Alkaloids from Zanthoxylum nitidum and their anti-proliferative activity against A549 cells by regulating the EGFR/AKT/mTOR pathway.

Zanthoxylum nitidum is frequently used as a traditional Chinese medicine and food supplement. Our previous study revealed that its constituent compounds were able to inhibit cancer cell proliferation. In our continuous exploration of bioactive compounds in Z. nitidum, we isolated ten alkaloids (1-10), including one new natural compound (1), and nine known alkaloids (2-10), from an ethanolic extract of the whole plant. The chemical structures were elucidated based on a combination of comprehensive NMR and HRESIMS analyses. Compounds 5, 8 and 10 exhibited significant antiproliferative effects against A549 cancer cell lines. We further elucidated the underlying molecular mechanisms of the antiproliferative activity of compound 8 in A549 human lung cancer cells. Compound 8 was found to induce cell cycle arrest in the G0/G1 phase via p53 activation and CDK4/6 suppression. Compound 8 also effectively inhibited cell migration through the modulation of the epithelial-mesenchymal transition (EMT), as indicated by the expression of biomarkers, such as N-cadherin downregulation and E-cadherin upregulation. Compound 8 significantly suppressed the activation of the EGFR/AKT/mTOR signalling pathway in A549 cells. These results indicate that alkaloid 8 from Z. nitidum has potential to be a lead antiproliferative compound in cancer cells.

Diisoprenyl Cyclohexene-Type Meroterpenoids with Cytotoxic Activity from a Mangrove Endophytic Fungus Aspergillus sp. GXNU-Y85.

Five new diisoprenyl cyclohexene-type meroterpenoids, aspergienynes J-N (1-5), along with three known analogues (6-8), were obtained from the mangrove endophytic fungal strain Aspergillus sp. GXNU-Y85. The chemical structures, including their absolute configurations, were established via spectroscopic data and comparison of experimental and calculated ECD spectra. Cytotoxicity assay results indicated that compound 8 had strong cytotoxicity against HeLa cancer cells, and its IC50 value was 11.8 µM. In addition, flow cytometry analysis revealed that the cytotoxicity of 8 was due to the induction of G1 cell cycle arrest and apoptosis in HeLa cells.

Diisoprenyl-cyclohexene-type meroterpenoids from a mangrove endophytic fungus Aspergillus sp. GXNU-Y65 and their anti-nonalcoholic steatohepatitis activity in AML12 cells.

Nine previously undescribed diisoprenyl-cyclohexene-type meroterpenoids, aspergienynes A-I, together with five known analogues, were obtained from the mangrove endophytic fungal strain Aspergillus sp. GXNU-Y65. The diisoprenyl-cyclohexene-type meroterpenoids were elucidated based on multispectroscopic analysis, and the previously undescribed compounds' absolute configurations were established via electronic circular dichroism calculations. Biological activity results indicated that aspergienyne C (compound 3) had strong anti-nonalcoholic steatohepatitis activity against AML12 cells treated with PA (Palmitic acid) + OA (Oleic acid). At the same concentration of 20 µM, 3 significantly reduced triglyceride (TG) content compared with fenofibrate (positive control) in PA + OA treated AML12 cells, and obviously increased phosphorylation of acetyl-CoA carboxylase.

Rational construction of graphitic carbon nitride composited Li-rich Mn-based oxide cathode materials toward high-performance Li-ion battery.

Li-rich Mn-based oxides (LRMOs) are considered as one of the most-promising cathode materials for next generation Li-ion batteries (LIBs) because of their high energy density. Nevertheless, the intrinsic shortcomings, such as the low first coulomb efficiency, severe capacity/voltage fade, and poor rate performance seriously limit its commercial application in the future. In this work, we construct successfully g-C3N4 coating layer to modify Li1.2Mn0.54Ni0.13Co0.13O2 (LMNC) via a facile solution. The g-C3N4 layer can alleviate the side-reaction between electrolyte and LMNC materials, and improve electronic conduction of LMNC. In addition, the g-C3N4 layer can suppress the collapse of structure and improve cyclic stability of LMNC materials. Consequently, g-C3N4 (4 wt%)-coated LMNC sample shows the highest initial coulomb efficiency (78.5%), the highest capacity retention ratio (78.8%) and the slightest voltage decay (0.48 V) after 300 loops. Besides, it also can provide high reversible capacity of about 300 and 93 mAh g-1 at 0.1 and 10C, respectively. This work proposes a novel approach to achieve next-generation high-energy density cathode materials, and g-C3N4 (4 wt%)-coated LMNC shows an enormous potential as the cathode materials for next generation LIBs with excellent performance.

