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Ginsenosides, the primary bioactive ingredients derived from the root of Panax ginseng, are eagerly in demand for tumor patients as a complementary and alternative drug. Ginsenosides have increasingly become a “hot topic” in recent years due to their multifunctional role in treating colorectal cancer (CRC) and regulating tumor microenvironment (TME). Emerging experimental research on ginsenosides in the treatment and immune regulation of CRC has been published, while no review sums up its specific role in the CRC microenvironment. Therefore, this paper systematically introduces how ginsenosides affect the TME, specifically by enhancing immune response, inhibiting the activation of stromal cells, and altering the hallmarks of CRC cells. In addition, we discuss their impact on the physicochemical properties of the tumor microenvironment. Furthermore, we discuss the application of ginsenosides in clinical treatment as their efficacy in enhancing tumor patient immunity and prolonging survival. The future perspectives of ginsenoside as a complementary and alternative drug of CRC are also provided. This review hopes to open up a new horizon for the cancer treatment of Traditional Chinese Medicine monomers.

Background: Myocardial fibrosis (MF) remains a prominent challenge in heart disease. The role of receptor-interacting protein kinase 3 (RIPK3)-mediated necroptosis is evident in the pathogenesis of numerous heart diseases. Concurrently, the activation of Ca2+/calmodulin-dependent protein kinase (CaMKII) is pivotal in cardiovascular disease (CVD). This study aimed to evaluate the impact and underlying mechanisms of RIPK3 on myocardial injury in MF and to elucidate the potential involvement of CaMKII. Methods: Building upon our previous research methods [1], wild-type (WT) mice and RIPK3 knockout (RIPK3 -/-) mice underwent random assignment for transverse aortic constriction (TAC) in vivo. Four weeks post-procedure, the MF model was effectively established. Parameters such as the extent of MF, myocardial injury, RIPK3 expression, necroptosis, CaMKII activity, phosphorylation of mixed lineage kinase domain-like protein (MLKL), mitochondrial ultrastructural details, and oxidative stress levels were examined. Cardiomyocyte fibrosis was simulated in vitro using angiotensin II on cardiac fibroblasts. Results: TAC reliably produced MF, myocardial injury, CaMKII activation, and necroptosis in mice. RIPK3 depletion ameliorated these conditions. The RIPK3 inhibitor, GSK'872, suppressed the expression of RIPK3 in myocardial fibroblasts, leading to improved fibrosis and inflammation, diminished CaMKII oxidation and phosphorylation levels, and the rectification of CaMKIIδ alternative splicing anomalies. Furthermore, GSK'872 downregulated the expressions of RIPK1, RIPK3, and MLKL phosphorylation, attenuated necroptosis, and bolstered the oxidative stress response. Conclusions: Our data suggested that in MF mice, necroptosis was augmented in a RIPK3-dependent fashion. There seemed to be a positive correlation between CaMKII activation and RIPK3 expression. The adverse effects on myocardial fibrosis mediated by CaMKII δ through RIPK3 could potentially be mitigated by the RIPK3 inhibitor, GSK'872. This offered a fresh perspective on the amelioration and treatment of MF and myocardial injury.

Recent studies have found that receptor interacting protein kinase 3 (RIPK3) can mediate CaMK Ⅱ phosphorylation and oxidation, open mitochondrial permeability transition pore (mPTP), and induce myocardial necroptosis. The increased expression or phosphorylation of RIPK3 is one of the important markers of necroptosis; Inhibition of CaMK Ⅱ phosphorylation or oxidation significantly reduces RIPK3 mediated myocardial necroptosis; Studies have shown that necroptosis plays an important role in the occurrence and development of cardiovascular diseases; Using the selective inhibitor GSK '872 of RIPK3 can effectively inhibit the occurrence and development of cardiovascular diseases, and can reverse cardiovascular and cardiac dysfunction caused by overexpression of RIPK3. In this review, we provide a brief overview of the current knowledge on RIPK3 in mediating necroptosis, inflammatory response, and oxidative stress, and discussed the role of RIPK3 in cardiovascular diseases such as atherosclerosis, myocardial ischaemia, myocardial infarction, and heart failure.

