Development and validation of serological dynamic risk score to predict outcome in gastric cancer with adjuvant chemotherapy: a multicentre, longitudinal, cohort study.

Background: Baseline serological biomarkers have the potential to predict the benefits of adjuvant chemotherapy in patients with gastric cancer. However, the fluctuating nature of postoperative recurrence risk makes precise treatment challenging. We aimed to develop a risk score in real-time predicting outcomes for postoperative GC patients using blood chemistry tests. Materials and methods: This was a retrospective, multicentre, longitudinal cohort study from three cancer centres in China, with a total of 2737 GC patients in the pTNM stage Ib to III. Among them, 1651 patients with at least two serological records were assigned to the training cohort. Model validation was carried out using separate testing data with area under curve (AUC). The least absolute shrinkage and selection operator (LASSO) and random forest-recursive feature elimination (RF-RFE) algorithm were used to select the parameters. Results: The Cox regression model derived six risk factors to construct a composite score (low-risk: 0-2 score; high risk: 3-6 score), including CEA, CA125, CA199, haemoglobin, albumin, and neutrophil to lymphocyte ratio. The risk score accurately predicted mortality in 1000-time bootstrap (AUROCs:0.658; 95% CI: 0.645, 0.670), with the highest AUROC (0.767; 95% CI: 0.743, 0.791) after 1 year since the gastrectomy. In validation dataset, the risk score had an AUROC of 0.586 (95% CI 0.544, 0.628). Furthermore, patients with high risk at 1 month derived significant clinical benefits from adjuvant chemotherapy (P for interaction <0.0001). Compared with the low-low-low risk group, the low-low-high risk group of the long-term state chain (risk state at baseline, 6 months, 1 year) had the worse OS (HR, 6.91; 95%CI: 4.27, 11.19) and DFS (HR, 7.27; 95%CI: 4.55, 11.63). Conclusion: The dynamic risk score is an accurate and user-friendly serological risk assessment tool for predicting outcomes and assisting clinical decisions after gastrectomy.

Hippocampal HDAC6 promotes POCD by regulating NLRP3-induced microglia pyroptosis via HSP90/HSP70 in aged mice.

BACKGROUND: Postoperative Cognitive Dysfunction (POCD) has attracted increased attention, but its precise mechanism remains to be explored. This study aimed to figure out whether HDAC6 could regulate NLRP3-induced pyroptosis by modulating the functions of HSP70 and HSP90 in microglia to participate in postoperative cognitive dysfunction in aged mice. METHODS: Animal models of postoperative cognitive dysfunction in aged mice were established by splenectomy under sevoflurane anesthesia. Morris water maze was used to examine the cognitive function and motor ability. Sixteen-months-old C57BL/6 male mice were randomly divided into six groups: control group (C group), sham surgery group (SA group), splenectomy group (S group), splenectomy + HDAC6 inhibitor ACY-1215 group (ACY group), splenectomy + HDAC6 inhibitor ACY-1215 + HSP70 inhibitor Apoptozole group (AP group), splenectomy + solvent control group (SC group). The serum and hippocampus of mice were taken after mice were executed. The protein levels of HDAC6, HSP90, HSP70, NLRP3, GSDMD-N, cleaved-Caspase-1 (P20), IL-1ß were detected by western blotting. Serum IL-1ß, IL-6 and S100ß were measured using ELISA assay, and cell localization of HDAC6 was detected by immunofluorescence. In vitro experiments, BV2 cells were used to validate whether this mechanism worked in microglia. The protein levels of HDAC6, HSP90, HSP70, NLRP3, GSDMD-N, P20, IL-1ß were detected by western blotting and the content of IL-1ß in the supernatant was measured using ELISA assay. The degree of acetylation of HSP90, the interaction of HSP70, HSP90 and NLRP3 were analyzed by coimmunoprecipitation assay. RESULTS: Splenectomy under sevoflurane anesthesia in aged mice could prolong the escape latency, reduce the number of crossing platforms, increase the expression of HDAC6 and activate the NLRP3 inflammasome to induce pyroptosis in hippocampus microglia. Using ACY-1215 could reduce the activation of NLRP3 inflammasome, the pyroptosis of microglia and the degree of spatial memory impairment. Apoptozole could inhibit the binding of HSP70 to NLRP3, reduce the degradation of NLRP3 and reverse the protective effect of HDAC6 inhibitors. The results acquired in vitro experiments closely resembled those in vivo, LPS stimulation led to the pyroptosis of BV2 microglia cells and the release of IL-1ß due to the activation of the NLRP3 inflammasome, ACY-1215 showed the anti-inflammatory effect and Apoptozole exerted the opposite effect. CONCLUSIONS: Our findings suggest that hippocampal HDAC6 promotes POCD by regulating NLRP3-induced microglia pyroptosis via HSP90/HSP70 in aged mice.

