Enantioselective Divergent Syntheses of Diterpenoid Pyrones.

Capitalizing a synergy between late-stage C(sp3)-H alkynylation and a series of transition metal-catalyzed alkyne functionalization reactions, we reported herein enantioselective divergent synthesis of 10 diterpenoid pyrones within 14-16 steps starting from chiral pool enoxolone, including the first enantioselective synthesis of higginsianins A, B, D, E, and metarhizin C. Our synthesis also highlights an unprecedented biomimetic oxidative rearrangement of α-pyrone into 3(2H)-furanone, as well as applications of Echavarren C(sp3)-H alkynylation reaction and Toste chiral counterion-mediated Au-catalyzed intramolecular allene hydroalkoxylation in natural product synthesis.

Knockdown of LOX-1 ameliorates bone quality and generation of type H blood vessels in diabetic mice.

Our previous studies have shown that lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1) is expressed in liver sinusoidal endothelial cells, and oxidized low-density lipoprotein induces liver sinusoidal dysfunction and defenestration through the LOX-1/ROS/NF-kB pathway, revealing that LOX-1 can mediate liver sinusoidal barrier function, involved in the regulation of non-alcoholic fatty liver disease. Here, we investigated whether, in the context of bone metabolic diseases, LOX-1 could affect bone quality and type H blood vessels in diabetic mice. We used db/db mice as model and found that LOX-1 knockdown can ameliorate bone quality and type H blood vessel generation in db/db mice. This further verifies our hypothesis that LOX-1 is involved in the regulation of bone quality and type H blood vessel homeostasis, thus inhibiting osteoporosis progression in db/db mice.

Effects of Guizhi and Erxian Decoction on menopausal hot flashes: insights from the gut microbiome and metabolic profiles.

AIMS: To examine the influence of GED on the gut microbiota and metabolites using a bilateral ovariectomized (OVX) rat model. We tried to elucidate the underlying mechanisms of GED in the treatment of menopausal hot flashes. METHODS AND RESULTS: 16S rRNA sequencing, metabonomics, molecular biological analysis, and fecal microbiota transplantation (FMT) were conducted to elucidate the mechanisms by which GED regulates the gut microbiota. GED significantly reduced OVX-induced hot flashes and improved disturbances in the gut microbiota metabolites. Moreover, FMT validated that the gut microbiota can trigger hot flashes, while GED can alleviate hot flash symptoms by modulating the composition of the gut microbiota. Specifically, GED upregulated the abundance of Blautia, thereby increasing l(+)-ornithine levels for the treatment of menopausal hot flashes. Additionally, GED affected endothelial nitric oxide synthase and heat shock protein 70 (HSP70) levels in the hypothalamic preoptic area by changing the gut microbiota composition. CONCLUSIONS: Our study illuminated the underlying mechanisms by which GED attenuated the hot flashes through modulation of the gut microbiota and explored the regulatory role of the gut microbiota on HSP70 expression in the preoptic anterior hypothalamus, thereby establishing a foundation for further exploration of the role of the gut-brain axis in hot flashes.

Electronic Noses: From Gas-Sensitive Components and Practical Applications to Data Processing.

Artificial olfaction, also known as an electronic nose, is a gas identification device that replicates the human olfactory organ. This system integrates sensor arrays to detect gases, data acquisition for signal processing, and data analysis for precise identification, enabling it to assess gases both qualitatively and quantitatively in complex settings. This article provides a brief overview of the research progress in electronic nose technology, which is divided into three main elements, focusing on gas-sensitive materials, electronic nose applications, and data analysis methods. Furthermore, the review explores both traditional MOS materials and the newer porous materials like MOFs for gas sensors, summarizing the applications of electronic noses across diverse fields including disease diagnosis, environmental monitoring, food safety, and agricultural production. Additionally, it covers electronic nose pattern recognition and signal drift suppression algorithms. Ultimately, the summary identifies challenges faced by current systems and offers innovative solutions for future advancements. Overall, this endeavor forges a solid foundation and establishes a conceptual framework for ongoing research in the field.

