Late-Stage Functionalization for the Divergent Synthesis of Podophyllotoxin Derivatives by Rhodium Catalysis.

Invited for the cover of this issue are Chunpu Li, Hong Liu and co-workers at Shanghai Institute of Materia Medica, Nanjing University of Chinese Medicine, and Hangzhou Institute for Advanced Study. The image depicts rhodium catalysis converting the readily available podophyllotoxin into four kinds of novel derivatives. Read the full text of the article at 10.1002/chem.202300960.

Late-Stage Functionalization for the Divergent Synthesis of Podophyllotoxin Derivatives by Rhodium Catalysis.

A divergent synthesis of podophyllotoxin derivatives from simple and readily available starting materials through a late-stage functionalization strategy by rhodium catalysis is reported here. This strategy uses the ketone and oxime in substrates as directing groups. Four kinds of novel podophyllotoxin derivatives have been obtained without any erosion of the enantiopurity, thus indicating the broad substrate scope of this method. Additionally, by using the newly developed strategy, 9 aa, which exhibited excellent anticancer activity, can be prepared by a sequential transformation. In particularly, 9 aa suppressed HeLa cells with IC50 values of 74.5 nM, thus providing a promising lead compound for future drug discovery.

ATP-Responsive Low-Molecular-Weight Polyethylenimine-Based Supramolecular Assembly via Host-Guest Interaction for Gene Delivery.

In this work, we report on an ATP-responsive low-molecular-weight polyethylenimine (LMW-PEI)-based supramolecular assembly. It formed via host-guest interaction between PEI (MW = 1.8 kDa)-α-cyclodextrin (α-CD) conjugates and PEI1.8k-phenylboronic acid (PBA) conjugates. The host-guest interaction between PEI1.8k-α-CD and PEI1.8k-PBA was confirmed by the 2D-NOESY chromatogram experiment and competition test. The ATP-responsive property of the supramolecular assembly was evaluated by a series of ATP-triggered degradation and siRNA release studies in terms of fluorescence resonance energy transfer, agarose gel electrophoresis assay, and the time course monitoring of the particle size and morphology. Confocal laser scanning microscopy confirmed the intracellular disassembly of the supramolecular polymer and the release of siRNA. The supramolecular assembly showed high buffering capability and was capable of protecting siRNA from RNase degradation. It had high cytocompatibility according to in vitro cytotoxicity and hemolysis assays. LMW-PEI-based supramolecular assembly facilitated cellular entry of siRNA via energy-dependent endocytosis. Moreover, the assembly/SR-A siRNA polyplexes at N/P ratio of 30 was most effective in knocking down SR-A mRNA and inhibiting uptake of modified LDL. Taken together, this work shows that ATP-responsive LMW-PEI-based supramolecular assembly is a promising gene vector and has potential application in treating atherosclerosis.

Drought sensitivity of aboveground productivity in Leymus chinensis meadow steppe depends on drought timing.

There is limited understanding of the combined effects of discrete climate extremes and chronic environmental changes on ecosystem processes and functioning. We assessed the interactions of extreme drought timing (45 days, in spring or summer) and nitrogen (N) addition in a full factorial field experiment in a Leymus chinensis-dominated meadow steppe in northeast China. We evaluated the resistance and recovery of the grassland (calculated in terms of aboveground biomass) to these two drought events. The spring drought reduced aboveground biomass by 28% in the unfertilized plots and by 33% in the fertilized plots, and the effects persisted during the subsequent post-drought period within the same growing season; however, the summer drought had no significant influence on aboveground biomass. Although there were no significant interactive effects between drought timing and N addition, we observed a potential trend of N addition increasing the proportion of aboveground biomass suppressed by spring drought but not summer drought. Moreover, the drought resistance of the aboveground biomass was positively correlated with the response of the belowground biomass to drought. One year after the extreme drought events, the spring drought effects on aboveground and belowground biomass were negligible. Our results indicate that the drought sensitivity of productivity likely depends on the phenological and morphological traits of the single highly dominant species (Leymus chinensis) in this meadow steppe.

A pine wood sample preparation method for high target and quality DNA extraction for detection of Esteya vermicola by PCR from living pine.

