[Overview of Meta-analysis of Lianhua Qingwen preparations in treatment of viral diseases].

This study aims to obtain higher-level evidence by overviewing the Meta-analysis of Lianhua Qingwen preparations in the treatment of viral diseases including influenza, coronavirus disease 2019(COVID-19), and hand, foot and mouth disease(HFMD). CNKI, Wanfang, VIP, China Clinical Trial Registry(ChiCTR), PubMed, EMbase, Web of Science, and Cochrane Library were searched for the Meta-analysis about the treatment of viral diseases with Lianhua Qingwen preparations from the database establishment to April 1, 2022. After literature screening and data extraction, AMSTAR2 and the grading of recommendations assessment, development and evaluations(GRADE) system were used to assess the methodological quality and evidence quality, respectively, and then the efficacy and safety outcomes of Lianhua Qingwen preparations in the treatment of viral diseases were summarized. Thirteen Meta-analysis were finally included, three of which were rated as low grade by AMSTAR2 and ten as very low grade. A total of 75 outcome indicators were obtained, involving influenza, COVID-19, and HFMD. According to the GRADE scoring results, the 75 outcome indicators included 5(6.7%) high-level indicators, 18(24.0%) mediate-level indicators, 25(33.3%) low-level evidence indicators, and 27(36.0%) very low-level indicators.(1)In the treatment of influenza, Lianhua Qingwen preparations exhibited better clinical efficacy than other Chinese patent medicines and Ribavirin and had similar clinical efficacy compared with Oseltamivir. Lianhua Qingwen preparations were superior to other Chinese patent medicines, Oseltamivir, and Ribavirin in alleviating clinical symptoms. They showed no significant differences from Oseltamivir or conventional anti-influenza treatment in terms of the time to and rate of negative result of viral nucleic acid test.(2)In the treatment of COVID-19, Lianhua Qingwen preparation alone or combined with conventional treatment was superior to conventional treatment in terms of total effective rate, main symptom subsidence rate and time, fever clearance rate, duration of fever, time to fever clearance, cough subsidence rate, time to cough subsidence, fatigue subsidence rate, time to fatigue subsidence, myalgia subsidence rate, expectoration subsidence rate, chest tightness subsidence rate, etc. Lianhua Qingwen preparations no difference from conventional treatment in terms of subsiding sore throat, nausea, diarrhea, loss of appetite, headache, and dyspnea. In terms of chest CT improvement rate, rate of progression to severe case, cure time, and hospitalization time, Lianhua Qingwen alone or in combination with conventional treatment was superior to conventional treatment.(3)In the treatment of HFMD, Lianhua Qingwen Granules was superior to conventional treatment in terms of total effective rate, average fever clearance time, time to herpes subsidence, and time to negative result of viral nucleic acid test.(4)In terms of safety, Lianhua Qingwen preparations led to low incidence of adverse reactions, all of which were mild and disappeared after drug withdrawal. The available evidence suggests that in the treatment of influenza, COVID-19, and HFMD, Lianhua Qingwen preparations can relieve the clinical symptoms, shorten the hospitalization time, and improve the chest CT. They have therapeutic effect and good safety in the treatment of viral diseases. However, due to the low quality of available studies, more high-quality clinical trials are needed to support the above conclusions.

Asymmetric Synthesis of Multifunctionalized 2,3-Benzodiazepines by a One-Pot N-heterocyclic Carbene/Chiral Palladium Sequential Catalysis.

We report the first example of the construction of chiral 2,3-benzodiazepine compounds which are of biologic and pharmaceutical relevance by asymmetric catalysis. Catalyzed by a thiazolium-derived carbene and a palladium-chiral bidentate phosphine complex in sequence, one-pot reaction between 1-(2-(2-nitrovinyl)aryl)allyl esters 1 with azodicarboxylates 2 took place efficiently at ambient temperature to produce 4-nitro-1-vinyl-1H-2,3-benzodiazepine-2,3-dicarboxylates 5 in good to excellent yields with an enantiomeric ratio of up to 95:5.

Selective Synthesis of Multifunctionalized 2,3-Dihydroinden-1-ones and 1,3-Dihydroisobenzofurans from the Reaction of o-Alkynylbenzaldehydes with Imines Steered by N-Heterocyclic Carbene/Copper(II) and N-Heterocyclic Carbene/Base Cascade Catalysis.

