Enrichment and immobilization of heavy metal ions from wastewater by nanocellulose/carbon dots-derived composite.

Heavy metal ions (HMIs) have been widely applied in various industries because of their excellent physicochemical properties. However, their discharging without appropriate treatment brought about serious pollution problems. So it is desirable but challenging to rapidly and completely clean up these toxic pollutants from water, especially utilizing environmentally friendly and naturally rich biomass materials. In this work, we prepared nanocellulose/carbon dots/magnesium hydroxide (CCMg) ternary composite using cotton via a simple hydrothermal method. The removal mechanism towards Cd2+ and Cu2+ was investigated using a combination of experimental techniques and density functional theory calculations. CCMg shows a good ability to remove HMIs. It is realized that the interaction between each component of CCMg and cadmium nitrate is mainly of hydrogen/dative bonds. Cadmium nitrate is preferentially enriched by the Mg(OH)2 moiety, proved by calculated thermodynamics, interfacial interactions and charges. After transformation, the cadmium carbonate precipitate is fixed on the surface by nanocellulose (NC) via chemical coupling; and of interest is that copper ion precipitates in the form of basic sulfate. Due to its high adsorption effect and simple recovery operation, CCMg is having a wide range of application prospects as a water treatment agent.

Intestinal Mucosal Barrier Is Regulated by Intestinal Tract Neuro-Immune Interplay.

Inflammatory bowel disease, irritable bowel syndrome and severe central nervous system injury can lead to intestinal mucosal barrier damage, which can cause endotoxin/enterobacteria translocation to induce infection and is closely related to the progression of metabolic diseases, cardiovascular and cerebrovascular diseases, tumors and other diseases. Hence, repairing the intestinal barrier represents a potential therapeutic target for many diseases. Enteral afferent nerves, efferent nerves and the intrinsic enteric nervous system (ENS) play key roles in regulating intestinal physiological homeostasis and coping with acute stress. Furthermore, innervation actively regulates immunity and induces inherent and adaptive immune responses through complex processes, such as secreting neurotransmitters or hormones and regulating their corresponding receptors. In addition, intestinal microorganisms and their metabolites play a regulatory role in the intestinal mucosal barrier. This paper primarily discusses the interactions between norepinephrine and ß-adrenergic receptors, cholinergic anti-inflammatory pathways, nociceptive receptors, complex ENS networks, gut microbes and various immune cells with their secreted cytokines to summarize the key roles in regulating intestinal inflammation and improving mucosal barrier function.

Enantioselective Synthesis of Axially Chiral Biaryls by Diels-Alder/Retro-Diels-Alder Reaction of 2-Pyrones with Alkynes.

The enantioselective synthesis of axially chiral biaryls by a copper-catalyzed Diels-Alder/retro-Diels-Alder reaction of 2-pyrones with alkynes is reported herein. Using electron-deficient 2-pyrones and electron-rich 1-naphthyl acetylenes as the reaction partners, a broad range of axially chiral biaryl esters are obtained in excellent yields (up to 97% yield) and enantioselectivities (up to >99% ee). DFT calculations reveal the reaction mechanism and provide insights into the origins of the stereoselectivities. The practicality and robustness of this reaction are showcased by gram-scale synthesis. The synthetic utilizations are demonstrated by the amenable transformations of the products.

Bidirectional Brain-gut-microbiota Axis in increased intestinal permeability induced by central nervous system injury.

Central nervous system injuries may lead to the disorders of the hypothalamic-pituitary-adrenal axis, autonomic nervous system, and enteric nervous system. These effects then cause the changes in the intestinal microenvironment, such as a disordered intestinal immune system as well as alterations of intestinal bacteria. Ultimately, this leads to an increase in intestinal permeability. Inflammatory factors produced by the interactions between intestinal neurons and immune cells as well as the secretions and metabolites of intestinal flora can then migrate through the intestinal barrier, which will aggravate any peripheral inflammation and the central nervous system injury. The brain-gut-microbiota axis is a complex system that plays a crucial role in the occurrence and development of central nervous system diseases. It may also increase the consequences of preventative treatment. In this context, here we have summarized the factors that can lead to the increased intestinal permeability and some of the possible outcomes.