Esteya vermicola is an endophytic fungus of pine wood nematode with demonstrated biocontrol efficacy. At present, the methods for detection of this fungus from pine wood is still inconvenient and inefficient such as thin-section microscopic observations. In the present study, a simple protocol was developed for wood sample preparation for effective extraction of fungal DNA from wood samples for PCR detection. The protocol of preparation of the sample involves washing in sterile water overnight on a shaking table followed by filtration and centrifugation to obtain the extracted DNA. The result indicates that with this sample preparation protocol, any proper DNA extraction method can be effectively used for the rapid and reliable detection of E. vermicola from pine wood. This method can provide valuable support for follow-up studies with practical applications, such as investigation of the growth rate of E. vermicola and how long it remains viable inside a pine tree.

Esteya vermicola Controls the Pinewood Nematode, Bursaphelenchus xylophilus, in Pine Seedlings.

Esteya vermicola (Ophiostomataceae) is an endoparasitic fungus that has great potential as a biological control agent against the pinewood nematode Bursaphelenchus xylophilus which causes pine wilt disease. We tested E. vermicola for control of pine wilt disease by spraying E. vermicola conidia on artificial wounds on pine seedlings, and the optimum E. vermicola treatment density and application time were also investigated in the greenhouse. The wounds were similar to those made by sawyer beetles (Coleoptera: Cerambycidae). Esteya vermicola treatments significantly increased the survival rate of pine seedlings that were infected by pinewood nematodes. Wounded plants sprayed with 107 CFU/ml E. vermicola had a 73.0% greater survival rate than nonwounded pine seedlings treated similarly. The treatment of pine seedlings with 107 CFU/ml E. vermicola 14 d before nematode infection increased their survival rate by 90.0%. The number of pinewood nematodes isolated from dead pine seedlings sprayed with E. vermicola was 76% less than the number of pinewood nematodes in the controls. Moreover, infected nematodes and the hyphae of E. vermicola were detected in the dead or wilting pine seedlings. Therefore, spraying E. vermicola on the wounds of pine seedlings made by sawyer beetles provides good control of the pine wilt disease that is caused by pinewood nematodes.

Effect of Aster tataricus on production of inflammatory mediators in LPS stimulated rat astrocytoma cell line (C6) and THP-1 cells.

Neuroinflammation is the commonest cause of neurodegenerative diseases such as Alzheimer's disease. Present investigation evaluates the inhibitory effect of ethanolic root extract of Aster tataricus (AS) on inflammatory mediators production in lipopolysaccharide (LPS) stimulated C6 cells. C6 cells were treated with AS (20 and 40 mg/kg) and nimesulide (NSL, 1.5 µg/ml) for 1 day. Thereafter various parameters such as production of ROS, release of nitrite, MDA, glutathione level and NF-κB translocation were estimated in C6 cell lines. Effect of AS was estimated on the expressions of tumor necrosis factor α (TNF-α) of human monocytic leukemia cell line (THP-1). It was observed that AS (20 and 40 mg/ml) treated group shows significant (p < 0.01) decrease in production of ROS, Nitrite release and MDA level in LPS activated C6 cell lines compared to negative control group. Moreover, treatment with it decreases glutathione level and inhibits the translocation of NF-κB in LPS activated C6 cell lines compared to negative control group. There were significant (p < 0.01) decreases in expression of TNF-α in AS treated group compared to negative control group in THP-1 cell lines. Present investigation concludes the anti neuroinflammatory effect of ethanolic extract of AS root by decreasing oxidative stress and attenuates the cytokine.

In vivo hair growth-stimulating effect of medicinal plant extract on BALB/c nude mice.

CONTEXT: Chrysanthemum zawadskii var. latilobum (Asteraceae) (CZ) and Polygonum multiflorum Thunb. (Polygonaceae) (PM) have been used traditionally to treat different systemic diseases and acclaimed for various biological activities including hair growth. OBJECTIVE: This study investigates the hair restoration efficacy of selected medicinal plant extracts on nude mice. MATERIALS AND METHODS: Nude mice genetically predisposed to pattern balding were used in this study. Topical methanol extracts of CZ and PM (10 mg/mouse/d) with standardized vehicle formulation, only vehicle (propylene glycol:ethanol:dimethyl sulfoxide, 67:30:3% v/v) and Minoxidil (2%) were applied daily for 40 consecutive days. RESULTS: In our study, the maximum hair score (2.5 ± 0.29) was obtained in the CZ-treated group. Histological observation revealed a significant increase (p < 0.001) in the number of hair follicles (HF) in CZ-treated mice (58.66 ± 3.72) and Minoxidil-treated mice (40 ± 2.71). Subsequently, immunohistochemical analysis also confirmed the follicular keratinocyte proliferation by detection of BrdU-labeling, S-phase cells in Minoxidil and CZ-treated mouse follicular bulb and outer root sheaths. CONCLUSION: Our study revealed the underlying mechanism of stimulating hair growth in athymic nude mice by repair the nu/nu follicular keratin differentiation defect. Thus, the topical application of CZ may represent a novel strategy for the management and therapy of certain forms of alopecia.

