Synthesis, cytotoxicity, and in vivo antitumor activity study of parthenolide semicarbazones and thiosemicarbazones.

Parthenolide is an important sesquiterpene lactone with potent anticancer activities. In order to further improve its biological activity, a series of parthenolide semicarbazone or thiosemicarbazone derivatives was synthesized and evaluated for their anticancer activity. Derivatives were tested in vitro against 5 human tumor cell lines, and many of these showed higher cytotoxicity than parthenolide. Five compounds were further studied for their antitumor activity in mice. The in vivo result indicated that compound 4d showed both promising antitumor activity against mice colon tumor and small side effects on immune systems. The cell apoptosis and cell cycle distribution of compound 4d were also studied. Molecular docking studies revealed multiple interactions between 4d and NF-κB. Our findings demonstrate the potential of semicarbazones as a promising type of compounds with anticancer activity.

Graphite Anode for a Potassium-Ion Battery with Unprecedented Performance.

Graphite as an anode for the potassium ion battery (PIBs) has the merits of low cost and potentially high energy density, while suffering from limited cycle time and inferior stability. Herein we, using a concentrated electrolyte, demonstrate that formation of a robust inorganic-rich passivation layer on the graphite anode could resolve these problems. Consequently, the PIBs with graphite anode could operate for over 2000 cycles (running time of over 17 months) with negligible capacity decay, and had a high area capacity over 7.36 mAh cm-2 with a high mass loading of 28.56 mg cm-2 . These unprecedented performances of graphite are comparable to that of traditional lithium-ion batteries, and may promote the rapidly development of high performance PIBs.

CerS6 triggered by high glucose activating the TLR4/IKKß pathway regulates ferroptosis of LO2 cells through mitochondrial oxidative stress.

Lipid metabolism disorders and mitochondrial dysfunction contribute to the progression of diabetes and chronic liver disease (CLD). Ferroptosis, as a form of cell death centered on reactive oxygen species (ROS) accumulation and lipid peroxidation, is closely related to mitochondrial dysfunction. However, whether there exists mechanistic links between these processes remains unknown. Here, to explore the molecular mechanism of diabetes complicated with CLD, we showed that high glucose could restrain the activity of antioxidant enzymes, promote mitochondrial ROS (mtROS) production, and induce a state of oxidative stress in the mitochondria of human normal liver (LO2) cells. We demonstrated that high glucose induced ferroptosis and promoted the development of CLD, which was reversed by the ferroptosis inhibitor Ferrostatin-1 (Fer-1). In addition, the mitochondria-targeting antioxidant Mito-TEMPO was used to intervene LO2 cells in high-glucose culture, and ferroptosis was found to be inhibited, whereas markers of liver injury and fibrosis improved. Furthermore, high glucose could promote ceramide synthetase 6 (CerS6) synthesis through the TLR4/IKKß pathway. The knockout of CerS6 in LO2 cells showed that mitochondrial oxidative stress was attenuated, ferroptosis was inhibited, and markers of liver injury and fibrosis were ameliorated. In contrast, the overexpression of CerS6 in LO2 cells showed the opposite changes and these changes were inhibited by Mito-TEMPO. In short, we positioned the study of lipid metabolism to a specific enzyme CerS6, with a high degree of specificity. Our findings revealed the mechanism by which the mitochondria act as a bridge linking CerS6 and ferroptosis, confirming that under high glucose conditions, CerS6 promotes ferroptosis through mitochondrial oxidative stress, eventually leading to CLD.

Dynamic Microenvironment-Adaptable Hydrogel with Photothermal Performance and ROS Scavenging for Management of Diabetic Ulcer.

Persistent bacterial infections and excessive oxidative stress prevent the healing of diabetic ulcers, leading to an increased disability rate. Current treatments fail to kill bacteria while simultaneously relieving oxidative stress. Herein, a dynamic microenvironment-adaptable hydrogel (BP@CAu) with photothermal performance and reactive oxygen species scavenging is presented for diabetic ulcer healing. This hydrogel prepared using a dynamic borate-ester could respond to acidity in the infection microenvironment for a controllable drug release. An excellent photothermal conversion effect was integrated in the hydrogel, which exhibited strong antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa. The hydrogel attenuated intracellular oxidative stress and inflammation and promoted cell migration. In a full-thickness skin defect model of diabetic rats, the BP@CAu hydrogel contributed to the fastest wound closure, with ideal reepithelialization, granulation tissue formation, and regeneration of blood vessels. Further mechanistic studies revealed that the hydrogel relieved oxidative stress and downregulated the expression of inflammatory cytokines, resulting in dramatic therapeutic effects on diabetic wounds. Therefore, this study provides a synergistic therapeutic strategy for efficient photothermal performance and reactive oxygen species scavenging in diabetic ulcers.

