A novel nanoplatform-based circCSNK1G3 affects CBX7 protein and promotes glioma cell growth.

Bioenvironmental and biological factors have the potential to contribute to the development of glioma, a type of brain tumor. Recent studies have suggested that a unique circular RNA called circCSNK1G3 could play a role in promoting the growth of glioma cells. It does this by stabilizing a specific microRNA called miR-181 and reducing the expression of a tumor-suppressor gene known as chromobox protein homolog 7 (CBX7). To further investigate circCSNK1G3 and its effects on glioma, we utilized a nanoplatform called adeno-associated virus (AAV)-RNAi.To explore the functional implications of circCSNK1G3, we employed siRNA to silence its expression. Along with these effects, the silencing of circCSNK1G3 led to a depletion of miR-181d and an upregulation of CBX7. When we introduced miR-181d mimics, which artificially increase the levels of miR-181d, the anti-glioma cell activity induced by circCSNK1G3 siRNA was almost completely reversed. Conversely, inhibiting miR-181d mimicked the effects of circCSNK1G3 silencing. Moreover, when we overexpressed circCSNK1G3 in glioma cells, we observed an elevation of miR-181d and a depletion of CBX7. We found that the growth of A172 xenografts (tumors) carrying circCSNK1G3 shRNA was significantly inhibited. In these xenograft tissues, we detected a depletion of circCSNK1G3 and miR-181d, as well as an upregulation of CBX7.

Guided internet-based LGBTQ-affirmative cognitive-behavioral therapy: A randomized controlled trial among sexual minority men in China.

OBJECTIVE: LGBTQ-affirmative cognitive-behavioral therapy (CBT) addresses minority stress to improve sexual minority individuals' mental and behavioral health. This treatment has never been tested in high-stigma contexts like China using online delivery. METHOD: Chinese young sexual minority men (n = 120; ages 16-30; HIV-negative; reporting depression and/or anxiety symptoms and past-90-day HIV-transmission-risk behavior), were randomized to receive 10 sessions of culturally adapted asynchronous LGBTQ-affirmative internet-based CBT (ICBT) or weekly assessments only. The primary outcome included HIV-transmission-risk behavior (i.e., past-30-day condomless anal sex). Secondary outcomes included HIV social-cognitive mechanisms (e.g., condom use self-efficacy), mental health (e.g., depression), and behavioral health (e.g., alcohol use), as well as minority stress (e.g., acceptance concerns), and universal (e.g., emotion regulation) mechanisms at baseline and 4- and 8-month follow-up. Moderation analyses examined treatment efficacy as a function of baseline stigma experiences and session completion. RESULTS: Compared to assessment only, LGBTQ-affirmative ICBT did not yield greater reductions in HIV-transmission-risk behavior or social-cognitive mechanisms. However, LGBTQ-affirmative ICBT yielded greater improvements in depression (d = -0.50, d = -0.63) and anxiety (d = -0.51, d = -0.49) at 4- and 8-month follow-up, respectively; alcohol use (d = -0.40) at 8-month follow-up; and certain minority stress (e.g., internalized stigma) and universal (i.e., emotion dysregulation) mechanisms compared to assessment only. LGBTQ-affirmative ICBT was more efficacious for reducing HIV-transmission-risk behavior for participants with lower internalized stigma (d = 0.42). Greater session completion predicted greater reductions in suicidality and rumination. CONCLUSIONS: LGBTQ-affirmative ICBT demonstrates preliminary efficacy for Chinese young sexual minority men. Findings can inform future interventions for young sexual minority men in contexts with limited affirmative supports.

To explore the protective effect of gastrodin on PC12 cells against oxidative stress induced by lead acetate based on network pharmacology.

