Unveiling Confinement Engineering for Achieving High-Performance Rechargeable Batteries.

The confinement effect, restricting materials within nano/sub-nano spaces, has emerged as an innovative approach for fundamental research in diverse application fields, including chemical engineering, membrane separation, and catalysis. This confinement principle recently presents fresh perspectives on addressing critical challenges in rechargeable batteries. Within spatial confinement, novel microstructures and physiochemical properties have been raised to promote the battery performance. Nevertheless, few clear definitions and specific reviews are available to offer a comprehensive understanding and guide for utilizing the confinement effect in batteries. This review aims to fill this gap by primarily summarizing the categorization of confinement effects across various scales and dimensions within battery systems. Subsequently, the strategic design of confinement environments is proposed to address existing challenges in rechargeable batteries. These solutions involve the manipulation of the physicochemical properties of electrolytes, the regulation of electrochemical activity, and stability of electrodes, and insights into ion transfer mechanisms. Furthermore, specific perspectives are provided to deepen the foundational understanding of the confinement effect for achieving high-performance rechargeable batteries. Overall, this review emphasizes the transformative potential of confinement effects in tailoring the microstructure and physiochemical properties of electrode materials, highlighting their crucial role in designing novel energy storage devices.

Bupi Yishen formula may prevent kidney fibrosis by modulating fatty acid metabolism in renal tubules.

BACKGROUND: Bupi Yishen formula (BYF), a traditional Chinese herbal mixture, has demonstrated better effectiveness than Losartan in preserving renal function and preventing composite severe adverse outcomes in patients with advanced chronic kidney disease (CKD) in a recent randomized controlled trial. Prior studies have shown that BYF exerts anti-inflammatory and anti-fibrotic effects in the kidneys of CKD models, but the underlying mechanisms have not been fully elucidated. PURPOSE: The aim of this study was to investigate the protective effects of BYF administration on profibrotic phenotypic changes in the kidney and to elucidate its fundamental mechanisms of action. METHODS: Adenine and 5/6 nephrectomy rat models were administered with two doses of BYF extract (15 or 30 g/kg/d) by intragastric administration, and Losartan treatment was used as a positive control group. The relationship between BYF renoprotection and restoration of fatty acid dysregulation was examined using the two fibrosis models and TGFb1-induced human tubular HK2 cells. Transcriptomic profiles of the fibrotic kidneys obtained from adenine-induced CKD rats were used to identify the key mechanisms that are affected by BYF intervention. Human relevance and clinical implications were established by re-analysis of the microarray databases of CKD patients and immunostaining on human biopsy specimens. RESULTS: BYF effectively prevented kidney histological damage and ameliorated renal malfunction in the adenine rat model of CKD. BYF robustly attenuated the significant increase in profibrotic and proapoptotic markers in fibrotic kidneys of adenine-induced CKD rats. Transcriptomic analyses of the fibrotic kidneys of the adenine rats identified fatty acid metabolism as the key dysregulated pathway affected by BYF prevention. BYF significantly reversed defective fatty acid oxidation (FAO) and the intracellular lipids accumulation in the fibrotic kidneys induced by 5/6 nephrectomy. Furthermore, BYF prevented dysfunctional fatty acid metabolism, which were associated with the significant improvement of TGFb1-induced profibrotic changes in HK2 human proximal tubular cells. Furthermore, analyses of kidney microarray databases and biopsy specimens of CKD patients suggested that FAO defect is common in CKD in humans. CONCLUSION: Our exploratory study found that BYF may exert protective effects on renal fibrosis by regulating the fatty acid metabolism of renal tubular cells, which may be a key mechanism for preventing kidney fibrosis in CKD.

Protective effects of the Bupi Yishen formula on renal fibrosis through PI3K/AKT signaling inhibition.

ETHNOPHARMACOLOGICAL RELEVANCE: The Bupi Yishen Formula (BYF) is a patented Chinese herbal compound that has been long used to treat chronic kidney disease (CKD) in the clinic. However, its main active ingredients and underlying mechanisms remain to be elucidated. AIM: Identify the major active ingredients of BYF and investigate its protective effects and specific molecular mechanisms in renal fibrosis. METHODS: First, we performed network pharmacology analysis combined with molecular docking to predict the main active compounds, potential therapeutic targets, and intervention pathways that might exert the anti-fibrotic effect of BYF in the kidney. Then, we validated the predictions in both adenine-induced CKD rats and TGFß1-induced HK-2 cells. RESULTS: A total of 233 common targets, 25 core targets, and 10 main active compounds from BYF were selected by network pharmacology analyses. Then, GO and KEGG functional enrichment analyses indicated that the renoprotection conferred by BYF against renal fibrosis was mainly associated with the PI3K/AKT signaling. Besides, the molecular docking showed that the 10 main active compounds of BYF were closely docked with three main PI3K/AKT pathway proteins. During the experimental validations, BYF improved renal impairment and alleviated fibrosis by inhibiting the PI3K/AKT signaling activity in the kidney of adenine-induced CKD model rats. Moreover, increased PI3K/AKT signaling activation was associated with fibrotic phenotype changes in adenine-induced CKD rats and TGFß1-induced HK-2 cells. On the other hand, BYF treatment reduced PI3K/AKT signaling activation and decreased renal fibrogenesis in a dose-dependent manner, thereby indicating that PI3K/AKT signaling was essential for BYF to exert its anti-fibrotic effects. Finally, the inhibitory effect of BYF on renal fibrogenesis was not enhanced while blocking the PI3K/AKT pathway with a broad spectrum PI3K inhibitor (LY294002). CONCLUSION: In the present study, we applied a comprehensive strategy based on systemic pharmacology to reveal the anti-fibrotic mechanisms of BYF, at least partially, through the inhibition of PI3K/AKT signaling activation. We also identified BYF as a potential therapeutic agent for renal fibrosis and CKD progression.

