Research Progress on Regulation of Immune Response by Tanshinones and Salvianolic Acids of Danshen (Salvia miltiorrhiza Bunge).

As one of the traditional Chinese herbs, Danshen (Salvia miltiorrhiza Bunge) has been widely studied and widely used in the treatment of cardiovascular, cerebrovascular, and other immune diseases. Tanshinones and salvianolic acids isolated from Danshen are considered to be the main components of its biological activity and pharmacology that play important roles in increasing the index of immune organs, regulating the number and function of immune cells, and releasing immunoreactive substances. Especially tanshinone IIA, cryptotanshinone, salvianolic acid B, and rosmarinic acid show good biological activity in treating rheumatoid arthritis, some immune-mediated inflammatory diseases, psoriasis, and inflammatory bowel disease. In order to understand their pharmacological effects and provide references for future research and clinical treatment, the regulation of immune response by tanshinones and salvianolic acids is summarized in detail in this paper. In addition, the challenges in their pharmacological development and the opportunities to exploit their clinical potential have been documented.

Insights into the mechanism of transcription factors in Pb2+-induced apoptosis.

The health risks associated with exposure to heavy metals, such as Pb2+, are increasingly concerning the public. Pb2+ can cause significant harm to the human body through oxidative stress, autophagy, inflammation, and DNA damage, disrupting cellular homeostasis and ultimately leading to cell death. Among these mechanisms, apoptosis is considered crucial. It has been confirmed that transcription factors play a central role as mediators during the apoptosis process. Interestingly, these transcription factors have different effects on apoptosis depending on the concentration and duration of Pb2+ exposure. In this article, we systematically summarize the significant roles of several transcription factors in Pb2+-induced apoptosis. This information provides insights into therapeutic strategies and prognostic biomarkers for diseases related to Pb2+ exposure.

Tensile Failure Behaviors of Adhesively Bonded Structure Based on In Situ X-ray CT and FEA.

Adhesive bonding plays a pivotal role in structural connections, yet the bonding strength is notably affected by the presence of pore defects. However, the invisibility of interior pores severely poses a challenge to understanding their influence on tensile failure behaviors under loading. In this study, we present a pioneering investigation into the real-time micro-failure mechanisms of adhesively bonded structures using in situ X-ray micro-CT. Moreover, the high-precision finite element analysis (FEA) of stress distribution is realized by establishing the real adhesive layer model based on micro-CT slices. The findings unveil that pores induce stress concentration within the adhesive layer during the tensile process, with stress levels significantly contingent upon pore sizes rather than their specific shapes. Consequently, larger pores initiate and propagate cracks along their paths, ultimately culminating in the failure of adhesively bonded structures. These outcomes serve as a significant stride in elucidating how pore defects affect the bonding performance of adhesively bonded structures, offering invaluable insights into their mechanisms.

Association between BMI and efficacy of SGLT2 inhibitors in patients with heart failure or at risk of heart failure: a meta-analysis based on randomized controlled trials.

INTRODUCTION: This meta-analysis aimed to investigate the effect of SGLT2 inhibitors on the prognosis in patients with heart failure (HF) or at risk of heart failure across different body mass index (BMI). METHODS: We searched PubMed, Embase, Web of Science, and Cochrane Library for all randomized controlled trials (RCTs) comparing SGLT2 inhibitors with placebo in patients with HF or at risk of HF and extracted relevant data up to April 2023 for meta-analysis. RESULTS: A total of 29,500 patients were enrolled in the selected five studies. The results showed that patients treated with SGLT2 inhibitors had lower heart failure hospitalization (HHF) or cardiovascular (CV) mortality compared to those taking placebo (hazard ratio (HR)=0.73, p<0.001). Patients taking SGLT2 inhibitors also had a lower all-cause mortality rate than those taking placebo (HR=0.85, p=0.017). In BMI subgroup analysis, the HHF rate in the experimental group was lower than that in the control group at BMI ≤24.9 kg/m2, 25.0-29.9 kg/m2, and ≥30.0 kg/m2. There was no significant difference in CV mortality between the two groups at BMI ≤24.9 kg/m2 (HR=0.91, p=0.331) and 25.0-29.9 kg/m2 (HR=0.92, p=0.307). However, when the BMI was ≥30.0 kg/m2, CV mortality with SGLT2 inhibitors was lower than in the control group (HR=0.79, p=0.002). When patients had a BMI ≤24.9 kg/m2 (HR=0.85, p=0.033) and 25.0-29.9 kg/m2 (HR=0.83, p=0.046), the all-cause mortality was lower in the experimental group than in the control group. However, there was no significant difference between the two groups in patients with a BMI ≥30.0 kg/m2 (HR=0.87, p=0.094). CONCLUSION: SGLT2 inhibitors improve prognosis in patients with HF or at risk of HF. This effect is affected by BMI.