Objective: Screening and predicting potential targets for gastrodin antioxidant stress based on network pharmacology methods, and exploring the effect of gastrodin on lead acetate induced oxidative stress in PC12 cells through cell experiments. Methods: Through the Pharmaper database Predict the target of action of gastrodin. Through OMIM and GeneCards to collect oxidative stress targets from database, and intersect with drug targets to obtain drug disease intersection targets; Construct a PPI network diagram using the STRING database. Perform GO enrichment analysis and KEGG pathway enrichment analysis on intersection targets through the DAVID platform. Lead acetate (PbAc) exposure was used to establish a lead poisoning cell model, and intracellular ROS levels, ALB, AKT1, and Caspase-3 levels were measured. Results: A total of 288 targets of gastrodin action, 638 targets related to oxidative stress, and 62 drug disease intersection targets were obtained, among which core targets such as ALB, AKT1, CASP3 may be closely related to oxidative stress. KEGG pathway analysis showed that gastrodin antioxidant stress mainly involved in lipid, cancer pathway and other signaling pathways. The results of the cell experiment showed that 50 µM is the optimal effective concentration for PbAc induced ROS production in PC12 cells. Gastrodin significantly increased the ROS content of PC12 cells treated with PbAc, Upregulation of ALB expression and downregulation of AKT1 and CASP3 expression. Conclusions: Gastrodin may alleviate PbAc-induced ROS in PC12 cells, indicating potential protective effects against oxidative stress. Further studies are needed to confirm these findings and explore the underlying mechanisms.

Development of a Prediction Model and Corresponding Scoring Table for Postherpetic Neuralgia Using Six Machine Learning Algorithms: A Retrospective Study.

INTRODUCTION: Postherpetic neuralgia (PHN), a complication of herpes zoster, significantly impacts the quality of life of affected patients. Research indicates that early intervention for pain can reduce the occurrence or severity of PHN. This study aims to develop a predictive model and scoring table to identify patients at risk of developing PHN following acute herpetic neuralgia, facilitating informed clinical decision-making. METHODS: We conducted a retrospective review of 524 hospitalized patients with herpes zoster at The First Affiliated Hospital of Zhejiang Chinese Medical University from December 2020 to December 2023 and classified them according to whether they had PHN, collecting a comprehensive set of 30 patient characteristics and disease-related indicators, 5 comorbidity indicators, 2 disease score values, and 10 serological indicators. Relevant features associated with PHN were identified using the least absolute shrinkage and selection operator (LASSO). Then, the patients were divided into a training set and a test set in a 4:1 ratio, with comparability tested using univariate analysis. Six models were established in the training set using machine learning methods: support vector machines, logistic regression, random forest, k-nearest neighbor, gradient boosting, and neural network. The performance of these models was evaluated in the test set, and a nomogram based on logistic regression was used to create a PHN prediction score table. RESULTS: Eight non-zero characteristic variables selected from the LASSO regression results were included in the model, including age [area under the curve (AUC) = 0.812, p < 0.001], Numerical Rating Scale (NRS) (AUC = 0.792, p < 0.001), receiving treatment time (AUC = 0.612, p < 0.001), rash recovery time (AUC = 0.680, p < 0.001), history of malignant tumor (AUC = 0.539, p < 0.001), history of diabetes (AUC = 0.638, p < 0.001), varicella-zoster virus immunoglobulin M (AUC = 0.620, p < 0.001), and serum nerve-specific enolase (AUC = 0.659, p < 0,001). The gradient boosting model outperformed other classifier models on the test set with an AUC of 0.931, 95% confidence interval (CI) (0.882-0.980), accuracy of 0.886 (95% CI 0.809-0.940). In the test set, our predictive scoring table achieved an AUC of 0.820 (95% CI 0.869-0.970) with accuracy of 0.790 (95% CI 0.700-0.864). CONCLUSION: This study presents a methodology for predicting the development of postherpetic neuralgia in shingles patients by analyzing historical case data, employing various machine learning techniques, and selecting the optimal model through comparative analysis. In addition, a logistic regression model has been used to create a scoring table for predicting the postherpetic neuralgia.

Metabolic dysfunction associated steatotic liver disease in patients with plaque psoriasis: a case-control study and serological comparison.