We report in this paper the N-heterocyclic carbene/transition metal and N-heterocyclic carbene/base cascade catalysis in the reaction of o-alkynylbenzaldehydes with N-acylimines, demonstrating the example of reaction pathways steered by catalysts. Under the catalysis of a thiazole carbene/Et3N followed by Cu(OAc)2 in acetonitrile at ambient temperature, o-alkynylbenzaldehydes underwent reaction with N-acylimines that were generated in situ from N-((aryl)(tosyl)methyl)amides to produce a pair of Z- and E-2-amido-3-benzylidene-1-indanones in 47-92% total yields. The reaction of the same substrates in the presence of a thiazole carbene and Cs2CO3, on the other hand, afforded (1 E,3 Z)-1-amidobenzylidene-3-benzylidene-1,3-dihydroisobenzofurans in 54-89% yields.

N-Heterocyclic Carbene/Palladium Cascade Catalysis: Construction of 2,2-Disubstitiuted Benzofuranones from the Reaction of 3-(2-Formylphenoxy)propenoates with Allylic Esters.

The cascade catalysis involving N-heterocyclic carbene (NHC) and palladium/ligand was demonstrated. In the presence of a triazolium salt, palladium catalyst, and base, the reaction of 3-(2-formylphenoxy)propenoates and allylic esters proceeded efficiently under mild conditions to afford 2-allylbenzofuran-3-one-2-acetates in moderated to good yields. An asymmetric cascade catalysis was achieved when (R)-BINAP was employed as a chiral ligand, producing enantiomerically enriched 2,2-disubstitiuted benzofuran-3-one derivatives with an ee up to 81%.

N-Heterocyclic Carbene/Lewis Acid Dual Catalysis for the Divergent Construction of Enantiopure Bridged Lactones and Fused Indenes.

The chiral triazole carbene and Ti(OPr-i)4 cocatalyzed reaction between α,ß-unsaturated aldehydes and 2-(aroylvinyl)benzaldehydes was systematically studied. A divergence in reaction pathways was observed under different reaction conditions. In benzene solvent and at ambient temperature, the reaction produced 4,5-dihydro-1,4-methanobenzo[c]oxepin-3-ones, the bridged caprolactones, as the major products in moderate yields with excellent enantioselectivity. The same reaction in dichloroethane and at 50 °C, however, gave 2,8-dihydrocyclopenta[a]indenes as the major products in most cases. The application of the method developed was demonstrated by the transformation of the bridged lactone products into enantiopure 4-hydroxy-1,2,3,4-tetrahydronaphthalene-2-carboxylic acids.

EDAG positively regulates erythroid differentiation and modifies GATA1 acetylation through recruiting p300.

Erythroid differentiation-associated gene (EDAG) has been considered to be a transcriptional regulator that controls hematopoietic cell differentiation, proliferation, and apoptosis. The role of EDAG in erythroid differentiation of primary erythroid progenitor cells and in vivo remains unknown. In this study, we found that EDAG is highly expressed in CMPs and MEPs and upregulated during the erythroid differentiation of CD34(+) cells following erythropoietin (EPO) treatment. Overexpression of EDAG induced erythroid differentiation of CD34(+) cells in vitro and in vivo using immunodeficient mice. Conversely, EDAG knockdown reduced erythroid differentiation in EPO-treated CD34(+) cells. Detailed mechanistic analysis suggested that EDAG forms complex with GATA1 and p300 and increases GATA1 acetylation and transcriptional activity by facilitating the interaction between GATA1 and p300. EDAG deletion mutants lacking the binding domain with GATA1 or p300 failed to enhance erythroid differentiation, suggesting that EDAG regulates erythroid differentiation partly through forming EDAG/GATA1/p300 complex. In the presence of the specific inhibitor of p300 acetyltransferase activity, C646, EDAG was unable to accelerate erythroid differentiation, indicating an involvement of p300 acetyltransferase activity in EDAG-induced erythroid differentiation. ChIP-PCR experiments confirmed that GATA1 and EDAG co-occupy GATA1-targeted genes in primary erythroid cells and in vivo. ChIP-seq was further performed to examine the global occupancy of EDAG during erythroid differentiation and a total of 7,133 enrichment peaks corresponding to 3,847 genes were identified. Merging EDAG ChIP-Seq and GATA1 ChIP-Seq datasets revealed that 782 genes overlapped. Microarray analysis suggested that EDAG knockdown selectively inhibits GATA1-activated target genes. These data provide novel insights into EDAG in regulation of erythroid differentiation.