A prediction model of elderly hip fracture mortality including preoperative red cell distribution width constructed based on the random survival forest (RSF) and Cox risk ratio regression.

An independent correlation between pre-RDW and 1-year mortality after surgery in elderly hip fracture can be used to predict mortality in elderly hip fracture patients and has predictive significance in anemia patients. With further research, a treatment algorithm can be developed to potentially identify patients at high risk of preoperative mortality. INTRODUCTION: Red blood cell distribution width (RDW) is an independent predictor of various disease states in elderly individuals, but its association with the prognosis of elderly hip fracture patients is controversial. This study aimed to evaluate the prognostic value of RDW in such patients, construct a prediction model containing RDW using random survival forest (RSF) and Cox regression analysis, and compare RDW in patients with and without anemia. METHODS: We retrospectively analyzed the data of elderly patients who underwent hip fracture surgery, selected the best variables using RSF, stratified the independent variables by Cox regression analysis, constructed a 1-year mortality prediction model of elderly hip fracture with RDW, and conducted internal validation and external validation. RESULTS: Two thousand one hundred six patients were included in this study. The RSF algorithm selects 12 important influencing factors, and Cox regression analysis showed that eight variables including preoperative RDW (pre-RDW) were independent risk factors for death within 1-year after hip fracture surgery in elderly patients. Stratified analysis showed that pre-RDW was still independently associated with 1-year mortality in the non-anemia group and not in the anemia group. The nomogram prediction model had high differentiation and fit, and the prediction model constructed by the total cohort of patients was also used for validation of patients in the anemia patients and obtained good clinical benefits. CONCLUSION: An independent correlation between pre-RDW and 1-year mortality after surgery in elderly hip fracture can be used to predict mortality in elderly hip fracture patients and has predictive significance in anemia patients.

Synthesis, Preclinical Evaluation, and First-in-Human PET Study of [68Ga]-Labeled Biphenyl-Containing PSMA Tracers.

Radioisotope-labeled prostate-specific membrane antigen (PSMA) PET tracers have gained popularity in diagnosing prostate cancer (PCa). This study aimed to improve the affinity and tumor-targeting capabilities of new PSMA tracers by increasing the number of pharmacophores that specifically bind to PSMA. Using biphenyl as a core scaffold, we investigated the relationship among spacer segments, affinity, and pharmacokinetic properties. In preclinical PET studies on mice with 22Rv1 tumors, compared with [68Ga]Ga-PSMA-11 (SUVmax = 3.37), [68Ga]Ga-PSMA-D5 (Ki = 0.15) showed higher tumor uptake (SUVmax = 3.51) and lower renal uptake (T/K = 1.84). In the first-in-human study, [68Ga]Ga-PSMA-D5 effectively detected small PCa-associated lesions and distant metastases. The advantages of [68Ga]Ga-PSMA-D5 include high tumor uptake, straightforward synthesis, and labeling, making it a promising PSMA PET tracer. Furthermore, [68Ga]Ga-PSMA-D5 contains a DOTA chelator, allowing convenient labeling with therapeutic radionuclides such as 177Lu and 225Ac, providing the potential for targeted radioligand therapy in PCa.

Efficacy of immune checkpoint inhibitors along with chemotherapy in non-small cell lung cancer and the impact on adverse reactions and serum tumor markers.

OBJECTIVE: To examine the efficacy of immune checkpoint inhibitors along with chemotherapy in non-small cell lung cancer (NSCLC) and the effect on adverse reactions and serum tumor markers. METHODS: Data of 112 NSCLC patients admitted to Geriatric respiratory department, Xi'an International Medical Center Hospital from February 2018 to March 2021 were analyzed retrospectively. Among them, 54 patients treated with concurrent chemotherapy were labeled as the control group (CG), and 58 patients treated with PD-1/PD-L1 inhibitors in addition to chemotherapy were the observation group (OG). The two groups were compared in terms of immune function indexes, therapeutic efficacy, incidence of adverse reactions, 1-year survival rate, serum tumor markers before and after treatment, and independent risk factors affecting patients' prognosis. RESULTS: Compared to the CG, the OG exhibited significantly better therapeutic efficacy. The levels of IgG, IgA and IgM 6 months after treatment were significantly higher in both groups than those before treatment, and the elevations in the OG were more evident than those in the CG, and the OG demonstrated markedly lower Recombinant Cytokeratin Fragment Antigen 21-1 (CYFRA21-1), Carcinoembryonic antigen (CEA) and Carbohydrate antigen 125 (CA125) levels after treatment than the CG did. Between the two groups, there was no significant difference identified in the incidence of adverse reactions, but the OG was observed to have much higher 1-year survival rate. The pathological stage, differentiation and treatment regimen were independent risk factors affecting patients' prognosis. CONCLUSION: For NSCLC patients, the adoption of PD-1/PD-L1 inhibitors following chemoradiotherapy shows potential in enhancing clinical efficacy, boosting patients' immune function, and improving long-term survival rates, with premising safety profile.

