Brunonianines D-F, three new C19-diterpenoid alkaloids from the Delphinium brunonianum, with therapeutic effect on ovarian cancer in vitro and in vivo.

The current standard treatment for ovarian cancer consists of surgery to reduce the size of the tumor, followed by treatment with chemotherapeutic drugs, which have major side effects. Therefore, finding a new natural product drug with fewer side effects is a strategy. Delphinium brunonianum (D. brunonianum) is a traditional Tibetan medicine, mainly from southern Tibet, China, whereas the chemical constituents in this plant remain elusive. The major metabolites in the dichloromethane fraction of D. brunonianum were analyzed and purified by HPLC and various column chromatography techniques. Nine diterpenoid alkaloids (1-9) and one amide alkaloid (10) were isolated from D. brunonianum, including three novel C19-type diterpenoid alkaloids (Brunonianines D-F) (1-3). Their structures were elucidated by 1D/2D NMR, HR-ESI-MS and single-crystal X-ray diffraction analyses. All compounds were evaluated for toxicity in four tumor cell lines. Most of the compounds exhibited potent inhibitory effects on Skov-3 cell lines, with IC50 values ranging from 2.57 to 8.05 µM. The western blotting experiment was used to further analyze the expression levels of molecules in the Bax/Bcl-2/Caspase-3 signaling pathway for compound 1. Molecular docking was performed to predict the binding modes of Brunonianine D with target proteins. In vivo experiments were also performed and evaluated in real time by monitoring the size of the Skov-3 tumor. Additionally, tumor H&E staining and the TUNEL assay used to evaluate anti-tumor effects.

Gaussian processes modeling for the prediction of polymeric nanoparticle formulation design to enhance encapsulation efficiency and therapeutic efficacy.

Conventional drugs have been facing various drug delivery obstacles, including first-pass metabolism for oral medications, drug degradation by cellular enzymes, off-target effects, and cytotoxicity of healthy cells. Nanoparticles (NP) application in drug delivery can compensate for these drawbacks to a great extent. NPs can be fabricated using different materials and structures to achieve desired therapeutic effects. For each type of NP material, its physicochemical properties determine compatibility with specific drugs and other supplemental compositions. The optimized material selection becomes prominent in NP development to improve NP performances. Due to the nature of NP fabrication, the process is long and expensive. To accelerate NP composition optimization, machine learning (ML) techniques are among the most promising methods for efficient data predictions and optimizations.As a proof-of concept, we created Gaussian Process (GP) models to make predictions for drug encapsulation efficiency (EE%) and therapeutic efficacy of 32 poly (lactic-co-glycolic acid) (PLGA) NPs that are formed with materials with different physicochemical properties. Two model drugs, doxorubicin (DOX) and docetaxel (DTX) were loaded separately. The IC50 values for the various NPs formulations were evaluated using the OVCAR3 epithelial ovarian cancer cell line. EE% GP model has the highest prediction accuracy with the lowest normalized root-mean-squared-error (RMSE) of 0.187. The DOX and DTX IC50 GP models have normalized RMSEs of 0.296 and 0.206, respectively, which are higher than that of the EE% GP model.

Electrochromic Devices Based on 2D MoO3-x/PEDOT:PSS Composite Film with Boosted Ion Transport.

Electrochromic materials allow for optical modulation and have attracted much attention due to their bright future in applications such as smart windows and energy-saving displays. Two-dimensional (2D) molybdenum oxide nanoflakes with combined advantages of high active specific surface area and natural layered structure should be highly potential candidates for electrochromic devices. However, the efficient top-down preparation of 2D MoO3 nanoflakes is still a huge challenge and the sluggish ionic kinetics hinder its electrochromic performance. Herein, we demonstrated a feasible thiourea-assisted exfoliation procedure, which can not only increase the yield but also reduce the thickness of 2D MoO3-x nanoflakes down to a few nanometers. Furthermore, electrophoretic-deposited MoO3-x nanoflakes were combined with poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS)-conjugated polymer to simultaneously enhance the ionic kinetics and electronic conductivity, with a diffusion coefficient of 3.09 × 10-10 cm2 s-1 and a charge transport resistance of 33.7 Ω. The prepared 2D MoO3-x/PEDOT:PSS composite films exhibit improved electrochromic performance, including fast switching speed (7 s for bleaching, 5 s for coloring), enhanced coloration efficiency (87.1 cm2 C-1), and large transmittance modulation (ΔT = 65%). This study shows outstanding potential for 2D MoO3-x nanoflakes in electrochromic applications and opens new avenues for optimizing the ion transport in inorganic-organic composites, which will be possibly inspired for other electrochemical devices.

