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Two endophytic bacteria, designated strains CQZ9-1

Heavy metal pollution is one of the most serious environmental problems. Nanofiltration is an effective and potential membrane separation technology for removal of heavy metal ions from water. However, the separation performance and chlorine resistance of the nanofiltration membrane should be further improved in industry. In this study, positively charged polyamide (PA-PDMC) nanofiltration membranes were fabricated to remove heavy metal ions from water. The obtained membrane had high flux and chlorine resistance by grafting methacryloxyethyltrimethyl ammonium chloride (DMC) on the surface of 2-bromoisobutyryl bromide (BIBB) immobilized polyamide (PA-Br1) membranes via surface-initiated atom transfer radical polymerization (SI-ATRP). The retentions to divalent cations of the as-prepared PA-PDMC membrane was above 90% with the flux of 82.5 L m-2 h-1. Furthermore, the PA-PDMC membrane showed a stable separation performance during a long-time filtration process of 168 h, which exhibited an exceptional chlorine resistance.

Clostridium butyricum (CB) exerts beneficial actions in several disorders. However, the impact and molecular cues of CB in fat metabolism remain elusive. This study demonstrates the CB inhibition of fat deposition by increasing the relative number of adipose tissue-resident Treg cells (aTregs).CB is administered orally to wild type (WT) mice fed with chow diet, which decrease fat deposition and adipogenic gene expression, associating with elevated serum levels of butyrate. Sodium butyrate (SB) feeding mimics the CB suppression of fat accumulation. Of note, the frequency of aTregs in both the CB and SB treatments, analyzed by flow cytometry, is markedly increased, accompanied by activated Wnt10b expression in white adipose tissues. However, CB and SB fail to inhibit fat deposition in Wnt10b-KO mice. Intriguingly, CB and SB are able to alleviate the obesity, fatty liver, and glucose abnormalities in high fat diet (HFD)-fed WT mice.These findings suggest that CB, through its metabolite butyrate, inhibits fat deposition via potentiating aTreg cell generation, and support the option of CB and SB for therapeutic interventions in obesity and related disorders.

Plasma 5′-AMP (pAMP) is elevated in mouse models of type 2 diabetes. However, the metabolic regulatory role of adenine nucleotides in type 2 diabetes remains unclear. Adenine nucleotides and their metabolites in plasma and liver were examined by HPLC. 1H NMR-based metabolomics analysis was performed to explore the changes of metabolites in mouse models of type 2 diabetes. Na+/K+ ATPase and Na+/H+ exchanger activity were measured in response to adenine nucleotide metabolites. Human recombinant protein tyrosine phosphatase 1B (PTP1B) was used for enzyme kinetic assays. Protein binding assays were performed with microscale thermophoresis. The intracellular pH of hepatocyte AML12 cell lines was measured using the BCECF-AM method. We also analysed pAMP levels in participants with type 2 diabetes. Elevation of pAMP was a universal phenomenon in all mouse models of type 2 diabetes including db/db vs lean mice (13.9 ± 2.3 μmol/l vs 3.7 ± 0.9 μmol/l; p

Surface-initiated atom transfer radical polymerization (SI-ATRP) can precisely control the graft length and graft density of polymers. In this work, nonfouling nanofiltration membrane with tunable zwitterionic layer was fabricated by grafting sulfobetaine methacrylate (SBMA) on the surface of 2-bromoisobutyryl bromide (BIBB) -immobilized polyamide membranes (PA-Brs) via SI-ATRP. Zwitterionic layer with different graft length and graft density can be adjusted by varying the BIBB concentration or ATRP time, which can thus tune water flux and antifouling property of the membranes. When BIBB concentration is 1.00 wt% and ATRP time is 0.2 h, the optimal flux is 63.9 L m−2 h−1. In addition, the amount of foulant adsorbed on membrane is less than 20 μg cm−2. Flux decline ratio is about 5% and flux recovery ratio is more than 98% when humic acid is used for dynamic test, suggesting a nonfouling performance of zwitterionic membrane with SBMA graft content above 26 mol%.

Tributyltin (TBT), a widely distributed environmental pollutant, is toxic to animals and human beings. Although its toxicity, especially the immunosuppressive effect, has been reported a lot, the underlying molecular mechanisms are still unclear. In this study, we investigated the mechanisms of TBT-induced cytotoxicity both in vitro and in vivo. TBT induced cell death in both J774A.1 macrophages and mouse bone marrow-derived macrophages (BMDMs) as measured by the LDH and Annexin V-FITC/PI dual staining assays. Pretreatment with RIP1 inhibitor Necrostatin-1 (Nec-1) or transfection with Rip1 siRNA significantly suppressed TBT-induced cytotoxicity in J774A.1 macrophages or human embryonic kidney cell line (HEK293 cells). TBT-induced cell death was also markedly inhibited in RIP3−/− BMDMs. In agreement with in vitro results, TBT-induced in vivo immunotoxic effects including leukocyte depletion and thymus atrophy were significantly attenuated in RIP3−/− mice or WT mice treated with Nec-1. Notably, the mortality rate induced by TBT was remarkably reduced in RIP3−/− mice (100% vs. 12.5% lethality) or Nec-1-treated mice (100% vs. 59.2% lethality) respectively. These results reveal a critical role of RIP1 and RIP3 in TBT-induced toxicity both in vitro and in vivo.