[Recent application advances of covalent organic frameworks for solid-phase extraction].

Covalent organic frameworks (COFs) are a type of crystalline porous polymers. It firstly prepared by thermodynamically controlled reversible polymerization to obtain chain units and connecting small organic molecular building units with a certain symmetry. These polymers are widely used in gas adsorption, catalysis, sensing, drug delivery, and many other fields. Solid-phase extraction (SPE) is a fast and simple sample pretreatment technology that can enrich analytes and improve the accuracy and sensitivity of analysis and detection; it is extensively employed in food safety detection, environmental pollutant analysis, and several other fields. How to improve the sensitivity, selectivity, and detection limit of the method during sample pretreatment have become a topic of great interest. COFs have recently been applied to sample pretreatment owing to their low skeleton density, large specific surface area, high porosity, good stability, facile design and modification, simple synthesis, and high selectivity. At present, COFs have also attracted extensive attention as new extraction materials in the field of SPE. These materials have been applied to the extraction and enrichment of diverse types of pollutants in food, environmental, and biological samples, such as heavy metal ions, polycyclic aromatic hydrocarbons, phenol, chlorophenol, chlorobenzene, polybrominated diphenyl ethers, estrogen, drug residues, pesticide residues, etc. COFs can be synthesized from different materials and exert different effects on different extracts. New types of COFs can also be synthesized via modification to achieve better extraction effects. In this work, the main types and synthesis methods of COFs are introduced, and the most important applications of COFs in the fields of food, environment and biology in recent years are highlighted. The development prospects of COFs in the field of SPE are also discussed.

Over-expression of EDAG in the myeloid cell line 32D: induction of GATA-1 expression and erythroid/megakaryocytic phenotype.

Erythroid differentiation-associated gene (EDAG), a hematopoietic tissue-specific transcription regulator, plays a key role in maintaining the homeostasis of hematopoietic lineage commitment. However, the mechanism and genes regulated by EDAG remain unknown. In this study, we showed that overexpression of EDAG in a myeloid cell line 32D led to an erythroid phenotype with increased number of benzidine-positive cells and up-regulation of erythroid specific surface marker TER119. The megakaryocytic specific marker CD61 was also induced significantly. Using a genome-wide microarray analysis and a twofold change cutoff, we identified 332 genes with reduced expression and 288 genes with increased expression. Among up-regulation genes, transcription factor GATA-1 and its target genes including EKLF, NF-E2, Gfi-1b, hemogen, SCL, hemoglobin alpha, beta and megakaryocytic gene GPIX were increased. Silencing of EDAG by RNA interference in K562 cells resulted in down-regulation of these genes. Taken together, EDAG functions as a positive regulator of erythroid/megakaryocytic differentiation in 32D cells associated with the induction of GATA-1 and its target genes.

Suppression of EDAG gene expression by phorbol 12-myristate 13-acetate is mediated through down-regulation of GATA-1.

EDAG, a hematopoietic tissue-specific protein, is involved in the regulation of proliferation, differentiation and apoptosis of hematopoietic cells. In this study, a dose-dependent inhibition of EDAG expression by PMA was observed in K562 cells. The responsive element for the PMA-induced inhibition was contained in the region between -211 and +32bp of the EDAG gene promoter. By oligonucleotide-directed mutagenesis, EMSA, ChIP and transient transfection assays, we found that two tandem repeat GATA-1 sites in the promoter of EDAG gene played an important role in the PMA-mediated down-regulation of the EDAG gene expression in K562 cells. The kinetics of EDAG expression during PMA induction showed that the levels of EDAG expression were down-regulated concomitantly with GATA-1 down-expression. Decreased GATA-1 expression by siRNA reduced expression of EDAG in K562 cells, and restored expression of GATA-1 significantly rescued EDAG expression from PMA-mediated suppression. Overexpression of EDAG in K562 cells inhibited the megakaryocytic differentiation induced by PMA which raised the interesting possibility that PMA induced K562 cells differentiation toward megakaryocytic phenotype through, at least in part, the inhibition of EDAG expression. In vivo analysis confirmed that EDAG was highly expressed in primitive progenitor cells and down-regulated in megakaryocytes which was consistent with the expression pattern of GATA-1. Furthermore, PKC and MAPK specific inhibitors treatment attenuated the down-regulation of EDAG induced by PMA. Taken together, these results suggest that the inhibition of the EDAG gene by PMA is mediated through down-regulation of transcription factor GATA-1 and involved the PKC/MAPK signaling pathway.