Geographical distribution and ecological niche dynamics of Crassostrea sikamea (Amemiya, 1928) in China's coastal regions under climate change.

Global climate change drives species redistribution, threatening biodiversity and ecosystem heterogeneity. The Kumamoto oyster, Crassostrea sikamea (Amemiya, 1928), one of the most promising aquaculture species because of its delayed reproductive timing, was once prevalent in southern China. In this study, an ensemble species distribution model was employed to analyze the distribution range shift and ecological niche dynamics of C. sikamea along China's coastline under the current and future climate scenarios (RCP 2.6-8.5 covering 2050 s and 2100 s). The model results indicated that the current habitat distribution for C. sikamea consists of a continuous stretch extending from the coastlines of Hainan Province to the northern shores of Jiangsu Province. By the 2050 s, the distribution range will stabilize at its southern end along the coast of Hainan Province, while expanding northward to cover the coastal areas of Shandong Province, showing a more dramatic trend of contraction in the south and invasion in the north by the 2100 s. In RCP8.5, the southern end retracts to the coasts of Guangdong, whereas the northern end covers all of China's coastal areas north of 34°N. C. sikamea can maintain relatively stable ecological niche characteristics, while it may occupy different ecological niche spaces under future climate conditions. Significant niche expansion will occur in lower temperature. We concluded C. sikamea habitats are susceptible to climate change. The rapid northward expansion of C. sikamea may open new possibilities for oyster farming in China, but it will also have important consequences for the ecological balance and biodiversity of receiving areas. It's imperative that we closely examine and strategize to address these repercussions for a win-win situation.

Suppressing Carrier Recombination in BiVO4/PEDOT:PSS Heterojunction for High-Performance Photodetector.

The organic-inorganic hybrid heterojunction is introduced for the first time to break through the performance bottleneck of BiVO4-based photodetectors. Through a facile solution process, a p-n heterojunction is established at the BiVO4/PEDOT:PSS interface, and the built-in electric field is designed to separate photogenerated charge carriers. The hybrid heterojunction outputs a significantly increased photocurrent, which is 24 000 times larger than that of the bare BiVO4 thin film. The photodetector shows a satisfactory performance with a responsivity (R) and specific detectivity (D*) of 107.8 mA/W and 4.13 × 1010 Jones at 482 nm illumination. In addition to the fast response speed (100 ms), the device also exhibits an impressive long-term stability with a negligible attenuation in photocurrent after more than 700 cycles. This work provides a novel strategy to suppress carrier recombination of BiVO4, and the coupling of metal oxides and organic semiconductors opens up a new avenue for fabricating high-performance photodetectors.

Brunonianines A-C, C20-diterpenoid alkaloids with cyano group from Delphinium brunonianum Royle.

Cyano tends to have better biological activity, but it is rarely reported in natural products, especially in the C20-diterpene alkaloids. Herein, three unprecedented C20-diterpenoid alkaloids, brunonianines A-C (1-3), possessing rare cyano functional group as well as an atisine backbone constructed from a phenethyl substituent and a tetrahydropyran ring, along with four C19-alkaloids (4-7) and one amide alkaloids (8), were isolated from the whole plant of Delphinium brunonianum Royle. Compounds 1-3 are also the first atisine type diterpenoid alkaloids with cyano group obtained from nature. The structures of the previously undescribed compounds were elucidated by HR-ESI-MS, 1D/2D NMR spectroscopic data and electronic circular dichroism calculations and single-crystal X-ray diffraction. Reasonable speculations have also been made regarding the biogenic synthetic pathways of compounds 1-3. In addition, the inhibitory activity of all compounds was also tested against four tumor lines: A549, Caco-2, H460 and Skov-3, where compound 2 (IC50 2.20 ± 0.21 µM) showed better inhibitory activity against Skov-3 cells than the hydroxycamptothecin. Using flow cytometry, cell staining, migration and invasion analysis, and Western blot, compound 2 was found to arrest cells in the G2/M phase and was able to effectively inhibit cell motility to achieve potent anti-tumor effects. In addition, compound 2 can effectively induce apoptosis by activating the Bax/Bcl-2/Caspase-3 signaling pathway.