Regarding the equipment in the cabin of a civil aircraft, the complexity of their shapes, the huge quantity, and the high requirements for engineering experience in cabin lighting design will result in huge change costs when design errors occur. This paper proposes a general cabin lighting design method, summarizes the elements that need to be considered in the cabin lighting design, and completes the cabin lighting design according to the design elements. In addition, the digital simulation method is used for verification during the design process. Finally, the data will be verified on the real sample, which checks the correctness of the design process, and lays the foundation for the future aircraft cabin lighting design and verification.

Linear proportional solenoid (LPS) is widely applied in different linear motion control systems as the electromagnetic actuator since its high reliability and low cost. LPS is difficult to optimize by changing a single variable due to amounts of structural design parameters, and each design parameter has a nonlinear relationship with the static electromagnetic force. This paper aims to improve LPS’s push force and response performance through magnetostatic finite element analysis (FEA) by ANSYS MAXWELL. This study compares FEA 2D model, 3D model and measurement results underrated coil current to verify the accuracy of FEA 2D model. In order to reveal the nonlinear relationship between shape design parameters and electromagnet design objectives, this study compares the influence degree of each variable on each design objective by conventional type LPS 2D FEA model. And for the purpose of improving LPS’s push force and response performance, a multi-objective optimization method has been proposed in this study based on genetic algorithm (GA) and magnetostatic FEA 2D model for optimizing the shape design parameters. All the study results were validated in both static conditions and dynamic conditions. The comparison between manufactured optimal type and conventional type results shows that the static push force in working stroke is improved 30.1%, displacement step response rise time is reduced 5.2% and 43.4%, and force step response rise time is reduced 20.5% and 44.6% with different return spring stiffness. Above all, LPS static and dynamic performance has been improved directly and the validation of proposed optimization method is verified in this paper.

Necroptosis, a key form of programmed lytic cell death, has gained recognition as an important driver in various inflammatory diseases. Inhibition of kinase activity of receptor interaction protein kinase 1 (RIPK1), which block the activation of the necroptosis pathway has shown therapeutic potential in many human diseases. In order to find new chemotypes of RIPK1 inhibitors, a virtual screening workflow was performed and led to the discovery of 8-benzoyl-3-benzyl-1,3,8-triazaspiro[4.5]decane-2,4-dione (compound 8) as a hit compound. Further structural optimization identified a series of 2,8-diazaspiro[4.5]decan-1-one derivatives as potent RIPK1 inhibitors. Among them, compound 41 exhibited prominent inhibitory activity against RIPK1 with an IC

Tributyltin (TBT), a bioaccumulative and persistent environmental pollutant, has been proposed as a metabolism disruptor and obesogen through targeting peroxisome proliferator-activated receptor gamma (PPARγ) receptor pathway. However, it remains unknown whether this biological effect occurs in macrophage, a cell type which cooperates closely with hepatocytes and adipocytes to regulate lipid metabolism. This study for the first time investigated the effect of TBT on PPARγ pathway in macrophages. Our results indicated that nanomolar levels of TBT was able to strongly activate PPARγ in human macrophages. TBT treatment also markedly increased the intracellular lipid accumulation, and enhanced the expression of lipid metabolism-related genes in macrophages, while these effects were all significantly down-regulated in PPARγ-deficient macrophages, confirming the involvement of PPARγ in TBT-induced lipogenesis. Next, a mouse model that C57BL/6 mice were orally exposed to TBT with the doses (250 and 500 μg/kg body weight) lower than NOAEL (no observed adverse effect level) was used to further investigate the in vivo mechanisms. And the in vivo results were consistent with cellular assays, confirming the induction of PPARγ and the increased expression of lipogenesis-regulating and lipid metabolism-related genes by TBT in vivo. In conclusion, this study not only provided the first evidence that TBT stimulated lipogenesis, activated PPARγ and related genes in human macrophages, but also provided insight into the mechanism of TBT-induced metabolism disturbance and obesity through targeting PPARγ via both in vitro cellular assays and in vivo animal models.

The epidemic of Coronavirus Disease 2019 has been a serious threat to public health worldwide. Data from 23 January to 31 March at Jiangsu and Anhui provinces in China were collected. We developed an adjusted model with two novel features: the asymptomatic population and threshold behavior in recovery. Unbiased parameter estimation identified faithful model fitting. Our model predicted that the epidemic for asymptomatic patients (ASP) was similar in both provinces. The latent periods and outbreak sizes are extremely sensitive to strongly controlled interventions such as isolation and quarantine for both asymptomatic and imported cases. We predicted that ASP serve as a more severe factor with faster outbreaks and larger outbreak sizes compared with imported patients. Therefore, we argued that the currently strict interventions should be continuously implemented, and unraveling the asymptomatic pool is critically important before preventive strategy such as vaccines., Highlights A mathematical model with threshold behavior in recovery and asymptomatic patients.Asymptomatic infections may trigger faster outbreak with larger outbreak size.COVID‐19 outbreak size and latent period are sensitive to mutual contacts.Strict interventions should be implemented to restrict potential outbreak.