Background: The relationship between plaque psoriasis and both MASLD and lean MASLD has not been sufficiently explored in the current literature. Method: This retrospective and observational study was carried out from January 2021 to January 2023 at The First Affiliated Hospital of Zhejiang Chinese Medical University. Patients diagnosed with plaque psoriasis and a control group consisting of individuals undergoing routine physical examinations were enrolled. The incidence of MASLD and lean MASLD among these groups was compared. Additionally, patients with plaque psoriasis were divided into those with MASLD, those with lean MASLD, and a control group with only psoriasis for a serological comparative analysis. Results: The incidence of MASLD in the observation group and the control group was 43.67% (69/158) and 22.15% (35/158), respectively (p < 0.01). Furthermore, the incidence of lean MASLD within the observation group and the control group was 10.76% (17/158) and 4.43% (7/158), respectively (p < 0.01). After controlling for potential confounding variables, plaque psoriasis was identified as an independent risk factor for MASLD with an odds ratio of 1.88 (95% cl: 1.10-3.21). In terms of serological comparison, compared to the simple psoriasis group, we observed a significant elevation in the tumor marker CYFRA21-1 levels in both groups compared to the control group with simple psoriasis (p < 0.01). Moreover, the MASLD group exhibited elevated levels of inflammatory markers and psoriasis score, whereas these effects were mitigated in the lean MASLD group. Conclusion: The prevalence of MASLD and lean MASLD is higher among patients with psoriasis. Those suffering from psoriasis along with MASLD show increased psoriasis scores and inflammatory markers compared to those without metabolic disorders. MASLD likely worsens psoriasis conditions, indicating the necessity of targeted health education for affected individuals to reduce the risk of MASLD, this education should include guidelines on exercise and diet. In serological assessments, elevated levels of cytokeratin 19 fragment (CYFRA21-1) were noted in both MASLD and lean MASLD groups, implying a potential synergistic role between psoriasis and MASLD.

Surface-Enhanced Raman Spectroscopy: Current Understanding, Challenges, and Opportunities.

While surface-enhanced Raman spectroscopy (SERS) has experienced substantial advancements since its discovery in the 1970s, it is an opportunity to celebrate achievements, consider ongoing endeavors, and anticipate the future trajectory of SERS. In this perspective, we encapsulate the latest breakthroughs in comprehending the electromagnetic enhancement mechanisms of SERS, and revisit CT mechanisms of semiconductors. We then summarize the strategies to improve sensitivity, selectivity, and reliability. After addressing experimental advancements, we comprehensively survey the progress on spectrum-structure correlation of SERS showcasing their important role in promoting SERS development. Finally, we anticipate forthcoming directions and opportunities, especially in deepening our insights into chemical or biological processes and establishing a clear spectrum-structure correlation.

Unraveling the role of microRNAs: potential biomarkers for gestational diabetes mellitus revealed through RNA sequencing analysis.

BACKGROUND: Gestational diabetes mellitus (GDM) poses significant health risks for both mothers and children, contributing to long-term complications such as type 2 diabetes and cardiovascular disease. This study explores the potential of microRNAs (miRNAs) as biomarkers for GDM by analyzing peripheral blood samples from GDM patients. METHOD: Ten samples, including peripheral blood from 5 GDM patients and 5 controls, were collected to perform the RNA sequencing analysis. Differentially expressed miRNAs were further validated by quantitative real-time polymerase chain reaction. RESULTS: A total of 2287 miRNAs were identified, 229 of which showed differential expression. Validation by qRT-PCR confirmed significant up-regulation of miR-5193, miR-5003-3p, miR-3127-5p, novel-miR-96, miR-6734-5p, and miR-122-5p, while miR-10395-3p was down-regulated. Bioinformatics analyses revealed the involvement of these miRNAs in pathways associated with herpes simplex virus 1 infection. CONCLUSION: This study provides insights into the differential expression of miRNAs in GDM patients and their potential roles in disease pathogenesis. It suggests that the differentially expressed miRNAs could serve as potential biomarkers for GDM, shedding light on the complex molecular mechanisms involved.

Spermidine attenuates monocrotaline-induced pulmonary arterial hypertension in rats by inhibiting purine metabolism and polyamine synthesis-associated vascular remodeling.

Ensuring the homeostatic integrity of pulmonary artery endothelial cells (PAECs) is essential for combatting pulmonary arterial hypertension (PAH), as it equips the cells to withstand microenvironmental challenges. Spermidine (SPD), a potent facilitator of autophagy, has been identified as a significant contributor to PAECs function and survival. Despite SPD's observed benefits, a comprehensive understanding of its protective mechanisms has remained elusive. Through an integrated approach combining metabolomics and molecular biology, this study uncovers the molecular pathways employed by SPD in mitigating PAH induced by monocrotaline (MCT) in a Sprague-Dawley rat model. The study demonstrates that SPD administration (5 mg/kg/day) significantly corrects right ventricular impairment and pathological changes in pulmonary tissues following MCT exposure (60 mg/kg). Metabolomic profiling identified a purine metabolism disorder in MCT-treated rats, which SPD effectively normalized, conferring a protective effect against PAH progression. Subsequent in vitro analysis showed that SPD (0.8 mM) reduces oxidative stress and apoptosis in PAECs challenged with Dehydromonocrotaline (MCTP, 50 µM), likely by downregulating purine nucleoside phosphorylase (PNP) and modulating polyamine biosynthesis through alterations in S-adenosylmethionine decarboxylase (AMD1) expression and the subsequent production of decarboxylated S-adenosylmethionine (dcSAM). These findings advocate SPD's dual inhibitory effect on PNP and AMD1 as a novel strategy to conserve cellular ATP and alleviate oxidative injuries, thus providing a foundation for SPD's potential therapeutic application in PAH treatment.