Structures and Tumor Cell Lines Proliferation Activities of Triterpenes Isolated from Astilbe grandis.

A total of seven compounds, including four triterpene acids and three triterpene lactones, were isolated from the ethanolic extract of the roots of Astilbe grandis Stapf ex Wils. Two of the triterpene lactones (1-2) were never reported before and compounds 3-5 were isolated for the first time from the plant. The structures of these compounds were all identified by spectroscopic analysis. Compounds 1-2 were analyzed by 2D NMR and their absolute configurations were determined using experimental CD in comparison with calculated ECD values. The structure of compound 1 was also further confirmed by single crystal X-ray diffraction analysis. The cytotoxicity of compounds 1-7 on A549, Caco-2, H460 and Skov-3 tumor cells were all evaluated using CCK-8. They all exhibited positive inhibitory effects on Caco-2 tumor cells with IC50 less than10 µM, while the inhibitory effects on H460 tumor cells were more moderate. Unfortunately, they displayed little apparent cytotoxicity to the other two types of cells.

Optimizing irrigation strategies for sustainable crop productivity and reduced groundwater consumption in a winter wheat-maize rotation system.

Inefficient irrigation practices have hindered crop yields, wasted irrigation water resources, and posed threats to groundwater levels and agricultural sustainability. This study evaluated different irrigation strategies for a winter wheat-summer maize rotation system to identify sustainable practices for maintaining yields while reducing groundwater depletion. A two-year field experiment was conducted, implementing three optimized irrigation strategies during the winter wheat season: I-4 (irrigated until the soil water content (SWC) of the 40 cm soil layer reaches 60% of field capacity (FC), I-6 (irrigated until the SWC of the 60 cm soil layer reaches 80% FC), and a rainfed (R) as control. Irrigation was repeated when the SWC dropped to the specified level. No irrigation level was used during the summer maize season, except for irrigation after sowing that ensuring the normal emergence of maize. WHCNS (Water Heat Carbon Nitrogen Simulator) model was developed to simulate soil water dynamics, field water consumption, and yield of both crops. The result indicated WHCNS model accurately simulated water dynamics, consumption, and grain yield. Compared to R treatment, the I-4 treatment significantly increased annual crop yield by 19.83%-28.65% (p < 0.05), while maintaining similar crop water productivity. Furthermore, the I-4 treatment achieved comparable yields to the I-6 treatment, but with a 33.91% reduction in irrigation water use, resulting in a 33.46% increase in crop water productivity and a 90.53% increase in irrigation water productivity. From a sustainable perspective, the I-4 treatment effectively reduced field water losses and maintained relatively high soil water storage, particularly in the topsoil, which was beneficial for the early growth of subsequent crops. The R treatment greatly contributed to groundwater recharge when precipitation was sufficient, while it led to severe yield losses. Overall, under the condition of annual rotation planting systems, the I-4 treatment sustainably maintained yields with less irrigation, decreasing groundwater consumption. This approach could conserve regional water resources and groundwater table while upholding agricultural productivity and achieving system sustainable water use.

From waste carbonated beverages to high performance electrochromic devices: a green and low-cost synthetic method for self-doped metal oxides.

Metal oxides with reversible optical modulation capability are in the spotlight for smart windows and other emerging optoelectronic devices. Improving the electrochromic performance at a low cost is the only way to popularize their applications. Herein, we demonstrate a facile and versatile strategy to synthesize high-performance electrochromic metal oxides, in which waste carbonated beverages are used as the raw materials for the first time. It can not only reduce the production cost of electrochromic materials, but also alleviate the environmental pollution caused by such liquid waste. With an ingenious carbonization pre-step, both nanoscale pores and oxygen vacancies are created in an annealed tungsten oxide thin film. Multiscale structure optimization endows the self-doped WO3-x films with excellent electrochromic properties such as large transmittance modulation (81.2%), high coloration efficiency (98.7 cm2 C-1) and good cycling stability. DFT calculations show that oxygen vacancies reduce the Li+ ion insertion energy barrier, which is conducive to the interfacial reaction in coloring and bleaching processes. Moreover, this approach is universal to other oxides such as vanadium pentoxide, molybdenum oxide and nickel oxide. The waste-to-value concept paves the way for cost-effective electrochromic materials and sheds light on the multiscale optimization of superior metal oxides.

