Cannabinoid Receptor Subtype 2 (Cb2R) Agonist Gw405833 Reduces Agonist-Induced Ca2+ Oscillations In Mouse Pancreatic Acinar Cells

Emerging evidence demonstrates that the blockade of intracellular Ca 2+ signals may protect pancreatic acinar cells against Ca 2+ overload, intracellular protease activation, and necrosis. The activation of cannabinoid receptor subtype 2 (CB 2 R) prevents acinar cell pathogenesis in animal models of acute pancreatitis. However, whether CB 2 Rs modulate intracellular Ca 2+ signals in pancreatic acinar cells is largely unknown. We evaluated the roles of CB 2 R agonist, GW405833 (GW) in agonist-induced Ca 2+ oscillations in pancreatic acinar cells using multiple experimental approaches with acute dissociated pancreatic acinar cells prepared from wild type, CB 1 R-knockout (KO), and CB 2 R-KO mice. Immunohistochemical labeling revealed that CB 2 R protein was expressed in mouse pancreatic acinar cells. Electrophysiological experiments showed that activation of CB 2 Rs by GW reduced acetylcholine (ACh)-, but not cholecystokinin (CCK)-induced Ca 2+ oscillations in a concentration-dependent manner; this inhibition was prevented by a selective CB 2 R antagonist, AM630, or was absent in CB 2 R-KO but not CB 1 R-KO mice. In addition, GW eliminated L-arginine-induced enhancement of Ca 2+ oscillations, pancreatic amylase, and pulmonary myeloperoxidase. Collectively, we provide novel evidence that activation of CB 2 Rs eliminates ACh-induced Ca 2+ oscillations and L-arginine-induced enhancement of Ca 2+ signaling in mouse pancreatic acinar cells, which suggests a potential cellular mechanism of CB 2 R-mediated protection in acute pancreatitis

Response of bacterial community metabolites to bacterial wilt caused by Ralstonia solanacearum: a multi-omics analysis

The soil microbial community plays a critical role in promoting robust plant growth and serves as an effective defence mechanism against root pathogens. Current research has focused on unravelling the compositions and functions of diverse microbial taxa in plant rhizospheres invaded by Ralstonia solanacearum, however, the specific mechanisms by which key microbial groups with distinct functions exert their effects remain unclear. In this study, we employed a combination of amplicon sequencing and metabolomics analysis to investigate the principal metabolic mechanisms of key microbial taxa in plant rhizosphere soil. Compared to the healthy tobacco rhizosphere samples, the bacterial diversity and co-occurrence network of the diseased tobacco rhizosphere soil were significantly reduced. Notably, certain genera, including Gaiella, Rhodoplanes, and MND1 (Nitrosomonadaceae), were found to be significantly more abundant in the rhizosphere of healthy plants than in that of diseased plants. Eight environmental factors, including exchangeable magnesium, available phosphorus, and pH, were found to be crucial factors influencing the composition of the microbial community. Ralstonia displayed negative correlations with pH, exchangeable magnesium, and cation exchange flux, but showed a positive correlation with available iron. Furthermore, metabolomic analysis revealed that the metabolic pathways related to the synthesis of various antibacterial compounds were significantly enriched in the healthy group. The correlation analysis results indicate that the bacterial genera Polycyclovorans, Lysobacter, Pseudomonas, and Nitrosospira may participate in the synthesis of antibacterial compounds. Collectively, our findings contribute to a more in-depth understanding of disease resistance mechanisms within healthy microbial communities and provide a theoretical foundation for the development of targeted strategies using beneficial microorganisms to suppress disease occurrence

Research progress on and molecular mechanism of vacuum sealing drainage in the treatment of diabetic foot ulcers

Diabetic foot ulcers (DFUs) are common chronic wounds and a common complication of diabetes. The foot is the main site of diabetic ulcers, which involve small and medium-sized arteries, peripheral nerves, and microcirculation, among others. DFUs are prone to coinfections and affect many diabetic patients. In recent years, interdisciplinary research combining medicine and material science has been increasing and has achieved significant clinical therapeutic effects, and the application of vacuum sealing drainage (VSD) in the treatment of DFUs is a typical representative of this progress, but the mechanism of action remains unclear. In this review, we integrated bioinformatics and literature and found that ferroptosis is an important signaling pathway through which VSD promotes the healing of DFUs and that System Xc-GSH-GPX4 and NAD(P)H-CoQ10-FSP1 are important axes in this signaling pathway, and we speculate that VSD is most likely to inhibit ferroptosis to promote DFU healing through the above axes. In addition, we found that some classical pathways, such as the TNF, NF-κB, and Wnt/β-catenin pathways, are also involved in the VSD-mediated promotion of DFU healing. We also compiled and reviewed the progress from clinical studies on VSD, and this information provides a reference for the study of VSD in the treatment of DFUs

Dual inhibition of AKT‐mTOR and AR signaling by targeting HDAC3 in PTEN‐ or SPOP‐mutated prostate cancer

