Chemical Synthesis and Insecticidal Activity Research Based on α-Conotoxins.

The escalating resistance of agricultural pests to chemical insecticides necessitates the development of novel, efficient, and safe biological insecticides. Conus quercinus, a vermivorous cone snail, yields a crude venom rich in peptides for marine worm predation. This study screened six α-conotoxins with insecticidal potential from a previously constructed transcriptome database of C. quercinus, characterized by two disulfide bonds. These conotoxins were derived via solid-phase peptide synthesis (SPPS) and folded using two-step iodine oxidation for further insecticidal activity validation, such as CCK-8 assay and insect bioassay. The final results confirmed the insecticidal activities of the six α-conotoxins, with Qc1.15 and Qc1.18 exhibiting high insecticidal activity. In addition, structural analysis via homology modeling and functional insights from molecular docking offer a preliminary look into their potential insecticidal mechanisms. In summary, this study provides essential references and foundations for developing novel insecticides.

Oridonin ameliorates carbon tetrachloride-induced liver fibrosis in mice through inhibition of the NLRP3 inflammasome.

Liver fibrosis is characterized by the activation of hepatic stellate cells (HSCs) and accumulation of the extracellular matrix. There are limitations in the current therapies for liver fibrosis. Recently, oridonin was shown to induce apoptosis in HSCs. Thus, we aimed to determine the roles of oridonin in chronic liver injury and fibrosis. Liver fibrosis was induced by CCl4 in mice injected intraperitoneally with oridonin for 6 weeks. The administration of oridonin significantly attenuated liver injury and reduced ALT levels. In addition, Sirius Red staining and the expression of α-smooth muscle actin (α-SMA) were significantly reduced by oridonin in murine livers with fibrosis. The expression of NLRP3, caspase-1, and IL-1ß was downregulated with the oridonin treatment. Furthermore, the expression of F4/80 in liver tissues was also decreased by oridonin treatment. These results demonstrate that oridonin ameliorates chronic liver injury and fibrosis. Mechanically, oridonin may inhibit the activity of the NLRP3 inflammasome and inflammation in the liver. These results highlight the potential of oridonin as a therapeutic agent for liver fibrosis.

[Early-term effectiveness comparison of suture hook suture via double posteromedial approaches and Fast-Fix total internal suture in treatment of Ramp lesions].

Objective: To compare the short-term effectiveness of suture hook suture via double posteromedial approaches and Fast-Fix total internal suture in treatment of Ramp lesions. Methods: A clinical data of 56 patients with anterior cruciate ligament rupture combined with Ramp lesions, who met the selection criteria and admitted between December 2021 and February 2023, was retrospectively analyzed. The Ramp lesions were sutured using suture hook via double posteromedial approaches under arthroscopy in 28 cases (group A) and treated with Fast-Fix total internal suture under arthroscopy in 28 cases (group B). There was no significant difference in age, gender, cause of injury, type of injury, time from injury to operation, side of injury, body mass index, and preoperative Lysholm score, visual analogue scale (VAS) score, and Tegner score between the two groups ( P>0.05). The patients were followed up regularly after operation, and the clinical and imaging healing of the Ramp lesion was evaluated according to the Barrett clinical healing standard and the MRI evaluation standard. Lysholm score, VAS score, and Tegner score were used to evaluate the function and pain degree of knee joint, and the results were compared with those before operation. Results: The incisions of the two groups healed by first intention. All patients were followed up 12-18 months (mean, 14.9 months). Postoperative McMurray tests were negative in both groups. The clinical healing rates of group A and group B were 71.4% (20/28) and 64.3% (18/28) at 6 months after operation, and 92.9% (26/28) and 82.1% (23/28) at 12 months after operation, respectively. The differences between the two groups was not significant ( χ 2=0.327, P=0.567; χ 2=0.469, P=0.225). There was no significant difference in Lysholm score, VAS score, and Tegner score between the two groups at each time point after operation ( P>0.05). The postoperative scores in the two groups significantly improved when compared with those before operation, and the scores at 12 months after operation further improved when compared with those at 6 months after operation, showing significant differences between the different time points in the two groups ( P<0.05). At last follow-up, MRI examination of the knee joint showed that there were 26 (92.9%), 2 (7.1%), and 0 (0) cases of complete healing, partial healing, and nonunion in the Ramp lesion of group A, and 25 (89.3%), 1 (3.6%), and 2 (7.1%) cases in group B, respectively. There was no significant difference between the two groups ( Z=-0.530, P=0.596). Conclusion: Suture hook suture via double posteromedial approaches and Fast-Fix total internal suture under arthroscopy are safe and reliable in the treatment of Ramp lesion, and the knee joint function significantly improves after operation.

