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An Fe-catalyzed visible-light induced condensation of alkylbenzenes with anthranilamides has been developed. Upon irradiation, the trivalent iron complex could generate chlorine radicals, which successfully abstracted the hydrogen of benzylic C-H bonds to form benzyl radicals. And these benzyl radicals were converted into oxygenated products under air conditions, which subsequently reacted with anthranilamides for the synthesis of quinazolinones.

A visible-light-induced chemodivergent synthesis of tetracyclic quinazolinones and 3-iminoisoindoliones has been developed. This chemodivergent reaction afforded two kinds of different products by substrate control. A detailed investigation of the reaction mechanism revealed that this consecutive photoinduced electron transfer (ConPET) cascade cyclization involved a radical process, and the aryl radical was the crucial intermediate. This method employed 4-DPAIPN as a photocatalyst and i -Pr 2 NEt as a sacrificial electron donor leading to metal-free conditions.

We previously demonstrated that two methyltransferase motifs, K-D-K-E and G-G-D, affect the pathogenicity of Newcastle disease virus (NDV) by regulating mRNA translation and virus transmission. Here, we compared the infectious centre area produced by the NDV strain, rSG10, and methyltransferase motifs mutant rSG10 strains in DF-1 cells. The results show that intercellular transmission was attenuated by methyltransferase motif mutations. We further determined the ability of mutant viruses to spread in cell-free and cell-to-cell situations. Cell-free transmission of rSG10-K1756A was not reduced, indicating that cell-to-cell transmission of rSG10-K1756A was decreased. Using a donor and target system, we demonstrated that NDV can spread from cell-to-cell directly. Furthermore, by comparing the protein distribution area of three strains when treated with 2% agar overlay, we found that rSG10-K1756A was defective in cell-to-cell transmission. Tunnelling nanotubes (TNTs) are an important mode for cell-to-cell transmission. Treatment of cells with cytochalasin D (CytoD) or nocodazole to inhibit the formation of TNTs, reduced protein levels in all strains, but rSG10-K1756A was the least affected. These results indicate that mutation of the K-D-K-E motif is likely to restricted the spread of NDV via TNTs. Finally, we observed that matrix protein (M) and fusion protein (F) promoted the formation of cellular extensions, which may be involved in the cell-to-cell spread of NDV. Our research reveals a novel mechanism by which methyltransferase motifs affect the cell-to-cell spread of NDV and provides insight into dissemination of paramyxoviruses.

Background: Helicobacter pylori (Hp) infection is highly prevalent globally and is predominantly managed by antibiotics. Recently, the anti-adhesive, antioxidant, antitoxin, immunomodulatory, anti-coagulant, and anti-infective activities of fucoidan, a polysaccharide extracted from brown seaweeds, have been widely studied, and the results showed promise. Fucoidan has the potential to be utilized in Hp eradication therapy. Our present clinical study was designed to evaluate the efficiency of Lewuyou ® , a fucoidan plant drink (FPD) in eradicating Hp in humans., Methods: This multi-center, clinical study was conducted between October 2020 and July 2021. Hp infection was confirmed by urea breath test (UBT). A total of 122 patients with confirmed Hp infection were enrolled; after exclusion of incomplete data, 85 eligible patients (37 males and 48 females aged 20-81 years) were included in the final analysis. FPD (50 mL per vial) was orally administered twice daily for a 4-week cycle, and 41 patients completed an 8-week cycle., Results: No adverse event (AE) was reported in all 122 participants who had consumed FPD. The Hp eradication rate and clearance rate were 77.6% (66/85) and 20.0% (17/85), respectively, after 4 weeks of FPD consumption and 80.5% (33/41) and 26.8 (11/41) , respectively, after 8 weeks of consumption., Conclusions: The 4- and 8-week protocols of FPD consumption were safe and effective at reducing Hp load on the gastric mucosa, with Hp eradicated in the majority of participants., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tgh.amegroups.com/article/view/10.21037/tgh-23-63/coif). All authors report that Blue Regale Clinical Nutrition Technology Co., Ltd. provides product support for this study. QHP is from Blue Regale Clinical Nutrition Technology Co., Ltd., Kunshan, China. The authors have no other conflicts of interest to declare., (2023 Translational Gastroenterology and Hepatology. All rights reserved.)

A photocatalytic chemodivergent reaction for the selectivity formation of C-S and C-N bonds in a controlled manner was proposed. The reaction medium, either neutral or acidic, is critical to dictate the formation of 2-amino-1,3,4-thiadiazoles and 1,2,4-triazole-3-thiones from isothiocyanates and hydrazones. This is a practical protocol to achieve the chemoselectivity under mild and metal-free conditions.

