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BACKGROUND AND AIMS There is accumulating evidence that gut microbiota plays a key role in cardiovascular diseases. Gut bacteria can transform dietary choline, l-carnitine, and trimethylamine N-oxide (TMAO) into trimethylamine, which can be oxidized into TMAO again in the liver. However, the alterations of the gut microbiota in large artery atherosclerotic (LAA) stroke and cardioembolic (CE) stroke have been less studied. METHODS AND RESULTS We performed a case-control study in patients with LAA and CE types of strokes. We profiled the gut microbiome using Illumina sequencing of the 16S ribosomal RNA gene (V4-V5 regions), and TMAO was determined via liquid chromatography-tandem mass spectrometry. Our results showed that the TMAO levels in the plasma of patients with LAA and CE strokes were significantly higher than those in controls (LAA stroke, 2931 ± 456.4 ng/mL; CE stroke, 4220 ± 577.6 ng/mL; healthy control, 1663 ± 117.8 ng/mL; adjusted p

In this work, zinc ferrite spinel with different zinc contents (ZnxFe3-xO4) was synthesized by a hydrothermal method and used for removing As(V) in aqueous solution. X-ray diffraction (XRD) results indicated that in the crystal structure of ZnxFe3-xO4, the zinc atoms tended to occupy the octahedral sites for x 0.6. The size of ZnxFe3-xO4 crystallites increased with the increasing zinc content. Batch adsorption experiments showed that the adsorption isotherms could be well described by the Langmuir model, while the adsorption kinetics followed the pseudo-second-order kinetic model. Zinc ferrite exhibited the highest adsorption capacity towards As(V) when x = 0.6. Study of the mechanism indicated that doping with zinc increased the number of surface hydroxyl groups on ferrite spinel, and thus enhanced the adsorption capacity when x = 0.6. This work revealed the effects of doping site and content of metal atoms on the adsorption ability of ferrite spinel towards As(V).

As an emerging micropollutant, organoarsenic has caused global ecosystem pollution, due to its degradation to highly toxic inorganic arsenic in the environment. Therefore, to remove the low-concentration organoarsenic from arsenic compounds from water, materials with high adsorption affinity are in urgent need. Herein, we reported an amino-modified metal–organic framework (MOF) with defects (UiO-66-D-NH2) to adsorb two typical organoarsenic forms p-arsanilic acid (p-ASA) and roxarsone (ROX). The adsorption affinity of UiO-66-D-NH2 was 3.8 and 3.0 times higher than that of original UiO-66 and defective UiO-66 without amino modification (UiO-66-D), while the removal rate exceeded 99.1% when the initial concentration of organoarsenic decreased to 1 mg L−1. UiO-66-D-NH2 also showed excellent adsorption behavior in simulated wastewater, with residual arsenic concentrations lower than 0.54 μg L−1. Mechanism studies showed a cooperation of the defects and –NH2 groups in UiO-66-D-NH2. The defects provided more Zr–OH sites in the metal node, leading to transformation of the As–O–Zr coordination from monodentate mononuclear to bidentate binuclear configuration, while –NH2 groups formed hydrogen bonds with both p-ASA and ROX as a secondary interaction to further reinforce the as-formed As–O–Zr complex. This work revealed that making cooperation by defect creation and amino modification could be an effective method to enhance the adsorption affinity of MOFs to low-concentration organoarsenic.

Considering p-arsanilic acid (p-ASA) as an organoarsenic pollutant, monitoring concentration of p-ASA is significant to maintain environmental security. Photoelectrochemical (PEC) detection is promisingly applied in environmental monitoring for its lower cost and simpler operation, compared to traditional techniques. However, general electrode materials of PEC sensors need to be modified with biological probes due to lack of specific binding sites to analytes, which may lead to complicated sensor fabrication and bio-recognizers inactivation during storage. Herein, a porphyrinic metal–organic framework/reduced graphene oxide (PCN-224/rGO) nanocomposite with simultaneously excellent photoelectric activity and strong binding characteristics was prepared and used to fabricate a PEC sensor for p-ASA detection avoiding the modification of bio-recognizers. Benefiting from the high conductivity of rGO, the separation efficiency of charge carriers was improved in PCN-224/rGO and thereby photocurrent gained an amplification of about 12 times. The PCN-224/rGO nanocomposite had strong affinity to p-ASA via Zr–O–As coordination and π–π stacking. Significantly, the binding of p-ASA could adjust the band position of PCN-224/rGO and facilitate oxygen reduction by releasing more photogenerated electrons, achieving photocurrent enhancement. The developed PEC sensor had a wide detection range, from 10 ng L−1 to 10 mg L−1, with a detection limit of 5.47 ng L−1. Furthermore, the sensor was successfully applied to monitor p-ASA in simulated natural water and swine manure lixivium. This study paved the way for the design of more efficient PEC sensors for environmental monitoring.