Durable lithium-ion insertion/extraction and migration behavior of LiF-encapsulated cobalt-free lithium-rich manganese-based layered oxide cathode.

Lithium-rich manganese-based cathode has made a subject of intense scrutiny for scientists and application researchers due to their exceptional thermal stability, high specific capacity, high operating voltage, and cost-effectiveness. However, the inclusion of cobalt, as a crucial component in lithium-rich manganese-based cathode materials, has become a cause for concern due to its limited availability and non-renewable nature, which eventually limits the growth of the battery industry and increase costs. Considering the poor stability of cobalt-free cathode, this work proposes a coating strategy of LiF through a simple high-temperature melting method. Directly coating LiF on Li1.2Ni0.2Mn0.6O2 surface is found to be an effective way to protect the cathode material, decrease metal solubility, and inhibit irreversible phase transition processes, thus leading to an improved electrochemical performance. As a result, the battery employing LiF coated Li1.2Ni0.2Mn0.6O2 cathode can be stabilized over 280 cycles and maintain a capacity of 110 mAh g-1 at 1C. What's more, the mechanisms of ion insertion/extraction behavior and ion migration process are also studied systematically. This study will open the avenue to develop a high-energy battery system with cobalt-free cathode.

Corydalis saxicola Bunting: A Review of Its Traditional Uses, Phytochemistry, Pharmacology, and Clinical Applications.

Corydalis saxicola Bunting (CSB), whose common name in Chinese is Yanhuanglian, is a herb in the family Papaveraceae. When applied in traditional Chinese medicine, it is used to treat various diseases including hepatitis, abdominal pain, and bleeding haemorrhoids. In addition, Corydalis saxicola Bunting injection (CSBI) is widely used against acute and chronic hepatitis. This review aims to provide up-to-date information on the botanical distribution, description, traditional uses, phytochemistry, pharmacology, and clinical applications of CSB. A comprehensive review was implemented on studies about CSB from several scientific databases, such as SciFinder, Elsevier, Springer, ACS Publications, Baidu Scholar, CNKI, and Wanfang Data. Phytochemical studies showed that 81 chemical constituents have been isolated and identified from CSB, most of which are alkaloids. This situation indicates that these alkaloids would be the main bioactive substances and that they have antitumour, liver protective, antiviral, and antibacterial pharmacological activities. CSBI can not only treat hepatitis and liver cancer but can also be used in combination with other drugs. However, the relationships between the traditional uses and modern pharmacological actions, the action mechanisms, quality standards, and the material basis need to be implemented in the future. Moreover, the pharmacokinetics of CSBI in vivo and the toxicology should be further investigated.

[Identification, biological characteristics, and control of pathogen causing Pinellia ternata soft rot in Hubei province].

This study was designed to identify the pathogen causing soft rot of Pinellia ternata in Qianjiang of Hubei province and screen out the effective bactericides, so as to provide a theoretical basis for the control of soft rot of P. ternata. In this study, the pathogen was identified based on molecular biology and physiological biochemistry, followed by the detection of pathogenicity and pathogenicity spectrum via plant tissue inoculation in vitro and the indoor toxicity determination using the inhibition zone method to screen out bactericide with good antibacterial effects. The control effect of the bactericide against P. ternata soft rot was verified by the leave and tuber inoculation in vitro. The phylogenetic tree was constructed based on the 16 S rDNA, dnaX gene, and recA gene sequences, respectively, and the result showed that the pathogen belonged to the same branch as the type strain Dickeya fangzhongdai JS5. The physiological and biochemical tests showed that the pathogen was identical to D. fangzhongdai, which proved that the pathogen was D. fangzhongdai. The pathogenicity test indicated that the pathogen could obviously infect leaves at 24 h and tubers in 3 d. As revealed by the indoor toxicity test, 0.3% tetramycin, 5% allicin, and 80% ethylicin had good antibacterial activities, with EC_(50) values all less than 50 mg·L~(-1). Tests in tissues in vitro showed that 5% allicin exhibited the best control effect, followed by 0.3% tetramycin and 10% zhongshengmycin oligosaccharide, and their preventive effects were better than curative effects. Therefore, 5% allicin can be used as the preferred agent for the control of P. ternata soft rot, and 0.3% tetramycin and 10% zhongshengmycin oligosaccharide as the alternatives. This study has provided a certain theoretical basis for the control of P. ternata soft rot.