Green and environmentally friendly and efficient separation adsorbents have attracted much attention in the treatment of heavy metal ions wastewater. In this study, xanthan gum (XG) was supported by fly ash magnetic beads (FAMB) to prepare adsorbent XG@FAMB. The effects of XG@FAMB dosage, pH value of the solution, adsorption time, and initial Pb (II) and Cu (II) concentration on its adsorption performance for Pb (II) and Cu (II) were investigated. The results show that under the conditions of pH 6, dosage of XG@FAMB 4.0 g/L, adsorption time 120 min, and initial concentration 60 mg/L, the maximum adsorption capacity of XG@FAMB for Pb (II) and Cu (II) was 14.93 mg/g and 14.88 mg/g, respectively. The adsorption process of Pb (II) and Cu (II) by XG@FAMB could be better described by the quasi-second-order kinetic model and Langmuir isothermal adsorption model, that is, the adsorption process is monolayer adsorption controlled by chemical action. The adsorption mechanism is that Pb (II) and Cu (II) coordinate with oxygen-containing functional groups hydroxyl and carboxyl on XG@FAMB surface, accompanied by electrostatic adsorption. XG@FAMB has the advantages of environmental protection of XG and easy solid-liquid separation of FAMB, and has a good removal effect on Pb (II) and Cu (II)., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: To investigate the effectiveness of two different functional three-dimensional (3D) laparoscopes in transanal total mesorectal excision (taTME). Methods: We retrospectively analyzed clinical data of 106 patients undergoing taTME of rectal cancer at the Affiliated Nanchong Central Hospital of North Sichuan Medical College between August 2017 and July 2020. Fifty-seven patients used the flexible 3D laparoscope (FTDL) and 49 patients used the rigid 3D laparoscope (RTDL). Results: Transabdominal operation duration in the FTDL group was shorter than in the RTDL group (125.5 ± 52.6 minutes versus 148.8 ± 59.3 minutes, P  = .034). However, transanal operation duration in the FTDL group was longer than in the RTDL group (77.3 ± 26.8 minutes versus 104.6 ± 34.1 minutes, P  = .000). There were no significant differences between the two groups in the number of harvested lymph nodes, total operation duration, postoperative complications, postoperative hospitalization, and quality of mesorectal specimen ( P  > .05). Conclusion: Synchronous two-team approach can be widely used in taTME. Making full use of the respective advantages of the two 3D laparoscopes is beneficial to improve the efficiency of taTME surgery. Clinical Trial Registration Number: NCT03416699.

Background: Acute intermittent porphyria (AIP) is a rare inherited disorder with extremely low prevalence. Early detection of patients with potential pathogenic hydroxymethylbilane synthase ( HMBS ) variants is crucial for clinical prognosis. This study was designed to investigate the prevalence of pathogenic HMBS variants in Chinese population., Methods: The China Metabolic Analysis Project (ChinaMAP) database was employed to predict the prevalence of pathogenic HMBS variants in the Chinese population according to the variant interpretation guidelines of The American College of Medical Genetics and Genomics (ACMG). And the prevalence of pathogenic HMBS variants in Mixed American (AMR), African/African American (AFR), and Non-Finnish European (NFE) populations were estimated based on the Genome Aggregation Database (gnomAD) genome V3.0 database according to the guidelines of ACMG. An epidemiological investigation of AIP was conducted in Hebei Province, China through collecting the annual newly-diagnosed AIP cases of inpatients in 32 comprehensive grade III A hospitals from January 2011 to December 2020 in Hebei, China., Results: A total of 5 pathogenic/likely pathogenic (P/LP) HMBS variants were identified and the prevalence of pathogenic HMBS variants was predicted to be 1/1,765. Furthermore, based on the gnomAD genome V3.0 database, the estimated prevalence of pathogenic HMBS variants was 1/1,367, 1/1,403, and 1/621 in AMR, AFR, and NFE populations, respectively. The distribution of these variants varied among different racial populations. Moreover, AIP patients were predominantly hospitalized in comprehensive grade III A tertiary hospitals in Hebei province over a 10-year period. A total of 39 patients were newly-diagnosed with AIP, and a majority of them were female (n=36). The annual incidence between 2011 and 2017 {0.03 [95% confidence interval (CI): 0.01 to 0.11] to 0.05 (95% CI: 0.07 to 0.14) per million population} was generally lower than [0.07 (95% CI: 0.03 to 0.17) to 0.08 (95% CI: 0.03 to 0.18) per million] in 2018 and thereafter., Conclusions: China has made great strides in the management of AIP. More nationwide epidemiological surveys and study of the prevalence rate of AIP patients in China are urgently required., Competing Interests: Conflicts of Interest: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-1600/coif). All authors reported that this study was supported by Grants from Hebei Provincial Science and Technology Plan Project (21377739D). The authors have no other conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