The potential for soil C sequestration and N fixation under different planting patterns depends on the carbon and nitrogen content and stability of soil aggregates.

The winter wheat-summer maize rotation system is common in the Huang-Huai-Hai Plain due to its consistent yield, however, it may cause soil quality degradation and increased risk of greenhouse gas emissions. To evaluate the effects of different planting patterns on soil organic carbon (SOC) and total nitrogen (TN) sequestration, as well as aggregate and C-N distribution, a three-year field experiment that included three annual double-cropping rotation patterns: winter wheat-maize (W-M), winter wheat-soybean (W-S), and winter wheat-sweet potato (W-SP) was conducted from 2020 to 2022, with W-M as the control. Our research revealed significant differences in soil carbon sequestration rates among the various planting systems. Specifically, the SOC stock in the W-S system was 12.21 % to 24.51 % higher than that of the W-M system and 10.28 % to 35.73 % higher than that of the W-SP system. While TN stock demonstrated an increase of 9.85 % to 37.39 % compared to the W-M system and 8.14 % to 67.43 % compared to the W-SP system. Moreover, SOC and TN sequestration were largely related to soil aggregates, with macroaggregates being the primary component in both W-S and W-M planting patterns, while microaggregates were more common in W-SP patterns. The accumulation of SOC and TN occurred mainly in macroaggregates, leading to a significant increase in C and N content in soil macroaggregates under the W-S planting pattern. The structural equation model suggested that the TN stock had both direct and indirect effects on SOC sequestration, with a total impact coefficient of 0.872. Our three-year field results indicate that the W-S model is advantageous in enhancing soil C and N sequestration capacity and had great potential in reducing greenhouse gas emissions in farmland.

Diversities and Shifts of Microbial Communities Associated with Farmed Oysters (Crassostrea gigas) and Their Surrounding Environments in Laoshan Bay Marine Ranching, China.

Pacific oysters (Crassostrea gigas) are widely cultured in Chinese marine ranching with high economic value. However, mass death of farmed oysters has occurred frequently in recent years because of diseases and environmental disturbance (e.g., high temperatures). In order to analyze the potential relationships between microorganisms and the death of farmed oysters, we compared the dynamics of bacterial and protist communities in oysters at different growth phases using high-throughput sequencing. The results showed that the microbial communities in farmed oysters significantly changed and were markedly different from microbes in natural oysters and the surrounding environments. The number of biomarker taxa among farmed oysters and their surrounding environments decreased gradually with the growth of oysters. During the mass death of farmed oysters, the microbial communities' abundance of ecological function genes changed, and the correlations among microorganisms disappeared. These results enrich our understanding of the dynamics of microbial communities in farmed oysters at different growth phases, illustrating the characteristics of interactions among microorganisms during the mass death of farmed oysters. Our study is beneficial to promote the healthy aquaculture of oysters.

Cell pyroptosis in picornavirus and its potential for treating viral infection.

Cell pyroptosis has received increased attention due to the associations between innate immunity and disease, and it has become a major focal point recently due to in-depth studies of cancer. With increased research on pyroptosis, scientists have discovered that it has an essential role in viral infections, especially in the occurrence and development of some picornavirus infections. Many picornaviruses, including Coxsackievirus, a71 enterovirus, human rhinovirus, encephalomyocarditis virus, and foot-and-mouth disease virus induce pyroptosis to varying degrees. This review summarized the mechanisms by which these viruses induce cell pyroptosis, which can be an effective defense against pathogen infection. However, excessive inflammasome activation or pyroptosis also can damage the host's health or aggravate disease progression. Careful approaches that acknowledge this dual effect will aid in the exploration of picornavirus infections and the mechanisms that produce the inflammatory response. This information will promote the development of drugs that can inhibit cell pyroptosis and provide new avenues for future clinical treatment.

Seasonal variations and co-occurrence networks of bacterial communities in the water and sediment of artificial habitat in Laoshan Bay, China.

