Cisplatin-induced acute kidney injury (AKI) remains a serious clinical complication, with excessive reactive oxygen species (ROS) recognized as key contributors. The natural antioxidant epigallocatechin-3-gallate (EGCG) shows promise in mitigating oxidative stress-related damage. However, its clinical application is limited by poor stability and low renal bioavailability. To address this, we developed a biocompatible nanoplatform by encapsulating EGCG within mesoporous polydopamine nanoparticles (EGCG-MPDA). Ultrasmall nanoparticles (<10 nm or <20 kDa) undergo rapid glomerular filtration and renal clearance, limiting therapeutic retention. While uncoated MPDA nanoparticles (∼200 nm) are large enough to avoid renal filtration, their size renders them highly susceptible to opsonization and MPS sequestration. To address this MPS-mediated clearance, we coated MPDA with a preclinically used BSA shell to create EGCG-MPDA@BSA. The biocompatible BSA corona acts as a "stealth" layer to attenuate opsonization, reduce early hepatic sequestration, and enhance interactions with peritubular endothelial cells, promoting nanoparticle passage into injured tubular epithelial cells. In a murine cisplatin-induced AKI model, EGCG-MPDA@BSA exhibited significantly enhanced therapeutic efficacy compared to uncoated nanoparticles and free EGCG. Transcriptomic and biochemical analyses revealed that its superior therapeutic efficacy arises from the activation of the Nrf2/HO-1/GPX4 antioxidant pathway, thereby alleviating oxidative stress, inflammation, and tubular damage. Collectively, this work presents an albumin corona strategy that enables effective renal retention of large nanoparticles, offering a safe, translatable approach for localized AKI therapy.

Background Prostate cancer is the most commonly diagnosed non-cutaneous malignancy in men and is the second-leading cause of cancer-related death. Castration-resistant pr ostate cancer (CRPC) persists despite low testosterone levels. Methods In this study, we investigated the combined effect of Celastrol and bicaluta mide on prostate cancer cells. We evaluated cytotoxicity, apoptosis, oxidative stress, ferro ptosis and the activation of the immune system in vivo and in vitro . Results Our findings revealed that the co-administration of Celastrol with bicalutamide enhanced cytotoxicity against prostate cancer cells, promoted cell apoptosis, induced oxi dative stress and ferroptosis. Importantly, it assisted bicalutamide in activating the immune system, triggering immunogenic cell death (ICD), and thereby enhancing immune thera py. This synergy resulted in a stronger anti-CRPC effect, improving the overall therapeutic efficacy. Conclusion Our study demonstrates the potential of the Celastrol and bicalutamide combination in treating castration-resistant prostate cancer. Further studies are warranted to explore the clinical application of this approach and its potential in improving patient outcomes. Funding information The author(s) declare that financial support was received for the research and/or publication of this article. This work was supported by Beijing Municipal Natural Science F oundation (grant no. BFHHQS20240003). ### Competing Interest Statement The authors have declared no competing interest.

Renal fibrosis represents a critical pathological hallmark in progressive chronic kidney disease (CKD), yet effective therapeutic strategies remain elusive. Emerging evidence suggests that impaired mitophagy contributes to its pathogenesis. This study investigated whether ruxolitinib alleviates renal fibrosis by enhancing PINK1/Parkin-mediated mitophagy. Network pharmacology was employed to explore the potential regulatory mechanisms of ruxolitinib in renal fibrosis treatment, revealing that ruxolitinib might exert therapeutic effects through modulation of inflammation, oxidative stress and mitophagy. Subsequent in vivo and in vitro studies demonstrated that ruxolitinib treatment not only attenuated renal fibrosis progression but also reduced inflammatory responses and oxidative stress while enhancing mitophagic activity. Mechanistically, the enhancement of mitochondrial autophagy and the amelioration of renal fibrosis by ruxolitinib might be mediated via the PINK1/Parkin pathway. These results suggest that ruxolitinib may ameliorate renal fibrosis by activating PINK1/Parkin-mediated mitophagy, providing new perspectives for CKD therapeutic development.