A partial deficiency of the heme biosynthetic enzyme hydroxymethylbilane synthase (HMBS) leads to acute intermittent porphyria (AIP), a severe neurovisceral, autosomal dominant disorder with low penetrance. Even though in-depth investigations of the HMBS variants have been carried out by researchers in Britain, France, Russia, and Sweden, this area remains uninvestigated in China owing to the rarity and lack of clinical understanding of the disease. In this study, 78 unrelated AIP patients revealed 48 different HMBS variants, of which 17 were novel. These included 22 missense variants, 9 splicings, 5 nonsense variants, 10 small deletions, 1 repeat insertion, and 1 complex deletion-insertion variant. The variant c.673C > T, found in 10 unrelated patients, was the most frequent variant, followed by the variant c.517C > T, found in 7 unrelated patients. We performed western blotting and immunofluorescence staining with four novel variants (c.653G > A, c.597dupC, c.726-727del, and c.1045_1046delAA) to detect the expression levels of mutant HMBSs. The results showed a variant-mediated decrease in the mutant-HMBS level, suggesting that the variant resulted in impaired gene product functions. Moreover, the in vitro functional verification in this study provided PS3_moderate evidence for American College of Medical Genetics and Genomics (ACMG) to grade the pathogenicity of novel variants in AIP., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Bio-desilication of fly ash containing a large amount of crystalline and amorphous silicate compound by silicate bacteria had the advantages of energy-saving, environment-friendly, and controllable cost. In this study, a bacteria strain with desilication ability on fly ash was isolated from the soil and identified as Bacillus amyloliquefaciens by 16sRNA and named ZGW-12. Through the bio-leaching treatment of fly ash by ZGW-12, it was found that the concentration of Si was 306.26 mg/L and the concentration of Al 3+ was 0.5 mg/L in the pulp. The mechanism of bio-leaching using ZGW-12 was investigated by XRD, HPLC, SEM, and FTIR. The organic acid and amino acid in the bacteria culture medium and the pulp were detected, and it was found that the content of the acidic metabolites in the pulp was much larger than that of the bacteria culture medium. The ore sample particles adsorbed a large number of bacteria cells and took place obvious corrosion. The surface of the ore sample undergone hydroxylation reaction, and the diffraction peak of the silicate crystal compound was unchanged. ZGW-12 exhibits good performance in retaining aluminum and extracting silicon aspect. AVAILABILITY OF DATA AND MATERIAL (DATA TRANSPARENCY): All data were true and valid., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: To investigate the effect of arsenic disulfide (AS 2 S 2 ) combined with itraconazole on the proliferation, apoptosis and hedgehog pathway of diffuse large B-cell lymphoma (DLBCL) cells., Methods: The human DLBCL cell OCI-LY3 was treated with different concentrations of AS 2 S 2 and itraconazole. Cell proliferation inhibition was detected by CCK-8, cell apoptosis rate was determined by flow cytometry. The expression levels of BCL-2, BAX, SMO and GLi1 were detected by Western blot., Results: The DLBCL cell viability was decreased significantly at 24, 48 or 72 h as cultured with itraconazole. Along with the increasing of itraconazole concentration, the DLBCL cell viability was significantly reduced as compared with that in control group, and the results showed statistically significant(r=-0.690，r=-0.639, r=-0.833, r=-0.808, r=-0.578). The inhibitory and apoptosis rates of the cells were significantly increased as compared with those of the single drug-treated group after treated by the combination of itraconazole and AS 2 S 2 (P<0.05). The protein levels of SMO and Glil were significantly down-regulated after treated by arsenic disulfide and itraconazole alone(P<0.01). The protein expression levels of SMO and Glil was down-regulated in the combined-treatment group(P<0.01)., Conclusion: Itraconazole can inhibit proliferation of DLBCL cells in a concentration-and time-dependent manner. In addition, the combination of AS 2 S 2 and itraconazole show a synergistic effects, which may be related with the down-regulated protein expression of SMO and Glil of Hedgehog signaling pathway.

The objective of this work was to study the impact of large petrochemical plants and mining operations on the accumulation of heavy metals in farmland and rice, as well as assess their potential risks on human health. The contents of seven heavy metals, Cd, Pb, Cr, Ni, Co, Cu, and Mn, were monitored in a typical polluted paddy soil-rice system near a petrochemical plant and mining area in Maoming, China. The results showed that the content of Cd in the soil exceeds the standard rate by 100%, and the single factor pollution index of Cd was 5.12, which is considered heavy pollution. Excessive heavy metals can inhibit and poison the growth of rice plants. Rice plants can maintain a certain level of heavy metal content by reducing the absorption or interception in the root cells, leading to great differences in the distribution of different heavy metals in plant tissues. Cadmium, Cu, Co, and Mn are easily absorbed from the soil by rice roots, while other heavy metals are relatively difficult to absorb by rice roots. Cuprum, Cd, Co, Pb, and Cr were mainly accumulated in the root of rice, but Mn and Ni migrate to the above ground plant tissues quickly. The brown rice produced in the paddy fields in the study area was seriously polluted. The concentration of Cd, Pb, and Ni in brown rice exceeded the standard by 100%, and Cr in brown rice also exceeded the standard by 80%. If residents consume rice from the study area, their daily intake of Cr and Cd will be 1.02 and 3.24 times higher, respectively, than the standard limit recommended by the FAO/WHO. The irrigation streams were polluted due to the discharge of petrochemical plants and mining wastewater, causing the serious pollution of heavy metals in the surrounding paddy fields. The rice produced in this area poses a serious risk to consumers, and so this problem of pollution should be addressed., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To establish the aGVHD mouse model，and investigate the regulatory effect and its mechanism of low-dose GSI combined with BMSC on aGVHD mice., Methods: C57BL/6 (H-2b) and BALB/c (H-2d) were selected as donor and recipient of allogeneic transplantation to establish the aGVHD mouse model. BALB/c mice were randomly divided into 6 groups, which were the bone marrow cell infusion after irradiation (BM) group; the bone marrow cells + spleen cells after irradiation (BM+SC) group; the bone marrow cells + spleen cells + DMSO (BM+SC+DMSO) (transplant control) group; bone marrow cells + splenocytes +GSI after irradiation (BM+SC+GSI) group; bone marrow cells + spleen cells + bone marrow mesenchymal stromal infusion after irradiation cell (BM+SC+BMSC) group; bone marrow cells + spleen cells + bone marrow mesenchymal stromal cells +GSI infused after irradiation (BM+SC+BMSC+GSI) group. The mice in the two groups containing GSI were intraperitoneally injected with GSI at 5 μmol/kg on day 1, 2, and 3 after transplantation with DMSO as a control. The general conditions, survival time and hematopoietic recovery of mice were observed, cytokines were detected by ELISA, and histopathological changes were detected by immunohistochemistry. The effects of low-dose GSI combined with BMSC on hematopoietic reconstruction and aGVHD development after allo-BMT were investigated., Results: The survival rate of the mice in BM+SC+BMSC+GSI combination group was 80% during the observation period, which was significantly higher than that in the other groups; the incidence of aGVHD was reduced in the BMSC GSI or their combination groups after 21 days of transplantation. GSI could partly promote the recovery of leukocytes, and show no significant delayed effect on the recovery platelets. Moreover, the level of Th1 cytokines (IFN-γ) in BM+SC+BMSC+GSI combined group was lower than that in BM+SC+GSI group (P<0.01), the level of Th2 cytokines (IL-4) in the combination group was higher than that in BM+SC+GSI group (P<0.01), also the level of IL-17 was significantly lower than that in the corresponding control group (P<0.001)., Conclusion: Low dose GSI combined with BMSC can promote hematopoietic reconstruction and regulate cytokines secretion including IFN-γ, IL-4 and IL-17. GSI combined with BMSC achieve the goal of synergistically inhibiting the occurrence and progression of aGVHD.