Mixed Potential Type Isoprene Sensor for the Application in Real-Time Monitoring of Biomarker Gases.

Monitoring of isoprene in exhaled breath is expected to provide a noninvasive and painless method for dynamic monitoring of physiological and metabolic states during exercise. However, for real-time and portable detection of isoprene, gas sensors have become the best choice for gas detection technology, which are crucial to achieving the goal of anytime, anywhere, human-centered healthcare in the future. Here, we first report a mixed potential type isoprene sensor based on a Gd2Zr2O7 solid electrolyte and a CdSb2O6 sensing electrode, which enables sensitive detection for isoprene with sensitivities of -21.2 mV/ppm and -65.8 mV/decade in the range of 0.05-1 and 1-100 ppm. The sensing behavior of the sensor follows the mixed potential sensing mechanism and was further verified by the electrochemical polarization curves. The significant differentiation between the sensor response to exhaled breath of healthy individuals and simulated breath containing different concentrations of isoprene demonstrates the potential of the sensor for the detection of isoprene in exhaled breath. Simultaneously, monitoring of isoprene during exercise signifies the feasibility of the sensor in dynamic monitoring of physiological indicators, which is not only of great significance for optimizing training and guiding therapeutic exercise intervention in sporting scenarios but also expected to help further reveal the interaction between exercise, muscle, and organ metabolism in medicine.

Revealing the Denoising Principle of Zero-Shot N2N-Based Algorithm from 1D Spectrum to 2D Image.

Denoising is a necessary step in image analysis to extract weak signals, especially those hardly identified by the naked eye. Unlike the data-driven deep-learning denoising algorithms relying on a clean image as the reference, Noise2Noise (N2N) was able to denoise the noise image, providing sufficiently noise images with the same subject but randomly distributed noise. Further, by introducing data augmentation to create a big data set and regularization to prevent model overfitting, zero-shot N2N-based denoising was proposed in which only a single noisy image was needed. Although various N2N-based denoising algorithms have been developed with high performance, their complicated black box operation prevented the lightweight. Therefore, to reveal the working function of the zero-shot N2N-based algorithm, we proposed a lightweight Peak2Peak algorithm (P2P) and qualitatively and quantitatively analyzed its denoising behavior on the 1D spectrum and 2D image. We found that the high-performance denoising originates from the trade-off balance between the loss function and regularization in the denoising module, where regularization is the switch of denoising. Meanwhile, the signal extraction is mainly from the self-supervised characteristic learning in the data augmentation module. Further, the lightweight P2P improved the denoising speed by at least ten times but with little performance loss, compared with that of the current N2N-based algorithms. In general, the visualization of P2P provides a reference for revealing the working function of zero-shot N2N-based algorithms, which would pave the way for the application of these algorithms toward real-time (in situ, in vivo, and operando) research improving both temporal and spatial resolutions. The P2P is open-source at https://github.com/3331822w/Peak2Peakand will be accessible online access at https://ramancloud.xmu.edu.cn/tutorial.

Hydroxy-Safflower Yellow A Mitigates Vascular Remodeling in Rat Pulmonary Arterial Hypertension.