Abstract AKT‐mTOR and androgen receptor (AR) signaling pathways are aberrantly activated in prostate cancer due to frequent PTEN deletions or SPOP mutations. A clinical barrier is that targeting one of them often activates the other. Here, we demonstrate that HDAC3 augments AKT phosphorylation in prostate cancer cells and its overexpression correlates with AKT phosphorylation in patient samples. HDAC3 facilitates lysine‐63‐chain polyubiquitination and phosphorylation of AKT, and this effect is mediated by AKT deacetylation at lysine 14 and 20 residues and HDAC3 interaction with the scaffold protein APPL1. Conditional homozygous deletion of Hdac3 suppresses prostate tumorigenesis and progression by concomitant blockade of AKT and AR signaling in the Pten knockout mouse model. Pharmacological inhibition of HDAC3 using a selective HDAC3 inhibitor RGFP966 inhibits growth of both PTEN‐deficient and SPOP‐mutated prostate cancer cells in culture, patient‐derived organoids and xenografts in mice. Our study identifies HDAC3 as a common upstream activator of AKT and AR signaling and reveals that dual inhibition of AKT and AR pathways is achievable by single‐agent targeting of HDAC3 in prostate cancer

Energy Efficient Utilization toward Rural Biomass Waste by Straw Biogas Engineering

In this article, we summarize and analyze the constraints and technical difficulties of biogas plants in clusters, storage and transportation yards, pretreatment yards, and anaerobic fields. Combined with Tyre’s own experience, several major techniques have been proposed. To guide and recommend the suitable technicians to decision makers, to acquire operation courses suitable for the general requirements of our biogas, and to promote the development of booth biogas seedlings in China, the use of environmental slam objects in a small and sufficient nonscale biogas program is formulated by the use of biogas funding alone. Current rating measures leverage the World Age Assessment (LCA) for the Integrated Booth Biogas Swing Type (typically 40,000 kWh) and Bio-Natural Gasoline Program (daily gasoline workload of 12,000 cubic curves). This is built upon the Environmental Impact Assessment and Analogy for Warships Both environmental stroke and sensitivity component analysis. These techniques include termination outlines, register analysis, dynamism drops for each performance stagecoach, and environmental issue calculations. According to the above summarization, when biogas dominates the family, the highest environmental emission becomes the biogas fermentation layer of the booth. Meanwhile, the most sympathetic substitute is the work cost of physical and chemical farting (mL g-1TS). The above two indicators denote the essence of biogas purification, and the choice of biogas purification technology. By evaluating the change in the impact of suppressing environmental emissions, the biogas substitute of scorpion charcoal has a remarkable improvement in the biogas equivalent of the charcoal-bright swing family. Comprehensive experimental results have demonstrated this conclusion

Low-Rank and Sparse Matrix Decomposition for Genetic Interaction Data

Background. Epistatic miniarray profile (EMAP) studies have enabled the mapping of large-scale genetic interaction networks and generated large amounts of data in model organisms. One approach to analyze EMAP data is to identify gene modules with densely interacting genes. In addition, genetic interaction score (S score) reflects the degree of synergizing or mitigating effect of two mutants, which is also informative. Statistical approaches that exploit both modularity and the pairwise interactions may provide more insight into the underlying biology. However, the high missing rate in EMAP data hinders the development of such approaches. To address the above problem, we adopted the matrix decomposition methodology “low-rank and sparse decomposition” (LRSDec) to decompose EMAP data matrix into low-rank part and sparse part. Results. LRSDec has been demonstrated as an effective technique for analyzing EMAP data. We applied a synthetic dataset and an EMAP dataset studying RNA-related processes in Saccharomyces cerevisiae. Global views of the genetic cross talk between different RNA-related protein complexes and processes have been structured, and novel functions of genes have been predicted

Piston Error Automatic Correction for Segmented Mirrors via Deep Reinforcement Learning

The segmented mirror co-phase error identification technique based on supervised learning methods has the advantages of simple application conditions, no dependence on custom sensors, a fast calculation speed, and low computing power requirements compared with other methods. However, it is often difficult to obtain a high accuracy in practical application situations with this method because of the difference between the training model and the actual model. The reinforcement learning algorithm does not need to model the real system when operating the system. However, it still retains the advantages of supervised learning. Thus, in this paper, we placed a mask on the pupil plane of the segmented telescope optical system. Moreover, based on the wide spectrum, point spread function, and modulation transfer function of the optical system and deep reinforcement learning—without modeling the optical system—a large-range and high-precision piston error automatic co-phase method with multiple-submirror parallelization was proposed. Finally, we carried out relevant simulation experiments, and the results indicate that the method is effective

Morphology and Sedimentation on Open-Coast Intertidal Flats of the Changjian Delta, China

On many intertidal flats, lateral aggradation and reworking by large tidal channels is the dominant sedimentary process. On the open-coast intertidal flats of the Changjiang Delta large laterally migrating tidal channels are absent. Instead, numerous shallow tidal creeks cut across the intertidal flats. On these flats, vertical rather than lateral migration dominates sedimentation. Observations over semidiurnal tidal cycles show that both flood and ebb tides have the potential to deposit their own mud-sand copulets, but four couplets per day are rarely preserved. Reworking by tidal currents and/or weak waves results in loss of tidal couplets or amalgamation of two or more thin couplets into a single thick couplet. Measurements of preserved couplets show that they can represent a single flooding or ebbing event (half day) to a period of several neap-spring cycles. Diastems within amalgamated couplets are generally not distinguishable. The key agent for reworking open-coast intertidal flat deposits is not tidal creek migration but seasonal storm waves. Seasonal storm deposits consist of a basal scour and sand-dominant laminae with mud pebbles, grading upward to mud-dominated layers of fair-weather deposits. Sand-dominated layers are also reworked