Infectious bursal disease virus (IBDV) and fowl adenovirus serotype 4 (FAdV-4) cause infectious bursal disease (IBD) and hydropericardium-hepatitis syndrome, respectively. Recently, studies have reported co-infections of poultry with IBDV and FAdV-4, which is an important problem in the poultry industry. Here, the variant IBDV strain ZD-2018-1 and FAdV-4 isolate HB1501 were used to assess the pathogenicity of co-infection in 1-day-old specific pathogen-free (SPF) chickens. Compared with chickens infected with only FAdV-4, those coinfected with IBDV and FAdV-4 showed enhanced clinical symptoms, higher mortality, more severe tissue lesions, and higher biochemical index levels. Furthermore, the expression of interleukin (IL)-6, IL-1β, and interferon-γ mRNAs in the IBDV-FAdV-4 coinfected chickens was delayed, and the antibody response levels were significantly lower in those birds compared with the FAdV-4-infected chickens. These results indicate that co-infection with variant IBDV ZD-2018-1 and FAdV-4 HB1501 could significantly promote the pathogenicity of FAdV-4 and reduce the immune response in chickens. This study provides the foundation for further investigation of the interaction mechanism in IBDV and FAdV-4 co-infection.

The immunoproteasome, a special isoform of the 20S proteasome, is expressed when the cells receive an inflammatory signal. Immunoproteasome inhibition proved efficacy in the treatment of autoimmune diseases. However, the role of the immunoproteasome in the pathogenesis of immune thrombocytopenia (ITP) remains unknown. We found that the expression of the immunoproteasome catalytic subunit, large multifunctional protease 2 (LMP2), was significantly upregulated in peripheral blood mononuclear cells of active ITP patients compared to those of healthy controls. No significant differences in LMP7 expression were observed between patients and controls. ML604440, an specific LMP2 inhibitor, had no significant impact on the platelet count of ITP mice, while ONX-0914 (an inhibitor of both LMP2 and LMP7) increased the number of platelets. In vitro assays revealed that ONX-0914 decreased the expression of FcγRI in ITP mice and decreased that of FcγRIII in ITP patients, inhibited the activation of CD4 + T cells, and affected the differentiation of Th1 cells in patients with ITP. These results suggest that the inhibition of immunoproteasome is a potential therapeutic approach for ITP patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Du, Xiang, Liu, Nie, Hou, Wang, Li, Xu, Teng, Peng, Hou and Shi.)

Oily sludge contains high concentrations of total petroleum hydrocarbons and heavy metals, which seriously impact the environment and human health. How to dispose of and use the oily sludge has attracted an increasing amount of attention. This study introduces harmless and resource-based oily sludge treatment technologies. It summarizes the technologies from various aspects, such as the process principle, influencing factors, advantages, and disadvantages, and analyzes and summarizes the status quo of the development of the technologies. In comparison, the direction of processing technology development is discussed to provide reference for processing technology improvements, optimization, and efficiency improvements.

The impacts of magnesium-ammonium-phosphate (MAP) precipitation on the performance and microbial dynamics in an anaerobic continuously stirred tank reactor (CSTR) coupled with sequencing batch reactor (SBR) for swine wastewater treatment were investigated. In CSTR-SBR systems, an overall higher removal efficiency for COD, NH 4 + and PO 4 3- as 98.6%, 98.7% and 97.9% was achieved with MAP precipitation, compared to CSTR-SBR without MAP pretreatment (i.e., 97.5, 74.3% and 19.9% for COD, NH 4 + and PO 4 3- , respectively). With MAP precipitation, the high C/N ratio of 6.6 after anaerobic CSTR was observed. The increase in the richness and diversity of microbial communities in CSTR with MAP was conducive to nitrogen and phosphorus removal, as well as biogas production. The core community was affiliated with bacterial phyla Firmicutes, Bacteroidetes, Proteobacteria, Cloacimonetes, and Spirochaetae. The study provide a new insight into the potential application of MAP precipitation as pretreatment for dealing with nutrient recovery from high-strength swine wastewater., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Porphyrias are a group of inherited metabolic diseases that include eight types, each of which is caused by a mutation that affects an enzyme of the heme biosynthetic pathway. When an enzyme defect has physiological significance, it leads to overproduction of pathway precursors prior to the defective step. The partial absence of the third enzyme in the heme biosynthetic pathway, porphobilinogen deaminase (PBGD) also known as hydroxymethylbilane synthase (HMBS), results in acute intermittent porphyria (AIP), which affects mainly women. Subjects who had AIP symptoms were deemed to have manifest AIP (MAIP). Clinical manifestations are usually diverse and non-specific. Acute AIP episodes may present with abdominal pain, nausea, and vomiting, and repeated episodes may result in a series of chronic injuries. Therefore, studying the mechanisms of acute and chronic manifestations of AIP is of great significance. This review aims to summarize the possible mechanisms of acute and chronic manifestations in patients with AIP., (2020, International Research and Cooperation Association for Bio & Socio - Sciences Advancement.)