Effects of Smart City Construction on the Quality of Public Occupational Health: Empirical Evidence From Guangdong Province, China.

This article takes the Guangdong Province of China as the research object and uses the difference-in-difference model to evaluate the impact of smart city construction on the quality of public occupational health and intercity differences. The obtained results show that smart city construction significantly improves the quality of public occupational health, and it is still valid after a series of robustness tests. The effect of this policy is stronger in cities that belong to the Pearl River Delta region or sub-provincial level cities. This study indicates that the central government should improve the pilot evaluation system and the performance appraisal mechanism of smart cities from the perspective of top-level design during the process of promoting smart city construction, which aims to correctly guide local governments to promote the construction of smart cities. To achieve the full improvement effect of smart city construction on the quality of public occupational health, local governments should implement smart city strategies in a purposeful and planned way according to the actual situation of the development of the jurisdiction.

The Impact of Local Economic Growth Target Setting on the Quality of Public Occupational Health: Evidence From Provincial and City Government Work Reports in China.

This article uses data from the government work reports of 31 provinces (autonomous regions and municipalities) in China and 21 cities in Guangdong Province of China to perform a fixed effect regression. It was found that economic growth target constraints and economic growth target gaps between countries and provinces, or between provinces and cities have a significant impact on the quality of public occupational health. The non-linear relationship between economic growth target setting and the quality of public occupational health was then discussed in detail, and the reliability of basic conclusions drawn was ensured by robustness and endogeneity tests. The results show that the effect of economic growth target constraints and gaps on the quality of public occupational health shows a "U-shaped" trend at both the provincial and city levels, which initially promotes and, eventually, inhibits. This relationship is closely related to the current economic system reforms, administrative reforms, and social transformation in China. Therefore, in emphasising high-quality economic development, the government should fully consider the actual state of the development of jurisdictions in setting economic goals to improve the quality of public occupational health in an orderly manner.

The neurotrophic and antineuroinflammatory effects of phenylpropanoids from Zanthoxylum nitidum var. tomentosum (Rutaceae).

Three novel lignans (1, 5 and 6) and two novel quinic acids (16 and 17) along with 15 known phenylpropanoids were obtained from the ethanol extract of Zanthoxylum nitidum var. tomentosum (Rutaceae). Their structures were confirmed by comprehensive spectroscopic data (NMR and HRESIMS), and the absolute configurations of all novel compounds were elucidated based on electronic circular dichroism (ECD) spectroscopic data. The production of nitric oxide (NO) in BV-2 microglial cells induced through lipopolysaccharide (LPS) was used to evaluate in vitro anti-neuroinflammatory activity of compounds 1-20. Compound 2, 3, 7 and 16 showed excellent inhibition of LPS-induced NO production. The structure-activity relationships of the isolates were investigated. In addition, the mechanism of action of 2 was elucidated by RT-PCR and Western blotting analysis, which indicated that it reduced neuroinflammatory mainly through NLRP3/caspase1 signaling pathways in LPS-induced BV2 microglial cells.

[Effects of biocontrol strain BZJN1 and streptoprofen on physicochemical properties and bacteria structure of rhizosphere soil of Atractylodes macrocephala].

