity 96A (FAM96A; also designated CIAO2A) is a cytosolic Fe-S assembly protein involved in the regulation of cellular Fe homeostasis. However, the biological function of FAM96A in vivo is still incompletely defined. Here, we tested the role of FAM96A in regulating organismal Fe metabolism, which is relevant to obesity and adipose tissue homeostasis. We found that in mice genetically lacking FAM96A globally, intracellular Fe homeostasis was interrupted in both white and brown adipocytes, but the systemic Fe level was normal. FAM96A deficiency led to adipocyte hypertrophy and organismal energy expenditure reduction even under nonobesogenic normal chow diet-fed conditions. Mechanistically, FAM96A deficiency promoted mechanistic target of rapamycin (mTOR) signaling in adipocytes, leading to an elevation of de novo lipogenesis and, therefore, fat mass accumulation. Furthermore, it also caused mitochondrial defects, including defects in mitochondrial number, ultrastructure, redox activity, and metabolic function in brown adipocytes, which are known to be critical for the control of energy balance. Moreover, adipocyte-selective FAM96A knockout partially phenocopied global FAM96A deficiency with adipocyte hypertrophy and organismal energy expenditure defects but the mice were resistant to high-fat diet-induced weight gain. Thus, FAM96A in adipocytes may autonomously act as a critical gatekeeper of organismal energy balance by coupling Fe metabolism to adipose tissue homeostasis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The metabolic alterations of amino acid metabolism are closely associated with inflammatory response. However, relatively little is known about the roles of phenylalanine (Phe)/tyrosine (Tyr) catabolites during inflammation. Nitisinone (NTBC) is an orphan drug used to treat hereditary tyrosinemia type I potentially by changing Phe/Tyr metabolic flow. In this study, we used NTBC as a tool to investigate the potential role of the Phe/Tyr catabolic pathway in inflammatory responses. We found that NTBC was effective in tempering the bacterial endotoxin lipopolysaccharide (LPS)-induced septic shock in mice. Mechanistically, the protective effect was related to the accumulation of a Phe/Tyr catabolic intermediate, 4-hydroxyphenylpyruvate (4-HPP), induced by the NTBC treatment. 4-HPP could inhibit NLRP3 inflammasome priming and activation processes and therefore reduce IL-1β release and pyroptosis. Like NTBC, 4-HPP was also effective in attenuating endotoxic shock in mice. Our results suggest the Phe/Tyr catabolic pathway as a potential immunoregulatory hub that may be exploited therapeutically to alleviate inflammation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Recent progress indicates that the gut microbiota plays important role in regulating the host's glucose homeostasis. However, the mechanisms remain unclear. Here, we reported that one integral member of the murine gut microbiota, the protozoan Tritrichomonas musculis could drive the host's glucose metabolic imbalance. Using metabolomics analysis and in vivo assays, we found that mechanistically this protozoan influences the host glucose metabolism by facilitating the production of a significant amount of free choline. Free choline could be converted sequentially by choline-utilizing bacteria and then the host to a final product trimethylamine N-oxide, which promoted hepatic gluconeogenesis. Together, our data reveal a previously underappreciated gut eukaryotic microorganism by working together with other members of microbiota to influence the host's metabolism. Our study underscores the importance and prevalence of metabolic interactions between the gut microbiota and the host in modulating the host's metabolic health. IMPORTANCE Blood glucose levels are important for human health and can be influenced by gut microbes. However, its mechanism of action was previously unknown. In this study, researchers identify a unique member of the gut microbes in mice that can influence glucose metabolism by promoting the host's ability to synthesis glucose by using nonglucose materials. This is because of its ability to generate the essential nutrient choline, and choline, aided by other gut bacteria and the host, is converted to trimethylamine N-oxide, which promotes glucose production. These studies show how gut microbes promote metabolic dysfunction and suggest novel approaches for treating patients with blood glucose abnormality.

The herpes virus entry mediator (HVEM) is an immune checkpoint molecule regulating immune response, but its role in tissue repair remains unclear. Here, we reported that HVEM deficiency aggravated hepatobiliary damage and compromised liver repair after 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced injury. A similar phenotype was observed in B and T lymphocyte attenuator (BTLA)-deficient mice. These were correlated with impairment of neutrophil accumulation in the liver after injury. The hepatic neutrophil accumulation was regulated by microbial-derived secondary bile acids. HVEM-deficient mice had reduced ability to deconjugate bile acids during DDC-feeding, suggesting a gut microbiota defect. Consistently, both HVEM and BTLA deficiency had dysregulated intestinal IgA responses targeting the gut microbes. These results suggest that the HVEM-BTLA signaling may restrain liver injury by regulating the gut microbiota., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kou, Zheng, Meng, Liu, Xu, Jing, Zhang, Wang, Han, Liu, Wei and Wang.)