Analysis of prognosis and influencing factors of 1737 cases of pediatric burns in a hospital of Anhui from 2013 to 2017 / 中华疾病控制杂志

Objective To analyze the prognosis of pediatric burns and its influencing factors. Methods Clinical data of 1 737 children with burns from January 2013 to December 2017 in the First Affiliated Hospital of Anhui Medical University was analyzed by retrospective method. The demographic, clinical features, and related factors affecting prognosis . Results Log-binominal regression model showed that the care rate was higher in children aged 1- and 3- compared with children aged 7-12 (all P<0.05); Boiling water burns had a higher care rate than electric shock and flame burns (including chemical burn) (all P<0.05); Moderate and severe burns had a higher care rate than heavy severe burns (all P<0.05); The unhealed rate of pediatric burns in summer was higher than burned in winter (RR=0.861,95% CI:0.690-1.074); Children without complications had a higher care rate (P<0.05); Children lived in rural areas have a higher unhealed rate than lived in urban areas (RR=0.713，95% CI:0.618-0.824). Conclusions The care rate of pediatric burns was 51.1%. Major influencing factors included children aged 7-12, burned by electric and flame (including chemical burns), burned severe extraordinarily, burned in summer, and with complications, lived in rural.

A novel benzothiazinethione analogue SKLB-TB1001 displays potent antimycobacterial activities in a series of murine models.

New chemotherapeutic compounds and regimens are needed to combat multidrug-resistant Mycobacterium tuberculosis. Here, we used a series of murine models to assess an antitubercular lead compound SKLB-TB1001. In the Mycobacterium bovis bacillus Calmette-Guérin and the acute M. tuberculosis H37Rv infection mouse models, SKLB-TB1001 significantly attenuated the mycobacterial load in lungs and spleens. The colony forming unit counts and histological examination of lungs from H37Rv infected mice revealed that the benzothiazinethione analogue SKLB-TB1001 as a higher dose level was as effective as isoniazid. Moreover, in a multidrug-resistant (MDR)-TB mouse model, SKLB-TB1001 showed significant activity in a dose-dependent manner and was more effective than streptomycin. These results suggested that SKLB-TB1001 could be an antitubercular drug candidate worth further investigation.

Discovery of novel N-(5-(tert-butyl)isoxazol-3-yl)-N'-phenylurea analogs as potent FLT3 inhibitors and evaluation of their activity against acute myeloid leukemia in vitro and in vivo.

FLT3 inhibitors have been explored as a viable therapy for acute myeloid leukemia (AML). However, the clinical outcomes of these FLT3 inhibitors were underwhelming except AC220. Therefore, the development of novel FLT3 inhibitors with high potency against both FLT3-WT and FLT3-ITD mutants are strongly demanded at the present time. In this study, we designed and synthesized a series of novel N-(5-(tert-butyl)isoxazol-3-yl)-N'-phenylurea derivatives as FLT3 inhibitors. SAR studies focused on the fused rings led to the discovery of a series of compounds with high potency against FLT3-ITD-bearing MV4-11 cells and significantly inhibitory activity toward FLT3. Among these compounds, N-(5-(tert-butyl)isoxazol-3-yl)-N'-(4-(7-methoxyimidazo[1,2-a]pyridin-2-yl)phenyl)urea (16i), displayed acceptable aqueous solubility, desirable pharmacokinetic profile and high cytotoxicity selectivity against MV4-11 cells. This compound can inhibit phosphorylation of FLT3 and induce apoptosis in a concentration-dependent manner. Further in vivo antitumor studies showed that 16i led to complete tumor regression in the MV4-11 xenograft model at a dose of 60 mg/kg/d while without observable body weight loss. This study had provided us a new chemotype of FLT3 inhibitors as novel therapic candidates for AML.

Synthesis and antitubercular evaluation of 4-carbonyl piperazine substituted 1,3-benzothiazin-4-one derivatives.