Phlorizin, an Important Glucoside: Research Progress on Its Biological Activity and Mechanism.

Phlorizin, as a flavonoid from a wide range of sources, is gradually becoming known for its biological activity. Phlorizin can exert antioxidant effects by regulating the IL-1ß/IKB-α/NF-KB signaling pathway. At the same time, it exerts its antibacterial activity by reducing intracellular DNA agglutination, reducing intracellular protein and energy synthesis, and destroying intracellular metabolism. In addition, phlorizin also has various pharmacological effects such as antiviral, antidiabetic, antitumor, and hepatoprotective effects. Based on domestic and foreign research reports, this article reviews the plant sources, extraction, and biological activities of phlorizin, providing a reference for improving the clinical application of phlorizin.

Enantioselective Synthesis of the 1,3-Dienyl-5-Alkyl-6-Oxy Motif: Method Development and Total Synthesis.

The 1,3-dienyl-5-alkyl-6-oxy motif is widely found in various types of bioactive natural products. However, present synthesis is mainly non-asymmetric which relied upon different olefination or transition metal-catalyzed cross-coupling reactions using enantioenriched precursors. Herein, based upon a newly developed enantioselective α-alkylation of conjugated polyenoic acids, a variety of 1,3-dienyl-5-alkyl-6-oxy motif (with E-configured internal olefin) was generated as the corresponding α-adducts in a highly enantioselective and diastereoselective manner. Utilizing 1,3-dienyl-5-alkyl-6-oxy motif as key intermediates, we further demonstrated their synthetic potential by expedient total syntheses of three types of natural products (glutarimide antibiotics, α-pyrone polyketides and Lupin alkaloids) within 4-7 steps.

Performance Prediction and Heating Parameter Optimization of Organic-Rich Shale In Situ Conversion Based on Numerical Simulation and Artificial Intelligence Algorithms.

In situ conversion technology is a green and effective way to realize the development of organic-rich shale. Supercritical CO2 can be used as a good heating medium for shale in situ conversion. Numerical simulation is an important means to explore the shale in situ conversion process, but it requires a lot of time and computational cost for in situ conversion simulation under different working conditions. Therefore, a computational framework for rapid prediction of shale in situ conversion development performance and heating parameter optimization is proposed by coupling artificial neural network (ANN) and particle swarm optimization (PSO). The results indicated that kerogen pyrolysis and hydrocarbon product release mainly occurred within 2 years of shale in situ conversion. The production curves of pyrolysis hydrocarbon obviously slowed after in situ conversion for 2 years. The database was constructed by a large number of in situ conversion simulations, and Pearson correlation analysis and the random forest method were adopted to obtain seven main controlling factors affecting reservoir temperature and hydrocarbon production. The determination coefficient of the obtained ANN-based prediction models is higher than 97%, and the mean square error (MSE) is lower than 0.3%. The basic reservoir case can choose to inject 350-450 °C supercritical CO2 (Sc-CO2) fluid with a rate of 600 m3/day to obtain a more promising development effect. The heating parameter optimization for three typical reservoir cases using PSO was performed, and reasonable injection temperature and injection rate were obtained. It realized accurate development prediction and rapid heating parameter optimization, which helps the effective application of shale in situ conversion development design.

Synergistic effects of biochar addition and filtration mode optimization on mitigating membrane fouling in high-solid anaerobic membrane bioreactors.

In this study, a high-solid anaerobic membrane bioreactor was established for treating food waste, and membrane fouling rates were regulated through multivariate modulation. The anaerobic membrane bioreactor operated stably at a high organic loading rate of 28.75 gCOD/L/d achieved a methane production rate of 8.03 ± 0.61 L/L/d. Experimental findings revealed that the most effective control of membrane fouling was achieved at a filtration- relaxation ratio (F/R) of 10/90 s. This indicates that a higher relaxation frequency provided improved the mitigation of membrane fouling. Compared with single F/R modulation, the combined modulation of biochar and F/R provided enhanced control over membrane fouling. Moreover, the addition of biochar altered the sludge properties of the reactor, thereby preventing the formation of a dense cake layer. Additionally, biochar enhanced the sheer force of the fluid on the membrane surface and facilitated the separation of pollutants during the relaxation stage, thereby contributing to improved control of membrane fouling.