Nephrotic syndrome (NS) is one of the most common pediatric kidney diseases characterized by massive proteinuria and generalized edema that accounts for considerable mortality. Although the etiology of NS is not yet fully understood, altered mitochondrial metabolism, higher levels of oxidative stress, and chronic inflammation are considered the main causes of NS. Thus, reducing the level of reactive oxygen species (ROS) and inhibiting inflammation may effectively improve NS. In this study, the small molecule compound ruxolitinib phosphate salt (RP) was identified and we found it could improve NS by inhibiting cellular inflammation and reducing ROS production to exert a cytoprotective effect, but it also had some side effects. A novel two-dimensional material, black phosphorus nanosheets (BPNSs), was used to efficiently load RP and proximal tubule cells (PTCs) targeting peptide G3-C12 through electrostatic interaction. The mod-ification of G3-C12 promoted cellular uptake of BPNSs, and the endocytosis of BPNSs@G3-C12 was primarily via micropinocytosis. RP@BPNSs@G3-C12 actively targeted PTCs and released RP in a pH-responsive manner in the acidic microenvironment of inflammation. It inhibited LPS-triggered activation of the NF-Kappa B and JNK signaling pathways in RAW264.7 cells, and reduced the production of inflammatory factors such as NO, TNF-alpha, and IL-6. RP@BPNSs@G3-C12 further exhibited cytoprotective effect against doxorubicin damage, oxidative stress and apoptosis. The anti-apoptotic effect may be mainly through the Caspase 3 signaling pathway. Moreover, RP@BPNSs@G3-C12 treatment could also reduce renal inflammation, improve renal injury, apoptosis and oxidative stress in vivo, thereby improve renal functions of NS patients.(c) 2022 Elsevier Ltd. All rights reserved.

Ginsenoside Rh2 (G-Rh2), a rare ginsenoside isolated from red ginseng, has considerable anti-cancer activity and induces apoptosis in a variety of cancer cells, but its activity in esophageal cancer cells is unclear. In this study, we examined the cytotoxic activity of (20S) G-Rh2 in highly differentiated esophageal squamous ECA109 cells and poorly differentiated esophageal squamous TE-13 cells. (20S) G-Rh2 exerted intense cytotoxicity in ECA109 and TE-13 cells with an IC50 of 2.9 and 3.7 μg/mL, respectively. After treatment with G-Rh2, Bcl-2, and Bcl-xL, the two main anti-apoptosis Bcl-2 family proteins upregulated, and Bax and Bak, the two key pro-apoptosis proteins translocated to mitochondria in both cell lines. At the same time, cytochrome c and Smac released from mitochondria, followed by caspase-9 activation, indicating that a mitochondria-mediated intrinsic apoptosis pathway was activated in both cell lines upon treatment with (20S) G-Rh2. It is noteworthy that (20S) G-Rh2 upregulated the transcription and protein expression of two death receptors, Fas and DR5, and subsequently activated Caspase-8 in the TE-13 cells but not in the ECA109 cells. Taken together, we demonstrated the potent anti-esophageal cancer cell activity of (20S) G-Rh2 and showed its working mechanism in two differentiated esophageal cancer cells, which can provide important evidence for developing an effective strategy for anti-esophageal cancer treatment.

The prevalence of obesity has reached alarming levels, which is considered a major risk factor for several metabolic diseases, including type 2 diabetes (T2D), non-alcoholic fatty liver, atherosclerosis, and ischemic cardiovascular disease. Obesity-induced chronic, low-grade inflammation may lead to insulin resistance, and it is well-recognized that macrophages play a major role in such inflammation. In the current review, the molecular mechanisms underlying macrophages, low-grade tissue inflammation, insulin resistance, and T2D are described. Also, the role of macrophages in obesity-induced insulin resistance is presented, and therapeutic drugs and recent advances targeting macrophages for the treatment of T2D are introduced.

Human serum albumin (HSA) is an important component of plasma, which has the functions of maintaining colloid osmotic pressure and capillary membrane stability, promoting blood circulation, and anti-oxidation. Three-dimensional structure of HSA determines its ability to bind and transport hormones and other substances. In this study we examined the interactions between HSA and ginsenoside Rg3, Rg5, Rk1, Rh2, and Rh4, which are the main cytotoxic ginsenosides extracted from red ginseng. Heat transfer generated by the specific interaction between HSA and each ginsenoside was measured using isothermal titration calorimetry (ITC) assay, which demonstrated that all these 5 ginsenosides bound to HSA with binding constants of 3.25, 1.89, 6.04, 2.07, and 5.17 × 105 M-1, respectively. Molecular docking also displayed that these ginsenosides interact with HSA at different sites of the HSA surface. Importantly, cell viability assay showed that the cytotoxicity of these ginsenosides reduced significantly at the presence of HSA in human vascular endothelial cells (HUVEC). Taken together, this study reveals the mechanism by which these ginsenosides are transported in vivo by not causing damage in vascular endothelium, and also suggests HSA might be an ideal carrier help to transport and execute these ginsenoside functions in human body.