Hepatocyte cell death and liver inflammation have been well recognized as central characteristics of nonalcoholic steatohepatitis (NASH), however, the underlying molecular basis remains elusive. The kinase receptor-interacting protein 1 (RIP1) is a key regulator of apoptosis, necroptosis and inflammation, we thus hypothesized that the kinase activity of RIP1 may be involved in the pathogenesis of NASH. Wild-type and RIP1 kinase-dead (Rip1K45A/K45A) mice were fed with methionine-and choline-deficient diet (MCD) or high-fat diet (HFD) to establish distinct NASH models. In both models, compared to WT mice, Rip1K45A/K45A mice exhibited significantly less liver injury, less steatosis, decreased inflammation, and less cell death in liver tissue. Moreover, hepatic fibrosis as characterized by Sirius Red staining, expression of α-SMA and other fibrosis markers, were significantly alleviated in Rip1K45A/K45A mice than WT controls. Furthermore, using bone marrow transplantation to create chimeric mice, we found that it is the RIP1 kinase in hematopoietic-derived macrophages contributing mostly to the disease progression in NASH. Results from in vitro studies were in agreement with the in vivo data, demonstrating that RIP1 kinase was required for inflammasome activation and cell death induced by saturated fatty acid (palmitic acid) in bone marrow-derived macrophages (BMDMs). At last, we also found that the phosphorylation and expression of RIP1 was obviously increased in patients with NAFLD or NASH, but not in healthy controls. In summary, our results indicate that RIP1 kinase is activated during the pathogenesis of steatohepatitis, and consequently induces inflammation and cell death in macrophages, contributing to the disease progression. Our study suggests that macrophage RIP1 kinase represents a specific and potential target for the treatment of NASH.

Gestational trophoblastic diseases (GTDs) are characterized by vascular abnormalities of the trophoblast, but their pathogenesis is unknown. Angiogenin (ANG) and matrix metalloproteinase (MMP)-2, which are molecules implicated in the angiogenic process, may play some role in this process.We determined ANG and MMP-2 in the placental tissues of 26 patients who had a benign mole (BM), 12 patients with gestational trophoblast neoplasia (GTN) (1 invasive hydatidiform mole, 10 choriocarcinomas, and 1 placental-site trophoblastic tumor), and 28 normal chorionic villi (NCV) subjects using immunohistochemistry staining. We obtained the serum samples from 20 patients with GTDs and 20 early pregnant women and evaluated them by the enzyme linked immunosorbent assay.ANG expression in GTN (66.7%) and BM (100%) samples were both significantly higher (strong/intermediate staining) than in NCV (60.7%) samples (P .001). Similarly, the immunoreactivities of MMP-2 in the GTN (66.7%) and BM (80.8%) samples were significantly elevated compared to that of the NCV (57.1%) samples (P .001). The levels of ANG and MMP-2 in the maternal serum of the GTN group were both significantly higher than those of the control group (P .001). ANG and MMP-2 expressions were associated with gestation age, clinical stage, and FIGO stage. A positive correlation between ANG and MMP-2 expression was observed (rs = 0.725; P .01).ANG and MMP-2 levels were significantly elevated in the placental tissues and maternal serum from patients with GTDs. Further studies with more patients may clarify the vascular abnormalities in GTDs and determine potential biomarkers in the differential diagnosis of GTDs.

Background The effectiveness of meditative movement (tai chi, yoga, and qigong) on COPD remained unclear. We undertook a systematic review and meta-analysis to determine the effectiveness of meditative movement on COPD patients. Methods We searched PubMed, Web of Science, EMBASE, and the Cochrane Center Register of Controlled Trials for relevant studies. The methods of standard meta-analysis were utilized for identifying relevant researches (until August 2017), quality appraisal, and synthesis. The primary outcomes were the 6-minute walking distance (6MWD), lung function, and dyspnea levels. Results Sixteen studies involving 1,176 COPD patients were included. When comparing with the control group, the 6MWD was significantly enhanced in the treatment group (3 months: mean difference [MD]=25.40 m, 95% CI: 16.25 to 34.54; 6 months: MD=35.75 m, 95% CI: 22.23 to 49.27), as well as functions on forced expiratory volume in 1 s (FEV1) (3 months: MD=0.1L, 95% CI: 0.02 to 0.18; 6 months: MD=0.18L, 95% CI: 0.1 to 0.26), and FEV1 % predicted (3 months: 4L, 95% CI: 2.7 to 5.31; 6 months: MD=4.8L, 95% CI: 2.56 to 7.07). Quality of life for the group doing meditative movement was better than the control group based on the Chronic Respiratory Disease Questionnaire dyspnea score (MD=0.9 units, 95% CI: 0.51 to 1.29) and fatigue score (MD=0.75 units, 95% CI: 0.42 to 1.09) and the total score (MD=1.92 units, 95% CI: 0.54 to 3.31). Conclusion Meditative movement may have the potential to enhance lung function and physical activity in COPD patients. More large-scale, well-designed, multicenter, randomized controlled trials should be launched to evaluate the long-range effects of meditative movement.