Sepsis, a syndrome of acute organ dysfunction induced by various infections, could lead to a very high mortality in hospitals despite the development of advanced medical technologies. Herein, a type of two-phase releasing immune-stimulating composite is developed by mixing alginate (ALG) with muramyl dipeptide (MDP) and the nanoparticle formulation of monophosphoryl lipid A (MPLA), the latter two are immunomodulatory agents with different release rates from the formed ALG hydrogel. The obtained two phase-releasing composite could provide instantaneous sepsis protection by the rapid release of MDP to enhance the phagocytic and bactericidal function of macrophages. Later on, such composite could further offer long-term sepsis protection by the sustained release of MPLA to continuously activate the immune system, via up-regulating the production of various pro-inflammatory cytokines, promoting the polarization of macrophages, and increasing the percent of natural killer (NK) cells in the lesion after sepsis challenge. Mice survived from sepsis challenge after such treatment could resist a second infection. Notably, treatment with our composite could increase the mouse survival rate in a cecal ligation and puncture (CLP) induced polymicrobial sepsis model. This work provides an easy-translatable immune-stimulating formulation for effective protection against sepsis under various triggering causes. Our strategy may be promising for long-term broad prevention against various infections, and could potentially be used to protect medical workers under a new pandemic before a reliable vaccine is available.

Objective. The role of trimethylamine N-oxide (TMAO) in cardiovascular diseases has been highlighted. Nevertheless, the associations of large-artery atherosclerotic (LAA) stroke with TMAO and blood lipid-related indices are little investigated. Methods. A cross-sectional comparative study was performed on 50 patients with LAA stroke and 50 healthy controls. Basic demographic data, common vascular risk factors, and blood lipid-related indices were collected. Plasma TMAO was detected through liquid chromatography tandem mass spectrometry. Multivariable unconditional logistic regression analyses were run to assess the associations of LAA stroke with plasma TMAO level and blood lipid-related indices. The area under the curve (AUC) of the receiver operating characteristic (ROC) was computed to assess the diagnostic performance of plasma TMAO level and blood lipid-related indices for LAA stroke. Results. Compared with healthy controls, the elevated plasma TMAO level (odds ratio [OR], 7.03; 95% confidence interval [CI], 2.86, 17.25; p < 0.01 ) and Apo-B (OR, 1.74; 95% CI, 1.06, 2.85; p = 0.03 ) were observed in LAA stroke patients, while lower Apo-A1 (OR, 0.56; 95% CI, 0.34, 0.91; p = 0.02 ), Apo-A1 to Apo-B ratio (OR, 0.29; 95% CI, 0.15, 0.56; p < 0.01 ), and HDL-C (OR, 0.56; 95% CI, 0.35, 0.91; p = 0.02 ) were found in LAA stroke patients after adjusted for age and gender. Moreover, plasma TMAO (AUC, 0.89; 95% CI, 0.83, 0.95), Apo-A1 (AUC, 0.81; 95% CI, 0.72, 0.89), Apo-B (AUC, 0.81; 95% CI, 0.73, 0.90), Apo-A1 to Apo-B ratio (AUC, 0.85; 95% CI, 0.78, 0.93), and HDL-C (AUC, 0.81; 95% CI, 0.72, 0.89) showed good diagnostic values for LAA stroke in adjusted models. Conclusions. The plasma TMAO level, Apo-A1, Apo-B, and HDL-C are important biomarkers for LAA stroke patients.

Layered double hydroxide (LDH), the only anionic clay in the environment, plays a key role in natural ion transportation. The ion retention effect of LDHs was traditionally attributed to ion exchange with low affinity. Here, we demonstrated an ultrastrong interaction between anions and LDHs induced by their inherent nanoconfinement using chromium ore processing residue (COPR) that contained several Cr(VI)-bonded LDHs as a probe. Hydrocalumite (Ca/Al-Cl LDH) was verified as the primary phase for Cr(VI) retention through two types of interactions such as ion exchange and Cr-Ca coordination. More significantly, the confined spacing between two layers of hydrocalumite provided spatial restriction and shielding effects to the intercalated Cr(VI), which enhanced Cr-Ca coordination by shortening the bonding distance and modulating the binding angle to achieve the lowest bonding energy. Such enhancement boosted Cr(VI) affinity up to 3.2 × 105 mL/g, which was 1-3 orders of magnitudes higher than ion exchange. The universality of this mechanism was verified using another Mg/Al-Cl LDH and various anions. This study broke the traditional awareness of low ion affinities of LDHs limited by single ion exchange and disclosed an essential mechanism for unexpected ion retention effects of anionic clays in nature.

