Photogenerated chlorine radicals activate C(sp3)-H bonds of alkylbenzenes to access quinazolinones.

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.

Visible-Light-Induced Chemodivergent Synthesis of Tetracyclic Quinazolinones and 3-Iminoisoindoliones via the Substrate Control Strategy.

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-Pr2NEt as a sacrificial electron donor leading to metal-free conditions.

A fucoidan plant drink reduces Helicobacter pylori load in the stomach: a real-world study.

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.

Chemodivergent Photocatalyzed Heterocyclization of Hydrazones and Isothiocyanates for the Selectivity Synthesis of 2-Amino-1,3,4-thiadiazoles and 1,2,4-Triazole-3-thiones.

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.

Methyltransferase K-D-K-E motif influences the intercellular transmission of Newcastle disease virus.

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.

Adsorption of Pb (II) and Cu (II) by magnetic beads loaded with xanthan gum.

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).

Reasonable Collocation of Two Different Functional 3D Laparoscopes May Improve the Efficiency of Transanal Total Mesorectal Excision Surgery Using a Synchronous Two-Team Approach?

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.

Acute intermittent porphyria: prevalence of pathogenic HMBS variants in China, and epidemiological survey in Hebei Province, China.

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.

Identification and molecular analysis of 17 novel variants of hydroxymethylbilane synthase in Chinese patients with acute intermittent porphyria.

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.

Investigation on bio-desilication process of fly ash based on a self-screened strain of Bacillus amyloliquefaciens and its metabolites.

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 Al3+ 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.

[Effects of Arsenic Disulfide Combined with Itraconazole on Proli- feration and Apoptosis and Hedgehog Pathway of Diffuse Large B-Cell Lymphoma Cells].

OBJECTIVE: To investigate the effect of arsenic disulfide (AS2S2) 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 AS2S2 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 AS2S2(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 AS2S2 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 Effect of γ-secretase Inhibitor Combined with BMSC on the aGVHD in Mice Model].

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.

Divergent patterns of heavy metal accumulation in paddy fields affect the dietary safety of rice: a case study in Maoming City, China.

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.

Experimental co-infection of variant infectious bursal disease virus and fowl adenovirus serotype 4 increases mortality and reduces immune response in chickens.

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-1ß, 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.

Performance and microbial community dynamics in anaerobic continuously stirred tank reactor and sequencing batch reactor (CSTR-SBR) coupled with magnesium-ammonium-phosphate (MAP)-precipitation for treating swine wastewater.

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, NH4+ and PO43-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, NH4+ and PO43-, 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.

A review of the application of different treatment processes for oily sludge.

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.

Acute intermittent porphyria: focus on possible mechanisms of acute and chronic manifestations.

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.

The challenge of managing comorbidities: a case report of primary Sjogren's syndrome in a patient with acute intermittent porphyria.

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.

An extremely rare combination of acute intermittent porphyria and Turner syndrome.

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.

Palladium-catalyzed synthesis of 5-amino-1,2,4-oxadiazoles via isocyanide insertion.

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.