Separation membranes with high perm-selectivity, good stability and anti-fouling properties are critical for water treatment and green chemical processing. We synthesized soft polymeric particles, zwitterionic nanogels (ZNGs), using a facile and straightforward surfactant-free emulsion polymerization. Novel thin-film nanocomposite membranes (TFNMs) containing ZNGs were prepared by interfacial polymerization using piperazine and trimesoyl chloride. The ZNG particles were well compactible with the polyamide membrane matrix, rendering high separation performance. Both the water permeability and solute selectivity, e. g., JH2O = 106.3 L m−2 h−1 MPa−1, RNa2SO4 = 97.8%, RNaCl = 31.6%, were increased compared to conventional polyamide thin-film membranes. The mechanism of this high performance was firstly studied in depth at molecular level with the positron annihilation spectroscopy. The existence of nanoscale pores in ZNGTFNMs provide preferential flow paths for water molecules, thus fostering the exceptional perm-selectivity coupled with remarkable stability and anti-fouling properties. Moreover, the as-prepared ZNGTFNMs were used for antibiotics desalination and concentration. For example, the antibiotic erythromycin content in mixed feed solution increases almost linearly from 100 to 360 mg L−1 (the value is 3.5 times higher than the original concentration) within 6 h continuous operation. Therefore, this ZNG embedded TFNMs exhibit great potential applications in water purification and salts/organics separation.

Heavy metal pollution is one of the most serious environmental problems. Nanofiltration (NF) is an effective and potential membrane separation technology for removal of heavy metal ions from water. However, the separation performance and chlorine resistance of NF membranes should be further improved in industry. Herein, to obtain exceptional water permeability and chlorine resistance, novel positively charged polyamide (PA-PDMC) NF membranes were fabricated by surface-initiated atom transfer radical polymerization (SI-ATRP), through which methacryloxyethyltrimethyl ammonium chloride (DMC) was grafted to the 2-bromoisobutyryl bromide (BIBB) exposed on the surface of polyamide (PA-Br1) membrane. The graft length of positively charged polymer chains were controlled by ATRP time, which furtherly exerted influences on the surface structures and properties of PA-PDMC membranes. At the optimal graft content, the retentions to MgCl2, CaCl2, CuCl2, ZnCl2 of the as-prepared PA-PDMC membrane were 92.8%, 90.8%, 93.5% and 96.8% respectively with the flux of 82.5 L m−2 h−1, which maintained stability during the long-term operation process of 168 h. Moreover, the PA-PDMC membrane exhibited exceptional chlorine resistance at the chlorination condition of 12,000 ppm h.

This paper employed a multi-objective Genetic Algorithm (GA) process to optimize the structure parameters of Linear Proportional Solenoid (LPS). And designed objectives include magnitude of static push force, stability of push force with displacement in working range and push force to mass ratio. A two-dimensional finite element analysis model is presented to reduce the large calculation time generated by GA process. The optimization process result of LPS shape parameters is obtained and the optimal LPS is manufactured. Through using a high-precision measuring device in the static push force test, a comparison result between conventional shape and optimal shape shows that the proposed optimization strategy is feasible.

Hepatic gluconeogenesis is the major contributor to the hyperglycemia observed in both patients and animals with type 2 diabetes. The transcription factor FOXO1 plays a dominant role in stimulating hepatic gluconeogenesis. FOXO1 is mainly regulated by insulin under physiological conditions, but liver-specific disruption of Foxo1 transcription restores normal gluconeogenesis in mice in which insulin signaling has been blocked, suggesting that additional regulatory mechanisms exist. Understanding the transcriptional regulation of Foxo1 may be conducive to the development of insulin-independent strategies for the control of hepatic gluconeogenesis. Here, we found that elevated plasma levels of adenine nucleotide in type 2 diabetes are the major regulators of Foxo1 transcription. We treated lean mice with 5'-AMP and examined their transcriptional profiles using RNA-seq. KEGG analysis revealed that the 5'-AMP treatment led to shifted profiles that were similar to db/db mice. Many of the upregulated genes were in pathways associated with the pathology of type 2 diabetes including Foxo1 signaling. As observed in diabetic db/db mice, lean mice treated with 5'-AMP displayed enhanced Foxo1 transcription, involving an increase in cellular adenosine levels and a decrease in the S-adenosylmethionine to S-adenosylhomocysteine ratio. This reduced methylation potential resulted in declining histone H3K9 methylation in the promoters of Foxo1, G6Pc, and Pepck. In mouse livers and cultured cells, 5'-AMP induced expression of more FOXO1 protein, which was found to be localized in the nucleus, where it could promote gluconeogenesis. Our results revealed that adenine nucleotide-driven Foxo1 transcription is crucial for excessive glucose production in type 2 diabetic mice.

Antifouling performance of nanofiltration membrane is critical in applications like water treatment. In this study, surface zwitterionization was conducted by 1, 3-propanesultone ring-opening directly on the nanofiltration membrane prepared by interfacial polymerization of 3,3′-diamino-N-methyldipropylamine and 1, 3, 5-benzenetricarboxylic chloride. The zwitterionic structures improve the hydrophilicity of nanofiltration membrane, thus increase the water permeability and antifouling performance. The zwitterionic membrane have a 72 L m−2 h−1 water flux at the optimize condition, which was about 2.4 times that of the pristine membrane without zwitterionization, and with a 89% rejection of MgCl2. Meanwhile, the zwitterionic membrane will have better antifouling performance to protein and polysaccharose. The flux recovery ratio of bovine serum albumin, sodium alginate and lysozyme were all above 95%. The prepared zwitterionic membrane presents prominent high water flux and fouling-resistance performance, indicating it's promising application potential in organic wastewater treatment.