Pollution characteristics, distribution and risk level of heavy metals in sediments of the Yangtze River estuary.

Pollution characteristics, distribution, risk and sources of 7 heavy metals in sediments of Yangtze River Estuary were investigated. Total concentration ranges of As, Cr, Cu, Cd, Pb, Zn and Ni were [0, 16.5], [1.48, 51.3], [2.66, 318], [0, 0.99], [35.6, 992], [8, 91.3] and [1.88, 108] mg/kg, respectively. Based on the potential ecological risk index and Geoaccumulation index, it was determined that Pb is the most polluted heavy metal. According to class I standard of "Marine sediment quality" of China, mean baseline levels multiples were Pb (8.34) > Cu (0.57) > Cr (0.37) > Zn (0.355) > Ni (0.352) > As (0.28) > Cd (0.00). The study also found the heavy metal content of Pb is the most serious, but most of the Pb content comes from the residual state, which has minimal impact on the environment. The East Nanhui Shoal was identified as the most polluted sub-area in terms of Pb pollution, followed by other specific locations. Considering the pollution level and transport costs, the study concluded that dredge soils of the Yangtze River Estuary Deepwater Channel are not suitable for the restoration of East Hengsha Shoal.

Identifying potential Q-markers for quality evaluation of Zhenyuan capsule by integrating chemical analysis, network pharmacology, molecular docking, and molecular dynamics simulations.

Quality markers (Q-markers) are of great significance for quality evaluation of herbal medicines. Zhenyuan Capsule (ZYC) is a kind of Chinese patent medicine used to treat cardiovascular diseases. However, reliable and effective Q-markers for ZYC are still lacking. Herein, a UHPLC-Q/Orbitrap-MS/MS was performed to characterise the preliminary chemical profile of ZYC. A total of 86 components were characterised among which 20 constituents were unambiguously identified by reference compounds. Based on network pharmacology, seven major ginsenosides with great importance in the network were identified as Q-markers among which ginsenoside Re with the highest betweenness was screened to inhibit the development of coronary heart disease (CHD) by binding with vascular endothelial growth factor A (VEGFA). Docking and molecular dynamics simulation studies suggested that ginsenoside Re stably bound to VEGFA. Quantitative determination and chemical fingerprinting analysis were performed using HPLC-DAD. The results showed that ginsenosides screened might function as potential Q-markers for ZYC.

Inhibitory effect and mechanism of hirsuteine on NCI­H1299 lung cancer cell lines.

Traditionally, the bark of Uncaria rhynchophylla (UR) has been employed for the treatment of hypertension, cancer, convulsions, haemorrhage, autoimmune disorders and other ailments. The primary aim of the present study was to explore the antiproliferative activity of hirsuteine (HTE) isolated from UR over a range of concentrations in human NSCLC NCI-H1299 cells and to explore the mechanisms underlying its therapeutic efficacy. The effects of HTE on cell viability were examined using Cell Counting Kit-8 (CCK-8) and colony formation assays, while apoptosis was assessed by flow cytometry. Cell cycle progression was additionally evaluated via propidium iodide staining, while reverse transcription-quantitative PCR and western blotting methods were employed to assess the protein levels and genes related to apoptosis and progression of the cell cycle, respectively. NCI-H1299 cell proliferation was markedly suppressed by HTE in a time- and dose-dependent manner. However, clear changes in cell morphology were also induced, resulting in G0-G1 phase cell cycle arrest, which was associated with cyclin E and CDK2 downregulation. HTE additionally induced robust NSCLC NCI-H1299 cell apoptosis, downregulation of Bcl-2 and upregulation of cytoplasmic cytochrome C, Bax, Apaf1, cleaved caspase-3 and cleaved caspase-9, which together drove the observed apoptotic cell death. HTE could effectively suppress human NSCLC NCI-H1299 cell growth by inducing apoptotic death in a dose-dependent fashion in vitro, therefore elucidating the mechanism by which this phytomedicine acts as a potent anticancer compound that warrants study as a treatment for human NSCLC patients.