Acute intermittent porphyria (AIP) is a rare inherited metabolic disease associated with heme metabolism. Primary Sjogren's syndrome (PSS) is a common autoimmune disease. The combined presence of AIP and PSS complicates treatment. A rare case of concomitant AIP and PSS is reported in this paper. A 30-year-old woman with AIP had recurrent acute abdominal pain, nausea and vomiting, constipation, persistent chest, back, and waist pain, red urine, positivity for porphobilinogen (PBG) in urine and a pathogenic mutation of the HMBS gene. Two and a half years after she was diagnosed with AIP, she was diagnosed with PSS based on dryness of the eyes and mouth, the elevation of immunoglobulins (IgG and IgA) and positive results on an anti-SS-A antibody test, an anti-SS-B antibody test, Schirmer's test and a labial gland biopsy. A mutation in the HMBS gene was detected in the patient and her cousin, but the patient had more severe AIP and more severe symptoms (such as epilepsy and a limp), which may be related to the co-morbidity of PSS. According to her PSS activity score, the patient had an ESSDAI score of 9 and required systemic treatment. However, potential medications were limited by AIP, so mycophenolate mofetil was eventually added to delay the progression of the primary disease., (2020, International Research and Cooperation Association for Bio & Socio - Sciences Advancement.)

A very rare case of acute intermittent porphyria (AIP) co-existing Turner syndrome (TS) is reported for the first time. A 32-year-old woman was diagnosed with AIP due to recurrent acute abdominal pain, red urine and pathogenic mutation of Hydroxymethyl synthetase (HMBS) gene. At the same time, TS was confirmed by Karyotype analysis results of 46,X,i(X)(q10), which accompanied by primary amenorrhea, elevated serum concentrations of follicle-stimulating hormone (FSH). Since the first attack of AIP, the patient has been increasingly depressed, and Psychiatry identified major depression. Duloxetine was chosen after careful deliberation, and the patient's mood stabilized. AIP had not recurred after half a year. Since sex hormones are the exacerbating factor of acute attack of AIP, sex hormone replacement therapy for TS was not administered. In conclusion, the conditions of AIP co-existing TS are complicate, and the treatment still needs to be improved by multiple disciplines in the follow-up., (2020, International Research and Cooperation Association for Bio & Socio - Sciences Advancement.)

A convenient and efficient palladium-catalyzed approach has been developed for the synthesis of 5-amino-1,2,4-oxadiazoles from amidoximes and isocyanides. Various 5-amino-1,2,4-oxadiazoles were obtained in moderate to high yields under mild conditions. The key to the success of this strategy involves new C-N bond and C-O bond formation via palladium-catalyzed isocyanide insertion.

Sequential vertical flow trickling filter and horizontal flow multi-soil-layering bioreactor were investigated for the treatment of decentralized domestic wastewater at various concentrations of sodium dodecyl benzene sulfonate (SDBS). Results have shown that the removal rate of COD could reach 92.1% at initial COD concentration of 960 mg/L (800 mg/L was provided by SDBS). NH 4 + -N concentration could be reduced from 52.4 to 9.71 mg/L without aeration. Besides, a quadratic function model was fit to describe the relationship between the relative activity of amylase and the protein content in extracellular polymer substance. SDBS could inhibit the transport and metabolisms of amino acids, lipids and carbohydrates in biofilms. The analysis of three-dimensional fluorescence diagram indicated that the peak in excitation/emission wavelengths = 310-340/370-430 nm was the characteristic peaks of some active substances such as some enzymes in EPS. Only Microbacterium could totally offset the toxicity of SDBS degradation products., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

We developed an efficient and novel protocol to synthesize 2-alkynyl oxazoles from tert-butyl isocyanide and alkynyl carboxylic acids. This method allowed the synthesis of diversely functionalized oxazoles under mild reaction conditions, coupled with operational simplicity and these functionalized oxazoles showed a certain degree of biological activity. Moreover, compounds 2b, 2h, 2k, 2n, 2p and 2t exhibited good anticancer activities in human gastric cancer cells (MGC803) and human bladder tumor cells (T24), with IC 50 below 20.0 μM.