Polysaccharide nanofiltration (NF) membrane with traditional modification normally suffers from poor water permeability as a result of its tight packing of polymeric chains. In this work, a novel membrane building block, polyelectrolyte complex (PEC) nanoparticles (NPs) armed with adjustable content of sulfated groups was developed using chitosan and dextran sulfate sodium. The sulfated polyelectrolyte complex membranes (SPECMs) were first prepared by solution-casting and glutaraldehyde crosslinking process, and their structural characteristics and surface properties were systematically investigated. Intrinsic aggregation structure combined with numerous sulfate groups attenuates packing density of polymeric chains and promotes hydrophilicity, endowing SPECMs with high flux and perm-selectivity. SPECMs achieved a water permeability of 6.71 L m−2 h−1 bar−1, which was ∼2.3 times higher than pristine sulfated chitosan membrane. The selectivity for NaCl/Na2SO4 separation and NaCl/methyl blue dye separation were as high as 13.1 and 850.0, respectively. Moreover, SPECMs featured efficient dye antifouling property with low flux decline ratio (6.8%) and high recovery ratio (96.8%), which was primarily attributed to its hydrophilicity and smooth surface. The prominent perm-selectivity associated with antifouling property suitably position SPECMs for practical small organic molecule/inorganic salt mixture separation in a long-term process.

Although multiple methods and materials have been developed to fabricate pH-responsive membranes, separating organics/inorganic salts mixtures and divalent/monovalent ions systems with these membranes still remains a challenging task. In this study, pH-responsive nanofiltration membranes (PCHMs) with tunable ion selectivity were first prepared with poly(carboxybetaine methacrylamide (CBMA) -co-N-(Hydroxymethyl) acrylamide) (PCHs) through surface coating and glutaraldehyde cross-linking method. The membrane ion selectivity towards divalent ions and monovalent ions can be well tuned by adjusting the pH of feeding solution. At pH 3.0, the retention of PCHM3 (CBMA content in PCHs is 48.8 mol%) to MgCl 2 (92.9%) is much higher than that to NaCl (3.4%). And by adjusting the feed pH value to pH 10.0, the retention to Na 2 SO 4 (91.8%) is much higher than that to NaCl (3.8%). While at neutral environment, PCHM3 allows the transport of the inorganic salts but blocks the transport of PEG800. It indicates that PCHMs could be a kind of high performance membranes for divalent/monovalent ions separation and organics/inorganic salts separation. Furthermore, the PCHMs possess a reversible and stable pH-responsive property, which is essential for practical charge-based separations. The responsiveness and adaptiveness of the PCHMs to the feeding solution make it being a versatile material for custom-designed membrane separations.

B cell-mediated humoral immunity plays a vital role in viral infections, including chronic hepatitis B virus (HBV) infection, which remains a critical global public health issue. Despite hepatitis B surface antigen-specific antibodies are essential to eliminate viral infections, the reduced immune functional capacity of B cells was identified, which was also correlated with chronic hepatitis B (CHB) progression. In addition to B cells, T follicular helper (Tfh) cells, which assist B cells to produce antibodies, might also be involved in the process of anti-HBV-specific antibody production. Here, we provide a comprehensive review of the role of various subsets of B cells and Tfh cells during CHB progression and discuss current novel treatment strategies aimed at restoring humoral immunity. Understanding the mechanism of dysregulated B cells and Tfh cells will facilitate the ultimate functional cure of CHB patients.

Superhydrophilic and antibacterial zwitterionic polyamide thin film composite nanofiltration membranes (ZTFCMs) with excellent water permeability and antibiotics selectivity were prepared through the interfacial polymerization of N-aminoethyl piperazine propane sulfonate (AEPPS) monomer with trimesoyl chloride (TMC) monomer on top of polysulfone ultrafiltration supporting membranes (PSF-UF). Chemical structures of the ZTFCMs were evaluated by attenuated total reflectance fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS) and element analysis (EA), with membrane microstructures and hydrophilicity being examined by microscopies and water contact angle, respectively. Superhydrophilic ZTFCMs were obtained with more AEPPS content on membrane surface, and they show excellent water permeability coupled with high erythromycin (ERY) retention. For example, the water permeability and retention to ERY of the ZTFCM (AEPPS aqueous concentration is 3.0 wt%) are 8.4 L m −2 h −1 bar −1 and 96.5% (applied pressure is 6 bar), respectively. In addition, the ERY concentration of the mixed feed increases exponentially from 100.0 to 350.7 mg L −1 with a treatment capacity of 61.6 L m −2 h −1 during 7.25 h continuous concentration operation. Furthermore, ZTFCMs show a stable and good separation performance during a long-time filtration process of 168 h and exhibit an exceptional antibacterial property assessed by Escherichia coli adhesion.