As an important modality for the local control of colorectal cancer (CRC), radiotherapy or neoadjuvant radiotherapy is widely applied in the clinic, but radioresistance has become a major obstacle for CRC radiotherapy. Here we reported that B7-H3, an important costimulatory molecule, is associated with radioresistance in CRC. The expression of B7-H3 was obviously increased in CRC cells after irradiation. The enhanced expression of B7-H3 promoted, while the knockdown of B7-H3 inhibited, colony formation and cell activity in CRC cells following radiation treatment. B7-H3 overexpression reduced S phase arrest and protected cell apoptosis induced by radiation, whereas B7-H3 knockdown had the opposite effects. In addition, B7-H3 blockade by 3E8, a specific B7-H3 antibody, significantly sensitized CRC cells to irradiation in vivo. Mechanistic analysis revealed that B7-H3 regulated KIF15 via RNA sequencing, which was in dependent of NF-κB pathway. And small interfering RNA (siRNA)-mediated KIF15 silencing or KIF15 blockade by the inhibitor SB743921 abolished the effect of B7-H3 on radioresistance in vitro and in vivo. Similar to B7-H3, we find that the protein expression levels of KIF15, which showed a positive correlation with B7-H3, was abnormal upregulated in cancer tissues than in adjacent normal tissues and associated with TNM stage. Finally, B7-H3/KIF15 enhanced resistance against irradiation in CRC cells via activating ERK1/2 signaling, a key pathway involved in radioresistance in cancer. Our findings reveal an alternative mechanism by which CRC cells can acquire radioresistance via the B7-H3/KIF15/ERK axis.

Gastric cancer is a common digestive tract tumor and the second most prevalent cancer. The prognosis of advanced gastric cancer is poor. Conversion therapy can reduce tumor burden, downgrade tumor, and increase the possibility of complete resection, thus prolonging the survival time of patients with gastric cancer. In conversion therapy, chemotherapy and targeted therapy are the main methods of medical treatment, which can control tumor growth and recurrence. As an antiangiogenic targeted drug, apatinib is widely used in the third-line treatment of advanced gastric cancer. Recent studies have shown that it may be of great help in rapid reduction of tumor stage and improvement of prognosis in conversion therapy. This study reported three cases of gastric cancer complicated with multiple abdominal and retroperitoneal lymph node metastases. After receiving apatinib combined with SOX regimen for four cycles, computed tomography showed that the focus and lymph node metastasis were reduced after treatment, and primary tumors were resected. Postoperative pathology result showed that the patients got R0 resection. After radical surgery, the maintenance therapy including apatinib was given. The progression-free survival time was more than 10 months. Apatinib combined with SOX regimen as a conversion therapy for advanced gastric adenocarcinoma increases the possibility of successful surgical resection, which might prolong the survival time of patients.

Background — With the establishment of the concept of the gut–brain axis, increasing evidence has shown that the gut microbiome plays an important role in the pathogenesis of cardiovascular diseases. Gut bacteria can transform dietary choline, L-carnitine, and trimethylamine N-oxide (TMAO) into trimethylamine, which can be oxidized into TMAO again in the liver and participate in atherogenesis. However, only few studies have described alterations in the gut microbiota composition and function in cardioembolic (CE) and large artery atherosclerotic (LAA) strokes.Methods and Results — A case–control study was performed on patients with LAA and CE strokes. TMAO was determined via liquid chromatography tandem mass spectrometry. Gut microbiome was profiled through Illumina sequencing of the 16S ribosomal RNA gene (V4–V5 regions). The TMAO levels in the plasma of patients with LAA and CE strokes were significantly increased (TMAO: LAA stroke, 2931±456.4 ng/mL vs. CE stroke, 4220±577.6 ng/mL vs. control, 1663±117.8 ng/mL; P < 0.05). The TMAO level in patients with LAA stroke was positively correlated with the carotid plaque area (rho = 0.333, 95% confidence interval = 0.08 to 0.55, and P = 0.0093). The composition and function of gut microbiomes in the LAA and CE stroke groups were significantly different from those of the asymptomatic control. In addition to the significantly increased α and β diversities, the gut microbiome composition and function showed that the LAA group had more microorganisms than the asymptomatic control group; such microorganisms convert dietary source choline, TMAO to TMA. Parabacteroides and Streptococcus exhibited the strongest association with LAA and CE strokes.Conclusions — This study established the compositional and functional alterations of gut microbiomes in patients with LAA and CE strokes and the relationship between plasma TMAO and gut microbiota. The findings suggest the potential of using gut microbiota as a biomarker for patients with LAA and CE strokes.