Tuberculosis (TB) remains a major human health problem. New therapeutic antitubercular agents are urgent needed to control the global tuberculosis pandemic. We synthesized a new series of 4-carbonyl piperazine substituted 1,3-benzothiazin-4-one derivatives and evaluated their anti-mycobacterial activities against Mycobacterium tuberculosis H37Ra as well as their druggabilities. The results showed that most of these derivatives, especially the compounds with simple alkyl side chains, exhibited good antitubercular activities and favorable aqueous solubilities with no obvious cytotoxicity. It suggested that the 4-carbonyl piperazine substituents in benzothiazinone scaffold were well tolerated, in which the compound 8h, with an antitubercular activity of MIC 0.008 µM, exhibited an excellent aqueous solubility of 104 µg/mL, which was 100-fold better than the potent DprE1 inhibitor Comp.1 (BTZ038), also more soluble than PBTZ169.

Discovery of imidazo[2,1-b]thiazole HCV NS4B inhibitors exhibiting synergistic effect with other direct-acting antiviral agents.

The design, synthesis, and SAR studies of novel inhibitors of HCV NS4B based on the imidazo[2,1-b]thiazole scaffold were described. Optimization of potency with respect to genotype 1b resulted in the discovery of two potent leads 26f (EC50 = 16 nM) and 28g (EC50 = 31 nM). The resistance profile studies revealed that 26f and 28g targeted HCV NS4B, more precisely the second amphipathic α helix of NS4B (4BAH2). Cross-resistance between our 4BAH2 inhibitors and other direct-acting antiviral agents targeting NS3/4A, NS5A, and NS5B was not observed. For the first time, the synergism of a series of combinations based on 4BAH2 inhibitors was evaluated. The results demonstrated that our 4BAH2 inhibitor 26f was synergistic with NS3/4A inhibitor simeprevir, NS5A inhibitor daclatasvir, and NS5B inhibitor sofosbuvir, and it could also reduce the dose of these drugs at almost all effect levels. Our study suggested that favorable effects could be achieved by combining 4BAH2 inhibitors such as 26f with these approved drugs and that new all-oral antiviral combinations based on 4BAH2 inhibitors were worth developing to supplement or even replace current treatment regimens for curing HCV infection.

Discovery and structure-activity relationships study of novel thieno[2,3-b]pyridine analogues as hepatitis C virus inhibitors.

Current treatment for hepatitis C is barely satisfactory, there is an urgent need to develop novel agents for combating hepatitis C virus infection. This study discovered a new class of thieno[2,3-b]pyridine derivatives as HCV inhibitors. First, a hit compound characterized by a thienopyridine core was identified in a cell-based screening of our privileged small molecule library. And then, structure activity relationship study of the hit compound led to the discovery of several potent compounds without obvious cytotoxicity in vitro (12c, EC50=3.3µM, SI >30.3, 12b, EC50=3.5µM, SI >28.6, 10l, EC50=3.9µM, SI >25.6, 12o, EC50=4.5µM, SI >22.2, respectively). Although the mechanism of them had not been clearly elucidated, our preliminary optimization of this class of compounds had provided us a start point to develop new anti-HCV agents.

Synthesis and structure-activity relationships evaluation of benzothiazinone derivatives as potential anti-tubercular agents.

N-Alkyl and heterocycle substituted 1,3-benzothiazin-4-one (BTZ) derivatives were synthesized. The anti-mycobacterial activities of these compounds were evaluated by determination of minimal inhibitory concentration (MIC) for Mycobacterium tuberculosis H37Ra and M. tuberculosis H37Rv. It was found that an extended or branched alkyl chain analog could enhance the potency, and activities of N-alkyl substituted BTZs were not affected by either nitro or trifluoromethyl at 6-position. Trifluoromethyl plays an important role in maintaining anti-tubercular activity in the piperazine or piperidine analogs. Compound 8o, which contains an azaspirodithiolane group, showed a MIC of 0.0001 µM against M. tuberculosis H37Rv, 20-fold more potent than BTZ043 racemate. These results suggested that the volume and lipophilicity of the substituents were important in maintaining activity. In addition, compound 8o was nontoxic to Vero cells and orally bioavailable in a preliminary pharmacokinetics study.