Efficient capture of radioactive iodine ( 129 I, 131 I) is of great significance in spent fuel treatment. In this paper, a new adsorbent named Catechin@ACF was successfully prepared through interface assembly of specific recognition gripper with plant polyphenols (catechin) on activated collagen fiber (ACF), and the catechin membrane with specific grip on iodine was successfully constructed on the surface of ACF. The results showed that the adsorbent assembled catechin membrane was rich in aromatic rings, hydroxyl groups and imine adsorption sites, and possessed specific recognition and capture characteristics of iodine. Moreover, the as-prepared Catechin@ACF showed excellent capture capacity for iodine vapor and iodine in organic solution with the maximum capture capacity of 2122.68 mg/g and 258.29 mg/g, respectively. In iodine-cyclohexane solution, the adsorption process was in according with the Pseudo first order kinetic and Langmuir isothermal model. In addition, the specific recognition and capture mechanism analysis indicated that the aromatic rings, phenolic hydroxyl groups and imine groups in the catechin membrane were the specific and effective grippers for iodine, and finally iodine formed a stable conjugated system with the adsorbent in the form of I - and I 3 - . Therefore, the as-prepared specific iodine capturer Catechin@ACF was expected to play a vital role in the capture of radioactive iodine in spent fuel off-gas because of its specific recognition, high capture capacity, large-scale preparation, and environment-friendly., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Extraction uranium from complicated aqueous solutions (seawater and nuclear wastewater) has been promoting the development of multi-functional adsorbents with high adsorption capacities and high selectivity. Here, we proposed a co-immobilization approach to preparing uranium adsorbents. Due to specific recognition and binding between functional groups, bayberry tannin (BT) and hydrous titanium oxide (HTO) were co-immobilized onto nano collagen fibrils (NCFs). The adsorption performances of NCFs-HTO-BT to uranium were systematically investigated in two aqueous systems, including nuclear wastewater and seawater. Results proved that NCFs-HTO-BT possessed the remarkable adsorption capacities and affinities for uranium in wastewater (393.186 mg g -1 ) and spiked seawater (14.878 mg g -1 ) with the uranium concentration of 320 mg g -1 and 8 mg g -1 , respectively. Based on characteristic analysis of the adsorbent before and after uranium adsorption, the hydroxyl groups of HTO, the adjacent phenolic hydroxyl groups of BT, and nitrogen-containing and oxygen-containing functional groups of NCFs were active sites for uranium adsorption., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

In this work, a new N-halamine precursor with two epoxy groups, 1,3-bis(2,3-epoxypropyl)-s-triazine-2,4,6-trione (BETT), was synthesized and used to enhance the compatibility between poly(lactic acid) (PLA) and poly (butylene adipate-co-terephthalate) (PBAT). The rheological analysis and GPC indicated that chain extension between PLA and PBAT occurred during the melt-blending in the presence of BETT. The PLA/PBAT chain extensions improved the compatibility between PLA and PBAT and hindered the crystallization of PLA. SEM images showed that PLA/PBAT blend gradually changed from the typical sea-island phase without BETT to a co-continuous structure with increase in amount of BETT. This showed that the interfacial compatibility between PLA and PBAT improved significantly on addition of BETT. Moreover, compared to PLA/PBAT blend, the mechanical properties of PLA/PBAT/BETT blends showed great improvement. Furthermore, the chlorinated PLA/PBAT/BETT sheets displayed excellent antibacterial activities against E. coli (CMCC 44103) and S. aureus (ATCC 6538) cultures, wherein the sheets with 17.5 ± 0.8 μg/cm 2 of the active chlorine could kill all inoculated bacteria within 30 min., (Copyright © 2020. Published by Elsevier B.V.)

Background: Well-designed mobile health (mHealth) interventions support a positive user experience; however, a high rate of disengagement has been reported as a common concern regarding mHealth interventions. To address this issue, it is necessary to summarize the design features that improve user engagement based on research over the past 10 years, during which time the popularity of mHealth interventions has rapidly increased due to the use of smartphones., Objective: The aim of this review was to answer the question "Which design features improve user engagement with mHealth interventions?" by summarizing published literature with the purpose of guiding the design of future mHealth interventions., Methods: This review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) checklist. Databases, namely, PubMed, Web of Science, Cochrane Library, Ovid EMBASE, and Ovid PsycINFO, were searched for English and Chinese language papers published from January 2009 to June 2019. Thematic analysis was undertaken to assess the design features in eligible studies. The Mixed Methods Appraisal Tool was used to assess study quality., Results: A total of 35 articles were included. The investigated mHealth interventions were mainly used in unhealthy lifestyle (n=17) and chronic disease (n=10) prevention programs. Mobile phone apps (n=24) were the most common delivery method. Qualitative (n=22) and mixed methods (n=9) designs were widely represented. We identified the following 7 themes that influenced user engagement: personalization (n=29), reinforcement (n=23), communication (n=20), navigation (n=17), credibility (n=16), message presentation (n=16), and interface aesthetics (n=7). A checklist was developed that contained these 7 design features and 29 corresponding specific implementations derived from the studies., Conclusions: This systematic review and thematic synthesis identified useful design features that make an mHealth intervention more user friendly. We generated a checklist with evidence-based items to enable developers to use our findings easily. Future evaluations should use more robust quantitative approaches to elucidate the relationships between design features and user engagement., (©Yanxia Wei, Pinpin Zheng, Hui Deng, Xihui Wang, Xiaomei Li, Hua Fu. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 09.12.2020.)