Purpose: The underlying causes of pulmonary arterial hypertension (PAH) often remain obscure. Addressing PAH with effective treatments presents a formidable challenge. Studies have shown that Hydroxysafflor yellow A (HSYA) has a potential role in PAH, While the mechanism underlies its protective role is still unclear. The study was conducted to investigate the potential mechanisms of the protective effects of HSYA. Methods: Using databases such as PharmMapper and GeneCards, we identified active components of HSYA and associated PAH targets, pinpointed intersecting genes, and constructed a protein-protein interaction (PPI) network. Core targets were singled out using Cytoscape for the development of a model illustrating drug-component-target-disease interactions. Intersection targets underwent analysis for Gene Ontology (GO) functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Selected components were then modeled for target interaction using Autodock and Pymol. In vivo validation in a monocrotaline-induced PAH (MCT-PAH) animal model was utilized to substantiate the predictions made by network pharmacology. Results: We associated HSYA with 113 targets, and PAH with 1737 targets, identifying 34 mutual targets for treatment by HSYA. HSYA predominantly affects 9 core targets. Molecular docking unveiled hydrogen bond interactions between HSYA and several PAH-related proteins such as ANXA5, EGFR, SRC, PPARG, PGR, and ESR1. Conclusion: Utilizing network pharmacology and molecular docking approaches, we investigated potential targets and relevant human disease pathways implicating HSYA in PAH therapy, such as the chemical carcinogenesis receptor activation pathway and the cancer pathway. Our findings were corroborated by the efficacious use of HSYA in an MCT-induced rat PAH model, confirming its therapeutic potential.

The effects of pks+ Escherichia coli and bile acid in colorectal tumorigenesis among people with cholelithiasis or cholecystectomy.

BACKGROUND AND AIM: Patients with cholelithiasis (CL) or cholecystectomy (CE) would have more chances of getting colorectal adenoma (CRA) or cancer (CRC). We aimed to figure out the effects of gut microbiota and bile acid on colorectal neoplasm in CL and CE patients. METHODS: This was a retrospective observational study that recruited 514 volunteers, including 199 people with normal gallbladders (normal), 152 CL, and 163 CE patients. Discovery cohort was established to explore the difference in gut microbiota through 16S rRNA and metagenomics sequencing. Validation cohort aimed to verify the results through quantitative polymerase chain reaction (qPCR). RESULTS: Significant enrichment of Escherichia coli was found in patients with cholelithiasis or cholecystectomy both in the discovery cohort (16S rRNA sequencing, PNormal-CL = 0.013, PNormal-CE = 0.042; metagenomics sequencing, PNormal-CE = 0.026) and validation cohort (PNormal-CL < 0.0001, PNormal-CE < 0.0001). Pks+ E. coli was found enriched in CL and CE patients through qPCR (in discovery cohort: PNormal-CE = 0.018; in validation cohort: PNormal-CL < 0.0001, PNormal-CE < 0.0001). The differences in bile acid metabolism were found both through Tax4Fun analysis of 16S rRNA sequencing (Ko00120, primary bile acid biosynthesis, PNormal-CE = 0.014; Ko00121, secondary bile acid biosynthesis, PNormal-CE = 0.010) and through metagenomics sequencing (map 00121, PNormal-CE = 0.026). The elevation of serum total bile acid of CE patients was also found in validation cohort (PNormal-CE < 0.0001). The level of serum total bile acid was associated with the relative abundance of pks+ E. coli (r = 0.1895, P = 0.0012). CONCLUSIONS: E. coli, especially pks+ species, was enriched in CL and CE patients. Pks+ E. coli and bile acid metabolism were found associated with CRA and CRC in people after cholecystectomy.

FGF19 promotes nasopharyngeal carcinoma progression by inducing angiogenesis via inhibiting TRIM21-mediated ANXA2 ubiquitination.

PURPOSE: Nasopharyngeal carcinoma (NPC) has characteristics of high invasion and early metastasis. Most NPC patients present with locoregionally advanced illness when first diagnosed. Therefore, it is urgent to discover NPC biomarkers. Fibroblast growth Factor 19 (FGF19) plays a role in various physiological or pathological processes, including cancer. In this research, we discovered the importance of FGF19 in NPC, and clarified its role in tumour angiogenesis. METHODS: Western blotting, immunohistochemistry and ELISA were used to investigate FGF19 expression in NPC. Then we took CCK8, colony formation, Transwell and wound healing assays to identify the influence of FGF19 on NPC malignant behaviours. The proliferative and metastatic capacity of FGF19 were evaluated in nude mice and zebrafish. The role of FGF19 in angiogenesis was investigated by tube formation and Matrigel plug angiogenesis assays. We then evaluated the variation in Annexin A2(ANXA2) levels with the treatment of FGF19. Lastly, co-immunoprecipitation and ubiquitination assays were performed to identify the mechanisms involved. RESULTS: FGF19 levels were elevated in tissues and serum of NPC patients and were associated with poor clinical stages. High expression of FGF19 promoted NPC malignant behaviours. In particular, FGF19 expression was correlated with microvessel density in tissues and NPC-derived FGF19 could accelerate angiogenesis in vitro and in vivo. Mechanistically, FGF19 influenced ANXA2 expression to promote angiogenesis. Moreover, tripartite motif-containing 21(TRIM21) interacted with ANXA2 and was responsible for ANXA2 ubiquitination. CONCLUSION: FGF19 promoted NPC angiogenesis by inhibiting TRIM21-mediated ANXA2 ubiquitination. It may serve as a noninvasive biomarker for NPC and provides new insights for therapy.