In this study, the effect of various supports on activation of peroxymonosulfate and consequent degradation of Acid Orange 7 (AO7) in aqueous solutions was examined at the presence of LaFeO 3 perovskite as catalyst. Results showed that the AO7 degradation efficiency by LaFeO 3 supported on different supports was in an order of LaFeO 3 /Al 2 O 3 (86.2%) > LaFeO 3 (70.8%) > LaFeO 3 /CeO 2 (59.0%) > LaFeO 3 /SiO 2 (52.3%) > LaFeO 3 /TiO 2 (32.2%). Moreover, the pseudo first-order rate constant for AO7 degradation by LaFeO 3 /Al 2 O 3 was 3.2 times than that by LaFeO 3 . The enhancement was attributed to its large surface area, abundant chemisorbed surface-active oxygen, redox property and faster electron transfer. AO7 degradation and the leaching of iron ions decreased with the increase of pH. Data of electron spin resonance spectroscopy and quenching experiments revealed that sulfate and hydroxyl radicals were generated on LaFeO 3 /Al 2 O 3 surface, while sulfate radicals were identified to be the main reactive species responsible for AO7 degradation. Mechanisms for peroxymonosulfate activation were consequently proposed. Furthermore, LaFeO 3 /Al 2 O 3 catalyst exhibited a superior stability after five cycles. This work provides a new approach for design of iron-based perovskite catalysts with high and stable catalytic activity for removal of organic pollutants from aqueous solutions., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The concentration of antibiotics in anaerobically digested swine wastewater (ADSW) usually gradually increases due to the addition of antibiotics in livestock feed. Lemna aequinoctialis was used to treatment synthetic ADSW contaminated by oxytetracycline (OTC) whose concentrations were 0.05, 0.25, 0.50 and 1.00 mg/L, and its influences on NH 3 -N and TP remove were investigated. The fresh weight, photosynthetic pigment and protein content of duckweed were also investigated. Results have shown that nutrient removal and duckweed growth followed the "dose-response" relationships, and 0.05 mg/L OTC could significantly promote the synthesis of photosynthetic pigments and proteins in duckweed. Meanwhile, the protein content gradually decreased during investigation. More important, the degradation products and possible degradation pathways of OTC were diagrammatized via liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS), and twelve intermediates were detected in the duckweed systems. This study can offer a novel view for phytoremediation of ADSW containing antibiotics by aquatic plants., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The Notch signaling pathway is a highly conserved cell signaling system that plays an essential role in many biological processes. Notch signaling regulates multiple aspects of hematopoiesis, especially during T cell develop-ment. Recent data suggest that Notch also regulates mature T cell differentiation and function. The latest data show that Notch also plays an essential role in alloreactive T cells mediating acute graft-versus-host disease (aGVHD), the most severe complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Notch inhibition in donor-derived T cells or blockade of individual Notch ligands and receptors after transplantation can reduce GVHD severity and mortality in mouse models of allo-HSCT, without causing global immunosuppression. These findings indicate Notch in T cells as an attractive therapeutic target to control aGVHD. In this article, the pathophysiology of aGVHD, the Notch signal pathway and aGVHD are reviewed.

Transition-metal-free synthesis of 4-pyrones via TfOH-promoted nucleophilic addition/cyclization of diynones and water has been developed. This transformation is simple, atom economical and environmentally benign, providing rapid and efficient access to substituted 4-pyrones.

Objective: To explore the tumor growth inhibition of gamma secretase inhibitor MRK003 on human multiple myeloma xenograft mice by inhibition of AKT and Notch1 expression., Methods: NOD/SCID mice were injected with human multiple myeloma cell lines RPMI8226 to establish a xenograft mouse model. Mice were randomized into two groups：the experimental group were injected with MRK003 at a dose of 5 mg× kg⁻¹×d⁻¹ for 14 days; the inhibitor was replaced by an equal saline in the control group. Mice were sacrificed by cervical dislocation on the next day after the last injection and tumor tissue was removed to detect the expression of Notch1 and AKT by immunohistochemistry., Results: After subcutaneous injection with RPMI8226, mice had tumor formation in 5-7 days and the largest tumor block in 10-12 days. Before RPMI8226 injection, the mean sizes of tumor block in the experimental and the control groups were 509.2 mm³, 511.2 mm³(P>0.05). 9 days after injection, the mean sizes of tumor tissue in the experimental and the control groups were 636.6 mm³, 691.2 mm³(P<0.01). On the next day after the last injection, the tumor sizes of the experimental and the control groups were 683.5 mm³ and 1798.7 mm³(P<0.01). The size of tumor block in the experimental group was significantly smaller than that of the control group(P<0.01). Immunohistochemistry staining showed that the positive expression rates of Notch1(11.1%, P<0.01) and AKT(13.3%, P<0.01) in experimental group were significantly decreased compared with the control group(Notch1: 95.6%; AKT: 93.3%). Western blot results showed that Notch1 and AKT protein in experimental group were significantly lower than those in the control group., Conclusion: MRK003 could inhibit the tumor growth of human multiple myeloma xenograft mice by downregulated expression of Notch1 signaling pathway.

Hyperlipidemia may lead to endothelial injury, due to its effects on homocysteine and vascular endothelial growth factor in the serum, and the mRNA expression levels of peroxisome proliferator-activated receptor-γ (PPARγ), and caspase-3 and -8 in the vascular wall. In order to prevent and mitigate the high-fat state that results from endothelial injury, this study examined the effect of folic acid (FA) and vitamin B 12 (VB12) on the expression of PPARγ and caspase-3 and -8 mRNA in the abdominal aortas of rats with hyperlipidemia. Sixty 4-week-old healthy male Sprague Dawley rats were randomly divided into five groups (each n=12): the normal control (NC), high-fat diet (HL), FA, VB 12 and FA+VB12 groups. Following one week of adaptive feeding, the FA, VB12 and FA+VB12 groups were subject to the intraperitoneal injection of FA (0.5 mg/day), VB 12 (0.05 mg/day) and FA+VB 12 (0.5 mg/day and 0.05 mg/day), respectively, while fed a high-fat diet. The rats in the NC group were injected intraperitoneally with 0.9% NaCl solution (0.5 ml/day) and fed a normal diet, whereas those in the HL group were fed a high-fat diet only. A reverse transcription-polymerase chain reaction (RT-PCR) assay demonstrated that at the end of week 12, the FA treatment had effectively increased the PPARγ mRNA level, while reducing the caspase-3 and -8 mRNA levels, compared with the high-fat diet treatment (P<0.05). The effect of FA on the expression of PPARγ and caspase-3 and -8 was enhanced when used in combination with VB 12 (P<0.05). These results revealed that the application of FA, alone or in combination with VB 12 , improves and mitigates the high-fat state that results from endothelial injury.