Tumor vaccines to induce robust immunity for cancer treatment have attracted tremendous interests in cancer immunotherapy. In this work, a type of cancer vaccine is prepared by using nanoscale coordination polymer (NCP) formed between Mn2+ ions and a nucleotide oligomerization binding domain 1 (Nod1) agonist, meso-2,6-diaminopimelic acid (DAP), as the organic ligand, to encapsulate a model protein antigen, ovalbumin (OVA). The obtained OVA@Mn-DAP nanoparticles could act as an effective tumor vaccine to promote the maturation of dendritic cells (DCs) as well as their antigen cross-presentation via increasing the cellular uptake of antigen and stimulating Nod1 pathway with DAP. Such OVA@Mn-DAP vaccine could migrate into lymph nodes after local injection, as revealed by in vivo magnetic resonance (MR) and fluorescence imaging. Importantly, vaccination with OVA@Mn-DAP could not only offer prophylactic to protect mice from challenged B16-OVA tumors but also result in significant therapeutic effect to inhibit growth of already-established tumors if in combination with anti-programmed cell death protein 1 antibody (α-PD-1) immune checkpoint blockade therapy. Therefore, this work presents an innovative platform to construct effective nanovaccine for tumor immunotherapy.

Summary Organometal compounds are an emerging environmental micropollutant. Their removal presents a challenge, while their typically low concentrations require capture materials with high affinities. Here, inspired by the natural phenomenon that the abundant hydrogen bonds of protein enhance their inorganic metal capture, we design a bio-inspired trap integrating a Zr coordination center on polyhydric nanocellulose (ZNC). ZNC shows an affinity (1.99 × 106 mg L−1) toward low-level organoarsenic, which is 10 times higher than reported materials, and thus exhibits excellent extraction efficiency (>99.9%). Similar enhancement is observed for other organometals (organotin and organophosphorus). This is attributed to the high-density H-bond network of ZNC, which enhances capture via modulating zirconium atom distance, changing coordination environment, and shortening coordination distance. This work explores potential applications of bio-inspired H-bonds for advanced removal of organometal micropollutants from wastewater.

Background: Tumor-specific neoantigens are considered as personalized and potential ultimate targets for cancer immunotherapy. Recently, neoantigen cancer vaccines have been designed to train the patient's immune system to specifically target and kill tumor cells. However, the safety and efficacy of neoantigen vaccines in pancreatic cancer treatment remain poorly understood. Methods: Personalized peptide neoantigen cancer vaccines were successfully designed and manufactured for pancreatic cancers with low tumor mutation burden. Seven patients with advanced pancreatic cancer refractory to standard treatments were enrolled and treated with personalized peptide neoantigen vaccine, iNeo-Vac-P01. Besides the evaluation of the safety and clinical efficacy of iNeo-Vac- P01, pre- and post-vaccination peripheral blood samples were collected to analyze the vaccine’s immunogenicity.Results: For all 7 patients, none sever vaccine-related adverse effects was witnessed. The mean progression free survival, overall survival (OS) and OS associated with vaccine treatment were 3.1, 24.1 and 8.3 months, respectively. For Patient P01, who had a 21-month OS associated with vaccine treatment, the abundance of the TCR clone remarkably increased after vaccination, indicating the potential of iNeo-Vac-P01 to specifically induce a subset of T cells to kill tumor cells. This study also demonstrated that the quantity of IFN-γ in peripheral blood might be a potential biomarker for OS.Conclusions: We believed that it was the first tentative study focused in the application of peptide-based neoantigen cancer vaccine in advanced pancreatic cancer. Promisingly, personalized peptide neoantigen vaccine might provide a new strategy to improve the limited clinical efficacy for pancreatic cancer.Trial registration: ClinicalTrials.gov, NCT03645148. Registered August 24, 2018 - Retrospectively registered, https://www.clinicaltrials.gov/ct2/show/NCT03645148?term=neoantigen&cond=Pancreatic+Cancer&cntry=CN&draw=2&rank=1

High frequency of RUNX1 mutation in myelodysplastic syndrome patients with whole-arm translocation of der(1;7)(q10;p10)

Intragastric gelation is a mechanism whereby a consumed liquid food gels under the acidic gastric condition. It was hypothesised that intragastric gelation would result in satiety due to delayed gastric emptying. Three treatment beverages that is soya protein isolate (SPI) with λ-carrageenan (SPI-LC; high viscosity, gelling), guar gum (SPI-GG; high viscosity) and no polysaccharide (SPI; low viscosity) were given to twenty participants in a randomised 3 × 3 double-blind within-subject crossover design trial and asked to rate their hunger and fullness scores (visual analogue scale; VAS) before and up to 60 min after consumption of the beverage. Results show that there were no significant effects on hunger, fullness and energy intake after consuming the SPI-LC (gelling) beverage compared to the SPI-GG beverage, but did evoke weak satiety signals up to 20 min after consumption when compared to the control (low-viscosity) SPI beverage. Therefore, intragastric gelation does not result in satiety in this study.