PPARγ has emerged as a master regulator of macrophage polarization and is the molecular target of the thiazolidinedione drugs. Here we show that apigenin binds and activates PPARγ by acting as a modulator. Activation of PPARγ by apigenin blocks p65 translocation into nuclei through inhibition of p65/PPARγ complex translocation into nuclei, thereby decreasing NF-κB activation and favoringM2 macrophage polarization. In HFD and ob/ob mice, apigenin significantly reverses M1 macrophage into M2 and reduces the infiltration of inflammatory cells in liver and adipose tissues, as well as decreases the levels of pro-inflammatory cytokines, thereby alleviating inflammation. Strikingly, apigenin reduces liver and muscular steatosis, decreases the levels of ALT, AST, TC and TG, improving glucose resistance obviously. Unlike rosiglitazone, apigenin does not cause significant weight gain, osteoporosis et al. Our findings identify apigenin as a modulator of PPARγ and a potential lead compound for treatment of metabolic disorders., Graphical Abstract Image 1, Highlights • Apigenin binds and activates PPARγ and significantly reverses the polarization of macrophages from M1 to M2 phenotype. • Activation of PPARγ by apigenin blocks p65 translocation through inhibiting p65/PPARγ complex translocation into nucleus. • Apigenin significantly attenuates metabolic inflammation and disorders without causing some side effects as TZD drugs do. PPARγ is the molecular target of the thiazolidinedione drugs to treat type II diabetes. However, TZD drugs have some side effects including cardiovascular failure, liver toxicity, bone fractures and potential carcinogenesis, which have greatly limited their clinical use. Here, we find apigenin, a flavonoid molecule abundant in various fruits and vegetables, can control macrophage fate to inhibit inflammation and metabolic syndrome without causing some side effects as TZD drugs. Further study indicates that apigenin can target PPARγ with a range of beneficial effects and may represent a lead compound for developing new therapies against metabolic disorders.

The poor dispensability of pristine carbon nanotubes in water impedes their implications in thin-film nanocomposite membranes for crucial utilities such as water purification. In this work, high-flux positively charged nanocomposite nanofiltration membranes were exploited by uniformly embedding poly(dopamine) modified multiwall carbon nanotubes (PDA-MWCNTs) in polyamide thin-film composite membranes. With poly(dopamine) modification, fine dispersion of MWCNTs in polyethyleneimine (PEI) aqueous solutions was achieved, which was interracially polymerized with trimesoyl chloride (TMC) n-hexane solutions to prepare nanocomposite membranes. The compatibility and interactions between modified MWCNTs and polyamide matrix were enhanced, attributed to the poly(dopamine) coatings on MWCNT surfaces, leading to significantly improved water permeability. At optimized conditions, pure water permeability of the PEI/PDA-MWCNTs/TMC nanofiltration membrane (M-4) was 15.32 L m(-2) h(-1) bar(-1), which was ∼1.6 times increased compared with that of pristine PEI/TMC membranes. Salt rejection of M-4 to different multivalent cations decreased in the sequence ZnCl2 (93.0%)MgCl2 (91.5%)CuCl2 (90.5%) ≈ CaCl2, which is well-suited for water softening and heavy metal ion removal.

Zwitterionic monomers have aroused great attraction for membrane preparation due to their tremendous hydrophilicity and antifouling properties. Zwitterionic diamine monomer N-aminoethyl piperazine propane sulfonate (AEPPS) was added into m-phenylenediamine (MPD) aqueous solution to react with trimesoyl chloride (TMC) via interfacial polymerization to fabricate zwitterionic thin film composite reverse osmosis membrane (TFCMZs). The membrane preparation conditions, including AEPPS content, TMC concentration and curing temperature, were systematically evaluated. The membrane surface hydrophilicity and antifouling properties of TFCMZs were greatly enhanced via introducing AEPPS into membranes. When tested with brackish water desalination conditions (2000 ppm NaCl feed solution at 1.5 MPa and 25 °C), the water flux of TFCMZs containing 10% AEPPS was significantly increased to be 54.5 ± 3.2 L·m− 2·h− 1, which is about an 82% increase compared with the pristine membrane, while the NaCl rejection remains above 98%. Furthermore, using tannic acid (TA) and sodium alginate (NaAlg) as model foulants, the TFCMZs displayed outstanding fouling-resistant and easy-cleaning properties. TFCMZs present both admirable separation and fouling-resistance performance, which indicates that TFCMZs have wide application potential for brackish water desalination.

Many immunostimulants act as vaccine adjuvants via activation of the innate immune system, although in many cases it is unclear which specific molecules contribute to the stimulatory activity. QS-21 is a defined, highly purified, and soluble saponin adjuvant currently used in licensed and exploratory vaccines, including vaccines against malaria, cancer, and HIV-1. However, little is known about the mechanisms of cellular activation induced by QS-21. We observed QS-21 to elicit caspase-1-dependent IL-1β and IL-18 release in antigen-presenting cells such as macrophages and dendritic cells when co-stimulated with the TLR4-agonist adjuvant monophosphoryl lipid A. Furthermore, our data suggest that the ASC-NLRP3 inflammasome is responsible for QS-21-induced IL-1β/IL-18 release. At higher concentrations, QS-21 induced macrophage and dendritic cell death in a caspase-1-, ASC-, and NLRP3-independent manner, whereas the presence of cholesterol rescued cell viability. A nanoparticulate adjuvant that contains QS-21 as part of a heterogeneous mixture of saponins also induced IL-1β in an NLRP3-dependent manner. Interestingly, despite the role NLRP3 plays for cellular activation in vitro, NLRP3-deficient mice immunized with HIV-1 gp120 and QS-21 showed significantly higher levels of Th1 and Th2 antigen-specific T cell responses and increased IgG1 and IgG2c compared with wild type controls. Thus, we have identified QS-21 as a nonparticulate single molecular saponin that activates the NLRP3 inflammasome, but this signaling pathway may contribute to decreased antigen-specific responses in vivo.