It is considered that intestinal barrier dysfunction and systemic endotoxemia drive obesity and its related complications. However, what causes barrier dysfunction remains to be elucidated. Here, we showed that the gut microbiota from high-fat diet (HFD)-fed mice had impaired ability to degrade dietary flavonoids, and in correspondence, the microbial-derived flavonoid metabolite desaminotyrosine (DAT) was reduced. Supplementation of DAT in the drinking water was able to counter the HFD-induced body fat mass accumulation and body weight increment. This is correlated with the role of DAT in maintaining mucosal immune homeostasis to protect barrier integrity. DAT could attenuate dextran sodium sulfate (DSS)-induced mucosal inflammation in a type I interferon signal-dependent manner. Furthermore, intraperitoneal injection of DAT-protected mice from bacterial endotoxin-induced septic shock. Together, we identified DAT as a gut microbiota-derived anti-inflammatory metabolite that functions to modulate local and systemic immune homeostasis. Our data support the notion of dysbiosis being an important driving force of mucosal barrier dysfunction and systemic metabolic complications., (© 2020 Federation of American Societies for Experimental Biology.)

Introduction: Toxigenic Clostridium difficile ( C. difficile ) is the main cause of antibiotic-associated diarrhea and can induce pseudomembranous colitis and infrequent toxic megacolon, which are potentially fatal. The standard antibiotic therapy for C. difficile infection (CDI) is limited by antibiotics' broad spectrum and further disruptive effects on indigenous microbiota. Probiotics may offer a prospective and alternative strategy for the prevention and treatment of CDI., Areas Covered: In this article, the mechanisms implying the probiotic effect against C. difficile and the safety profile highlighting the patient groups with inappropriate application of probiotics were reviewed from 2015 to 2020., Expert Opinion: Although many strains with ability against C. difficile have been reported, the usage of probiotics for CDI prevention and/or treatment is scarce since the number of clinical trials is not sufficient to prove probiotics' efficacy and safety in CDI treatment, especially for premature infant and immunocompromised patient. Especially, there are few well-defined clinical studies supporting safety of probiotics for CDI. A few strains from Lactobacillus and Saccharomyces genus have been studied more extensively than other probiotic strains through clinical trials for CDI. Thus, more clinical intervention studies regarding the benefit and the comprehensive safety assessments of probiotics for CDI are needed.

Our current understanding of the host-microbiota interaction in the gut is dominated by studies focused primarily on prokaryotic bacterial communities. However, there is an underappreciated symbiotic eukaryotic protistic community that is an integral part of mammalian microbiota. How commensal protozoan bacteria might interact to form a stable microbial community remains poorly understood. Here, we describe a murine protistic commensal, phylogenetically assigned as Tritrichomonas musculis , whose colonization in the gut resulted in a reduction of gut bacterial abundance and diversity in wild-type C57BL/6 mice. Meanwhile, dietary nutrient and commensal bacteria also influenced the protozoan's intestinal colonization and stability. While mice fed a normal chow diet had abundant T. musculis organisms, switching to a Western-type high-fat diet led to the diminishment of the protozoan from the gut. Supplementation of inulin as a dietary fiber to the high-fat diet partially restored the protozoan's colonization. In addition, a cocktail of broad-spectrum antibiotics rendered permissive engraftment of T. musculis even under a high-fat, low-fiber diet. Furthermore, oral administration of Bifidobacterium spp. together with dietary supplementation of inulin in the high-fat diet impacted the protozoan's intestinal engraftment in a bifidobacterial species-dependent manner. Overall, our study described an example of dietary-nutrient-dependent murine commensal protozoan-bacterium cross talk as an important modulator of the host intestinal microbiome. IMPORTANCE Like commensal bacteria, commensal protozoa are an integral part of the vertebrate intestinal microbiome. How protozoa integrate into a commensal bacterium-enriched ecosystem remains poorly studied. Here, using the murine commensal Tritrichomonas musculis as a proof of concept, we studied potential factors involved in shaping the intestinal protozoal-bacterial community. Understanding the rules by which microbes form a multispecies community is crucial to prevent or correct microbial community dysfunctions in order to promote the host's health or to treat diseases., (Copyright © 2020 American Society for Microbiology.)

This study evaluated compliance with the comprehensive smoke-free law in public indoor places introduced in Shanghai in March 2017. Observations and PM2.5 monitoring over 30 min intervals in 8 types of the venue were conducted three times: within a month before implementation and 3- and 12-months post implementation. Observations of evidence of smoking decreased from 66.2% before legislation to 52.8% three months after ( p = 0.002) and 49.7% one year after ( p < 0.001). The density of lit cigarettes also reduced significantly after implementation ( p < 0.001). When adjusting for outdoor, indoor PM2.5 levels were significantly lower after the legislation, but only by a small amount (three months later: -0.27, p = 0.08; one year later: -0.12; p = 0.03). Evidence of compliance was weakest in farmer's markets and bars, and smoking in male toilets did not change significantly. The reduction in smoking was affected by the management performance of their obligations. The comprehensive smoke-free law led to modest reductions in smoking and PM2.5 levels as a result, but from levels suggesting quite high levels of pre-compliance. However, compliance was limited in some areas, suggesting more effort is required on management to gain better compliance in some places like farmer's markets, bars, and toilets.