Uncovering Bupi Yishen Formula Pharmacological Mechanisms Against Chronic Kidney Disease by Network Pharmacology and Experimental Validation.

Chronic kidney disease (CKD) is a leading public health problem with high morbidity and mortality, but the therapies remain limited. Bupi Yishen Formula (BYF) - a patent traditional Chinese medicine (TCM) formula - has been proved to be effective for CKD treatment in a high-quality clinical trial. However, BYF's underlying mechanism is unclear. Thus, we aimed to reveal BYF pharmacological mechanism against CKD by network pharmacology and experimental studies. Network pharmacology-based analysis of the drug-compound-target interaction was used to predict the potential pharmacological mechanism and biological basis of BYF. We performed a comprehensive study by detecting the expression levels of fibrotic and inflammatory markers and main molecules of candidate signal pathway in adenine-induced CKD rats and TGF-ß1-induced HK-2 cells with the treatment of BYF by western blotting and RT-qPCR analyses. Using small interfering RNA, we assessed the effect of BYF on the TLR4-mediated NF-κB mechanism for CKD renal fibrosis and inflammation. Network pharmacology analysis results identified 369 common targets from BYF and CKD. Based on these common targets, the BYF intervention pathway was analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. We found that Toll-like receptor (TLR) and NF-κB signaling pathways were enriched. Then, we demonstrated that BYF significantly improved the adenine-induced CKD rat model condition by kidney dysfunction improvement and reversing renal fibrosis and inflammation. Subsequently, we investigated BYF's effect on the TLR4/NF-κB signaling pathway. We found that TLR4 and phospho-NF-κB (p-p65 and p-IKßα) expression was significantly upregulated in adenine-induced CKD rats, then partially downregulated by BYF. Furthermore, BYF inhibited fibrotic and inflammatory responses, as well as TLR4, p-p65, and p-IKßα in TGF-ß1-induced HK-2 cells. Additionally, the BYF inhibitory effect on fibrosis and inflammation, and NF-κB pathway activation were significantly reduced in TGF-ß1-induced HK-2 cells transfected with TLR4 siRNA. Altogether, these findings demonstrated that the suppression of TLR4-mediated NF-κB signaling was an important anti-fibrotic and anti-inflammatory mechanism for BYF against CKD. It also provided a molecular basis for new CKD treatment drug candidates.

Comprehensive phenotypic analysis and quantitative trait locus identification for grain mineral concentration, content, and yield in maize (Zea mays L.).

KEY MESSAGE: Understanding the correlations of seven minerals for concentration, content and yield in maize grain, and exploring their genetic basis will help breeders to develop high grain quality maize. Biofortification by enhanced mineral accumulation in grain through genetic improvement is an efficient way to solve global nutrient malnutrition, in which one key step is to detect the underlying quantitative trait loci (QTL). Herein, a maize recombinant inbred population (RIL) was field grown to maturity across four environments (two locations × two years). Phenotypic data for grain mineral concentration, content and yield were determined for copper (Cu), iron (Fe), manganese (Mn), zinc (Zn), magnesium (Mg), potassium (K) and phosphorus (P). Significant effects of genotype, location and year were observed for all investigated traits. The strongest location effects were found for Zn accumulation traits probably due to distinct soil Zn availabilities across locations. Heritability (H (2)) of different traits varied with higher H (2) (72-85 %) for mineral concentration and content, and lower (48-63 %) for mineral yield. Significant positive correlations for grain concentration were revealed between several minerals. QTL analysis revealed 28, 25, and 12 QTL for mineral concentration, content and yield, respectively; and identified 8 stable QTL across at least two environments. All these QTL were assigned into 12 distinct QTL clusters. A cluster at chromosome Bin 6.07/6.08 contained 6 QTL for kernel weight, mineral concentration (Mg) and content (Zn, K, Mg, P). Another cluster at Bin 4.05/4.06 contained a stable QTL for Mn concentration, which were previously identified in other maize and rice RIL populations. These results highlighted the phenotypic and genetic performance of grain mineral accumulation, and revealed two promising chromosomal regions for genetic improvement of grain biofortification in maize.

The role of maize root size in phosphorus uptake and productivity of maize/faba bean and maize/wheat intercropping systems.

Interspecific root/rhizosphere interactions affect phosphorus (P) uptake and the productivity of maize/faba bean and maize/wheat intercropping systems. The aim of these experiments was to determine whether manipulation of maize root growth could improve the productivity of the two intercropping systems. Two near isogenic maize hybrids (the larger-rooted T149 and smaller-rooted T222) were intercropped with faba bean and wheat, under conditions of high- and low-P availability. The larger-rooted T149 showed greater competitive ability than the smaller-rooted T222 in both maize/faba bean and maize/wheat intercropping systems. The higher competitive ability of T149 improved the productivity of the maize/faba bean intercropping system in P-sufficient conditions. In maize/wheat intercropping systems, root growth, shoot biomass, and P uptake of maize were inhibited by wheat, regardless of the P-supply. Compared with T222, the larger-rooted T149 suffered less in the intercropping systems. The total biomass of the maize/wheat intercropping system was higher for wheat/T149 than for wheat/T222 under low-P conditions. These data suggested that genetic improvement of maize root size could enhance maize growth and its ability to compete for P resources in maize/faba bean and maize/wheat intercropping systems. In addition, depending on the P availability, larger maize roots could increase the productivity of intercropping systems.