A staining method for assessing the viability of Esteya vermicola conidia.

The viability of conidia of Esteya vermicola, a potentially important biocontrol agent against the pinewood nematode Bursaphelenchus xylophilus, is usually determined by cultivation for 18-48 h in culture medium. As an alternative to this labor-intensive method, we have developed a rapid, simple, and low-cost staining method for assessing E vermicola conidia survival rates. A mixture of neutral red and methylene blue was found to be the most optimal among several stains that also included safranin O and Janus green B. This mixture stained nonviable conidia blue, in contrast to viable conidia, which were stained red in the cytoplasm and blue in the cell wall. This method may be particularly useful for traditional research laboratories, as it provides rapid results using common, relatively inexpensive laboratory equipment.

Aqueous extract of red deer antler promotes hair growth by regulating the hair cycle and cell proliferation in hair follicles.

Deer antlers are the only mammalian appendage capable of regeneration. We aimed to investigate the effect of red deer antler extract in regulating hair growth, using a mouse model. The backs of male mice were shaved at eight weeks of age. Crude aqueous extracts of deer antler were prepared at either 4 °C or 100 °C and injected subcutaneously to two separate groups of mice (n = 9) at 1 mL/day for 10 consecutive days, with water as a vehicle control group. The mice skin quantitative hair growth parameters were measured and 5-bromo-2-deoxyuridine was used to identify label-retaining cells. We found that, in both the 4 °C and the 100 °C deer antler aqueous extract-injection groups, the anagen phase was extended, while the number of BrdU-incorporated cells was dramatically increased. These results indicate that deer antler aqueous extract promotes hair growth by extending the anagen phase and regulating cell proliferation in the hair follicle region.

The Role of Triggers in Physical Activity among College Students: An Extended Model of the Theory of Planned Behavior.

OBJECTIVE: This study aims to extend the Theory of Planned Behavior with Triggers (TPBT) to improve the prediction of physical activity (PA) behavior using the TPB model. METHODS: Questionnaires, including the TPB scale, PA rating scale (PARS-3), and triggers scale, were administered to 596 Chinese college students, and the data were analyzed using SPSS 23.0 and AMOS 24.0. RESULTS: Subjective norm (SN), attitude (AT), and perceived behavioral control (PBC) all significantly and positively affected behavioral intention (BI). The path coefficient of PA behavior was significantly influenced by the interaction term of three types of triggers and BI, and the TPB with Triggers (TPBT) model improved the explanation rate of PA behavior. CONCLUSION: Triggers have a moderating effect on the relationship between BI and PA behavior, and the TPBT model better explains college students' PA behavior. Among the three dimensions of triggers, people are more receptive to facilitator and signal triggers than spark triggers. This has practical implications for practitioners designing interventions to promote PA among college students.

Different responses of foliar nutrient resorption efficiency in two dominant species to grazing in the desert steppe.

Nitrogen and phosphorus resorption (NRE and PRE) is a critical nutrient conservation mechanism maintaining plant growth in already disturbed barren ecosystems. The complexity of plant nutrient resorption variations in long-term grazing regions is regulated by plant traits, nutritional utilization strategies, and soil conditions following changes in grazing patterns. Therefore, a detailed investigation into their underlying mechanism is still required. Here we investigated leaf nutrient concentration and resorption in dominant species Cleistogenes songorica (C. squarrosa) and Stipa breviflora (S. breviflora) response to 15-years continuous grazing (moderate and heavy grazing) in desert steppe. Moderate grazing enhanced green leaf N and P content in C. songorica and partially increased N content in S. breviflora. Heavy grazing consistently increased N content in C. songorica, but its P content as well as N and P content in S. breviflora were largely stable. Moderate grazing enhanced NRE but unaffected PRE in both S. breviflora and C. songorica. Heavy grazing reduced NRE and PRE in C. songorica. Although soil variables (nutrients and moisture) did not affect foliar nutrients, it's a key driver of nutrient resorption efficiency. Of all measured influence factors, soil moisture is the one most important and negatively correlated with NRE and PRE in S. breviflora. While it was not observed in C. songorica. In S. breviflora, its NRE was adversely linked with soil N, in addition, both NRE and PRE were positively associated with green leaf nutrients. Senesced leaf nutrients are the predominant factor influencing nutrient resorption efficiency in C. songorica, which were adversely associated. Overall, our results indicate significant variations in nutrient resorption efficiency patterns between the two dominant species due to divergent plant adaptation strategies to grazing and the local environment. The foliar nutritional status and soil conditions may play significant roles in regulating nutrient resorption in arid long-term grazing desert steppe.