Bifidobacterium inhabiting the human and animal intestinal tract is known for its health-promoting effect. Tolerance to acid stress is crucial for bifidobacteria to survive and then exert their beneficial effects in the gut. A long-term adaptation in successive batch cultures was used as evolutionary engineering strategy to improve acid stress tolerance in an industrial probiotic strain, B. longum JDM301. Its derivative, JDM301AR showed higher resistance to several stress conditions, including acid stress than the parental strain, JDM301. To better understand bifidobacterial acid stress response, the changes of fatty acid (FA) in cell membrane of these two strains were determined. A shift in the production of FA in cell membrane, characterized by increased C14:0 was found, when JDM301AR was exposed to low-pH environment. It was implied that the increased production of C14:0 is associated with the acquisition of acid-tolerant phenotype for JDM301AR. High-throughput RNA-sequencing was performed to analyze the changes of gene expression profile after acid-exposure. The transcriptional profiles of JDM301AR and JDM301 under normal condition and acid stress were compared to reveal the different acid response between them. A total of 5 genes involved in FA metabolism were upregulated and no downregulated genes were found in response to acid stress in JDM301AR. The up-regulated BLJ&#95;0565 and BLJ&#95;1105 may play important roles in the modification of membrane FA composition of JDM301AR after acid exposure. Overall, these results suggested that successive batch cultures induced the acid stress tolerance of B. longum involved in transcriptional and physiological responses, including modification of cell wall and cell membrane, metabolism of amino acid and neutralization of internal pH by strengthening NH 3 production and transport.

Background: Tyrosine kinase inhibitors (TKIs) can significantly prolong overall survival for patients with advanced non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR)-mutation or anaplastic lymphoma kinase (ALK)-rearrangement. However, the real-world evaluation status of ALK/EGFR in China remains unclear., Methods: We conducted a prospective study including 1134 patients with cytologically or histologically confirmed advanced NSCLC (stage IIIb-IV) at 12 Chinese hospitals., Results: The most common evaluation methods were amplification-refractory mutation system for EGFR status and immunohistochemistry targeting D5F3 for ALK status. Among patients with non-squamous, the EGFR mutation rate was 44.1% and the ALK rearrangement rate was 10.0%. Among patients with squamous cell carcinoma, the EGFR mutation rate was 8.3% and the ALK rearrangement rate was 3.7%. Among all patients, gender (HR = 1.7, 95%CI = 1.2-2.4, P = 0.006), smoking history (HR = 1.8, 95%CI = 1.3-2.7, P = 0.001), histology (HR = 5.0, 95%CI = 2.4-10.1, P < 0.001), and brain metastases (HR = 1.5, 95%CI = 1.1-2.2, P = 0.017) were independent predictors of EGFR mutation, while age (HR = 2.6, 95%CI = 1.7-4.1, P < 0.001) was an independent predictor of ALK rearrangement. The median time from tumor diagnosis to EGFR or ALK status confirmation was 7 and 5 days, respectively. Targeted therapy rate was 73.8% in EGFR-positive patients and 51.4% in ALK-positive patients. There was a negative correlation between the first-line targeted therapy rate and the EGFR mutation detection period (r = -0.152, P = 0.02), while no significant correlation among patients with ALK rearrangement (r = -0.179, P = 0.076)., Conclusion: Squamous NSCLC patients should also be routinely tested to determine their EGFR/ALK statuses. The first-line targeted therapy rate remains low in Chinese patients with NSCLC., (© 2019 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Objective : The aim of this study was to identify the potential psychological mechanism of well-being in migrants in Shanghai, China. Methods : A cross-sectional study was conducted in 2018. First, a literature review was conducted to understand the salutogenesis of migrants in China. Then, 2573 random participants were recruited from six workplaces and public places in six districts of Shanghai. The Chinese versions of the Patient Health Questionnaire-9 (PHQ-9), the Personal Wellbeing Index (PWI), and the Sense of Coherence (SOC) Scale were used to evaluate the depression, subjective well-being (SWB), and SOC of migrants. The t -test, ANOVA, and multiple linear regression and structural equation models (SEM) were used to analyze the correlations and paths among generalized resistant resources (GRRs), SOC, PHQ, and SWB. Results : The subjects were aged between 18 and 58 (mean, 28.17; SD, 6.99). SOC showed a positive correlation with SWB ( r = 0.46, p < 0.001) and a negative correlation to PHQ ( r = -0.53, p < 0.001). After controlling for the demographic characteristics, we found that PHQ, SOC (comprehensibility, manageability, meaningfulness), and GRRs (income ratio, marital status) contributed 33.3% of the variance in SWB, and their linear regression coefficients were: -0.32 ( p < 0.001), 0.09 ( p < 0.001), 0.09 ( p < 0.001), 0.15 ( p < 0.001), 0.06 ( p < 0.05), and 0.16 ( p < 0.05), respectively. These findings not only confirmed the direct association among SOC, PHQ and SWB, but also verified two underlying mechanisms regarding the mediating effect of SOC by using SEM: (1) GRRs (income ratio, marital status) are positively associated with a higher SOC, which further contributes to favorable SWB; and (2) PHQ is negatively associated with poor SWB indirectly via SOC. Conclusion : Migrant workers with low SOC and high PHQ are vulnerable to poor well-being levels. Meanwhile, GRRs (income ratio, marital status) may strengthen the SOC level, and can be regarded as the basis of intervention. Further investigation may be needed to focus on external psychological support factors., Competing Interests: The authors declare no conflict of interest.