Enantiomerically pure tribenzotriquinacenes (TBTQs) bearing two monofunctionalized aromatic nuclei were synthesized for the first time and their optical properties and absolute configuration determined. A remarkably regioselective bis-formylation of the fully bridgehead methylated parent TBTQ hydrocarbon with MeOCHCl(2)/TiCl(4) afforded a mixture of two C(s)-symmetrical (achiral) difunctionalized derivatives together with one C(1)-symmetrical (chiral) isomer. Reduction and subsequent column chromatography furnished the three respective benzylic TBTQ dialcohols. Optical resolution of the racemic 2,6-bis(hydroxymethyl) derivative was achieved via the diastereomeric (R)-1,1'-bi-2-naphthol ethers and the absolute configuration of the enantiomers was determined by CD exciton model analysis. The electronic circular dichroism (ECD) spectra and the specific rotation of the enantiomers were found to agree with the results of DFT calculations. Among the C(s)-symmetrical isomers, the "proximal" 2,11-dialdehyde and the corresponding benzylic dialcohol were identified by 2D NMR spectroscopy and X-ray crystallographic analysis, respectively, and used as the starting point for the synthesis of several novel dithiametacyclophanes. These include the first "dimeric" tribenzotriquinacene-based cyclophanes bearing the bowls of the two TBTQ units attached to each other in a syn (concave-concave) or anti (convex-concave) configuration. The usefulness of such thiacyclophanes as fluorescent chemosensors for different metal ions is also demonstrated.

alpha-Pyridoin (1, 1,2-di(2-pyridyl)-1,2-ethenediol) is a unique enediol antioxidant. To explore the detailed antioxidant mechanism of alpha-pyridoin, we synthesized alpha-pyridoin and its 5,5'- or 6,6'-bis-substituted derivatives (2-7) and compared their capacities to scavenge galvinoxyl radical (GO*) and protect human red blood cells (RBCs) from oxidative haemolysis. It was found that the compounds (5 and 6) with a methyl or methoxy group at the 5-position exhibit significantly higher GO*-scavenging and anti-haemolysis activities than other derivatives and vitamin C. Kinetic analysis of the GO*-scavenging reaction and the effect of added base on the reaction rate revealed that in ethyl acetate, the reaction occurs primarily by the direct hydrogen atom transfer (HAT mechanism). However, in ethanol that supports ionization, the kinetics of the process is mostly governed by sequential proton loss electron transfer (SPLET mechanism).

Objective: To observe the validity and safety of Kangxin capsule curing the patients with vascular dementia (VaD)., Patients and Methods: Fifty-six patients with vascular dementia of kidney deficiency and blood stagnation type were selected on the basis of defined diagnostic criteria and were randomly divided into Kangxin group (29) and control group (27), observing the relevant accumulation scores in dementia scale before and after treatment and changes of endothelin (ET), sex hormone, immunity and routine examinations., Results: Kangxin capsule can effectively improve the symptom of patients with VaD of senile kidney deficiency and blood stagnation type, and the average value of curative effect index of 29 patients in the treatment group is 23.01>/=20%, i.e. effective; compared with that before treatment, both CD(4) and CD(4).CD(8)(-1) rises (P<0.05) after the treatment with Kangxin capsule; for the male VaD patients of the Kangxin group, T level increases (P<0.05) and estrodial (E(2)).testerone (T)(-1) value decreases (P<0.05) after the treatment; for the female VaD patients of the Kangxin group, E(2), E(2).T(-1) value increases a great deal (P<0.05) compared with that before treatment; ET level of both groups decreased on average (P<0.01), and did not demonstrate any obvious toxic side effect., Conclusions: Kangxin capsule is a valid and safe preparation of Chinese traditional medicine for curing VaD of senile kidney deficiency and blood stagnation type.

Background: Polyamine biosynthesis is controlled primarily by ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AdoMetDC). Polyamine concentrations are elevated in colorectal cancer. Depletion of polyamine content in colorectal cancer by chemotherapy is related to tumor regression and impaired tumorigenicity. The current study evaluates the therapeutic effects of antisense ODC and AdoMetDC sequences on colorectal cancer in vitro and in vivo., Methods: Antisense ODC and AdoMetDC sequences were cloned into an adenoviral vector (Ad-ODC-AdoMetDCas). The human colon cancer cell lines, HT-29 and Caco-2, were infected with Ad-ODC-AdoMetDCas as well as with control vector. Viable cell counting, determination of polyamine concentrations, cell cycle analysis, and Matrigel invasion assays were performed in order to assess properties of tumor growth and invasiveness. Furthermore, the antitumor effects of Ad-ODC-AdoMetDCas were also evaluated in vivo in a nude mouse tumor model., Results: Our study demonstrated that adenovirus-mediated ODC and AdoMetDC antisense expression inhibits tumor cell growth through a blockade of the polyamine synthesis pathway. This inhibitory effect cannot be reversed by the administration of putrescine. Tumor cells were arrested at the G1 phase of the cell cycle after gene transfer and had reduced invasiveness. The adenovirus also induced tumor regression in established tumors in nude mice., Conclusions: Our study suggests that Ad-ODC-AdoMetDCas has antitumor activity and therapeutic potential for the treatment of colorectal cancer., (2006 John Wiley & Sons, Ltd.)