Organic/inorganic phosphorus partition and transformation in long-term paddy cultivation in the Pearl River Delta, China.

Identification and quantification of different soil phosphorus (P) fractions level are important for improving agricultural productivity and developing sustainable management practices in these agricultural soils under long-term cultivation. However, few studies have been conducted to investigate P fractions level and their transformation in these soils. This study was conducted to characterize P fractions as affected by different paddy cultivation ages (200, 400-yr and 900-yr) among soils of the Pearl River Delta Plain in China. A sequential chemical fractionation scheme and 31P nuclear magnetic resonance spectroscopy (31P NMR) were employed to quantify various P fractions and speciation. Results showed soil easily-labile P, moderately-labile P and non-labile P had a positive relationship with total P (TP) and available P (AP). Analysis with 31P NMR spectroscopy revealed that inorganic P including orthophosphate (Ortho-P) and pyrophosphate (Pyro-P) increased with cultivation age, while organic species monoester phosphate (Mono-P) and diester phosphate (Diester-P) decreased. Moreover, acid phosphatase (AcP), neutral phosphatase (NeP), exchangeable Ca and sand contents are the main factors that affected the transformation of soil P composition, and non-labile P (Dil.HCl-Pi) and Pyro-P had significant contribution to soil P availability by affecting P activation coefficient. Therefore, long-term paddy cultivation, influenced by these soil parameters including NeP, AcP, exchangeable Ca and sand, accelerated the transformation of soil organic P/non-labile P to inorganic P.

A Molecular Dynamics Study on the Dislocation-Precipitate Interaction in a Nickel Based Superalloy during the Tensile Deformation.

In the present paper, the dislocation-precipitate interaction in the Inconel 718 superalloy is studied by means of molecular dynamics simulation. The atomistic model composed of the ellipsoidal Ni3Nb precipitate (γ″ phase) and the Ni matrix is constructed, and tensile tests on the composite Ni3Nb@Ni system along different loading directions are simulated. The dislocation propagation behaviors in the precipitate interior and at the surface of the precipitate are characterized. The results indicate that the dislocation shearing and bypassing simultaneously occur during plastic deformation. The contact position of the dislocation on the surface of the precipitate could affect the penetration depth of the dislocation. The maximum obstacle size, allowing for the dislocation shearing on the slip planes, is found to be close to 20 nm. The investigation of anisotropic plastic deformation behavior shows that the composite system under the loading direction along the major axis of the precipitate experiences stronger shear strain localizations than that with the loading direction along the minor axis of the precipitate. The precipitate size effect is quantified, indicating that the larger the precipitate, the lower the elastic limit of the flow stress of the composite system. The dislocation accumulations in the precipitate are also examined with the dislocation densities given on specific slip systems. These findings provide atomistic insights into the mechanical behavior of nickel-based superalloys with nano-precipitates.

Effect of Residual Stress Induced by Different Cooling Methods in Heat Treatment on the Fatigue Crack Propagation Behaviour of GH4169 Disc.

In this study, the effects of residual stress induced by three different cooling methods during heat treatment on the crack propagation behaviour of the GH4169 disc were investigated. Different levels of stress fields were induced to the specially designed discs by using air cooling (AC), air jetting cooling (AJC) and water quenching (WQ) methods and were quantitated by numerical simulation. These discs were then subjected to prefabricated cracking, and crack propagation tests were conducted on a spin tester with two load spectrums. Crack growth behaviour was depicted via the surface replica technique and fracture morphology. Regarding the linear superposition of residual stress and centrifugal force, the crack propagation behaviour of different discs was simulated using the FRANC3D software. AJC and WQ introduced compressive residual stress (-259 MPa and -109 MPa, respectively) into the disc compared with the AC method (about -1.5 MPa). The AJC method increases the crack propagation life of the disc by introducing residual compressive stress into the area near the surface of the central hole to inhibit the opening of the crack surface. When the fatigue load was low, this inhibition effect was more significant.