The conformation and stability of zein in solution are closely associated with its solvation process and influence the mechanical properties of the related zein-based materials. In this work, a common solvent dimethyl sulfoxide (DMSO) was used to dissolve zein, rather than solvents frequently used such as aqueous ethanol and acetic acid. It was found that DMSO could dissolve zein readily and the solution was stable for at least 2 weeks. Rheological analysis and small-angle X-ray scattering (SAXS) were employed to characterize the zein DMSO solution. Results of rheological analysis suggested a Huggins coefficient of 0.24, indicating DMSO to be a good solvent for zein. SAXS results revealed that zein adopted an elongated conformation and had dimensions of 2.8 nm × 2.8 nm × 14.8 nm in DMSO solution. Moreover, robust zein films were fabricated from zein DMSO solutions. The content of residual DMSO in the films was determined to be approximately 15 wt % by thermogravimetric analysis, in consistence with the value obtained by other two methods. The film showed a large breaking strain of 320.6% with a considerable breaking stress of 1.9 MPa, yielding a breaking energy of 376.2 MJ/m 3 . Therefore, the ease of dissolution and good mechanical performance of the final zein-based material make DMSO a potential solvent for fabrication of zein materials, thereby improving the scope of practical applications of zein.

In this study, zein, a renewable natural biopolymer from corn, was used to prepare a new biodegradable material with poly(butylene adipate-terephthalate) (PBAT) by reactive blending in the presence of poly(ethylene glycol diglycidyl ether) (PEGDGE). The effects of blending temperature and zein content on the morphology and mechanical and thermal properties of PBAT/zein blends with or without PEGDGE were investigated. Because of the high reactivity of the epoxy group in PEGDGE, the interfacial compatibility between zein and PBAT was improved greatly, and zein exhibited as a spheral phase with smaller size and finer dispersion in the PBAT matrix after the introduction of PEGDGE. Therefore, PEGDGE served as a plasticizer and reactive compatibilizer in the PBAT/zein blending system. Both the tensile strength and elongation at break of the blends with PEGDGE were improved greatly compared with those of the blends without PEGDGE but decreased gradually with the increase of zein content. These findings may provide a feasible way to utilize zein widely, and the new biodegradable blends with excellent stretchability could be used as packing materials in the future., Competing Interests: The authors declare no competing financial interest.

The physiologic signals that regulate beige adipogenesis remain incompletely understood, especially those that limit browning and prevent overexpenditure of energy. In this study, the TNF family member cytokine lymphotoxin-like inducible protein that competes with glycoprotein D for herpesvirus entry on T cells (LIGHT), also known as TNF super family protein 14 (TNFSF14), can inhibit adipose precursor differentiation into beige adipocytes. In acute cold stress, LIGHT deficiency in mice accelerated browning in the subcutaneous white adipose tissue (scWAT). Further experiments showed that LIGHT interacting with lymphotoxin-β receptor (LTβR) on adipose precursors blocked beige fat biogenesis. LTβR signals attenuated the JNK pathway, which contributed to their antibeiging effect. Blocking JNK activation using a small molecular inhibitor prevented cold-induced scWAT beiging. Furthermore, LIGHT/LTβR signals acted as an attenuator of white adipogenesis. LIGHT deficiency in mice promoted obesity during high-fat diet feeding. These findings identify the LIGHT axis as a regulator of adipose tissue homeostasis and suggest that LIGHT signaling functions as a mechanism to divert energy in favor of immune activation.-Kou, Y., Liu, Q., Liu, W., Sun, H., Liang, M., Kong, F., Zhang, B., Wei, Y., Liu, Z., Wang, Y. LIGHT/TNFSF14 signaling attenuates beige fat biogenesis.

Background: Clostridium difficile (C. difficile) is a main cause of antibiotic-associated diarrhoea in humans. Several studies have been performed to reveal the prevalence rate of C. difficile in cats and dogs. However, little is known about the epidemiology of C. difficile in healthy pets in China. This study aimed to assess the burden of C. difficile shedding by healthy dogs and cats in China. Furthermore, the genetic diversity and antimicrobial susceptibility patterns of the recovered isolates were determined., Methods: A total of 175 faecal samples were collected from 146 healthy dogs and 29 cats. C. difficile strains were isolated and identified from the feces of these pets. The characterized C. difficile strains were typed by multilocus sequence typing (MLST), and the MICs of the isolates were determined against ampicillin, clindamycin, tetracycline, moxifloxacin, chloramphenicol, cefoxitin, metronidazole and vancomycin by the agar dilution method., Results: Overall, 3 faecal samples (1.7%) were C. difficile culture positive. One sample (0.7%) from a dog was C. difficile culture positive, while two cats (7.0%) yielded positive cultures. The prevalence rate differed significantly between cats and dogs. These isolates were typed into 3 MLST genotypes and were susceptible to chloramphenicol, tetracycline, metronidazole and moxifloxacin and resistant to ampicillin, clindamycin and cefoxitin. Notably, one strain, D141-1, which was resistant to three kinds of antibiotics and carried toxin genes, was recovered in the faeces of a healthy dog., Conclusion: Our results suggest that common pets may be a source of pathogenic C. difficile, indicating that household transmission of C. difficile from pets to humans can not be excluded.