Mixed Potential Type Acetone Sensor with Ultralow Detection Limit for Diabetic Ketosis Breath Analysis.

Breath analysis using gas sensors is an emerging method for disease screening and diagnosis. Since it is closely related to the lipid metabolism and blood ketone concentration of the body, the detection of acetone content in exhaled breath is helpful for the screening and monitoring of diabetes and ketosis. The development of an acetone sensor with high selectivity, stability, and low detection limit has been the research focus for this purpose. Here, we developed a mixed potential type acetone sensor based on Gd2Zr2O7 solid electrolyte and CoSb2O6 sensing electrode. The developed sensor exhibits an extremely low detection limit of 10 ppb, enabling linear detection for acetone in an extremely wide range of 10 ppb-100 ppm. The good results of systematic evaluation on selectivity, repeatability, and stability prove the superior reliability of the sensor, which is a prerequisite for the application in actual breath detection. The ability of the sensor to distinguish healthy people from diabetic ketosis patients was confirmed by using the sensor to detect the breath of healthy people and diabetic patients, proving the feasibility of the sensor in the diagnosis and monitoring of diabetic ketosis.

Self-Healing, Laminated, and Low Resistance NH3 Sensor Based on 6,6',6″-(Nitrilotris(benzene-4,1-diyl))tris(5-phenylpyrazine-2,3-dicarbonitrile) Sensing Material Operating at Room Temperature.

With the rapid development of the concept of the Internet of Things (IoT), gas sensors with the function of simulating the human sense of smell became irreplaceable as a key element. Among them, ammonia (NH3) sensors played an important role in respiration tests, environmental monitoring, safety, and other fields. However, the fabrication of the high-performance device with high stability and resistance to mechanical damages was still a challenge. In this work, polyurethane (PU) with excellent self-healing ability was applied as the substrate, and the sensor was designed from new sensitive material design and device structure optimization, through applying the organic molecule with groups which could absorb NH3 and the laminated structure to shorten the electronic transmission path to achieve a low resistance state and favorable sensing properties. Accordingly, a room temperature flexible NH3 sensor based on 6,6',6″-(nitrilotris(benzene-4,1-diyl))tris(5-phenylpyrazine-2,3-dicarbonitrile) (TPA-3DCNPZ) was successfully developed. The device could self-heal by means of a thermal evaporation assisted method. It exhibited a detection limit of 1 ppm at 98% relative humidity (RH), as well as great stability, selectivity, bending flexibility, and self-healing properties. The improved NH3 sensing performance under high RH was further investigated by complex impedance plots (CIPs) and density functional theory (DFT), attributing to the enhanced adsorption of NH3. The TPA-3DCNPZ based NH3 sensors proved to have great potential for application on simulated exhaled breath to determine the severity of kidney diseases and the progress of treatment. This work also provided new ideas for the construction of high-performance room temperature NH3 sensors.

Mechanisms of acupuncture for primary dysmenorrhea based on PI3K/Akt/mTOR signaling pathway in rats. / 基于PI3K/Akt/mTORä¿¡å·é€šè·¯æŽ¢è®¨ç”µé’ˆæ²»ç–—åŽŸå‘æ€§ç—›ç»å¤§é¼ çš„æœºåˆ¶.