Aim: To construct a recombinant adenovirus that can simultaneously express both antisense ornithine decarboxylase (ODC) and adenosylmethionine decarboxylase ( AdoMetDC ) and detect its inhibitory effect on the intracellular polyamine pool and colorectal cancer cell growth., Methods: A 205-bp cDNA of AdoMetDC was reverse-inserted into recombinant pAdTrack-ODCas vectors and recombined with pAdEasy-1 vectors in AdEasy-1 cells. Positive clones were selected and transfected into the packaging cell HEK293 after they were linearized by PacI. Green fluorescent protein expression was used to monitor the process of adenovirus packaging. The ODC and AdoMetDC protein levels were identified by western blotting, and intracellular polyamine content was detected by reverse-phase high performance liquid chromatography. A viable cell count was used to determine the growth of HT-29 cells with or without exogenous polyamine., Results: Sequencing confirmed that AdoMetDC cDNA was successfully ligated into the pAdTrack-ODCas vector. GFP expression in 293 cells during virus packing and amplification was observed by fluorescence microscopy. Western blotting demonstrated that both ODC and AdoMetDC were downregulated by Ad-ODC-AdoMetDCas, and consequently 3 kinds of polyamine (putrescine, spermidine and spermine) were reduced to very low levels. HT-29 cell growth was significantly inhibited as compared with control conditions, and growth arrest was not reversed by exogenous putrescine., Conclusion: The successfully constructed recombinant adenovirus, Ad-ODC-AdoMetDCas, blocked polyamine synthesis and has therapeutic potential for treating colorectal cancer in vitro.

Objective: To investigate the effect of arterial elongation on the arteries and to set up a new method for vessel repair., Methods: This study was performed in 24 arteries that underwent different traumatic deficit and acute intra-operative elongation repair. The vessels were harvested and studied by histology, electron microscopy, and immunohistochemistry on day 1, 7 and 28 after operation., Results: The total unobstructed rate was 100% for deficit group as well as control experimental group. The content of collagen and elastin at various intervals showed no significant difference, the ratio of them also had no significant difference. Following anastomosis, the compliance of arteries was decreased, the peak value of proliferative cell nuclear antigen (PCNA) positive cell percentage was less than 20%, the internal diameter of elongation and anastomosis edge had no significant difference between deficit group and control group. There were no marked differences in pathological changes between deficit group and control group., Conclusion: Acute intraoperative artery elongation after balloon dilatation is a simple, safe, and effective alternative to vein interposition in the repair of traumatic arterial injuries. It appears to be a useful method in the emergency treatment.

Objective: To investigate fluid resuscitation affecting the result of treatment of patients with traumatic shock., Methods: Two hundred and fifty-six cases of patients with traumatic shock treated in our hospital between January 1989 and December 2002 were analysed retrospectively, and the volume-effect relationship between fluid resuscitation during the first hour and future of traumatic shock was summarised., Results: The successful rate of resuscitation was 73.05 percent (187 cases), and traumatic mortality was 26.95 percent (69 cases). After 1-hour trauma, the survival rate was 52.27 percent in patients with 1 liter of resuscitation fluid, 75.90 percent in patients with 15-20 liter of resuscitation fluid, and 78.29 percent of more than 20 liter resuscitation fluid, 86.79 percent in mild shock, 80.34 percent in middle shock and 54.65 percent in severe shock., Conclusion: Severe trauma and shock, hypotension and incorrect resuscitation manipulation are the main factors affecting the result of resuscitation and treatment of traumatic shock. It is important to early and correctly expand, especially at the first hour. The aim of resuscitation of traumatic shock is to maintain the hemodynamics and correct O2 defect.

Objective: Development of systemic lupus erythematosus (SLE) is not only associated with single loci of HLA gene, but also possibly related to certain haplotypes and genotypes of MHC. In the present study the authors explored association of HLA-A, B, DR haplotype and genotype with SLE in Chinese children, analyzed a large family with multiple SLE patients and genetic origin of SLE patients with HLA-DRB1 * 15, to discover the influence of linkage disequilibrium of HLA gene on SLE., Methods: HLA-A, B, DR alleles were tested in 53 patients with SLE and 40 cases with their parents, 35 patients with SLE and HLA-DRB * 15 positive and 27 cases with their parents, a large family with SLE (18 members of three generations) and also 78 normal controls and 43 cases with their parents by microlymphocytotoxicity test and polymerase chain reaction - sequence specific primers (PCR-SSP). HLA-A, B, DR haplotype and genotype of SLE patients and controls were statistically calculated. The SLE patients with HLA-DRB1 * 15 and controls were analyzed for either the gene originated from the paternal or the maternal side., Results: The variety of the haplotype in patient group (64/80) was less than that in control group (74/86). Only 9 haplotypes were found common between the patient group and control group. The frequency of the haplotype HLA-A9B40DRB1 * 15 was significantly higher in patient group than that in control group (P < 0.05), RR was 10.726 0. Five members of the large family had haplotype A9B40DRB1 * 15, 2 of them were patients with SLE, 1 of them was positive for ANA and had Raynaud's phenomenon and 2 of them were normal. The rest of the family members were normal. The frequency of genotypes DRB1 * 09/DRB1 * 15 and DRB1 * 03/DRB1 * 15 in SLE group was significantly higher than that of control group (P < 0.05), RR was 7.772 7 and 14.272 7, respectively. The number of SLE children with gene HLA-DRB1 * 15 derived from their fathers was significantly higher than that of the children with the gene derived from the mothers., Conclusion: These findings suggested that haplotype HLA-A9B40DRB1 * 15 and genotypes HLA-DRB1 * 09/DRB1 * 15, HLA-DRB1 * 03/DRB1 * 15 were correlated with SLE. The predisposition of multiple loci seems to have an additive effect. The children with their gene HLA-DRB1 * 15 derived from their fathers might more easily suffer from SLE than those with the gene derived from their mothers, the underlying mechanism needs further studies.