Current evidence to support extensive use of probiotics in inflammatory bowel disease is limited and factors that contribute to the inconsistent effectiveness of clinical probiotic therapy are not completely known. Here, we used Bifidobacterium longum JDM 301 as a model probiotic to study potential factors that may influence the effect of probiotics in experimental colitis. We found that the effect of B. longum JDM 301 in tempering experimental colitis varied across individual mice even with the same genetic background. The probiotic efficacy was highly correlated with the host gut microbial community features. Consumption of a diet rich in fat could exacerbate mucosal injury-induced colitis but could not change the host responsiveness to B. longum JDM 301 treatment, suggesting of potential mechanistic differences between regulating colitis pathogenesis, and modulating probiotic efficacies by the gut microbiota. Together, our results suggest that personalized microbiome features may modify the probiotic therapeutic effect and support the idea of personalized probiotic medicine in inflammatory bowel disease.

The color changes corresponding to chromophore structures in lignin caused by exposure of Eucalyptus ( Eucalyptus grandis and E. urophylla ) to heat were investigated. Eucalyptus wood powders were heat treated under saturated steam atmospheres for 10 h at 110 °C, 130 °C and 150 °C. The lignin was isolated before and after heat treatment. The physicochemical properties of the lignin and changes in chromophore structures during heat treatment was evaluated through wet chemical analysis, Fourier transform infrared spectroscopy (FTIR), diffuse reflectance ultraviolet-visible spectroscopy (DRUV-Vis), gel permeation chromatography (GPC), X-ray photoelectron spectroscopy (XPS) and 13 C Cross polarization magic angle spinning nuclear magnetic resonance ( 13 C CPMAS NMR). Wood color darkened and reddened with the increase in pressure and temperature. Depolymerization and dehydration reactions occurred via demethoxylation with heat treatment in saturated steam at 110 °C or 130 °C. Lignin condensed to form insoluble compounds after heat treatment in saturated steam at 150 °C. G units increased and S units decreased through demethylation during heat treatment, as revealed by FTIR and 13 C-NMR analysis.

Probiotics might offer an attractive alternative to prevent and control Clostridium difficile ( C. difficile ) infection (CDI). Limited information is available on the ability of commercially used bifidobacterial strains to inhibit C. difficile . This study examined the anti-clostridial effects of Bifidobacterium longum JDM301, a widely used commercial probiotic strain in China, in vitro and in vivo . In vitro evaluation revealed a significant reduction in C. difficile counts when JDM301 was co-cultured with C. difficile , which was correlated with the significant decrease in clostridial toxin titres (TcdA and TcdB). Furthermore, the cell-free culture supernatants (CFS) of JDM301 inhibited C. difficile growth and degraded TcdA and TcdB. Notably, the results showed that acid pH promoted the degradation of TcdA by CFS from JDM301. Furthermore, comparative studies among 10 B. longum strains were performed, which showed that the inhibitory effect of CFS from JDM301 was similar with the other 8 B. longum strains and higher than strain BLY1. However, when it was neutralized, the significant different was lost. When present together, it was suggested that the acid pH induced by probiotics not only played important roles in the growth inhibition against C. difficile resulting in the reduction of toxins titres, but also directly promoted the degradation of clostridial toxin. In vivo studies proved that JDM301 partially relieved damage to tissues caused by C. difficile and also decreased the number of C. difficile and toxin levels. In summary, our results demonstrated that the commercial strain, JDM301 could be considered a probiotic able to exert anti-toxin capability and most of the CFS from Bifidobacterium were able to inhibit the growth of C. difficile , depending on acid pH. These results highlighted a potential that JDM301 could be helpful in preventing CDI and that most of the bifidobacterial strains could (at least partially) exert protective effects by reducing toxin titres through growth inhibition against toxigenic C. difficile .

Bifidobacterium longum strain JDM301, a widely used commercial strain in China, encodes at least two MazEF-like modules and one RelBE-like toxin-antitoxin (TA) system in its chromosome, designated MazE 1 F 1 Bif , MazE 2 F 2 Bif , and RelBE Bif , respectively. Bacterial TA systems play an important role in several stress responses, but the relationship between these TA systems is largely unknown. In this study, the interactions between MazF 1 Bif and MazE 2 Bif or RelB Bif were assessed in B. longum strain JDM301. MazF 1 Bif caused the degradation of tufA Bif mRNA, and its toxicity was inhibited by forming a protein complex with its cognate antitoxin, MazE 1 Bif Notably, MazF 1 Bif toxicity was also partially neutralized when jointly expressed with noncognate antitoxin MazE 2 Bif or RelB Bif Our results show that the two noncognate antitoxins also inhibited mRNA degradation caused by MazF 1 Bif toxin. Furthermore, the physical interplay between MazF 1 Bif and its noncognate antitoxins was confirmed by immunoprecipitation. These results suggest that MazF 1 Bif can arrest cell growth and that MazF 1 Bif toxicity can be neutralized by its cognate and noncognate antitoxins. These results imply that JDM301 uses a sophisticated toxin-antitoxin interaction network to alter its physiology when coping with environmental stress. IMPORTANCE Although toxin-antitoxin (TA) systems play an important role in several stress responses, the regulatory mechanisms of multiple TA system homologs in the bacterial genome remain largely unclear. In this study, the relationships between MazE 1 F 1 Bif and the other two TA systems of Bifidobacterium longum strain JDM301 were explored, and the interactions between MazF 1 Bif and MazE 2 Bif or RelB Bif were characterized. In addition, the mRNA degradation activity of MazF 1 Bif was demonstrated. In particular, the interaction of the toxin with noncognate antitoxins was shown, even between different TA families (MazF 1 Bif toxin and RelB Bif antitoxin) in JDM301. This work provides insight into the regulatory mechanisms of TA systems implicated in the stress responses of bifidobacteria., (Copyright © 2017 American Society for Microbiology.)