Understanding carotenoid biosynthetic pathway control points using metabolomic analysis and natural genetic variation.

Advances in analytical methodologies, including those coupled with mass spectrometry (gas chromatography and liquid chromatography; GC-MS and LC-MS) have facilitated profiling of carotenoids in complex plant extracts. The combination of metabolomic data together with diverse germplasm resources provides a means to discover the underlying genetic factors responsible for modulating the carotenoid biosynthetic pathway. Here we summarize metabolomics methodologies for large-scale metabolite analysis and provide guidelines for genetic analysis to leverage natural variation for identification of genes encoding biosynthetic pathway enzymes based on linkage mapping and/or genome-wide association studies (GWAS). We also demonstrate the workflow for identifying genes in carotenoid biosynthesis based on natural variation using case studies in several species.

Does the Adoption of Climate-Smart Agricultural Practices Impact Farmers' Income? Evidence from Ghana.

People's lives, particularly farmers', have been affected by extreme weather conditions that have reduced the yield of numerous crops due to climate change. Climate-smart agriculture practices can reduce or eliminate greenhouse gas emissions and have the propensity to increase farm income and productivity. Therefore, the purpose of this study is to ascertain whether CSA practices impact farmers' income. This study includes all cocoa farmers in the selected districts in the Ashanti Region. The population includes those who live in the six cocoa production villages. The multistage sampling procedure was considered based on the dominants of literature. The study used an endogenous switching regression framework to examine the effects of the adoption of climate-smart agricultural practices (CSAPs) on farmers' income. While estimating treatment effects, telasso uses lasso techniques to select the appropriate variable sets. The results revealed that gender, farm experience, age, household size, and farm size do not significantly influence the adoption of irrigation and crop insurance. The study revealed a significant positive impact of access to credit on adopting irrigation and crop insurance. The adoption of climate-smart practices has a positive coefficient. This indicates that if all respondents in each region adopts these practices, their income would increase significantly. This study shows that adopting irrigation practices leads to an increase in household income of 8.6% and 11.1%, respectively, for cocoa farmers. Crop insurance has a positive coefficient and is statistically significant on household income, on-farm, and off-farm. This paper shows that climate-smart practices such as crop insurance can positively influence farmers' income in Ghana. We also conjecture that crop insurance is the most effective and efficient climate-smart practice among the various agricultural practices. The study suggests that access to credit and mass awareness should be compulsory modules coupled with the consistent training of farmers on new technologies for effective policy implementation. Expanding access to extension officers could enhance farmers' adaptive capacity and warrant the efficiency of implemented practices.

Carbon Dots@rGO Paper as Freestanding and Flexible Potassium-Ion Batteries Anode.

Carbonaceous materials, especially with graphite-layers structure, as anode for potassium-ion batteries (PIBs), are the footstone for industrialization of PIBs. However, carbonaceous materials with graphite-layers structure usually suffer from poor cycle life and inferior stability, not to mention freestanding and flexible PIBs. Here, a freestanding and flexible 3D hybrid architecture by introducing carbon dots on the reduced graphene oxide surface (CDs@rGO) is synthesized as high performance PIBs anode. The CDs@rGO paper has efficient electron and ion transfer channels due to its unique structure, thus enhancing reaction kinetics. In addition, the CDs provide abundant defects and oxygen-containing functional groups, which can improve the electrochemical performance. This freestanding and flexible anode exhibits the high capacity of 310 mAh g-1 at 100 mA g-1, ultra-long cycle life (840 cycles with a capacity of 244 mAh g-1 at 200 mA g-1), and excellent rate performance (undergo six consecutive currents changing from 100 to 500 mA g-1, high capacity 185 mAh g-1 at 500 mA g-1), outperforming many existing carbonaceous PIB anodes. The results may provide a starting point for high-performance freestanding and flexible PIBs and promote the rapid development of next-generation flexible batteries.

Genome assembly of wild tea tree DASZ reveals pedigree and selection history of tea varieties.

Wild teas are valuable genetic resources for studying domestication and breeding. Here we report the assembly of a high-quality chromosome-scale reference genome for an ancient tea tree. The further RNA sequencing of 217 diverse tea accessions clarifies the pedigree of tea cultivars and reveals key contributors in the breeding of Chinese tea. Candidate genes associated with flavonoid biosynthesis are identified by genome-wide association study. Specifically, diverse allelic function of CsANR, CsF3'5'H and CsMYB5 is verified by transient overexpression and enzymatic assays, providing comprehensive insights into the biosynthesis of catechins, the most important bioactive compounds in tea plants. The inconspicuous differentiation between ancient trees and cultivars at both genetic and metabolic levels implies that tea may not have undergone long-term artificial directional selection in terms of flavor-related metabolites. These genomic resources provide evolutionary insight into tea plants and lay the foundation for better understanding the biosynthesis of beneficial natural compounds.