Soil microorganisms are one of the important biological indictors of soil quality and can reflct the comprehensive ecological environment characteristics of the soil. The research of soil microbial diversity is the key to know the ecological functions and balance with soil. In this paper, high-throughput sequencing on PCR-amplified 16 S rRNA gene V3-V4 fragments was used to determine the bacterial diversity in rhizosphere soil of A. macrocephala under the treatment with BZJN1 or streptoprofen. The results showed that there were no significant differences of the bacteria in A. macrocephala rhizosphere soil of the streptoprofen treatment group and the biocontrol BZJN1 treatment group. All the soil bacteria was classified into 25 categories,67 classes, 108 orders, 167 families and 271 generas, except some unidentified bacteria. Proteobacteria(30.7%-34.8%) was the dominant phylum, of which Alphaproteobacteria(16.8%-18.5%) was the dominant subgroup. Compared with the control group, the relative abundance of multiple phylums bacteria in the rhizosphere soil of A. macrocephala was significantly changed in the streptoprofen treatment group and the biocontrol BZJN1 treatment group. In addition, RDA analysis showed that there was connection with different environmental factors and microbial communities. The abundance of the three genera in the rhizosphere soil of A. macrocephala was significantly positively correlated with Invertase, Urease and AP. PICRUSt function prediction results showed that BZNJ1 could enhance some bacterial functions and promote the plant growth. Biocontrol is a new type of green and safety control pest method. BZNJ1 significantly enhances some bacterial functions on the basis of effectively preventing root rot of A. macrocephala and promoting plant growth, and has no significant effect on the soil bacterial community structure. All the results can provide theoretical support for popularization of BZNJ1.

Identification of Cyt2Ba from a New Strain of Bacillus thuringiensis and Its Toxicity in Bradysia difformis.

Bradysia difformis is one of the most damaging pests in mushroom production in China. In this study, eight Bacillus thuringiensis strains were analyzed for insecticidal activity in B. difformis. The strain JW-1 showed the highest insecticidal activity against B. difformis larvae, but did not inhibit the mycelial growth of Pleurotus ostreatus and P. geesteranus. The 16S rRNA gene (1397 bp) and cyt2 gene (792 bp) were obtained from strain JW-1. The phylogenetic tree based on 16S rRNA gene and Cyt2 toxin showed that strain JW-1 was a member of B. thuringiensis and Cyt2 toxin belonged to Cyt2Ba toxin cluster. The Cyt2Ba toxin from strain JW-1 was overexpressed in E. coli as a fusion protein and the fusion protein (70 kDa) was purified by Ni-IDA affinity chromatography. The purified Cyt2Ba fusion protein was toxic to B. difformis larvae (LC50 was 2.25 ng/mL). The identification of Cyt2Ba from strain JW-1 and confirmation of the insecticidal activity of Cyt2Ba in B. difformis provided a new means of biological control of the important pest in mushroom production.

Anti-inflammatory activity of isobutylamides from zanthoxylum nitidum var. tomentosum.

Inflammation is a very common and important basic pathological process. There is still a great need for the isolation of effective anti-inflammatory agents from plants. In this paper, five new isobutylamides, zanthoxylumamides E-I (1-5), and four known isobutylamides (6-9) were isolated from Zanthoxylum nitidum var. tomentosum (Rutaceae). Chiral resolution of seven racemic isobutylamides (1-4 and 6-8) was successfully performed, and the absolute configurations of two stereoisomers of 1-4 were validated by ECD and NMR. The obtained isobutylamides were evaluated in vitro anti-inflammatory activity with the lipopolysaccharide (LPS)-stimulated production of nitric oxide (NO) in murine macrophage RAW264.7 cells. Compound 8 exhibited significant inhibition of LPS-induced NO production. The underlying molecular mechanisms of the anti-inflammatory activity of 8 revealed that it suppressed the NO production through the modulation of myeloid differentiation factor 88 (MyD88) and interferon regulatory factor 3 (IRF3) signaling pathways.

[Effects of Nanoscale Zero-valent Iron (nZVI) on Denitrifying Performance of an Upflow Granular Sludge Bed Reactor].