In this study, the structural characterization of Sphallerocarpus gracilis polysaccharide (SGP) and its hypoglycaemic activities are reported for the first time. SGP, which has a weight average molar mass (M w ) of 7.413×10 5 , was isolated from Sphallerocarpus gracilis and purified by ion-exchange chromatography. The polysaccharide is composed of rhamnose, arabinose, mannose, glucose and galactose, with the molar ratio of 4.12: 8.99: 5.45: 65.94: 15.50. The mechanism underlying the hypoglycaemic effect of SGP was evaluated. Experimental results showed that SGP protected pancreatic β-cells from alloxan damage by several possible mechanisms, including: (1) repairing free radical damage; (2) reducing the apoptosis of pancreatic β-cells by inhibiting the activities of caspase-3 and bax, and enhancing the activity of bcl-2; (3) stimulating insulin secretion and upregulating the pancreatic and duodenal homeobox 1 gene and the insulin gene and the pancreatic in pancreatic β-cells. The results obtained in this study suggest that SGP may be a promising therapeutic agent in the treatment of diabetes mellitus., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Toxin-antitoxin (TA) systems are widespread in bacteria and archaea. However, the roles of chromosomally encoded TA systems in bacterial physiology are still open to debate. In this study, a TA module-relBE in Bifidobacterium longum JDM301 (relBE(Bif)) was identified and its function in stress response was evaluated. Bioinformatics analysis of the whole genome sequences of JDM301 revealed a pair of linked genes encoding a RelBE-like TA system (RelBE(Bif)). Our results revealed a bicistronic operon formed by relBE(Bif) in JDM301. Over-expression of RelE(Bif) had a toxic effect on Escherichia coli, which could be neutralized by co-expression of its cognate antitoxin, RelB(Bif) Our data also demonstrated that RelE(Bif) is an mRNA interferase and that the activity of RelE(Bif) can be inhibited by RelB(Bif) These results suggest that RelE(Bif) is a toxic nuclease which arrests cell growth through mRNA degradation, and that the activity of RelE(Bif) can be abolished by co-expression of RelB(Bif) In addition, we also found that the expression of RelBE(Bif) is increased during osmotic stress, suggesting that RelBE(Bif) is activated under this adverse condition. Our results imply that the RelBE(Bif) TA module may represent a cell growth modulator which helps B. longum to deal with osmotic stress., (© The Author 2016. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The pH-sensitive hydrogels composed of sodium caseinate (SC) and N,O-carboxymethyl chitosan (NOCC) were prepared and a new method to characterize the gelation process was presented in this work. Reological tests suggested that RSC/NOCC=3/7 (the weight ratio of SC and NOCC) was the best ratio of hydrogel. The well-developed three-dimensional network structures in the hydrogel were confirmed by AFM. Two structural parameters, tIS and tCS, denoted as the initial and critical structure formation time, respectively, were used to provide an exact determination of the start of structure formation and description of gelation process. The gelation process strongly depended on temperature changes, a high temperature resulted in an early start of gelation. The non-kinetic model suggested the higher activation energy in the higher temperatures was disadvantageous to structure formation, and vice versa. Due to the smart gel reported here was very stable at room temperature, we believed that the gel is required for applications in drug delivery or could be exploited in the development of potential application as molecular switches in the future., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Sphallerocarpus gracilis (S. gracilis) is a little-investigated edible plant and used as traditional Chinese medicine. In this study, polysaccharide extracted from S. gracilis,deproteined and purified. The polysaccharide (SGP) was chemically modified to obtain its sulfated derivatives (S-SGP) using the method of chlorosulfonic acid/pyridine (CSA/Pyr). In order to acquire the derivative with the highest degree of substitution (DS), the optimum conditions of the sulfation were obtained based on response surface design (RSD), and the structural characterizations and antioxidant properties of the S-SGP were comparatively investigated by Fourier transform infrared spectrometry (FT-IR), GC-MS analysis, size exclusion chromatography (SEC), and DPPH radical assay, hydroxyl radical assay, superoxide radical assay, and reducing power assay, respectively. Results showed that the modification was successful, and obtained the optimum combination of conditions. Compared with SGP, the sulfated polysaccharide with relatively the decreased degree of molecular weight (Mw) but the same composition of monosaccharides exhibited better antioxidant activities in DPPH, hydroxyl, superoxide radical and reducing power assay. These results indicated that the antioxidant activities in vitro of the S-SGP from S. gracilis may be related to combined effects of Mw, monosaccharide composition, and sulfate content., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The heterotrimeric G protein subunit Gsα couples receptors to activate adenylyl cyclase and is required for the intracellular cAMP response and protein kinase A (PKA) activation. Gsα is ubiquitously expressed in many cell types; however, the role of Gsα in neural crest cells (NCCs) remains unclear. Here we report that NCCs-specific Gsα knockout mice die within hours after birth and exhibit dramatic craniofacial malformations, including hypoplastic maxilla and mandible, cleft palate and craniofacial skeleton defects. Histological and anatomical analysis reveal that the cleft palate in Gsα knockout mice is a secondary defect resulting from craniofacial skeleton deficiencies. In Gsα knockout mice, the morphologies of NCCs-derived cranial nerves are normal, but the development of dorsal root and sympathetic ganglia are impaired. Furthermore, loss of Gsα in NCCs does not affect cranial NCCs migration or cell proliferation, but significantly accelerate osteochondrogenic differentiation. Taken together, our study suggests that Gsα is required for neural crest cells-derived craniofacial development.