Necroptosis is a newly discovered mechanism of cell death, and its key regulatory role is attributed to the interaction of receptor-interacting protein kinases (RIPKs) RIPK1 and RIPK3. Ca2+/calmodulin-dependent protein kinase (CaMKII) is a newly discovered RIPK3 substrate, and its alternative splicing plays a fundamental role in cardiovascular diseases. In the present study, we aimed to explore the role and mechanism of necroptosis and alternative splicing of CaMKIIδ in myocardial hypertrophy. Transverse aortic constriction (TAC) was performed on wild-type and knockout mice to establish the model of myocardial hypertrophy. After 3 weeks, echocardiography, cardiac index, cross-sectional area of myocardial cells, hypertrophic gene expression, myocardial damage, and fibers were assessed. Moreover, we detected the levels of inflammatory factors (IL-6 and TNF-α) and examined the expressions of necroptosis-related proteins RIPK3, RIPK1, and phosphorylated MLKL. Meanwhile, we tested the expression levels of splicing factors ASF/SF2 and SC-35 in an attempt to explore CaMKII δ. The relationship between variable splicing disorder and the expression levels of splicing factors ASF/SF2 and SC-35. Further, we also investigated CaMKII activation, oxidative stress, and mitochondrial ultrastructure. In addition, wild-type mice were administered with a recombinant adeno-associated virus (AAV) carrying RIPK3, followed by TAC surgery to construct a model of myocardial hypertrophy, and the above-mentioned indicators were tested after 3 weeks. The results showed that RIPK3 deficiency could alleviate cardiac dysfunction, myocardial injury, aggravation of necrosis, and CaMKII activation induced by TAC surgery in mice with myocardial hypertrophy. Tail vein injection of AAV could reverse cardiac dysfunction, myocardial damage, aggravation of necrosis, and CaMKII activation in mice with myocardial hypertrophy. These results proved that RIPK3 could be used as a molecular intervention target for the prevention and treatment of myocardial hypertrophy.

Some studies have reported that the activation of Ca2+/calmodulin dependent protein kinase (CaMKII) plays a vital role in the pathogenesis of cardiovascular disease. Moreover, receptor interacting protein kinase 3 (RIPK3)-mediated necroptosis is also involved in the pathological process of various heart diseases. In the present study, we aimed to investigate the effect of RIPK3-regulated CaMKII on necroptosis in heart failure (HF) and its underlying mechanism. Wild type (WT) and RIPK3-depleted (RIPK3–/–) mice were treated with transverse arch constriction (TAC). After 6 weeks, echocardiography, myocardial injury, CaMKII activity, necroptosis, RIPK3 expression, mixed lineage kinase domain-like protein (MLKL) phosphorylation, and mitochondrial ultrastructure were measured. The results showed that TAC aggravated cardiac dysfunction, CaMKII activation, and necroptosis in WT mice. However, depletion of RIPK3 alleviated cardiac insufficiency, CaMKII activation, and necroptosis in TAC-treated mice. To verify the experimental results, WT mice were transfected with AAV-vector and AAV-RIPK3 shRNA, followed by TAC operation. The findings were consistent with the expected results. Collectively, our current data indicated that the activation of CaMKII, MLKL and necroptosis in HF mice were increased in a RIPK3-dependent manner, providing valuable insights into the pathogenesis and treatment strategy of HF.

Necroptosisis a regulatory programmed form of necrosis. Receptor interacting protein kinase 3 (RIPK3) is a robust indicator of necroptosis. RIPK3 mediates myocardial necroptosis through activation of calcium/calmodulin-dependent protein kinase II (CaMKII) in cardiac ischemia-reperfusion (I/R) injury and heart failure. However, the exact mechanism of RIPK3 in advanced glycation end products (AGEs)-induced cardiomyocytes necroptosis is not clear. In this study, cardiomyocytes were subjected to AGEs stimulation for 24 h. RIPK3 expression, CaMKII expression, and necroptosis were determined in cardiomyocytes after AGEs stimulation. Then, cardiomyocytes were transfected with RIPK3 siRNA to downregulate RIPK3 followed by AGEs stimulation for 24 h. CaMKIIδ alternative splicing, CaMKII activity, oxidative stress, necroptosis, and cell damage were detected again. Next, cardiomyocytes were pretreated with GSK′872, a specific RIPK3 inhibitor to assess whether it could protect cardiomyocytes against AGEs stimulation. We found that AGEs increased the expression of RIPK3, aggravated the disorder of CaMKII δ alternative splicing, promoted CaMKII activation, enhanced oxidative stress, induced necroptosis, and damaged cardiomyocytes. RIPK3 downregulation or RIPK3 inhibitor GSK′872 corrected CaMKIIδ alternative splicing disorder, inhibited CaMKII activation, reduced oxidative stress, attenuated necroptosis, and improved cell damage in cardiomyocytes.