Model-Based Reinforcement Learning With Isolated Imaginations.

World models learn the consequences of actions in vision-based interactive systems. However, in practical scenarios like autonomous driving, noncontrollable dynamics that are independent or sparsely dependent on action signals often exist, making it challenging to learn effective world models. To address this issue, we propose Iso-Dream++, a model-based reinforcement learning approach that has two main contributions. First, we optimize the inverse dynamics to encourage the world model to isolate controllable state transitions from the mixed spatiotemporal variations of the environment. Second, we perform policy optimization based on the decoupled latent imaginations, where we roll out noncontrollable states into the future and adaptively associate them with the current controllable state. This enables long-horizon visuomotor control tasks to benefit from isolating mixed dynamics sources in the wild, such as self-driving cars that can anticipate the movement of other vehicles, thereby avoiding potential risks. On top of our previous work (Pan et al. 2022), we further consider the sparse dependencies between controllable and noncontrollable states, address the training collapse problem of state decoupling, and validate our approach in transfer learning setups. Our empirical study demonstrates that Iso-Dream++ outperforms existing reinforcement learning models significantly on CARLA and DeepMind Control.

Transcriptome and anatomical analysis of Stipa breviflora in response to different grazing intensities in desert steppe.

Stipa breviflora is a dominant species in the desert steppe of Northern China. Grazing is the main land use pattern of grassland, which could cause a variety of adaptive evolutionary mechanisms in plant community composition as well as individual plant growth and morphological characteristics. However, very little is known about the morphological structure and transcriptional regulation response to different grazing intensities in S. breviflora. In this study, transcriptome and anatomical analyses of S. breviflora under different grazing intensities, including no grazing, moderate grazing, and heavy grazing, were performed. The anatomical analysis results showed that epidermis cells and xylems significantly thicken with grazing intensity, suggesting that grazing results in increasing lignification. Furthermore, the components of cell walls such as lignin, cellulose, hemicellulose, and pectin were all increased dramatically and significantly under both moderate and heavy grazing. Transcriptome analysis showed that the differentially expressed genes related to different grazing intensities were also engaged in plant cell wall formation and in photosynthesis and respiration. In addition, the activities of ATP synthase and Rubisco-activating enzyme increased significantly with enhanced grazing intensity and differed significantly between moderate and heavy grazing intensities. The trends in transcriptome and plant phenotype changes are consistent. Taken together, these results indicated that S. breviflora has evolved a grazing tolerance strategy under long-term grazing conditions, influencing photosynthesis and respiration in terms of its own structure and enzyme activities in the body, to maintain normal life activities under different grazing conditions.

An emission model for inhalable chemicals from children's play mats based on partition coefficients.

Inhalable chemicals found in children's play mats can be slowly released into indoor environments and consequently threaten human health. In this study, the partition coefficients of seven inhalable chemicals between play mats and air were calculated by headspace gas chromatography-mass spectrometry based on the law of conservation of mass and the principle of equilibrium of headspace bottles. Furthermore, an emission source model for the residual ratio of the inhalable chemicals in play mats was established. Most substances found in play mats have large partition coefficients owing to the complex void structure of the mats, which adsorbs a large number of organic pollutants. The partition coefficient is not only related to the boiling point and environmental temperature, but also the specific material and the adsorption of the organic pollutant onto the material. The emission source model for children's play mats developed in this study can characterize the decay of the inhalable chemicals over time. The data showed that after eight days of placing the play mat in a ventilated environment, the residual ratio of seven inhalable chemicals did not exceed 15 %.

LCST ion gels fabricating "all-in-one" smart windows: thermotropic, electrochromic and power-generating.

