Recent studies have indicated that the expression of ubiquitin-specific protease 51 (USP51), a novel deubiquitinating enzyme (DUB) that mediates protein degradation as part of the ubiquitin‒proteasome system (UPS), is associated with tumor progression and therapeutic resistance in multiple malignancies. However, the underlying mechanisms and signaling networks involved in USP51-mediated regulation of malignant phenotypes remain largely unknown. The present study provides evidence of USP51's functions as the prominent DUB in chemoresistant triple-negative breast cancer (TNBC) cells. At the molecular level, ectopic expression of USP51 stabilized the 78 kDa Glucose-Regulated Protein (GRP78) protein through deubiquitination, thereby increasing its expression and localization on the cell surface. Furthermore, the upregulation of cell surface GRP78 increased the activity of ATP binding cassette subfamily B member 1 (ABCB1), the main efflux pump of doxorubicin (DOX), ultimately decreasing its accumulation in TNBC cells and promoting the development of drug resistance both in vitro and in vivo. Clinically, we found significant correlations among USP51, GRP78, and ABCB1 expression in TNBC patients with chemoresistance. Elevated USP51, GRP78, and ABCB1 levels were also strongly associated with a poor patient prognosis. Importantly, we revealed an alternative intervention for specific pharmacological targeting of USP51 for TNBC cell chemosensitization. In conclusion, these findings collectively indicate that the USP51/GRP78/ABCB1 network is a key contributor to the malignant progression and chemotherapeutic resistance of TNBC cells, underscoring the pivotal role of USP51 as a novel therapeutic target for cancer management.

Stem-leaf saponins from Panax notoginseng (SLSP) comprise numerous PPD-type saponins with diverse pharmacological properties; however, their role in Parkinson's disease (PD), characterized by microglia-mediated neuroinflammation, remains unclear. This study evaluated the effects of SLSP on suppressing microglia-driven neuroinflammation in experimental PD models, including the 1-methyl-4-phenylpyridinium (MPTP)-induced mouse model and lipopolysaccharide (LPS)-stimulated BV-2 microglia. Our findings revealed that SLSP mitigated behavioral impairments and excessive microglial activation in models of PD, including MPTP-treated mice. Additionally, SLSP inhibited the upregulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX2) and attenuated the phosphorylation of PI3K, protein kinase B (AKT), nuclear factor-κB (NFκB), and inhibitor of NFκB protein α (IκBα) both in vivo and in vitro. Moreover, SLSP suppressed the production of inflammatory markers such as interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α) in LPS-stimulated BV-2 cells. Notably, the P2Y2R agonist partially reversed the inhibitory effects of SLSP in LPS-treated BV-2 cells. These results suggest that SLSP inhibit microglia-mediated neuroinflammation in experimental PD models, likely through the P2Y2R/PI3K/AKT/NFκB signaling pathway. These novel findings indicate that SLSP may offer therapeutic potential for PD by attenuating microglia-mediated neuroinflammation.
Animals ; Panax notoginseng/chemistry* ; Saponins/pharmacology* ; Microglia/immunology* ; Mice ; NF-kappa B/immunology* ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/immunology* ; Phosphatidylinositol 3-Kinases/genetics* ; Male ; Parkinson Disease/immunology* ; Mice, Inbred C57BL ; Disease Models, Animal ; Plant Leaves/chemistry* ; Neuroinflammatory Diseases/drug therapy* ; Humans

Head and neck tumor is a common malignant tumor with increasing incidence and mortality worldwide. Traditional diagnostic methods for head and neck tumor are limited by the lack of specific biomarkers and the limitation of invasive detection methods, as well as high time cost and a high rate of misdiagnosis. Therefore, research on head and neck tumor diagnosis based on new technologies is needed. Hyperspectral imaging (HSI) is a non-contact optical imaging technique that captures a series of images in multiple spectral bands to generate a hyperspectral image cube. HSI has shown its corresponding potential in the early diagnosis, tumor margin identification and clinical research of head and neck cancer.

Objective To monitor the cumulative terrestrial γ radiation dose around Shidaowan nuclear power plant, Shandong, China before operation, to analyze the dose levels and influencing factors, and to estimate the annual effective dose to local residents. Methods Fifty-six monitoring sites were selected within 30 km around the nuclear power plant. The environmental γ radiation dose was measured by the thermoluminescence dosimeter monitoring method. The γ radiation dose levels were investigated for 369 days in four monitoring periods (January 16 to April 14, April 15 to July 20, July 21 to October 21, 2021, and October 22, 2021 to January 20, 2022 for periods I to IV, respectively). Relations between γ radiation and monitoring time, altitude, distance from the nuclear power plant were analyzed, and the annual effective dose of terrestrial γ radiation to residents was estimated to reflect the background terrestrial γ radiation level in the area. Results The average values of terrestrial γ radiation dose rate in the four monitoring periods in the area were (76.196 ± 3.366), (81.773 ± 6.144), (93.554 ± 7.449), and (97.604 ± 9.396) nGy/h, respectively, and the terrestrial γ radiation dose rate in the whole year was (87.282 ± 6.589) nGy/h. The effective dose to residents was 0.428 mSv. The terrestrial γ radiation level was high from July 2021 to January 2022. There was no significant difference in the γ radiation dose rate at the monitoring sites with different distance from the nuclear power plant. No impact upon the terrestrial γ radiation dose by the altitude was observed in this study. Conclusion The terrestrial γ radiation level around Shidaowan nuclear power plant in 2021 was at the background level.