Metabolism serves mammalian feeding and active behavior, and is controlled by circadian clock. The molecular mechanism by which clock factors regulate metabolic homeostasis under oxidative stress is unclear. Here, we have characterized that the daily oxygen consumption rhythm was deregulated in Per1 deficient mice. Per1 deficiency impaired daily mitochondrial dynamics and deregulated cellular GPx-related ROS fluctuations in the peripheral organs. We identified that PER1 enhanced GPx activity through PER1/GPX1 interaction in cytoplasm, consequently improving the oxidative phosphorylation efficiency of mitochondria. Per1 expression was specifically elevated in the fasting peripheral organs for protecting mitochondrial from oxidation stress. These observations reveal that Per1-driven mitochondrial dynamics is a critical effector mechanism for the regulation of mitochondrial function in response to oxidation stress., Graphical abstract Image 1, Highlights • PER1 regulates daily metabolic rhythm uncoupled from feeding oscillations. • Per1 deficiency impairs mitochondrial dynamics and deregulates ROS fluctuations. • PER1 interactions with GPX1 and increases mitochondrial ROS clearance. • Fasting elevates Per1 expression to protect mitochondrial from oxidation stress.

Bisphenol A (BPA) and its replacement analog, bisphenol S (BPS), have been proposed as environmental obesogen to disrupt the lipid metabolism through regulating peroxisome proliferator-activated receptor gamma (PPARγ) receptor. However, there is a dearth of information on whether this biological effect can occur in human macrophage, a cell type which closely interacts with adipocytes and hepatocytes to control lipid metabolism. Here, we for the first time investigate the activity of BPA and BPS on PPARγ pathway in human macrophages. The results demonstrated that BPA and BPS served as activators of PPARγ in human macrophage cell line, and significantly induced the expression of lipid metabolism-related genes, including fatty acid binding protein 4 (FABP4), cluster of differentiation 36 (CD36) and nuclear receptor subfamily 1 group H member 3 (NR1H3). In PPARγ knockout cells, expression of these genes was down-regulated, suggesting that these genes are dependent on PPARγ. The underlying mechanisms were further investigated using an in vivo mouse model, and the results confirmed the induction of PPARγ and its respective target genes in mice following exposure to BPA or BPS. Moreover, the observed alteration of PPARγ expression highly correlated with the disturbance of metabolism profiles in liver tissues as detected by 1H Nuclear Magnetic Resonance (NMR)-based metabonomics. Overall, this study provided the first evidence that BPA and BPS activated PPARγ and its target genes in human macrophages, and provided comprehensive information to confirm that BPA and BPS disturb the metabolism through targeting PPARγ via both in vitro assays and in vivo animal models.

Limited proteolysis of gasdermin D (GSDMD) generates an N-terminal pore-forming fragment that controls pyroptosis in macrophages. GSDMD is processed via inflammasome-activated caspase-1 or -11. It is currently unknown whether macrophage GSDMD can be processed by other mechanisms. Here, we describe an additional pathway controlling GSDMD processing. The inhibition of TAK1 or IκB kinase (IKK) by the Yersinia effector protein YopJ elicits RIPK1- and caspase-8–dependent cleavage of GSDMD, which subsequently results in cell death. GSDMD processing also contributes to the NLRP3 inflammasome–dependent release of interleukin-1β (IL-1β). Thus, caspase-8 acts as a regulator of GSDMD-driven cell death. Furthermore, this study establishes the importance of TAK1 and IKK activity in the control of GSDMD cleavage and cytotoxicity.

Piceatannol, a natural derivative of resveratrol, has been shown to exert similar anti-oxidant and anti-inflammatory effects as resveratrol. However, it remains unknown whether piceatannol has hepatoprotective effect against acute liver injury. In this study, we investigated the in vivo effect of piceatannol on D-GalN/LPS-induced fulminant hepatic failure (FHF), and its in vitro effect on ER stress-inducing drug thapsigargin (TG)-induced proinflammatory cytokines production and ROS release. Our results indicated that piceatannol markedly decreased the mortality rate, reduced the serum levels of alanine transaminase and aspartic aminotransferase, ameliorated the liver damage induced by D-GalN/LPS in mice. In addition, piceatannol reduced the expression of proinflammatory cytokines, including TNF-α, IL-1β and IL-6, the expression of ER stress markers CHOP and phosphorylated-IRE1α, and the generation of oxidative stress in D-GalN/LPS-treated mouse liver. In vitro results were consistent with in vivo observations, demonstrating that piceatannol suppressed the secretion of proinflammatory cytokines, inflammasome activation and the production of ROS induced by TG with or without LPS priming in J774A.1 macrophages. Our study proposes piceatannol as a promising medication for preventing acute liver failure and the mechanisms may be related to its inhibitory effects on ER stress, inflammation and oxidative stress.

Endoplasmic reticulum (ER) stress contributes to the development and progression of many chronic inflammatory diseases, including type 2 diabetes, obesity, atherosclerosis, neurodegenerative diseases, and cancer. ER stress has been reported to induce inflammasome activation and release of mature IL-1β, which contributes to many inflammatory diseases. The molecular mechanisms that activate the inflammasome during ER stress are still poorly understood. Here we report that the kinase receptor-interacting protein 1 (RIP1) plays an important role in ER stress-induced activation of inflammasome. Inhibition of RIP1 kinase activity by Necrostatin-1 or siRNA-mediated RIP1 knockdown significantly reduced ER stress-induced caspase-1 cleavage and IL-1β secretion in both bone marrow-derived macrophages (BMDMs) and J774A.1 macrophages. We speculate that the mitochondria fission factor dynamin-related protein 1 (DRP1) and reactive oxygen species (ROS) might function as the effectors downstream of RIP1 to mediate inflammasome activation. Our study reveals a critical role for RIP1 in regulating ER stress-induced inflammation responses, and proposes RIP1 as a potential pharmaceutical target to treat diseases resulting from unresolved ER stress-related inflammation.