[Impact of Newly Build Lead-Acid Battery Agglomeration Area on the Surrounding Soil Environment: A Study Based on the Spatial Characteristics of Heavy Metals].

To determine whether the newly built lead-acid battery agglomeration area in a town in northern Zhejiang had an impact on the surrounding soil environment after seven years of operation, 76 samples of surface soil around the lead-acid battery concentration area were collected, and the contents of Hg, As, Cu, Zn, Pb, Cd, Ni, and Cr in the soil were determined. Based on the spatial distance of the agglomeration area and 50, 450, and 850 m from the agglomeration area boundary, the soil environmental quality was evaluated using the single factor index, Nemerow comprehensive pollution index, and potential ecological risk index methods. The spatial distribution characteristics of the heavy metals were analyzed using the geostatistical method, and the sources of heavy metals affecting the soil environment were determined by correlation analysis. The results showed that the average contents of Hg, Zn, and Pb in eight heavy metals were higher than their corresponding background values at all spatial scales. The average Cd content in spatial scales other than the agglomeration area was larger than its background value. Only As at 50 m was greater than its background value, whereas the average content of other elements at all spatial distances was lower than their corresponding background values. The spatial variability was high for Hg and Cd but not obvious for other elements. This implies that the influence of regional activities was concentrated mainly on Hg and Cd; the content of both increased with distance from the agglomeration area. Hg and Cd exceeded the risk screening values and were distributed mainly at 450 m and 850 m; 33.33% and 38.89% Hg points and 27.78% and 55.56% Cd points were observed at these distances, respectively. The spatial distribution characteristics of Hg and Cd were consistent with their contents; only Zn and Pb had scattered points that exceeded the risk screening values and generally no obvious spatial distribution characteristics. According to the risk analysis of soil comprehensive pollution caused by the eight heavy metals, Cd was the main source of soil comprehensive pollution risk at a contribution rate of 36.73%, which caused the soil at 850 m to be in a state of alert. Soil ecological risk at a medium level occurred mainly at 450 m and 850 m outside the agglomeration area from Hg and Cd. The contribution rates to the soil quality at these distances were 46.30% and 39.37% for Hg and 38.98% and 49.30% for Cd, respectively. This indicates that regional activities caused Hg and Cd to be the main elements affecting soil quality in the study area. The results of geostatistics and multivariate statistical analysis showed that Hg and Cd were diffused inward from the periphery of the agglomeration area on the axis of the local main wind direction (northeast-southwest), and the main sources of both were coal-burning activities of enterprises in the periphery of the agglomeration area. In summary, the newly build lead-acid battery agglomeration area has not significantly affected the accumulation of heavy metals in the agglomeration area and in the surrounding soil after seven years of operation.

[Responses of sap flow to natural rainfall and continuous drought of tree species growing on bedrock outcrops]. / å‡ºéœ²åŸºå²©ç”Ÿå¢ƒå ¸åž‹æ¤ç‰©æ ‘å¹²æ¶²æµå¯¹è‡ªç„¶é™æ°´å’Œè¿žç»­å¹²æ—±çš„å“åº”ç‰¹å¾.

This study focused on bedrock outcrops, a very common habitat in karst region of southwest China. To reveal the responses of plant transpiration to natural rainfall and continuous drought, two tree species typical to this habitat, Radermachera sinica and Triadica rotundifolia, were selected as test materials. A rainout shelter was used to simulate continuous drought. The sap flow dynamics were monitored using the method of Granier's thermal dissipation probe (TDP). Our results showed that sap flow density increased to different degrees after rain in different stages of the growing season. Sap flow density of the deciduous species T. rotundifolia was always higher than that of the semi-deciduous species R. sinica. After two months without rainfall input, both species exhibited no obvious decrease in sap flow density, indicating that rainfall was not the dominant source for their water uptake, at least in the short-term. Based on the regression relationships between sap flow density and meteorological factors before and after rainfall, as well as at different stages of continuous drought, we found that the dynamics of meteorological factors contributed little to plant transpiration. The basic transpiration characteristics of both species were not changed in the circumstance of natural rainfall and short-term continuous drought, which would be closely related to the special water storage environments of bedrock outcrops and the reliance on deep water sources by tree species.