An experimental study was conducted to determine the characteristics of the flame spread and droplets of metal-polyethylene (PE) sandwich panels during combustion. The mass-loss rate, average flame height, temperature, and fire spread rate were investigated. The results showed that the fire spread rate, mass change of the droplets, average flame height, and temperature increased with an increase in the sample length, except for the mass loss rate of the 40 cm-long sample. The time interval between the droplets decreased, and the flame pulsation frequency increased. The relationship between the flame height and sample length was determined. During the combustion process, bending deformation and top flame phenomena occurred due to the shrinkage of the PE, which increased the fire risk. The distance between the outer surface of the expanded metal aluminum layer and the insulation panel increased with an increase in the panel length. A schematic diagram of the fire spread of the metal sandwich panel was established based on the observations and theoretical analysis. The mechanism and combustion behavior of the metal sandwich panels were determined to provide references for the construction of metal sandwich panels of exterior walls.

The two-stroke engine is a common power source for small and medium-sized unmanned aerial vehicles (UAV), which has wide civil and military applications. To improve the engine performance, we chose a prototype two-stroke small areoengine, and optimized the geometric parameters of the scavenging ports by performing one-dimensional (1D) and three-dimensional (3D) computational fluid dynamics (CFD) coupling simulations. The prototype engine is tested on a dynamometer to measure in-cylinder pressure curves, as a reference for subsequent simulations. A GT Power simulation model is established and validated against experimental data to provide initial conditions and boundary conditions for the subsequent AVL FIRE simulations. Four parameters are considered as optimal design factors in this research: Tilt angle of the central scavenging port, tilt angle of lateral scavenging ports, slip angle of lateral scavenging ports, and width ratio of the central scavenging port. An evaluation objective function based on the Benson/Bradham model is selected as the optimization goal. Two different operating conditions, including the take-off and cruise of the UAV are considered. The results include: (1) Orthogonal experiments are analyzed, and the significance of parameters are discussed; (2) the best factors combination is concluded, followed by simulation verification; (3) results before and after optimization are compared in details, including specific scavenging indexes (delivery ratio, trapping efficiency, scavenging efficiency, etc.), conventional performance indicators, and the sectional views of gas composition distribution inside the cylinder.

Under the challenge of climate change, fuel-based vehicles have been receiving increasingly harsh criticism. To promote the use of battery electric vehicles (BEVs) as an alternative, many researchers have studied the deployment of BEVs. This paper proposes a new method to choose locations for new BEV charging stations considering drivers’ perceived time cost and the existing infrastructure. We construct probability equations to estimate drivers’ demanding time for charging (and waiting to charge), use the Voronoi diagram to separate the study area (i.e., Shanghai) into service areas, and apply an optimization algorithm to deploy the charging stations in the right locations. The results show that (1) the probability of charging at public charging stations is 39.6%, indicating BEV drivers prefer to charge at home; (2) Shanghai’s central area and two airports have the busiest charging stations, but drivers’ time costs are relatively low; and (3) our optimization algorithm successfully located two new charging stations surrounding the central area, matching with our expectations. This study provides a time-efficient way to decide where to build new charging stations to improve the existing infrastructure.

Soybean can cause allergy in both humans and animals. The herein study aims to identify the antigenic determinants (epitopes) of β-conglycinin that lead to allergy in different animal species (swine, bovine, and rats). The epitopes of β-conglycinin were identified through co-immunoprecipitation and mass spectrometry. The binding abilities of seven identified epitope peptides to allergic sera of three animal species were compared by ELISA and dot-blot techniques. Some epitope peptides could be recognized by the three animal allergic sera, while most epitopes showed some differences in binding abilities to the different animal sera. The strongest reaction using swine sera was detected with peptides α2, β2, and β3, but the biggest sensitive regions for bovine and rats were peptides α2, β1, and β4. Most epitopes of β-conglycinin exhibited different binding abilities to the three animal sera, in which the biggest sensitive regions were peptides α2, β2, and β3 for swine, but peptides α2, β1, and β4 were detected for bovine and rats.