Two new supramolecular compounds were synthesized and characterized with the formula of [Cu(bipy)2(OAc)]·(DBrS)1/2·5H2O 1, [Co(phen)2(CO3)]·(DBrS)1/2·5H2O 2 (H2DBS = meso-2,3-dibromosuccinic acid; bipy = 2,2’-bipyridine; phen = 1,10-phenanthroline). The crystal structures of complexes were determined by X-ray single-crystal diffraction. Complex 1 represents R6 water clusters and complex 2 stabilizes in a 1D water tape notated T4(2)6(2). For 2, the 2D layer is defined as a 2D (3,4,6)-connected network with the Schlafli symbol of (4·5·6)4(42·5·6·72)(42·5)2(44·52·62·74·93). Results about i.r. spectra and elemental analyses are presented.

Two coordination polymers, Cu(bipy)(DBrS) 1 and Co(bipy)(H2O)2(DBrS) 2 with bipy = 2,2′-bipyridine, H2DBrS = meso-2,3-dibromosuccinic acid represent rare examples of metal complexes with meso-2,3-dibromosucciniato ligand. Within 1, the CuN2O4 octahedra are interlinked by DBrS2− anions in a μ 2-κ 2ΟΟ′:κ 2Ο″Ο″′ coordination mode to form $${}_{\infty }^{1}$$ [Cu(bipy)(DBrS)2/2] chains, which are further assembled into 2D supramolecular layers by interchain π···π stacking interactions. In 2, the six-coordinated Co2+ ions are bridged by DBrS2− anions in a μ 2-κΟ:κΟ′ fashion to form $${}_{\infty }^{1}$$ [Co(bipy)(H2O)2(DBrS)2/2] polymer chains and the adjacent 1D chains interconnected by weak C–H···O hydrogen bonds to construct 2D supramolecular layers. The temperature-dependent magnetic susceptibility shows that 2 obeys Curie–Weiss law χ m = C/(T − Θ) with C = 2.16 cm3 K mol−1 and Θ = −0.40 K and the best fit gave a weak antiferromagnetic coupling (J = −0.89 cm−1) among Co2+ ions. Results about infrared spectra and elemental analyses are also presented. In the present paper, we have discussed the syntheses and crystal structures of two metal–organic based 1D polymers of Cu(II) and Co(II) respectively, and magnetic behavior in the temperature range 2–300 K of the Co(II) compound. The compounds feature 1D chains based on bridging dibromosucciniato. The Cu(II) compound represents the first example of meso-2,3-dibromosuccinic acid coordination polymers that exhibit μ 2-κ 2ΟΟ′:κ 2Ο″Ο″′ coordination mode.

A series of carefully designed polyamide thin film composite nanofiltration membranes (TFCMs) were prepared via interfacial polymerization of piperazine (PIP), N-aminoethyl piperazine (AEP) or N-aminoethyl piperazine propane sulfonate (AEPPS) with trimesoyl chloride (TMC) on top of hydrolysed polyacrylonitrile ultrafiltration supporting membranes (hPAN-UF). Chemical structures of the TFCMs were evaluated by attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and X-ray photoelectron spectroscopy (XPS). The cross section and surface characteristics of the TFCMs were examined by scanning electron microscopy (SEM), atomic force microscopy (AFM), water contact angle measurements and zeta potential. Membrane fouling characteristics were studied by the adsorption of bovine serum albumin (BSA) and lysozyme (LYZ). Varying the diamine affected the structure of the resulting membranes, which ultimately defined separation performance and antifouling property. The results of water contact angle indicated zwitterionic membranes were more hydrophilic, which incorporated polyamide selective layer thickness to account for their high water flux (80.3 L m−2 h−1). Compared with other TFCMs, zwitterionic membranes showed an improved antifouling property due to their high hydrophilicity, low surface electrical charges and smooth surface roughness. These results provide important insights into the high water permeability and low fouling characteristics of zwitterionic nanofiltration membranes from molecular structure and interfacial polymerization process.

Two metal oxygen connectivities Cu(II) complexes [Cu3(H2O)2(μ 3–OH)2(μ 2–OAc)2(DBrS)]⋅4H2O 1 and [Cu3(H2O)4(DBrS)2](DBrSM)⋅4H2O 2 have been synthesized (H2DBrS = HOOC–(CHBr)2–COOH, DBrSM = (3aR,6aS)-3a,6a-dibromo-3,6-dioxohexahydrofuro[3,4-c]furan-1,4-bis(olate)). Within 1, two CuO5 square pyramid are edge-shared to generate di-square pyramids, each of which are corner-shared to one another CuO6 octahedron to form polyhedral copper oxygen chains. The resulted polynuclear single chains are bridged by meso-2,3-dibromossuccinate anions to generate 2D layers. Compound 2 features a trimer polyhedrons unit with two CuO5 square pyramid and CuO6 octahedron, which are further interconnected by meso-2,3-dibromossuccinate anions into 3D coordination polymer. The study of magnetic property indicates that antiferromagnetic coupling interactions exist between the adjacent Cu(II) ions.