Notoginsenoside R1 attenuates breast cancer progression by targeting CCND2 and YBX3.

BACKGROUND: Breast cancer (BC) is a common malignancy with highly female incidence. So far the function of notoginsenoside R1 (NGR1), the extract from Panax notoginseng, has not been clearly elucidated in BC. METHODS: Optimal culture concentration and time of NGR1 were investigated by cell counting kit-8 assay. Cell proliferation ability was measured by colony formation assays. Transwell assay was used to detect the effect of NGR1 on cell migration and invasion. The apoptosis rate of cells between each group was measured by TUNEL assay. RESULTS: NGR1 treatment has an inhibitory effect on proliferation, migration, invasion, and angiogenesis and a stimulating effect on cell cycle arrest and apoptosis of Michigan Cancer Foundation-7 (MCF-7) cells. The 50% growth inhibitory concentration for MCF-7 cells at 24 h was 148.9 mmol/L. The proportions of MCF-7 cells arrested in the G0/G1 phase were 36.94±6.78%, 45.06±5.60%, and 59.46±5.60% in the control group, 75, and 150 mmol/L groups, respectively. Furthermore, we revealed that NGR1 treatment attenuates BC progression by targeted downregulating CCND2 and YBX3 genes. Additionally, YBX3 activates phosphatidylinositol 3-phosphate kinase (PI3K)/protein kinase B (Akt) signaling pathway by activating kirsten rat sarcoma viral oncogene, which is an activator of the PI3K/Akt signaling pathway. CONCLUSION: These results suggest that NGR1 can act as an efficacious drug candidate that targets the YBX3/PI3K/Akt axis in patients with BC.

Effect of the SiCl4 Flow Rate on SiBN Deposition Kinetics in SiCl4-BCl3-NH3-H2-Ar Environment.

To improve the thermal and mechanical stability of SiCf/SiC or C/SiC composites with SiBN interphase, SiBN coating was deposited by low pressure chemical vapor deposition (LPCVD) using SiCl4-BCl3-NH3-H2-Ar gas system. The effect of the SiCl4 flow rate on deposition kinetics was investigated. Results show that deposition rate increases at first and then decreases with the increase of the SiCl4 flow rate. The surface of the coating is a uniform cauliflower-like structure at the SiCl4 flow rate of 10 mL/min and 20 mL/min. The surface is covered with small spherical particles when the flow rate is 30 mL/min. The coatings deposited at various SiCl4 flow rates are all X-ray amorphous and contain Si, B, N, and O elements. The main bonding states are B-N, Si-N, and N-O. B element and B-N bonding decrease with the increase of SiCl4 flow rate, while Si element and Si-N bonding increase. The main deposition mechanism refers to two parallel reactions of BCl3+NH3 and SiCl4+NH3. The deposition process is mainly controlled by the reaction of BCl3+NH3.

Microstructure and Dielectric Properties of LPCVD/CVI-SiBCN Ceramics Annealed at Different Temperatures.

SiBCN ceramics were introduced into porous Si3N4 ceramics via a low-pressure chemical vapor deposition and infiltration (LPCVD/CVI) technique, and then the composite ceramics were heat-treated from 1400 °C to 1700 °C in a N2 atmosphere. The effects of annealing temperatures on microstructure, phase evolution, dielectric properties of SiBCN ceramics were investigated. The results revealed that α-Si3N4 and free carbon were separated below 1700 °C, and then SiC grains formed in the SiBCN ceramic matrix after annealing at 1700 °C through a phase-reaction between free carbon and α-Si3N4. The average dielectric loss of composites increased from 0 to 0.03 due to the formation of dispersive SiC grains and the increase of grain boundaries.