Smart windows always respond to single stimuli, which cannot satisfy various needs in practical applications. Smart windows that integrate thermotropic, electrochromic and power-generating functions in one device is highly challenging yet important in satisfying on-demand light modulation and energy efficiency in practical applications. Herein, a thermoresponsive lower critical solution temperature (LCST) ion gel was fabricated via a facile in situ polymerization of butyl acrylate in a conventional ionic liquid to explore "all in one" smart windows. The ion gel-assembled smart windows are thermotropic and electrochromic with a reliable adjustment of light transparency as well as power-generating, enabled by the ionic Soret effect of ionic liquids. Additionally, the ion gels demonstrated self-defensive robust mechanical properties, thermal insulating and antifogging properties. With such an interdisciplinary and comprehensive study of the ion gels, the LCST ion gels could fulfil the requirements of genius windows with high energy-saving potential and exceptional climate adaptability, such as shut-down of light transmission in summer, daily solar energy collection, and colour changes on demand. It conceptually updates smart windows from an energy saving to an energy supplier in buildings. It is the first time to explore the "all in one" smart windows based on integrated multifunctional ionic liquids, which could greatly bridge the gap between the materials and buildings to accelerate practical applications of smart windows.

Enhancement of antitumor activity by combination of tumor lysate-pulsed dendritic cells and celecoxib in a rat glioma model.

Using dendritic cell (DC)-based vaccines for treatment of gliomas has emerged as a meaningful and feasible treatment approach for inducing long-term survival, but this approach so far has failed to generate significant clinical responses. In the present study, we demonstrated that glioma lysate-pulsed DCs in combination with celecoxib, a selective cyclooxygenase 2 (COX-2) inhibitor, showed more significantly enhanced antitumor activity with increased apoptosis of tumor cells, reduced neovascularization, and developed a strong cytotoxic T lymphocyte (CTL) response in tumor-bearing rats. Celecoxib may reduce production of prostaglandin E2 and modulate the balance between T helper 1 (Th1) cytokines and T helper 2 (Th2) cytokines by increasing the pivotal Thl cytokine interleukin-12 and reducing Th2 cytokine interleukin-10. Taken together, our results demonstrated that selective inhibition of COX-2 using celecoxib combined with DC-based immunotherapy could act as an important novel strategy for improving future treatment of malignant gliomas.

Effect of nutrition and environmental factors on the endoparasitic fungus Esteya vermicola, a biocontrol agent against pine wilt disease.

The nematophagous fungus Esteya vermicola has tremendous potential for biological control. This species exhibits strong infectious activity against pinewood nematodes, whereas the study on the effect of nutrition and environmental factors is still of paucity. Carbon (C), nitrogen (N), pH value, temperature, and water activity have great impact on the fungal growth, sporulation, and germination. In nutrition study, the greatest number of conidia (2.36 × 10(9) per colony) was obtained at the C:N ratio of 100:1 with a carbon concentration 32 g l(-1). In addition, the germination rate and radial growth of E. vermicola were used to evaluate the effects of environmental conditions and they were optimized as following: pH 5.5, 26 °C and water activity of 0.98. Our results also confirmed that variation of environmental factors has a detrimental influence on the efficacy of active conidia and growth of fungus. Moreover, under above optimal condition, the biocontrol efficacy was significantly improved in regard to the increase of adhesive and mortality rate, which highlight the study on the application of E. vermicola as pine wilt disease biocontrol agent.

Ginsenosides Rb1 and Rd regulate proliferation of mature keratinocytes through induction of p63 expression in hair follicles.

Ginsenosides Rb1 and Rd are the two main types of ginsenosides in Panax ginseng and have been used as an additive to against alopecia. However, the mechanisms involved are largely unknown. To determine how ginsenosides prevent hair loss, we topically applied protopanaxadiol-type ginsenosides Rb1 and Rd over the shaved skin of B57CL/6 mice, and monitored and assessed them for 35 days. We then investigated the effects of ginsenosides on cell genesis in different phases of adult hair follicles (HFs), using 5-bromo-2'-deoxyuridine as a marker for dividing cells. Moreover, p63, a specific marker and a major regulator of keratinocyte progenitor cells of the multi-layered epithelia, was detected in epidermis. Results indicated that treatment with ginsenosides Rb1 and Rd increased cell proliferation in both anagen and telogen of HFs. However, it had no significant effect on the survival of cells in the bulge and upper follicle region. Investigation of p63 demonstrated that up-regulation of p63 expression in the matrix and outer root sheath might be one of the mechanisms by which ginsenosides Rb1 and Rd promote cell proliferation in HFs. Our study reveals a novel mechanism by which ginsenoside promotes hair growth through p63 induction in follicular keratinocytes and indicates that ginsenosides Rb1 and Rd might be developed as a therapeutic agent for the prevention of hair loss.