This study reported a quality improver of gluten-free food formulated using hydrothermally treated polysaccharide mixtures (HTT-PSM) of glutinous rice flour and xanthan gum at different concentrations. The pasting and viscoelastic properties were determined by rapid visco analyser and rheometer respectively. The results showed that HTT-PSM had a lower gelatinisation temperature, higher peak viscosity and weaker gel strength than native glutinous rice flour. The incorporation of HTT-PSM into rice dough decreased the dough development time and stability significantly; and increased its extensibility from 2.8 mm to 11.9 mm. Its high extensibility attribute enabled the dough to make gluten-free noodles with higher tensile strength and similar texture profile as compared to wheat noodles. Sensory evaluation showed that the overall texture of the gluten-free noodles was acceptable, but not as comparable to wheat noodles. Positive correlations were observed between xanthan gum content and peak viscosity, gel strength, noodle tensile strength, hardness and chewiness.

Excessive nutrient input to surface water, including nitrate, exacerbates water eutrophication. Clarifying the proportions of different nitrate sources in the aquatic environment is critical for improving the polluted water. However, nitrate sources in river basins are very complex and not clearly understood. In this study, nitrogen concentrations and nitrate isotopic compositions were determined to estimate the spatiotemporal variation in nitrate sources in the Yuntaishan River basin, Nanjing, East China, from March 2019 to January 2020. The results showed that the concentrations of total nitrogen (TN), ammonium (NH4+-N), and nitrate (NO3&minus, N) changed in the ranges of 0.53&ndash, 18.0 mg/L, 0.01&ndash, 15.4 mg/L, and 0.06&ndash, 9.3 mg/L, respectively, wherein NO3&minus, N was the main nitrogen form. Higher nitrogen concentrations appeared in winter and in the downstream parts of the river. In the entire river basin, the NO3&minus, N mainly originated from sewage (67%) and soil (26%), with clear spatial variations. NO3&minus, N in the Yunba sub-watershed was mainly derived from sewage (78%), which was higher than that in other tributaries, i.e., Shengli River (44%) and Yangshan River (49%). This was due to the fact that that Shengli and Yangshan sub-watersheds were covered by urban areas and were equipped with a complete sewage treatment system. In addition, the contributions of sewage to NO3&minus, N rose from 60% upstream to 86% downstream, suggesting the increasing influence of the point source of sewage. The results showed that 53% of NO3&minus, N in the basin outlet originated from the point source of sewage near the M4 site. Sewage contributed 75% of NO3&minus, N in the rainy season and 67% of NO3&minus, N in the dry season, suggesting the weakly temporal variation. Our results highlight the spatiotemporal variations in sources of NO3&minus, N. These results will aid in the development of measures needed to control nitrogen pollution in river basins.

Bacterial infection has been a great threat to dermal wounds, especially to difficult-to-heal diabetic wounds. It is known that reactive oxygen species (ROS) generated by wounds or bacterial infection could further impede wound healing. Here, a type of ROS-scavenging hydrogel is developed by using polyvinyl alcohol (PVA) cross-linked by a ROS-responsive linker. The obtained hydrogel could act as an effective ROS-scavenging agent to promote the wound closure by decreasing the ROS level and up-regulating M2 phenotype macrophages around the wound. Importantly, such hydrogel formed in the wound could allow release of therapeutics, including mupirocin to kill bacteria, and granulocyte-macrophage colony-stimulating factor (GM-CSF) to accelerate the wound closure, in responsive to endogenous ROS existing in the wound microenvironment. Remarkably, our drug-loaded ROS-scavenging hydrogel could be employed to effectively treat various types of wounds including difficult-to-heal diabetic wounds with bacterial infection. Therefore, this work presents an effective strategy based on ROS-scavenging hydrogel for wound healing under various kinds of complications.

Anti-solvent precipitation of zein was employed in conjunction with spray drying to reduce the usage of ethanol and to encapsulate the aqueous extract of green jelly leaf (Cyclea barbata Miers) antioxidants. Different concentrations of zein (0.35, 0.7, 1.05 and 1.4% w/v) and Hydroxypropylmethyl cellulose (HPMC) (5, 10, 15, 20% w/w) in several different formulations were investigated. The spray dried powders were characterised in terms of their encapsulation efficiency, morphology, average particle size and the antioxidant release. Result shows that encapsulation of green jelly leaf antioxidants using zein were possible with encapsulation efficiency between ~50 and 70%, where a higher concentration of zein in feed solution had favoured better encapsulation efficiency. The spray dried powder produced were relatively small (~6–10 μm) with spherical structure. The addition of HPMC also aided in delaying the agglomeration of zein nano-precipitates in the feed solution through its interaction with zein via hydrogen bonding. These results suggested that zein protein could have a potential application to encapsulate water soluble antioxidant for application in high water content food products.