Graphene Armored with a Crystal Carbon Shell for Ultrahigh-Performance Potassium Ion Batteries and Aluminum Batteries.

Graphene is of great significance in energy storage devices. However, a graphene-based electrode is difficult to use in direct applications due to the large surface area and flexibility, which leads to the excessive consumption of electrolyte, low Coulombic efficiency, and electrode shedding behaviors. Herein, a special crystal carbon@graphene microsphere (CCGM) composite was successfully synthesized. The scalable carbonaceous microsphere composite displays a small specific surface area and a superior structure stability. As a potassium ion battery electrode in a half-cell, CCGM delivers an initial capacity of 297.89 mAh g-1 with a high Coulombic efficiency of about 99%. It achieves an excellent cyclic stability with no capacity loss after 1250 cycles at the low current density of 100 mA g-1 with a long performing period of more than one year. As the cathode for an aluminum battery, a reversible specific capacity of 99.1 mAh g-1 at 1000 mA g-1 is obtained. CCGM delivers a long cycle performance of about 10 000 cycles at 4000 mA g-1 with a capacity retention of nearly 100%. Our design provides a fresh thought for the improvement of graphene-based materials, and it will greatly facilitate the application of graphene in the field of energy storage.

Shortcomings/Limitations of Blockwise Granger Causality and Advances of Blockwise New Causality.

Multivariate blockwise Granger causality (BGC) is used to reflect causal interactions among blocks of multivariate time series. In particular, spectral BGC and conditional spectral BGC are used to disclose blockwise causal flow among different brain areas in various frequencies. In this paper, we demonstrate that: 1) BGC in time domain may not necessarily disclose true causality and 2) due to the use of the transfer function or its inverse matrix and partial information of the multivariate linear regression model, both of spectral BGC and conditional spectral BGC have shortcomings and/or limitations, which may inevitably lead to misinterpretation. We then, in time and frequency domains, develop two new multivariate blockwise causality methods for the linear regression model called blockwise new causality (BNC) and spectral BNC, respectively. By several examples, we confirm that BNC measures are more reasonable and sensitive to reflect true causality or trend of true causality than BGC or conditional BGC. Finally, for electroencephalograph data from an epilepsy patient, we analyze event-related potential causality and demonstrate that both of the BGC and BNC methods show significant causality flow in frequency domain, but the spectral BNC method yields satisfactory and convincing results, which are consistent with an event-related time-frequency power spectrum activity. The spectral BGC method is shown to generate misleading results. Thus, we deeply believe that our new blockwise causality definitions as well as our previous NC definitions may have wide applications to reflect true causality among two blocks of time series or two univariate time series in economics, neuroscience, and engineering.

Implementing a "free" tuberculosis (TB) care policy under the integrated model in Jiangsu, China: practices and costs in the real world.

BACKGROUND: In the 1990s, China introduced a "free" tuberculosis (TB) care policy under the national TB control program. Recently, as a part of a new TB diagnosis and treatment model, it has been recommended that the integrated model scale up. This paper examines whether or not TB designated hospitals in the selected project sites have provided TB care according to the national and local guidelines, and analyzes the actual practices and expenditures involved in completing TB treatment. It also explores the reasons why "free" TB care in China cannot be effectively implemented under the integrated model. METHODS: This study was conducted in three counties of Zhenjiang city, Jiangsu province. Mixed methods were used, which comprised reviewing the national and local TB control guidelines, conducting TB patient surveys, collecting TB inpatient and outpatient hospital records, and conducting qualitative interviews with stakeholders. Descriptive statistics were used for quantitative data analysis across counties and in order to compare patients who received only outpatient care and those who received both outpatient and inpatient care. The chi-square test and analysis of variance were performed where necessary. Qualitative data were analyzed using the framework approach. RESULTS: Although the national TB care guidelines recommend outpatient care as a basis for TB treatment in China, we found high hospital admission rates for TB patients ranging from 39 % in Yangzhong county to 83 % in Dantu county. Almost all outpatient TB patients paid for lab tests and over 80 % paid for liver protection drugs and around 70 % paid for image examinations. These three components accounted for three-quarters of the total outpatient expenditure. For patients who received only outpatient care, the total expenditure upon completion of TB treatment was on average 1,135 Chinese yuan. For patients who received outpatient and inpatient care, the total expenditure upon completion of TB treatment was 11,117 Chinese yuan. CONCLUSION: The "free" TB care policy under the integrated model has not been effectively implemented in China. There has been substantial spending on non-recommended services, examinations, and drugs for TB treatment.