Young Sca-1+ bone marrow stem cell-derived exosomes preserve visual function via the miR-150-5p/MEKK3/JNK/c-Jun pathway to reduce M1 microglial polarization.

BACKGROUND: Polarization of microglia, the resident retinal immune cells, plays important roles in mediating both injury and repair responses post-retinal ischemia-reperfusion (I/R) injury, which is one of the main pathological mechanisms behind ganglion cell apoptosis. Aging could perturb microglial balances, resulting in lowered post-I/R retinal repair. Young bone marrow (BM) stem cell antigen 1-positive (Sca-1+) cells have been demonstrated to have higher reparative capabilities post-I/R retinal injury when transplanted into old mice, where they were able to home and differentiate into retinal microglia. METHODS: Exosomes were enriched from young Sca-1+ or Sca-1- cells, and injected into the vitreous humor of old mice post-retinal I/R. Bioinformatics analyses, including miRNA sequencing, was used to analyze exosome contents, which was confirmed by RT-qPCR. Western blot was then performed to examine expression levels of inflammatory factors and underlying signaling pathway proteins, while immunofluorescence staining was used to examine the extent of pro-inflammatory M1 microglial polarization. Fluoro-Gold labelling was then utilized to identify viable ganglion cells, while H&E staining was used to examine retinal morphology post-I/R and exosome treatment. RESULTS: Sca-1+ exosome-injected mice yielded better visual functional preservation and lowered inflammatory factors, compared to Sca-1-, at days 1, 3, and 7 days post-I/R. miRNA sequencing found that Sca-1+ exosomes had higher miR-150-5p levels, compared to Sca-1- exosomes, which was confirmed by RT-qPCR. Mechanistic analysis found that miR-150-5p from Sca-1+ exosomes repressed the mitogen-activated protein kinase kinase kinase 3 (MEKK3)/JNK/c-Jun axis, leading to IL-6 and TNF-α downregulation, and subsequently reduced microglial polarization, all of which contributes to reduced ganglion cell apoptosis and preservation of proper retinal morphology. CONCLUSION: This study elucidates a potential new therapeutic approach for neuroprotection against I/R injury, via delivering miR-150-5p-enriched Sca-1+ exosomes, which targets the miR-150-5p/MEKK3/JNK/c-Jun axis, thereby serving as a cell-free remedy for treating retinal I/R injury and preserving visual functioning.

Design and Characterization of Squaramic Acid-Based Prostate-Specific Membrane Antigen Inhibitors for Prostate Cancer.

Prostate-specific membrane antigen (PSMA) overexpressed on prostate cancer (PCa) cells is a satisfactory theranostic target in PCa. To seek novel non-glutamate-urea-based PSMA inhibitors by the strategy of bioisosterism, 10 ligands were designed, synthesized, and characterized. Among them, ligands 17, 18, and 21-24 bearing the squaramic acid moiety proved to be potent PSMA inhibitors, with Ki values ranging from 0.40 to 2.49 nM, which are comparable or higher in inhibitory potency compared to previously reported glutamate-urea-based inhibitors. Docking studies of 15, 17, and 19 were carried out to explore their binding mode in the active site of PSMA. Two near-infrared (NIR) probes, 23 (λEM = 650 nm) and 24 (λEM = 1088 nm), displayed favorable in vivo NIR imaging and successful NIR-II image-guided tumor resection surgery in PSMA-positive tumor-bearing mice, which demonstrated the effectiveness of these new squaramic acid-based inhibitors.

Morphology regulation of zero-valent iron nanosheets supported on microsilica for promoting peroxymonosulfate activation.

Combing the assisted dispersion strategy of support with the wet chemical reduction method, a novel nano-zero valent iron/microsilica (nZVI/M) composite was successfully fabricated, where the 2D nZVI nanosheets were uniformly anchored and covered on the surface of microsilica. The introduction of microsilica notably relieved the agglomeration effect of nZVI nanosheets, which induced the improvement of specific surface area (45.68 m2/g) and pore volume (0.172 cm3/g), and thereby exposing more active sites for bisphenol A (BPA) removal. The optimized nZVI/M-0.6 displayed the superior catalytic performance in the presence of peroxymonosulfate (PMS) with the degradation rate of BPA reached above 97% within 3 min and a higher constant rate of 0.659 min-1, which was approximately 3.9 times as high as that of nZVI/PMS system. The homogeneously dispersion of nZVI nanosheets on microsilica benefited for the assembly of the pollutants and boosting the kinetics of the catalytic degradation process. As a highly efficient PMS activator, it could well maintain the catalytic activity in different real water samples. The quenching experiments verified that SO4•- played the dominate role for BPA removal. This work offered novel insights for designing and preparing iron-based persulfate activator for wastewater treatment.