OBJECTIVES: To observe the effect of electroacupuncture(EA) on phosphatidylinositol-3-kinases(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR) signaling pathway of uterus tissue in rats with primary dysmenorrhea(PDM), so as to investigate its mechanisms underlying improvement of PDM. METHODS: Thirty healthy non-pregnant female SD rats were randomly divided into blank, model and EA groups, with 10 rats in each group. The PDM model was established by subcutaneous injection of estradiol diphenhydrate combined with intraperitoneal injection of oxytocin. For rats of the EA group, EA(50 Hz, a tolerable current intensity) was applied to "Guanyuan"(CV4) and bilateral "Sanyinjiao"(SP6) for 20 min, once a day for 10 consecutive days. The number of writhing, wri-thing score, and writhing latency were observed. The uterine histopathological changes were observed by H.E. staining, and the ultrastructural changes of uterine tissue cells in each group were observed by transmission electron microscopy. The contents of prostaglandin E2(PGE2), prostaglandin F2α(PGF2α) and ratios of PGF2α/PGE2 in the serum and uterine tissue were detected by ELISA. The relative expression levels of PI3K, Akt and mTOR and their phosphorylation proteins in the uterine tissue were detected by Western blot and the ratios were calculated. RESULTS: Compared with the blank group, the number and score of writhing, latency of writhing, pathological injury score, contents of PGF2α and ratios of PGF2α/PGE2 in the serum and uterine tissue, and the levels of p-PI3K/PI3K, p-Akt/Akt and p-mTOR/mTOR in the uterine tissue were significantly increased in the model group(P<0.01, P<0.05), while contents of PGE2 in the serum and uterine tissue were reduced(P<0.05). In comparison with the model group, the number of writhing and writhing score, pathological injury score, contents of PGF2α and ratios of PGF2α/PGE2 in both the serum and uterine tissue, the levels of p-PI3K/PI3K, p-Akt/Akt and p-mTOR/mTOR were obviously decreased(P<0.05, P<0.01), whereas the writhing latency was considerably prolonged in the EA group(P<0.01), with elevated contents of PGE2 in the serum and uterine tissue(P<0.05). H.E. staining showed slight dilation of uterine glandular cavity, and severe endometrial edema with extensive cell shedding and a large number of vacuole-like degeneration, apoptosis, pyknosis or fragmentation or disappearance of the nucleus, and neutrophil infiltration in the model group, which were relatively milder in the EA group. Ultrastructural results showed irregular fibroblasts of uterine tissue cells, obvious cytoplasmic edema, reduction in cytoplasmic electron density, seriously irregular nuclei, severe edema of mitochondria with dissolved matrix, fracture and disappearance of mitochondrial crests and vacuolation, and moderate dilation of rough endoplasmic reticulum in the model group, which were milder in the EA group. CONCLUSIONS: EA can improve pain and uterine inflammatory response in PDM rats, which may be associated with its functions in reducing uterine PGF2α and down-regulating PI3K/Akt/mTOR signaling.

[Role and mechanisms of CHI3L1 in coronary artery lesions in a mouse model of Kawasaki disease-like vasculitis]. / CHI3L1åœ¨å·å´Žç— æ ·è¡€ç®¡ç‚Žå°é¼ æ¨¡åž‹å† çŠ¶åŠ¨è„‰æŸä¼¤ä¸­çš„ä½œç”¨åŠæœºåˆ¶ç ”ç©¶.

OBJECTIVES: To explore the role and potential mechanisms of chitinase-3-like protein 1 (CHI3L1) in coronary artery lesions in a mouse model of Kawasaki disease (KD)-like vasculitis. METHODS: Four-week-old male SPF-grade C57BL/6 mice were randomly divided into a control group and a model group, with 10 mice in each group. The model group mice were intraperitoneally injected with 0.5 mL of lactobacillus casei cell wall extract (LCWE) to establish a mouse model of KD-like vasculitis, while the control group mice were injected with an equal volume of normal saline. The general conditions of the mice were observed on the 3rd, 7th, and 14th day after injection. Changes in coronary artery tissue pathology were observed using hematoxylin-eosin staining. The level of CHI3L1 in mouse serum was measured by enzyme-linked immunosorbent assay. Immunofluorescence staining was used to detect the expression and localization of CHI3L1, von Willebrand factor (vWF), and α-smooth muscle actin (α-SMA) in coronary artery tissue. Western blot analysis was used to detect the expression of CHI3L1, vWF, vascular endothelial cadherin (VE cadherin), Caspase-3, B cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), nuclear factor κB (NF-κB), and phosphorylated NF-κB (p-NF-κB) in coronary artery tissue. RESULTS: The serum level of CHI3L1 in the model group was significantly higher than that in the control group (P<0.05). Compared to the control group, the expression of CHI3L1 in the coronary artery tissue was higher, while the expression of vWF was lower in the model group. The relative expression levels of CHI3L1, Bax, Caspase-3, NF-κB, and p-NF-κB were significantly higher in the model group than in the control group (P<0.05). The relative expression levels of vWF, VE cadherin, and Bcl-2 were lower in the model group than in the control group (P<0.05). CONCLUSIONS: In the LCWE-induced mouse model of KD-like vasculitis, the expression levels of CHI3L1 in serum and coronary arteries increase, and it may play a role in coronary artery lesions through endothelial cell apoptosis mediated by inflammatory reactions.