Biokinetic and microbial insights into regulatory mechanisms of long-chain fatty acid degradation during food waste-lipid co-digestion within anaerobic membrane bioreactor.

This study investigated the effects of varying lipid ratios on the anaerobic co-digestion of high-lipid food waste (FW) in a mesophilic anaerobic membrane bioreactor (AnMBR). At a lipid concentration of 5 %, optimal biogas production (3.84 L/L/d) and lipid removal efficiency (78 %) were achieved; however, increasing lipid concentrations resulted in significant accumulations of long-chain fatty acids (LCFAs) and volatile fatty acids (VFAs). Batch tests further demonstrated the impact of various types of LCFAs, with stearic acid showing the slowest microbial growth rate (0.033d-1), confirming its role in the accumulation of acetate-dominated VFAs, potentially limiting the methanogenesis process at elevated lipid levels. Furthermore, at 8 % lipid content, the downregulation of key LCFA degradation enzymes and dominance of hydrogenotrophic methanogens indicated adverse conditions. The importance of the intricate interplay between LCFA degradation kinetics and microbial community for the system efficiency was evidenced, offering insights for optimizing and managing high-lipidic wastes.

Toward Intelligent Display with Neuromorphic Technology.

In the era of the Internet and the Internet of Things, display technology has evolved significantly toward full-scene display and realistic display. Incorporating "intelligence" into displays is a crucial technical approach to meet the demands of this development. Traditional display technology relies on distributed hardware systems to achieve intelligent displays but encounters challenges stemming from the physical separation of sensing, processing, and light-emitting modules. The high energy consumption and data transformation delays limited the development of intelligence display, breaking the physical separation is crucial to overcoming the bottlenecks of intelligence display technology. Inspired by the biological neural system, neuromorphic technology with all-in-one features is widely employed across various fields. It proves effective in reducing system power consumption, facilitating frequent data transformation, and enabling cross-scene integration. Neuromorphic technology shows great potential to overcome display technology bottlenecks, realizing the full-scene display and realistic display with high efficiency and low power consumption. This review offers a comprehensive summary of recent advancements in the application of neuromorphic technology in displays, with a focus on interoperability. This work delves into its state-of-the-art designs and potential future developments aimed at revolutionizing display technology.

Magnetic Soft Microrobot Design for Cell Grasping and Transportation.

Manipulating cells at a small scale is widely acknowledged as a complex and challenging task, especially when it comes to cell grasping and transportation. Various precise methods have been developed to remotely control the movement of microrobots. However, the manipulation of micro-objects necessitates the use of end-effectors. This paper presents a study on the control of movement and grasping operations of a magnetic microrobot, utilizing only 3 pairs of electromagnetic coils. A specially designed microgripper is employed on the microrobot for efficient cell grasping and transportation. To ensure precise grasping, a bending deformation model of the microgripper is formulated and subsequently validated. To achieve precise and reliable transportation of cells to specific positions, an approach that combines an extended Kalman filter with a model predictive control method is adopted to accomplish the trajectory tracking task. Through experiments, we observe that by applying the proposed control strategy, the mean absolute error of path tracking is found to be less than 0.155 mm. Remarkably, this value accounts for only 1.55% of the microrobot's size, demonstrating the efficacy and accuracy of our control strategy. Furthermore, an experiment involving the grasping and transportation of a zebrafish embryonic cell (diameter: 800 µm) is successfully conducted. The results of this experiment not only validate the precision and effectiveness of the proposed microrobot and its associated models but also highlight its tremendous potential for cell manipulation in vitro and in vivo.

Room-temperature low-threshold avalanche effect in stepwise van-der-Waals homojunction photodiodes.