Optimizing Li1.3Al0.3Ti1.7(PO4)3 Particle Sizes toward High Ionic Conductivity.

NASICON-type Li1.3Al0.3Ti1.7(PO4)3 (LATP) has attracted a lot of attention because of its high ionic conductivity and stability to air and moisture. However, the size effect of LATP primary particles on ionic conductivity is ignored. In this study, different sizes of LATP particles are prepared to investigate the morphology, relative density, and ionic conductivity of the LATP solid electrolyte. The influences of particle size and sintering temperature on the microstructure, phase composition, and electrical properties of LATP ceramics were systematically studied. The medium-sized LATP particle (2 µm) presents a great microstructure with a high relative density of over 97%, the highest ionic conductivity of 6.7 × 10-4 S cm-1, and an activation energy of 0.418 eV. The Li-Li symmetric cells and Li-LFP batteries delivering good electrochemical performance were fabricated with highly conductive LATP ceramics. These results make significant strides in elucidating the relationship between the particle sizes of LATP and its electrochemical performance.

H3PO4-Induced Nano-Li3PO4 Pre-reduction Layer to Address Instability between the Nb-Doped Li7La3Zr2O12 Electrolyte and Metallic Li Anode.

Solid-state batteries based on a metallic Li anode and nonflammable solid electrolytes (SEs) are anticipated to achieve high energy and power densities with absolute safety. In particular, cubic garnet-type Nb-doped Li7La3Zr2O12 (Nb-LLZO) SEs possess superior ionic conductivity, are feasible to prepare under ambient conditions, have strong thermal stability, and are of low cost. However, the interfacial compatibility with Li metal and Li dendrite hazards still hinder the applications of Nb-LLZO. Herein, a quick and efficient solution was applied to address this issue, generating a nano-Li3PO4 pre-reduction layer from the reaction of H3PO4 with the ion-exchanged passivation layer (Li2CO3/LiOH) on the surface of Nb-LLZO. A lithiophilic, electrically insulating interlayer is in situ created when the Li3PO4 modified layer interacts with molten Li, successfully preventing the reduction of Nb5+. The interlayer, which mostly consists of Li3P and Li3PO4, also has a high shear modulus and relatively high Li+ conductivity, which effectively inhibit the growth of Li dendrites. The Li|Li3PO4|Nb-LLZO|Li3PO4|Li symmetric cells stably cycled for over 5000 h at 0.05 mA cm-2 and over 1000 h at a high rate of 0.15 mA cm-2 without any short circuits. The LiFePO4 and S/C hybrid solid-state batteries using the modified Nb-LLZO electrolyte also demonstrated good electrochemical performances, confirming the practical application of this interfacial engineering in various solid-state battery systems. This work offers an efficient solution to the instability issue between the Nb-LLZO SE and metallic Li anode.

Identification and Analysis of Stress-Associated Proteins (SAPs) Protein Family and Drought Tolerance of ZmSAP8 in Transgenic Arabidopsis.