Chiral N-heterocyclic carbene/Lewis acid cooperative catalysis of the reaction of 2-aroylvinylcinnamaldehydes: a switch of the reaction pathway by Lewis acid activation.

The chiral N-heterocyclic carbene/Lewis acid co-catalyzed reaction of 2-aroylvinylcinnamaldehydes produced good yields of indeno[1,2-c]furan-1-one derivatives with excellent enantioselectivity and diastereoselectivity. A switch of intramolecular cyclization to intermolecular dimerization was achieved by the cooperative catalysis of chiral triazole carbene and Ti(OPr-i)4 catalysts.

[Water use strategy of Eucalyptus urophylla ×E. grandis on karst hillslope based on isotope analysis.] / åŸºäºŽç¨³å®šåŒä½ç´ çš„å–€æ–¯ç‰¹å¡åœ°å°¾å·¨æ¡‰æ°´åˆ†åˆ©ç”¨ç‰¹å¾.

Using stable isotope techniques, water sources and water use efficiencies of Eucalyptus urophylla ×E. grandis (exotic tree species) and Liquidambar formosana (native tree species, as a reference) were studied in a typical karst artificial forest, and the risk of drought stress of the plantation was discussed. The results showed that the isotope value of shallow soil water (0-50 cm) had obvious gradient features and was similar to the recent rain, while that of deep water was more stable and different from the shallow soil water. The soil water content in wet season (May and September) was higher than in dry season (October), and was higher in upslope than in downslope segment. The main water source of L. formosana was shallow soil water, which corresponded to high water use efficiency in different seasons. The main water sources for E. urophylla ×E. grandis on the upper slope and downslope segments were both shallow soil water in wet season, however, the sum of average water using the proportion of deep soil water increased for the downslope segment in the end of wet season. In dry season, E. urophylla ×E. grandis on the downslope segment mainly used shallow soil water, while it used deeper soil water on the upslope segment when soil water was relatively low. Meanwhile, the water use efficiency of E. urophylla ×E. grandis was lower compared with L. formosana, which revealed E. urophylla ×E. grandis did not get enough water supply under drought stress. The above results indicated that E. urophylla ×E. grandis would encounter high risk of water stress if extreme drought events happened in karst regions in the coming future.

Erythroid differentiation-associated gene interacts with NPM1 (nucleophosmin/B23) and increases its protein stability, resisting cell apoptosis.

Erythroid differentiation-associated gene (EDAG) is a haematopoietic tissue-specific transcription regulator that plays a key role in maintaining the homeostasis of haematopoietic lineage commitment. In acute myeloid leukaemia (AML) patients, the high expression level of EDAG is associated with poor prognosis. NPM1 (nucleophosmin/B23), a ubiquitous nucleolar phosphoprotein, comprises a multifunctional protein that is involved in several cellular processes, including ribosome biogenesis, centrosome duplication, cell cycle progression, cell growth and transformation. Various studies have implicated NPM1 overexpression in promoting tumour cell proliferation, blocking the differentiation of leukaemia cells and resisting apoptosis. In the present study, using co-immunoprecipitation, we characterized EDAG as a physiological binding partner of NPM1; The N-terminal (amino acids 1-124) region of EDAG interacts with the N-terminal (amino acids 118-187) of NPM1. Under cycloheximide treatment, the stability of NPM1 protein was enhanced by EDAG overexpression, whereas knockdown of EDAG by lentivirus-mediated small interfering RNA resulted in an increased degradation rate of NPM1 in K562 cells. During 4ß-phorbol l2-myristate 13-acetate-induced K562 megakaryocytic differentiation, overexpression of EDAG prevented the down-regulation of NPM1 proteins, whereas knockdown of EDAG accelerated the down-regulation of NPM1. EDAG deletion mutant lacking the binding domain with NPM1 lost the ability to stabilize NPM1 protein. Furthermore, knockdown of EDAG in K562 cells led to increased cell apoptosis induced by imatinib, and re-expression of NPM1 attenuated the increased apoptosis. These results suggest that EDAG enhances the protein stability of NPM1 via binding to NPM1, which plays a critical role in the anti-apoptosis of leukaemia cells.