Avalanche or carrier-multiplication effect, based on impact ionization processes in semiconductors, has a great potential for enhancing the performance of photodetector and solar cells. However, in practical applications, it suffers from high threshold energy, reducing the advantages of carrier multiplication. Here, we report on a low-threshold avalanche effect in a stepwise WSe2 structure, in which the combination of weak electron-phonon scattering and high electric fields leads to a low-loss carrier acceleration and multiplication. Owing to this effect, the room-temperature threshold energy approaches the fundamental limit, Ethre ≈ Eg, where Eg is the bandgap of the semiconductor. Our findings offer an alternative perspective on the design and fabrication of future avalanche and hot-carrier photovoltaic devices.

Mir-142-3P regulates MAPK protein family by inhibiting 14-3-3η to enhance bone marrow mesenchymal stem cells osteogenesis.

Clinical studies have found 14-3-3η to be associated with osteoporosis through undefined mechanisms. We aimed to investigate the role of 14-3-3η in osteoporosis and its potential associations with miRNAs. The Gene Expression Omnibus(GEO) and Human Protein Atlas 1 databases were analyzed to examine both the mRNA and protein expression of 14-3-3η in OP. Gene enrichment analyses were performed to explore the underlying mechanism of 14-3-3η based on DAVID. miRWalk was used to predict the associated miRNAs. The statistics were analysed by R software and SPSS software. 14-3-3η was overexpressed and knock down expressed in BMSCs by lentiviral vector transfecting. And BMSCs were induced by hypoxia. qRT-PCR and Western-Blot verified the expression of mRNA and protein. Scratch assay detected the migration of osteocytes. Co-immunoprecipitation and luciferase assay studied the 14-3-3η targeted protein and miRNA. overexpression and knock down of miRNA to verify the relationship of 14-3-3η and target genes. The 14-3-3η mRNA expression level was low in patients with osteoporosis, as corroborated by immunohistochemical staining images. Functional analyses revealed enrichment of the MAPK-associated cascade. 14-3-3η was correlated with MAPK family proteins and five key miRNAs, including mir-142-3p. In addition, 14-3-3η knockdown in BMSCs increased the mRNA and protein expression levels of Hif-α, VEGF, BMP-2, OPN, OST, and Runx2, and enhanced the cells migration ability. Under hypoxic conditions, Hif-α and BMP-2 protein expression levels were upregulated, whereas those of 14-3-3η and MAPK3 were downregulated. Co-immunoprecipitation experiments showed decreased binding of 14-3-3η to MAPK3. 14-3-3η knockdown produced the same results as hypoxia induction. Adding caspase3 inhibitor and knocking down 14-3-3η again prevented MAPK3 cleavage by caspase3 and inhibited BMP-2 expression. Moreover, under hypoxic conditions, miR-142-3P expression was upregulated and luciferase assays revealed 14-3-3η as its target gene. miR-142-3P overexpression decreased mRNA and protein levels of 14-3-3η and MAPK3, while increasing BMP-2 expression. miR-142-3P knockdown reversed these results. BMSC osteogenesis was suppressed by 14-3-3η, whereas miRNA-142-3p promoted it through the inhibition of 14-3-3η.

Prostate transmembrane androgen inducible protein 1 (PMEPA1): regulation and clinical implications.

Prostate transmembrane androgen inducible protein 1 (PMEPA1) can promote or inhibit prostate cancer cell growth based on the cancer cell response to the androgen receptor (AR). Further, it can be upregulated by transforming growth factor (TGF), which downregulates transforming growth factor-ß (TGF-ß) signaling by interfering with R-Smad phosphorylation to facilitate TGF-ß receptor degradation. Studies have indicated the increased expression of PMEPA1 in some solid tumors and its functioning as a regulator of multiple signaling pathways. This review highlights the multiple potential signaling pathways associated with PMEPA1 and the role of the PMEPA1 gene in regulating prognosis, including transcriptional regulation and epithelial mesenchymal transition (EMT). Moreover, the relevant implications in and outside tumors, for example, as a biomarker and its potential functions in lysosomes have also been discussed.