Stress-associated proteins (SAPs), a class of A20/AN1 zinc finger proteins, play vital roles in plant stress response. However, investigation of SAPs in maize has been very limited. Herein, to better trace the evolutionary history of SAPs in maize and plants, 415 SAPs were identified in 33 plant species and four species of other kingdoms. Moreover, gene duplication mode exploration showed whole genome duplication contributed largely to SAP gene expansion in angiosperms. Phylogeny reconstruction was performed with all identified SAPs by the maximum likelihood (ML) method and the SAPs were divided into five clades. SAPs within the same clades showed conserved domain composition. Focusing on maize, nine ZmSAPs were identified. Further promoter cis-elements and stress-induced expression pattern analysis of ZmSAPs indicated that ZmSAP8 was a promising candidate in response to drought stress, which was the only AN1-AN1-C2H2-C2H2 type SAP in maize and belonged to clade I. Additionally, ZmSAP8 was located in the nucleus and had no transactivation activity in yeast. Overexpressing ZmSAP8 enhanced the tolerance to drought stress in Arabidopsis thaliana, with higher seed germination and longer root length. Our results should benefit the further functional characterization of ZmSAPs.

Developing Preparation Craft Platform for Solid Electrolytes Containing Volatile Components: Experimental Study of Competition between Lithium Loss and Densification in Li7La3Zr2O12.

Li7La3Zr2O12 (LLZO) is one of the most promising candidate solid electrolytes for high-safety solid-state batteries. However, similar to other solid electrolytes containing volatile components during high-temperature sintering, the preparation of densified LLZO with high conductivity is challenging involving the complicated gas-liquid-solid sintering mechanism. Further attention on establishing low-cost laborastory-scale preparation craft platform of LLZO ceramic is also required. This work demonstrates a "pellet on gravel" sintering strategy, which is performed in a MgO crucible and box furnace under ambient air without any special equipment or expensive consumables. In addition, the competition between lithium loss from the sintering system and internal grain densification is critically studied, whereas the influences of particle surface energy, Li-loss amount, and initial excess Li2O amount are uncovered. Based on the sintering behavior and mechanism, optimized craft platform for preparing dense LLZO solid electrolytes including mixing, calcination, particle tailoring and sintering is provided. Finally, exemplary Ta-doped LLZO pellets with 2 wt % La2Zr2O7 additives sintered at 1260-1320 °C for 20 min deliver Li+ conductivities of ∼9 × 10-4 S cm-1 at 25 °C, relative densities of >96%, and a dense cross-sectional microstructure. As a practical demonstration, LLZO solid electrolyte with optimized performance is applied in both Li-Li symmetric cells and Li-S batteries. This work sheds light on the practical production of high-quality LLZO ceramics and provides inspiration for sintering ceramics containing volatile compounds.

Effects of pyrolysis temperature on soil-plant-microbe responses to Solidago canadensis L.-derived biochar in coastal saline-alkali soil.

Because salinity of coastal soils is drastically increasing, the application of biochars to saline-alkali soil amendments has attracted considerable attention. Various Solidago-canadensis-L.-derived biochars prepared through pyrolysis from 400 to 600 °C were applied to coastal saline-alkali soil samples to optimise the biochar pyrolysis temperature and investigate its actual ecological responses. All biochars reduced the soil bulk density and exchangeable sodium stress and increased soil water-holding capacity, cation exchange capacity, and organic matter content. Principal-component-analysis results showed that pyrolysis temperature played an important role in the potential application of biochars to improve the coastal saline-alkali soil, mainly contributed to ameliorating exchangeable sodium stress and decreasing biochar-soluble toxic compounds. Furthermore, soil bulk density and organic matter, as well as carboxylic acids, phenolic acids and amines of biochar were major driving factors for bacterial community composition. Compared to low-temperature biochar (pyrolyzed below 550 °C), which showed higher toxicity for Brassica chinensis L. growth due to the higher content of carboxylic acids, phenols and amines, high-temperature biochar (pyrolyzed at or above 550 °C) possessed less amounts of these toxic functional groups, more beneficial soil bacteria and healthier for plant growth. Therefore, high-temperature biochar could be applied as an effective soil amendment to ameliorate the coastal saline-alkali soil with acceptable environmental risk.

Remediation of cadmium-contaminated soil with biochar simultaneously improves biochar's recalcitrance.