OX40L (CD252, TNFSF4), a type II transmembrane protein which like other tumor necrosis factor ligands, involved in the costimulation and differentiation of T cells, functions as a positive signal in immune response. To investigate the biological function of soluble OX40L (sOX40L), three functional anti-OX40L monoclonal antibodies (mAbs) 3D2, 3F7 and 2H3 were obtained by hybridoma technology. Besides, specificity of the mAbs was further demonstrated by ELISA, Western blot and Immunofluorescence experiments. We also developed a novel enzyme-linked immunosorbent assay (ELISA) based on two anti-human OX40L antibodies 3D2 and 3F7 with different epitopes. Using the ELISA system, we found that sOX40L in the sera of healthy donors increases in an age-dependent manner and that enhanced sOX40L expression in some autoimmune diseases especially in rheumatoid arthritis (RA) patients, suggesting the potential diagnostic significance of sOX40L in the autoimmune diseases. Together, these data demonstrate that the existence of circulating sOX40L in human sera might play an important role in immunoregulation.

Nano-Mg(OH)2 is attracting great attention as adsorbent for pre-concentration and recovery of rare earth elements (REEs) from low-concentration solution, due to its superior removal efficiency for REEs and environmental friendliness. However, the nanoparticles also cause some severe problems during application, including aggregation, blockage in fixed-bed column, as well as the difficulties in separation and reuse. Herein, in order to avoid the mentioned problems, a carbon cloth (CC) supported nano-Mg(OH)2 (nano-Mg(OH)2@CC) was synthesized by electrodeposition. The X-ray diffraction and scanning electron microscopy analysis demonstrated that the interlaced nano-sheet of Mg(OH)2 grew firmly and uniformly on the surface of carbon cloth fibers. Batch adsorption experiments of Eu(III) indicated that the nano-Mg(OH)2@CC composite maintained the excellent adsorption performance of nano-Mg(OH)2 toward Eu(III). After adsorption, the Eu containing composite was calcined under nitrogen atmosphere. The content of Eu2O3 in the calcined material was as high as 99.66%. Fixed-bed column experiments indicated that no blockage for Mg(OH)2@CC composite was observed during the treatment, while the complete blockage of occurred to nano-Mg(OH)2 at an effluent volume of 240 mL. Moreover, the removal efficiency of Mg(OH)2@CC was still higher than 90% until 4,200 mL of effluent volume. This work provides a promising method for feasible application of nanoadsorbents in fixed-bed process to recycle low-concentration REEs from wastewater.

Background Lipotoxicity plays an important role in the pathogenesis of kidney injury. Our previous study demonstrated that activation of local renin-angiotensin system (RAS) was involved in saturated free fatty acids palmitic acid (PA)-induced tubular cell injuries. The current study aims to investigate whether suppression of RAS by combination of direct renin inhibitor aliskiren and noncanonical RAS pathway chymase inhibitor chymostatin attenuates PA or cholesterol induced-endoplasmic reticulum stress (ER stress) and apopotosis in cultured human proximal tubular HK2 cells. Methods HK2 cells were treated with saturated fatty acid PA (0.6 mM) for 24 h or cholesterol (10 μg/ml) for 6d with or without chymostatin and/or aliskiren. Expressions of the ER stress associated proteins and apoptosis markers were detected by western blotting. The mRNA levels of RAS components were measured by real-time qPCR. Results Combination treatment of chymostatin and aliskiren markedly suppressed PA or cholesterol-induced ER stress, as reflected by increased BiP, IRE1α, phosphorylated-eIF2α and ATF4 as well as proapoptotic transcription factor CHOP. The ratio of Bax/Bcl-2 and cleaved caspase-3, two markers of apoptosis were upregulated by PA or cholesterol treatment. PA treatment was also associated with increased levels of angiotensinogen and angiotensin type 1 receptor (AT1R) mRNA expression. Combination treatment of chymostatin and aliskiren markedly suppressed PA or cholesterol-induced ER stress and apoptosis. The protective effect of two inhibitors was also observed in primary cultured cortical tubular cells treated with PA. In contrast, chymostatin and/or aliskiren failed to prevent ER stress induced by tunicamycin. Conclusions These results suggested that combination treatment of chymostatin and aliskiren attenuates lipid-induced renal tubular cell injury, likely through suppressing activation of intracellular RAS. Electronic supplementary material The online version of this article (10.1186/s12944-018-0818-1) contains supplementary material, which is available to authorized users.