Marine bacteria in the seawater and seafloor are essential parts of Earth's biodiversity, as they are critical participants of the global energy flow and the material cycles. However, their spatial-temporal variations and potential interactions among varied biotopes in artificial habitat are poorly understood. In this study, we profiled the variations of bacterial communities among seasons and areas in the water and sediment of artificial reefs using 16S rRNA gene sequencing, and analyzed the potential interaction patterns among microorganisms. Distinct bacterial community structures in the two biotopes were exhibited. The Shannon diversity and the richness of phyla in the sediment were higher, while the differences among the four seasons were more evident in the water samples. The seasonal variations of bacterial communities in the water were more distinct, while significant variations among four areas were only observed in the sediment. Correlation analysis revealed that nitrite and mud content were the most important factors influencing the abundant OTUs in the water and sediment, respectively. Potential interactions and keystone species were identified based on the three co-occurrence networks. Results showed that the correlations among bacterial communities in the sediment were lower than in the water. Besides, the abundance of the top five abundant species and five keystone species had different changing patterns among four seasons and four areas. These results enriched our understanding of the microbial structures, dynamics, and interactions of microbial communities in artificial habitats, which could provide new insights into planning, constructing and managing these special habitats in the future.

Comparative analysis of microbial communities between water and sediment in Laoshan Bay marine ranching with varied aquaculture activities.

We profiled and compared the bacterial and protist community compositions and dynamics in the Laoshan Bay marine ranching involving varied aquaculture activities. The dominant species, differential species and community compositions among the five aquaculture areas, two habitats and two periods were significantly different. The relationships between microbial communities and environmental factors were analyzed. We found that microbial communities in the water were more sensitive to the environmental changes than sediment, and the responses of bacterial and protist communities to the disturbances were varied. To meet the challenges of higher aquaculture density, the proportion of the positive correlations among co-occurrence networks in the water increased markedly from July to November; while the positive proportion in the sediment was stable. Potential ecological interactions and keystone taxa between bacteria and protists were studied. These results advanced our understanding of how mariculture stressors affect microbial communities in marine ranching.

Outer Membrane Vesicles Derived from Salmonella enterica Serotype Typhimurium Can Deliver Shigella flexneri 2a O-Polysaccharide Antigen To Prevent Shigella flexneri 2a Infection in Mice.

Shigellosis has become a serious threat to health in many developing countries due to the severe diarrhea it causes. Shigella flexneri 2a is the principal species responsible for this endemic disease. Despite multiple attempts to design a vaccine against shigellosis, no effective vaccine has been developed yet. Lipopolysaccharide (LPS) is both an essential virulence factor and an antigen protective against Shigella, due to its outer domain, termed O-polysaccharide antigen. In the present study, S. flexneri 2a O-polysaccharide antigen was innovatively biosynthesized in Salmonella and attached to core-lipid A via the ligase WaaL, with purified outer membrane vesicles (OMVs) utilized as vaccine vectors. Here, we identified the expression of the heterologous O-antigen and have described the isolation, characterization, and immune protection efficiency of the OMV vaccine. Furthermore, the results of animal experiments indicated that immunization of mice with the OMV vaccine induced significant specific anti-Shigella LPS antibodies in the serum, with similar trends in IgA levels from vaginal secretions and fluid from bronchopulmonary lavage, both intranasally and intraperitoneally. The OMV vaccine derived from both routes of administration provided significant protection against virulent S. flexneri 2a infection, as judged by a serum bactericidal assay, opsonization assay, and challenge test. This vaccination strategy represents a novel and improved approach to control shigellosis by the combination of Salmonella glycosyl carrier lipid bioconjugation with OMVs. IMPORTANCEShigella, the cause of shigellosis or bacillary dysentery, is a major public health concern, especially for children in developing countries. An effective vaccine would control the spread of the disease to some extent. However, no licensed vaccine against Shigella infection in humans has so far been developed. The Shigella O-antigen polysaccharide is effective in stimulating the production of protective antibodies and so could represent a vaccine antigen candidate. In addition, bacterial outer membrane vesicles (OMVs) have been used as antigen delivery platforms due to their nanoscale properties and ease of antigen delivery to trigger an immune response. Therefore, the present study provides a new strategy for vaccine design, combining a glycoconjugated vaccine with OMVs. The design concept of this strategy is the expression of Shigella O-antigen via the LPS synthesis pathway in recombinant Salmonella, from which the OMV vaccine is then isolated. Based on these findings, we believe that the novel vaccine design strategy in which polysaccharide antigens are delivered via bacterial OMVs will be effective for the development and clinical application of an effective Shigella vaccine.