Biochar sequesters cadmium (Cd) by immobilisation, but the process is often less effective in field trials than in the laboratory. Therefore, the involvement of soil components should be considered for predicting field conditions that could potentially improve this process. Here, we used biochar derived from Spartina alterniflora as the amendment for Cd-contaminated soil. In simulation trials, a mixture of kaolin, a representative soil model component, and S. alterniflora-derived biochar immobilised Cd by forming silicon-aluminium-Cd-containing complexes. Interestingly, the biochar recalcitrance index value increased from 48% to 53%-56% because of the formation of physical barriers consisting of kaolinite minerals and Cd complexes. Pot trials were performed using Brassica chinensis for evaluating the effect of S. alterniflora-derived biochar on plant growth in Cd-contaminated soil. The bio-concentration factor values in B. chinensis were 24%-31% after soil remediation with biochar than in control plants. In summary, these results indicated that soil minerals facilitated Cd sequestration by biochar, which reduced Cd bioavailability and improved the recalcitrance of this soil amendment. Thus, mechanisms for effective Cd remediation should include biochar-soil interactions.

Quantitative Structure-Toxicity Relationship analysis of combined toxic effects of lignocellulose-derived inhibitors on bioethanol production.

This study performed a Quantitative Structure-Toxicity Relationship (QSTR) model to evaluate the combined toxicity of lignocellulose-derived inhibitors on bioethanol production. Compared with all the control groups, the combined systems exhibited lower conductivity values, higher oxidation-reduction potential values, as well as maximum inhibition rates. These results indicated that the presence of combined inhibitors had a negative effect on the bioethanol fermentation process. Meanwhile, QSTR model was excellent for evaluating the combined toxic effects at lower ferulic acid concentration (([1:4] × IC50)) and (([1:1] × IC50)), due to higher R2 values (0.994 and 0.762), lower P values (0.000 and 0.023) and relative error values (less than 30%). The obtained results also showed that the combined toxic effects of ferulic acid and representative lignocellulose-derived inhibitors were relevant to different molecular descriptors. Meanwhile, the interactions of combined inhibitors were weaker when ferulic acid was at low concentration ([1:4] × IC50).

A study of cadmium remediation and mechanisms: Improvements in the stability of walnut shell-derived biochar.

Biochar has been recognized as an efficient soil amendment for cadmium remediation in recent years. In the present study, biochar was prepared using walnut shell, and it was incubated in Cd(NO3)2 and kaolin for 15 days. Different chemical forms of cadmium in kaolin and biochar were determined, and the stability of biochar was evaluated by R50 using TGA analysis. It was found that walnut shell derived biochar could reduce the mobility of cadmium. After incubation, the R50, biochar value increased from 61.31% to 69.57%-72.24%, indicating that the stability of biochar was improved. The mechanisms that initiated improvements in biochar stability were investigated by XPS, XRD and SEM-EDS analysis. The result showed that the enhanced biochar stability is likely due to physical isolation and the formation of precipitates and complexes, formed on the surface or interior of the biochar. The results suggested that walnut shell-derived biochar can be used as a cadmium sorbent for soil remediation.

A rapid and sensitive HPLC-MS/MS method for determination of an aminopyridazine derived anti-neuroinflammatory agent (ZW14) in dog plasma: Application to a pharmacokinetic study.

The unclear etiology of Alzheimer's disease leaves a large space for drug exploration. A novel anti-neuroinflammation agent (ZW14) was previously determined to have comparable efficacy to the marketed drug (donepezil) in the Aß-induced model mice. Herein, a sensitive and rapid HPLC-MS/MS quantitative method was developed and validated for the further evaluation of ZW14 in dogs. Plasma samples were processed by liquid-liquid extraction with ethyl acetate and separated on Luna C18 column (2.1 mm × 50 mm, 1.7 µm) at room temperature with a flow rate of 0.2 mL/min. The analyte and IS were all detected by monitoring the precursor → product ion transition at unit resolution using multiple reaction monitoring (MRM) scan mode with positive ionization mode. No endogenous interference was observed and the linear range was 0.05-1500 ng/mL with the lower limit of quantification of 0.05 ng/mL. The intra- and inter-day precisions were within 10.9%, while the accuracy was all between 96.0% and 110%. The developed method was successfully applied to the pharmacokinetic study of ZW14 in beagle dogs after oral and intravenous administration of 2 mg/kg. The oral bioavailability of ZW14 was 26.3% with half-life of 2.6h.