Nanotechnology-mediated anti-inflammatory therapy is emerging as a novel strategy for the treatment of inflammation-induced injury. However, one of the main hurdles for these anti-inflammatory nano-drugs is their potential toxic side effects in vivo. Herein, we uncovered that polydopamine (PDA) nanoparticles with their structure and chemical properties similar to melanin, a natural bio-polymer, displayed a significant anti-inflammation therapeutic effect on acute inflammation-induced injury. PDA with enriched phenol groups functioned as a radical scavenger to eliminate reactive oxygen species (ROS) generated during inflammatory responses. As revealed by in vivo photoacoustic imaging with a H2O2-specific nanoprobe, PDA nanoparticles remarkably reduced intracellular ROS levels in murine macrophages challenged with either H2O2 or lipopolysaccharide (LPS). The anti-inflammatory capacity of PDA nanoparticles was further demonstrated in murine models of both acute peritonitis and acute lung injury (ALI), where diminished ROS generation, reduced proinflammatory cytokines, attenuated neutrophil infiltration, and alleviated lung tissue damage were observed in PDA-treated mice after a single dose of PDA treatment. Our work therefore presents the great promise of PDA nanoparticles as a biocompatible nano-drug for anti-inflammation therapy to treat acute inflammation-induced injury.

Endometriosis is still a major problem in obstetrics and gynecology. While GZFLW (Gui Zhi Fu Ling Wan) has been originally used for treating gynecological diseases, however, the molecular mechanism that GZFLW acts on endometriosis is not clear. To investigate the molecular mechanism that GZFLW plays role on endometriosis, iTRAQ (isobaric tags for relative and absolute quantification) proteomics and human endometrial stromal cells (Y14) obtained from a patient with endometriosis were used in in vitro study. Our results demonstrated that GZFLW decreased Y14 cells proliferation while increased cells apoptosis. The differential expression protein VPS53 (Vacuolar protein sorting 53 homolog) was predicted by iTRAQ coupled LC-MS/MS and further identified by western blot. Besides, GZFLW induced VPS53 protein level by promoting its stabilization. Our findings highlight a novel role for VPS53 in gynecology and provide a potent therapeutic strategy against endometriosis.

Background Overexpression of cyclin D1 dependent kinases 4 and 6 (CDK4/6) is a common feature of many human cancers including leukemia. LEE011 is a novel inhibitor of both CDK4 and 6. To date, the molecular function of LEE011 in leukemia remains unclear. Methods Leukemia cell growth and apoptosis following LEE011 treatment was assessed through CCK-8 and annexin V/propidium iodide staining assays. Cell senescence was assessed by β-galactosidase staining and p16INK4a expression analysis. Gene expression profiles of LEE011 treated HL-60 cells were investigated using an Arraystar Human LncRNA array. Gene ontology and KEGG pathway analysis were then used to analyze the differentially expressed genes from the cluster analysis. Results Our studies demonstrated that LEE011 inhibited proliferation of leukemia cells and could induce apoptosis. Hoechst 33,342 staining analysis showed DNA fragmentation and distortion of nuclear structures following LEE011 treatment. Cell cycle analysis showed LEE011 significantly induced cell cycle G1 arrest in seven of eight acute leukemia cells lines, the exception being THP-1 cells. β-Galactosidase staining analysis and p16INK4a expression analysis showed that LEE011 treatment can induce cell senescence of leukemia cells. LncRNA microarray analysis showed 2083 differentially expressed mRNAs and 3224 differentially expressed lncRNAs in LEE011-treated HL-60 cells compared with controls. Molecular function analysis showed that LEE011 induced senescence in leukemia cells partially through downregulation of the transcriptional expression of MYBL2. Conclusions We demonstrate for the first time that LEE011 treatment results in inhibition of cell proliferation and induction of G1 arrest and cellular senescence in leukemia cells. LncRNA microarray analysis showed differentially expressed mRNAs and lncRNAs in LEE011-treated HL-60 cells and we demonstrated that LEE011 induces cellular senescence partially through downregulation of the expression of MYBL2. These results may open new lines of investigation regarding the molecular mechanism of LEE011 induced cellular senescence. Electronic supplementary material The online version of this article (doi:10.1186/s12935-017-0405-y) contains supplementary material, which is available to authorized users.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are characterized by an excessive inflammatory response within the lungs and severely impaired gas exchange resulting from alveolar-capillary barrier disruption and pulmonary edema. The costimulatory protein B7H3 functions as both a costimulator and coinhibitor to regulate the adaptive and innate immune response, thus participating in the development of microbial sepsis and pneumococcal meningitis. However, it is unclear whether B7H3 exerts a beneficial or detrimental role during ALI. In the present study we examined the impact of B7H3 on pulmonary inflammatory response, polymorphonuclear neutrophil (PMN) influx and lung tissue damage in a murine model of lipopolysaccharide (LPS)-induced direct ALI. Treatment with B7H3 protected mice against LPS-induced ALI, with significantly attenuated pulmonary PMN infiltration, decreased lung myeloperoxidase (MPO) activity, reduced bronchoalveolar lavage fluid (BALF) protein content and ameliorated lung pathological changes. In addition, B7H3 significantly diminished LPS-stimulated PMN chemoattractant CXCL2 production by inhibiting NF-κB p65 phosphorylation and substantially attenuated LPS-induced PMN chemotaxis and transendothelial migration by down-regulating CXCR2 and Mac-1 expression. These results demonstrate that B7H3 substantially ameliorates LPS-induced ALI and this protection afforded by B7H3 is predominantly associated with its inhibitory effect on pulmonary PMN migration and infiltration.