Asymmetric cell division, which plays fundamental roles in generating cell diversity during development, requires elaborate interactions between extrinsic cues and intrinsic cues. However, the precise nature of this type of interaction and its involving signaling mechanisms are poorly understood. Here, we demonstrate that Gαs is present in the proliferative region of ventricular zone in mouse developing neocortex and co-localizes with intrinsic cell fate determinant protein Numb in dividing apical progenitors. Targeted ablation of Gαs subunit in the cortical progenitor causes an alteration from asymmetric to symmetric cell division, consequently leading to increased progenitor proliferation. Mechanistically, we show that Gαs deletion significantly reduces Numb expression and activates notch signaling. Therefore, these results reveal a novel role of Gαs in control of neural progenitor asymmetric cell division via suppressing Numb mediated Notch signaling inhibition., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Core-shell structured multifunctional nanocarriers (NCs) of ZnO quantum dots-conjugated gold nanoparticles (Au NPs) as core and amphiphilic hyperbranched block copolymer as shell were synthesized for targeted anticancer drug delivery. The amphiphilic hyperbranched block copolymer contained poly(l-lactide) (PLA) inner arm and folate (FA)-conjugated a sulfated polysaccharide from Gynostemma pentaphyllum Makino (GPPS-FA) outer arm. The structure and properties of core-shell structured multifunctional nanocarriers were characterized and determined by UV-visible spectra, FT-IR spectra, X-ray diffraction (XRD), fluorescence spectroscopy and TEM analyses. The release results indicated that camptothecin (CPT) release from NCs at pH 7.4 was much greater than that at pH 5.3. The cytotoxicity studies showed that both the blank NCs and the CPT-loaded NCs provided high anticancer activity against Hela cells. Furthermore, nanocarriers gained specificity to target model cancer cells in this study due to the enhanced cell uptake mediated by FA moiety. The results indicated that the NCs not only had great potential as tumor-targeted drug delivery nanocarrier, but also had an assistant role in the treatment of cancer., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

A series of eight novel podophyllotoxin derivatives were designed, synthesized and evaluated for biological activities. The antiproliferative activities were tested against a panel of human cancer cell lines (K562, SGC, Hela and HepG) and the inhibition of tubulin polymerization was also evaluated. Compound 8e displayed significant antiproliferative activities for all four cell lines and strong levels of tubulin polymerization inhibition effect. Combined with cell apoptosis and cell cycle analysis, it demonstrated that compound 3e that effectively interfere with tubulin dynamics prevent mitosis in cancer cells, leading to cell cycle arrest and, eventually dose dependent apoptosis. All experimental measurements were also supported by molecular docking simulations of colchicine binding site, which revealed the governing forces for the binding behavior and a good relationship with anti-tubulin activity and antiproliferative activities. The synthesis and biological studies provided an interesting new class of antitubulin agents for development of lead compounds and also a direction for further structure modification to obtain more potent anti-cancer drugs., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Sulfated modification of a polysaccharide obtained from Radix hedysari (RHP) was studied. Four sulfated derivatives (RHPS) with variable degrees of substitution (DS) were obtained by the chlorosulfonic acid method with ionic liquids (ILs) as solvent and 4-dimethylaminopyridine (DMAP) as catalyst. The structures of RHPS were characterized by FT-IR spectra and ¹³C NMR spectra, and the results indicated that the sulfated groups were modified mainly at the C-6 position and C-2 position. Four kinds of RHPS showed different DS ranging from 0.63 to 1.45, and different weight-average molecular mass (Mw) ranging from 60.8 to 71.1 kDa with a little degradation. Compared with RHP, all of RHPS exhibited obvious antitumor activity on A549 cells and BGC-823 cells in vitro. However, they had no obvious influence on HEK293 cells, which indicated that they had low toxicity to normal cells. Flow cytometric studies indicated that the treatment of RHPS against A549 cells and BGC-823 cells could mediate the cell-cycle arrest in the G1 phase., (Copyright © 2012 Elsevier B.V. All rights reserved.)