Background: Transdermal drug delivery system (TDDS) curing rheumatoid arthritis (RA) for long-term treatment can improve patients' compliance and reduce the accumulation of drug side effects. However, TDDS is constrained by the tight junction of the stratum corneum and low permeation efficiency. It is necessary to adopt proper permeation methods to ensure the therapeutic effect. The transethosome (TE), which is derived from transfersome and ethosome (E), containing a high content of ethanol along with an edge activator or permeation enhancer, has superior deformability and higher permeation efficiency. Methods and Results: In this study, sinomenine hydrochloride-loaded TE was decorated with ascorbic acid to form antioxidant surface transethosome (AS-TE). It was revealed that TE and AS-TE containing sodium deoxycholate can effectively increase the entrapment efficiency of hydrophilic drug, and has superior deformability and higher permeation efficiency than E group. The plasma pharmacokinetics of rabbits showed that TE group and AS-TE group had similar blood concentration and bioavailability; however, micro-dialysis on synovial fluid demonstrated that AS-TE group had higher drug concentration. In RA rat models, the alleviation of the joint swell of AS-TE group was more obvious in the course of 3 weeks of treatment. The inflammatory cytokines and erythrocyte sedimentation rate were significantly lower than those in the negative control group and TE1 group. Conclusion: AS-TE, which can enhance transdermal permeability and drug deposition for the oxidant stress of RA, had further research potential to serve as a TDDS of RA.

Because of the uncertainty of the external environment, high penetration of renewable energy such as wind power and solar energy in the modern power system renders the traditional automatic generation control (AGC) methods more challenging. An improved AGC method named predictive optimal proportional integral differential plus second order derivative (PO-PID+DD) for multi-area interconnected grid is proposed in this paper to reduce the negative impacts of the uncertainty which is caused by the high penetration of renewable energy. Firstly, the mathematical model of the AGC system of multi-area power grid with penetration of photovoltaic (PV) and wind power is built. Then, PO-PID + DD controller is presented to improve the system robustness with respect to system uncertainties. In order to obtain the predictive sequence of the integral system output, the characteristic of the controller is included in the system model. Thus, according to the predictive sequence and designed objective function, the input of the controller can be readjusted to obtain the optimal effect of AGC. An IEEE 39-bus system is introduced as an example to testify the feasibility and effectiveness of the proposed method. The simulation results indicate that the system controlled by the proposed controller has desired dynamic performances.

Dantrolene sodium (DS) is the only drug specifically used for the treatment of malignant hyperthermia. Nevertheless, its clinical application is significantly restricted due to its aqueous insolubility and the limited formulations available in clinical practice. In order to solve these problems, a novel mixed micelle composed of phospholipid and Cremophor EL was designed and evaluated. The mixed micelle was prepared using a stirring- ultrasonic method. The Dynamic Light Scattering (DLS) results showed that the micelle was small in size (12.14 nm) and narrowly distributed (PdI = 0.073). Transmission Electron Microscopy (TEM) images showed that the micelle was homogeneous and spherical. The stability study indicated that the system was stable for storage and dilution with distilled water, while the safety testing showed that the micelle was safe for intravenous administration with low hemolysis rates and low allergic reaction rates. In the pharmaceutics study, the Cmax and AUC0-t of the DS-loaded micelle were 4- and 4.5- folds higher than that of the DS. Therefore, the constructed phospholipid-Cremophor EL mixed micelle is a promising drug delivery system for DS.

Background: Ginsenoside compound K(C-K), a major metabolite of ginsenoside, exhibits anticancer activity in various cancer cells and animal models. A cell signaling study has shown that C-K inhibited nuclear factor-kappa B (NF-kappa B) pathway in human astroglial cells and liver cancer cells. However, the molecular targets of C-K and the initiating events were not elucidated. Methods: Interaction between C-K and Annexin A2 was determined by molecular docking and thermal shift assay. HepG2 cells were treated with C-K, followed by a luciferase reporter assay for NF-kappa B, immunofluorescence imaging for the subcellular localization of Annexin A2 and NF-kappa B p50 subunit, coimmunoprecipitation of Annexin A2 and NF-kappa B p50 subunit, and both cell viability assay and plate clone formation assay to determine the cell viability. Results: Both molecular docking and thermal shift assay positively confirmed the interaction between Annexin A2 and C-K. This interaction prevented the interaction between Annexin A2 and NF-kappa B p50 subunit and their nuclear colocalization, which attenuated the activation of NF-kappa B and the expression of its downstream genes, followed by the activation of caspase 9 and 3. In addition, the overexpression of Annexin A2-K320A, a C-K binding-deficient mutant of Annexin A2, rendered cells to resist C-K treatment, indicating that C-K exerts its cytotoxic activity mainly by targeting Annexin A2. Conclusion: This study for the first time revealed a cellular target of C-K and the molecular mechanism for its anticancer activity. (C) 2018 The Korean Society of Ginseng, Published by Elsevier Korea LLC.