β-amyloid protein (Aβ) accumulation in cerebral centers involved in cognition and memory is a pivotal pathological feature of Alzheimer's disease (AD). The onset process of type 2 diabetes mellitus (T2DM) has a number of similarities compared with AD. Thus, it is hypothesized that the pharmacological therapy employed for the treatment of T2DM may help to prevent and ameliorate the symptoms of AD. This study demonstrated that Exendin-4, which is a glucagon-like peptide-1 analogue which is used as a therapeutic drug for T2DM, markedly antagonized Aβ fragment-induced attenuation of spatial learning and memory ability, as indicated by a Morris water maze experiment. In addition, we investigated the potential underlying electrophysiological and molecular mechanisms. The results indicate that Exendin-4 rescued long-term potentiation from Aβ1-42-induced damage in the rat hippocampal CA1 region in vivo, and antagonized Aβ1-42-induced reduction of cyclic adenosine monophosphate and phosphorylated-cAMP response element-binding protein in rat hippocampal tissue using ELISA and western blot analysis, respectively. Thus, the results of the present study provide theoretical support for the application of Exendin-4 for improving AD.

Purpose Cardiopulmonary bypass (CPB) during pediatric cardiac surgery often elicits a systemic inflammatory response followed by a compromised immune response, which has been attributed to the morbidity of postoperative infection; however, the underlying mechanism(s) has not yet been fully elucidated. We hypothesized that CPB inhibits the activation of Toll-like receptor (TLR) signal transduction pathways, thereby causing an immunosuppressive state after pediatric cardiac surgery. Methods We examined 20 children with congenital heart disease undergoing pediatric cardiac surgery. Results Cardiopulmonary bypass differentially affected lipopolysaccharide (LPS)- or bacterial lipoprotein (BLP)–stimulated ex vivo production of proinflammatory and anti-inflammatory cytokines, with significantly diminished tumor necrosis factor α , interleukin (IL) 1 β , IL-6, and IL-8, but substantially enhanced IL-10 production. Consistent with the reduced inflammatory response, CPB strongly inhibited LPS- or BLP-activated TLR signal transduction pathways in monocytes with down-regulated expression of CD14, TLR4, and TLR2 and with suppressed phosphorylation of nuclear factor κ B p65, p38, and extracellular signal-regulated kinase 1/2. Conclusions These results indicate that CPB during pediatric cardiac surgery causes substantially reduced production of inflammatory cytokines in response to bacterial component LPS or BLP stimulation, which is associated with CPB-induced suppression of TLR-mediated signal transduction pathways. This reduced inflammatory response after CPB in children with congenital heart disease may predispose them to an increased risk of postoperative infection.

As new media, ceramic-corrosion-cell fillers (Cathode Ceramic-corrosion-cell Fillers – CCF, and Anode Ceramic-corrosion-cell Fillers – ACF) employed in electrobath were investigated for cyclohexanone industry wastewater treatment. 60.0 wt% of dried sewage sludge and 40.0 wt% of clay, 40.0 wt% of scrap iron and 60.0 wt% of clay were utilized as raw materials for the preparation of raw CCF and ACF, respectively. The raw CCF and ACF were respectively sintered at 400 °C for 20 min in anoxic conditions. The physical properties (bulk density, grain density and water absorption), structural and morphological characters and toxic metal leaching contents were tested. The influences of pH, hydraulic retention time (HRT) and the media height on removal of COD Cr and cyclohexanone were studied. The results showed that the bulk density and grain density of CCF and ACF were 869.0 kg m −3 and 936.3 kg m −3 , 1245.0 kg m −3 and 1420.0 kg m −3 , respectively. The contents of toxic metal (Cu, Zn, Cd, Pb, Cr, Ba, Ni and As) were all below the detection limit. When pH of 3–4, HRT of 6 h and the media height of 60 cm were applied, about 90% of COD cr and cyclohexanone were removed.