(E)-3-Dimethyl-amino-1-(1,3-thia-zol-2-yl)prop-2-en-1-one.

In the title compound, C8H10N2OS, the 3-(dimethyl-amino)-prop-2-en-1-one unit is approximately planar [give r.m.s. deviation] and the mean plane through the seven non-H atoms makes a dihedral angle of 8.88 (3)° with the thia-zole ring. The carbonyl and ring C=N double bonds adjacent to the carbonyl group are trans [N-C-C-O = 172.31 (15) °], while the conformation of the carbonyl and propene double bonds is cis [O-C-C-C = 2.2 (2)°]. In the crystal, short C-H⋯N and C-H⋯O inter-actions together with C-H⋯π inter-actions generate a three-dimensional network.

[Genetic diversity of Pseudosciaena polyactis in Zhoushan based on mitochondrial DNA D-loop region sequences].

Pseudosciaena polyactis is an economically important species of marine fish in China that is currently declining due to overexploitation, environmental pollution and related factors. Research in to the genetic structure of Pseudosciaena polyactis populations plays a key role in protecting and promoting sustainable utilization. We collected 53 individuals of Pseudosciaena polyactis from Zhoushan, Zhejiang and sequenced and amplified the mitochondrial DNA (mtDNA) D-loop region using Polymerase Chain Reactions (PCR). The sequence length of the 53 individuals ranged from 795 to 801 bp. The sequences were analyzed by Clustal X1.83, MEGA3.1 and DnaSP4.0. The results showed that the average base content of T, C, A, G was 30.3%, 23.1%, 32.3% and 14.3%, respectively and there were 93 transition or transversion sites, including 53 single nucleotide mutation sites and 40 parsimony informative sites, which accounted for 11.6% of the length of the analyzed sequences. In total, we identified 52 haplotypes and found haplotype diversity (hd) of 0.9993, average number of nucleotide differences were 9.73875 (k), and nucleotide diversity (Π) of 0.01233. The average genetic distance of haplotypes was 0.012, and the average transition/transversion was 4.305. Based on mitochondrial DNA D-loop region sequences, these results indicate that the genetic diversity of the Pseudosciaena polyactis population in Zhoushan is currently at a medium level.

The influence of changes in the levels of calcitonin gene-related peptide and neuropeptide Y on cardiac function of severe burn patients during shock stage / 中华烧伤杂志

<p><b>OBJECTIVE</b>To investigate the influence of the changes in the levels of calcitonin gene-related peptide (CGRP) and neuropeptide Y (NPY) on cardiac function of severe burn patients during shock stage.</p><p><b>METHODS</b>Sixty severe burn patients with total burn surface area larger than 30% were enrolled as experiment group (E group) , and they received fluid resuscitation and debridement during shock stage. Sixty healthy volunteers were enrolled as control group (C group). The changes in the plasma level of CGRP, NPY and cTnT in E and C groups were observed at 1, 3, 6, 12, 24, 48 post-burn hours (PBH). The correlation among the CGRP, NPY and cTnT in the C group were analyzed.</p><p><b>RESULTS</b>At 3 PBH, the plasma level of CGRP in E group (28 +/- 6) ng/L was lower than that in C group (55 +/- 7) ng/L , and it reached the lowest level at 12 PBH (15 +/- 4)ng/L . It was still lower than that in C group at 48 PBH (P < 0.05). The levels of NPY and cTnT in E group were significantly increased at 1PBH [(136 +/- 20) ng/L, (0.41 +/- 0.08) microg/L] compared with that in C group[ (86 +/- 13) ng/L, (0.16 +/- 0.06) microg/L], peaking at 12PBH [(189 +/- 31) ng/L, (1.78 +/- 0. 47) microg/L], and remaining higher than those in C group at 48PBH. There exhibited obvious negative correlation between the changes in the level of CGRP and cTnT ( r = -0.76, P < 0.01), while obvious positive correlation was found between the changes in level of NPY and cTnT ( r = 0.79, P < 0.01).</p><p><b>CONCLUSION</b>The decrease in CGRP level and the increase in NPY level might play important roles in myocardial injury during shock stage of severe burn patients.</p>