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia seen in clinical settings, which has been associated with substantial rates of mortality and morbidity. However, clinically available drugs have limited efficacy and adverse effects. We aimed to investigate the mechanisms of action of andrographolide (Andr) with respect to AF. We used network pharmacology approaches to investigate the possible therapeutic effect of Andr. To define the role of Andr in AF, HL-1 cells were pro-treated with Andr for 1 h before rapid electronic stimulation (RES) and rabbits were pro-treated for 1 d before rapid atrial pacing (RAP). Apoptosis, myofibril degradation, oxidative stress, and inflammation were determined. RNA sequencing (RNA-seq) was performed to investigate the relevant mechanism. Andr treatment attenuated RAP-induced atrial electrophysiological changes, inflammation, oxidative damage, and apoptosis both in vivo and in vitro. RNA-seq indicated that oxidative phosphorylation played an important role. Transmission electron microscopy and adenosine triphosphate (ATP) content assay respectively validated the morphological and functional changes in mitochondria. The translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) to the nucleus and the molecular docking suggested that Andr might exert a therapeutic effect by influencing the Keap1-Nrf2 complex. In conclusions, this study revealed that Andr is a potential preventive therapeutic drug toward AF via activating the translocation of Nrf2 to the nucleus and the upregulation of heme oxygenase-1 (HO-1) to promote mitochondrial bioenergetics.
Animals ; Rabbits ; Atrial Fibrillation/metabolism* ; Kelch-Like ECH-Associated Protein 1/metabolism* ; Signal Transduction ; NF-E2-Related Factor 2/pharmacology* ; Molecular Docking Simulation ; Oxidative Stress ; Energy Metabolism ; Mitochondria/metabolism* ; Inflammation/metabolism* ; Heme Oxygenase-1

Purpose: The role of vacuolar protein sorting 34 (Vps34), an indispensable protein required for cell vesicular trafficking, in the biological behavior of hepatocellular carcinoma (HCC) has yet to be studied. Materials and Methods: In the present study, the expression of Vps34 in HCC and the effect of Vps34 on HCC cell invasion was detected both in vivo and in vitro. Furthermore, by modulating the RILP and Rab11, which regulate juxtanuclear lysosome aggregation and recycling endosome respectively, the underlying mechanism was investigated. Results: Vps34 was significantly decreased in HCC and negatively correlated with the HCC invasiveness both in vivo and in vitro. Moreover, Vps34 could promote lysosomal juxtanuclear accumulation, reduce the invasive ability of HCC cells via the Rab7-RILP pathway. In addition, the deficiency of Vps34 in HCC cells affected the endosome-lysosome system, resulting in enhanced Rab11 mediated endocytic recycling of cell surface receptor and increased invasion of HCC cells. Conclusion Our study reveals that Vps34 acts as an invasion suppressor in HCC cells, and more importantly, the endosome-lysosome trafficking regulated by Vps34 has the potential to become a target pathway in HCC treatment.

Objective: To understand the prevalence of overweight and obesity, dietary habits and main food intake frequency among primary school students in Shenyang, so as to provide a reference for exploring the effect of diet related factors on the development of overweight and obesity in children. Methods: A total of 2 041 students from two primary schools in a certain district of Shenyang were selected by convenience sampling in May 2017, with height and weight measured, meanwhile the questionnaire survey regarding dietary habits and the frequency of main food intake were administered. Results: The rates of overweight and obesity were 18.4% and 22.1% respectively, and the rate of overweight and obesity in boys (21.0%，27.8%) were significantly higher than that in girls (15.8%,16.2%)(χ 2=22.45,53.40，P<0.01). The results of univariate analysis showed that frequency of eating breakfast, eating speed, appetite, picky eaters or not, and the frequency of fruit, seafood and canned food intake were associated with overweight and obesity in primary school students (χ 2=7.67，97.92，229.70，95.88，6.40，6.58，7.96，P<0.05). Multivariate Logistic regression analysis showed that slow eating speed (OR=0.46, 95%CI=0.29-0.69) and normal eating speed (OR=0.47, 95%CI=0.32-0.69) were associated with lower rates of overweight and obesity; good appetite (OR=43.73, 95%CI=5.88-325.36) was associated with higher rates of overweight and obesity in primary school students (P<0.01). Conclusion The detection rate of overweight and obesity is relatively high among primary school students in Shenyang, and the rate of obesity is already higher than that of overweight; The frequency of common food intake has little impact on the development of overweight and obesity in primary school students, but fast eating speed and good appetite are the risks of overweight and obesity among them.

bjective? To compare the appLication effects of power peripheraLLy inserted centraL catheter saLine onLy Locking option (Power PICC SOLO) and power PICC among chemotherapy patients in department of oncoLogy. Methods? Patients who were pLaced in the PICC of the First AffiLiated HospitaL of Zhengzhou University from January to November 2017 were randomLy divided into groups. Among them, 76 patients with Power PICC SOLO were incLuded in the observation group,80 patients with Power PICC were incLuded in the controL group. We compared the incidence of PICC reLated compLications, comfort, expenses of maintaining catheter and retention time of patients between two groups. ResuLts? There were statisticaL differences in the incidence of catheter obstruction and skin injury, comfort as weLL as maintenance time of patients between two groups (P＜ 0.05). ConcLusions? Power PICC SOLO is with the Low incidence of compLications, maintenance cost and high comfort of patients, and saves the maintenance time and reduce nurses' workLoad which is can be worthy of generaLized and appLied among cancer patients with chemotherapy.