Effects of abnormal expression of CD73 on malignant phenotype of nasopharyngeal carcinoma.

Cluster of differentiation (CD) 73, encoded by the NT5E gene, plays important enzymatic and non-enzymatic roles in cells. There is growing evidence show that CD73 is a key regulator in the development of tumor. Nasopharyngeal carcinoma (NPC) is one of the most common cancers in east and southeast Asia. It is urgent to know more about the mechanism of NPC development and find diagnostic markers for the patients. In this research, we carried out western blot, immunohistochemistry and qRT-PCR to investigate the expression level of CD73 and found that NPC tissues had higher level of CD73 than normal tissues. We also detected the relationship between its expression level with the clinicopathological features and prognosis of NPC patients. The results showed that CD73 expression was related to the clinical stages, lymph node metastasis and survival state of NPC patients. More importantly, patients with higher expression of CD73 had poorer prognosis. Then, CD73 was knocked down in NPC cells (CNE2 and CNE1), and its effects on cell proliferation and migration were investigated by CCK8, colony formation, Transwell and wound-healing assays. We found that knocking down the expression of CD73 in NPC cells could inhibit cells malignant phenotype. Collectively, CD73 plays important roles in NPC malignant behavior and might act as a novel target for the diagnosis and treatment of NPC.

Pattern Recognition with Temperature Regulation: A Single YSZ-Based Mixed Potential Sensor Classifies Multiple Mixtures of Isoprene, n-Propanol, and Acetone.

Gas sensors integrated with machine learning algorithms have aroused keen interest in pattern recognition, which ameliorates the drawback of poor selectivity on a sensor. Among various kinds of gas sensors, the yttria-stabilized zirconia (YSZ)-based mixed potential-type sensor possesses advantages of low cost, simple structure, high sensitivity, and superior stability. However, as the number of sensors increases, the increased power consumption and more complicated integration technology may impede their extensive application. Herein, we focus on the development of a single YSZ-based mixed potential sensor from sensing material to machine learning for effective detection and discrimination of unary, binary, and ternary gas mixtures. The sensor that is sensitive to isoprene, n-propanol, and acetone is manufactured with the MgSb2O6 sensing electrode prepared by a simple sol-gel method. Unique response patterns for specific gas mixtures could be generated with temperature regulation. We chose seven algorithm models to be separately trained for discrimination. In order to realize more accurate discrimination, we further discuss the selection of suitable feature parameters and its reasons. With temperature regulation coefficients which are easily available as feature input to model, a single sensor is verified to achieve elevated accuracy rates of 95 and 99% for the discrimination of seven gases (three unary gases, three binary gas mixtures, and one ternary gas mixture) and redefined six gas mixtures. This article provides a potential new approach via a mixed potential sensor instead of a sensor array that could provide a wide application prospect in the field of electronic nose and artificial olfaction.

Seeing Is Not Necessarily Believing: Is the Surface-Enhanced Raman Spectroscopy Signal Really from the Target?

Reagent purity is crucial to experimental research, considering that the ignorance of ultratrace impurities may induce wrong conclusions in either revealing the reaction nature or qualifying the target. Specifically, in the field of surface science, the strong interaction between the impurity and the surface will bring a non-negligible negative effect. Surface-enhanced Raman spectroscopy (SERS) is a highly surface-sensitive technique, providing fingerprint identification and near-single molecule sensitivity. In the SERS analysis of trace chloromethyl diethyl phosphate (DECMP), we figured out that the SERS performance of DECMP is significantly distorted by the trace impurities from DECMP. With the aid of gas chromatography-based techniques, one strongly interfering impurity (2,2-dichloro-N,N-dimethylacetamide), the byproduct during the synthesis of DECMP, was confirmed. Furthermore, the nonignorable interference of impurities on the SERS measurement of NaBr, NaI, or sulfadiazine was also observed. The generality ignited us to refresh and consolidate the guideline for the reliable SERS qualitative analysis, by which the potential misleading brought by ultratrace impurities, especially those strongly adsorbed on Au or Ag surfaces, could be well excluded.