We study scaled group consensus problems of the first/second-order multi-agent dynamics under continuous/discrete-time settings. For a directed multi-agent network with finite sub-networks, the scaled group consensus is concerned with this case that all the sub-networks reach consensus, separately, while maintain the given ratios among the multiple consensus. First/second-order distributed protocols with continuous/discrete data are designed to solve the scaled group consensus problems, and then necessary and sufficient criteria are established to guarantee the agents’ states reaching the scaled group consensus asymptotically applying both algebraic and analytical tools. Finally, the effectiveness of the theoretical results are verified by several simulation examples.

Annexin A2, a multifunctional tumor associated protein, promotes nuclear factor-kappa B (NF-κB) activation by interacting with NF-κB p50 subunit and facilitating its nuclear translocation. Here we demonstrated that two ginsenosides Rg5 (G-Rg5) and Rk1 (G-Rk1), with similar structure, directly bound to Annexin A2 by molecular docking and cellular thermal shift assay. Both Rg5 and Rk1 inhibited the interaction between Annexin A2 and NF-κB p50 subunit, their translocation to nuclear and NF-κB activation. Inhibition of NF-κB by these two ginsenosides decreased the expression of inhibitor of apoptosis proteins (IAPs), leading to caspase activation and apoptosis. Over expression of K302A Annexin A2, a mutant version of Annexin A2, which fails to interact with G-Rg5 and G-Rk1, effectively reduced the NF-κB inhibitory effect and apoptosis induced by G-Rg5 and G-Rk1. In addition, the knockdown of Annexin A2 largely enhanced NF-κB activation and apoptosis induced by the two molecules, indicating that the effects of G-Rg5 and G-Rk1 on NF-κB were mainly mediated by Annexin A2. Taken together, this study for the first time demonstrated that G-Rg5 and G-Rk1 inhibit tumor cell growth by targeting Annexin A2 and NF-κB pathway, and G-Rg5 and G-Rk1 might be promising natural compounds for targeted cancer therapy.

High penetration of wind power in the modern power system renders traditional automatic generation control (AGC) methods more challenging, due to the uncertainty of the external environment, less reserve power, and small inertia constant of the power system. An improved AGC method named predictive optimal 2-degree-of-freedom proportion integral differential (PO-2-DOF-PID) is proposed in this paper, which wind farm will participate in the load frequency control process. Firstly, the mathematical model of the AGC system of multi-area power grid with penetration of wind power is built. Then, predictive optimal 2-degree-of-freedom PID controller is presented to improve the system robustness considering system uncertainties. The objective function is designed based on the wind speed and whether wind farm takes part in AGC or not. The controller solves the optimization problem through the predictive theory while taking into account given constraints. In order to obtain the predictive sequence of output of the whole system, the characteristic of the 2-DOF-PID controller is integrated in the system model. A three interconnected power system is introduced as an example to test the feasibility and effectiveness of the proposed method. When considering the penetration of wind power, two cases of high wind speed and low wind speed are analyzed. The simulation results indicate that the proposed method can effectively deal with the negative influence caused by wind power when wind power participates in AGC.

In order to mitigate the negative influence of geographical dispersity of modern power system and the penetration of renewable energy, a system compensation based model predictive AGC method is proposed in this paper. A compensation unit is introduced in AGC system to reduce the influence of PV power output fluctuation. Furthermore, because the distributed power system is geographically dispersed, which leads to some defects such as time delay and packet dropouts, a selection and optimization algorithm is presented to obtain the appropriate variable when delays exist. Finally, a two-area interconnected power grid with PV systems is shown as an example to testify the feasibility and effectiveness of the proposed method. The simulation results indicate that the system controlled by the proposed method has the expected dynamic performance.

AIM:To get BCG HSP70 protein with excellent biologic activity through E.coli. expression and purification. METHODS: BCG HSP70 gene was amplified by PCR and inserted into vector pMD18-T. After confirmed by sequencing,the gene was subcloned into expression vector pET28a. Recombinant pET28a/HSP70 was transformed into E.coli. BL21(DE3). Recombinant BCG HSP70 protein was expressed with IPTG induction and the purified protein was then identified by SDS-PAGE and Western blot. And its effect on the proliferation of mouse splenocytes was observed. RESULTS: Gene encoding BCG HSP70 which was identical with that published in GenBank was successfully obtained by PCR. SDS-PAGE analysis showed a protein with relative molecular mass of 70 000 was expressed. When the purified protein was detected by Western blot analysis,a specific protein with a molecular mass of 70 000 could be visualized. The purity of the purified protein was about 96.5%. The purified protein could stimulate the proliferation of mouse splenocytes significantly. CONCLUSION: BCG HSP70 is expressed and purified successfully,which would lay a foundation for further research on BCG HSP70 and BCG.