In order to examine the effects of nanoscale zero-valent iron (nZVI) on the performance of denitrifying granular sludge (DGS) in a continuous flow model, the variations of nitrogen removal efficiency in the reactor, sludge morphology, and denitrifying characteristics at different influent nZVI concentrations were investigated in an upflow sludge bed (USB). The results showed that nZVI concentrations lower than 5 mg·L-1 did not influence the nitrogen removal performance of the reactor significantly, and the activity of DGS was improved slightly. When the influent nZVI concentration was in the range of 5 to 10 mg·L-1, the DGS could adapt to the biological inhibition of nZVI partially, with the increase of sludge concentration and grain size. However, the higher total iron contents in the sludge resulted in the lower denitrifying activity of the DGS. The removal efficiencies of COD and NO3--N in the reactor decreased to 23.3% and 20.3%, respectively, at the influent nZVI concentration of 30 mg·L-1. Moreover, the DGS was a dark color and of a smaller grain size because of the adsorption of a large amount of nZVI, while the microbe density, such as that of the bacillus species, on the granule surface decreased significantly. In the recovery phase, the nitrogen removal performance of the reactor could almost reach its initial level at nZVI=0 mg·L-1 during an operation of 20 days due to the fast growth of heterotrophic microbes on the surface of the DGS.

[Performance Recoverability of Denitrifying Granular Sludge Under the Stressing Effect of Nanoscale Zero-valent Iron].

To explore the potential stressing effect of nanoscale zero-valent iron (nZVI) on denitrifying granular sludge (DGS), the evolution of DGS denitrifying performance under different C/N ratios was investigated in this study, by carrying out batch tests of eight successive periods with the nZVI shock-loading. The results showed that the specific denitrification rate of µ value decreased when the nZVI dosage was higher than 5 mg · L⁻¹. Meanwhile, a positive correlation between the inhibition ratio (IR) of µ value and substrate C/N ratios or nZVI dosage was observed. When the nZVI dosage reached 100 mg · L⁻¹, both extracellular protein and polysaccharides concentrations decreased obviously. It would be beneficial to promote the recovery of DGS denitrifying activity and reduce the COD demanding to remove unit mass of nitrate, by increasing external carbon source with C/N ratios of higher than 4. On the basis of Freundlich and Langmuir adsorption isotherms, when higher C/N ratio was provided, stronger bioadsorption of nZVI would be achieved. During the recovery period, a significant improvement of DCS denitrifying performance under the high C/N ratio was expected, due to the continuous washout of total iron in sludge phase (Qe), while the µ value would reach or approach the one of the control group when Qe was lower than 0.4 mg · g⁻¹.

[Start-up Performance of ANAMMOX Enrichment with Different Inoculated Sludge in Anaerobic Baffled Reactor].

Two anaerobic baffled reactors (ABR) were compared for anaerobic ammonium oxidation (ANAMMOX) enrichment using synthetic wastewater with different inoculated sludge, the mixed anaerobic flocculent sludge/granular sludge (R1) and anaerobic activated sludge (R2). The research showed the ANAMMOX activity occurred in both reactors allowing continuous removal of ammonium and nitrite, in which the ammonia and nitrite nitrogen loading was about 54.5-68.0 g (m3 x d)(-1), when maintaining the temperature at 30-35 degrees C, pH at 7.5 +/- 0.5 and HRT at 26 h. However, the ANAMMOX reaction was successfully started after 120 d and 125 d, respectively. The removal rules of the two reactors were basically similar, and the enrichment processes occurred in both reactors could be divided into 4 phases, which were sluggish phase, expressive phase, enhanced phase and steady phase. In the steady phase, the average removal rates of NH4+ -N, NO2- -N were higher than 90%, and the average removal load achieved 57.3-67.9 g x (m3 x d)(-1). Moreover, the ammonium removal load in R1 was slightly higher than that in R2. Additionally, more than 90% of nitrogen was dramatically removed in the first compartment of ABR. Meanwhile, the color of sludge gradually changed from brown, litter bed brown to black along with the flow direction, which was similar to the removal rule of nitrogen. In a word, the results showed the different inoculated sludge did not cause obvious differences in the starting rule and the removal characteristics of ANAMMOX reactor.