Case report: Long response to PD-1 blockade after failure of trastuzumab plus chemotherapy in advanced Epstein-Barr virus-associated gastric cancer.

Background: Trastuzumab-containing chemotherapy is the first-line treatment for advanced gastric cancer (GC) with HER2 positive. Although PD-1 inhibitors significantly improved the outcome of GC patient's refractory to previous chemotherapy regimens, few studies explore the role of anti-PD-1 therapy overcomes resistance to trastuzumab plus chemotherapy in advanced Epstein-Barr Virus-associated gastric cancer (EBVaGC) with PD-L1 and HER2 positive. Case Presentation: We report a case of advanced EBVaGC in a 45-year-old man presenting with fatigue, dysphagia, and weight loss for several months. Initial endoscopy revealed a large tumor at the gastroesophageal junction. Computed tomography revealed GC accompanied by multiple lymph nodes and hepatic and pulmonary metastases. The immunohistochemistry indicated that HER-2 and PD-L1 were overexpressed, and tumor cells were positive for EBV-encoded small RNA (EBER) by in situ hybridization. Trastuzumab plus DCS was started as first-line chemotherapy with a PFS of 4 months and shifted to trastuzumab plus FOLFIRI or gemcitabine as second-/third-line therapy. After five-cycle nivolumab monotherapy, the patient received partial response and was treated with total radical gastrectomy plus sequential radiotherapy. He continued the postoperative immunotherapy over 30 cycles with a PFS of 28 months. Due to a new abdominal lymph node metastasis confirmed by PET-CT, he received toripalimab as the next-line treatment and achieved complete remission as the best objective response. Summary: We presented an advanced HER2-positive EBVaGC patient with PD-L1 high expression, refractory to trastuzumab plus chemotherapy, and had a durable clinical benefit sequence with a single dose of the PD-1 inhibitor.

Defect Engineering Modulated Iron Single Atoms with Assist of Layered Clay for Enhanced Advanced Oxidation Processes.

Single-atom catalysts (SACs) feature maximum atomic utilization efficiency; however, the loading amount, dispersibility, synthesis cost, and regulation of the electronic structure are factors that need to be considered in water treatment. In this study, kaolinite, a natural layered clay mineral, is applied as the support for g-C3 N4 and single Fe atoms (FeSA-NGK). The FeSA-NGK composite exhibits an impressive degradation performance toward the target pollutant (>98% degradation rate in 10 min), and catalytic stability across consecutive runs (90% reactivity maintained after three runs in a fluidized-bed catalytic unit) under peroxymonosulfate (PMS)/visible light (Vis) synergetic system. The introduction of kaolinite promotes the loading amount of single Fe atoms (2.57 wt.%), which is a 14.2% increase compared to using a bare catalyst without kaolinite, and improved the concentration of N vacancies, thereby optimizing the regulation of the electronic structure of the single Fe atoms. It is discovered that the single Fe atoms successfully occupied five coordinated N atoms and combined with a neighboring N vacancy. Consequently, this regulated the local electronic structure of single Fe atoms, which drives the electrons of N atoms to accumulate on the Fe centers. This study opens an avenue for the design of clay-based SACs for water purification.

Prevalence and correlates of cigarette smoking among Dulong adults in China: A cross-sectional survey in 2020.

Background: The Dulong people are one of the minorities in China with the lowest population. In recent years, the lifestyle of the Dulong people has also changed drastically due to income growth and urbanization. This study aims to identify cigarette smoking prevalence and potential risk factors among Dulong adults in China. Methods: This study was conducted among 1,018 adults based on the Dulong Health Status Investigation and Evaluation (DHSIE) in Gongshan Dulong and Nu Autonomous County of Yunnan province, Southwest China. A cross-sectional design and face-to-face questionnaire were used to collect cigarette smoking habits and demographic information. Data were weighted by post-stratification weights according to the age and gender composition of Dulong resident. We also analyzed univariate and multivariate unconditional logistic regression to explore current smoking correlates. Results: The weighted prevalence of ever-smoking, currently smoking, and formerly smoking among Dulong adults is 31.3, 27.7, and 3.6%, respectively. The prevalence of ever-smoking and currently smoking among male participants (57.0 and 50.6%) is much higher than that of female participants (4.0 and 3.4%). Nearly 60% of ever-smokers and current smokers smoked more than 20 cigarettes per day, which are higher than former smokers (35.2%). Among current smokers, 33.1% relapsed, and 28.3% intend to quit smoking. By adjusting for potential confounding variables, multiple logistic regression analysis indicated that male participants (OR = 48.982, 95% CI: 25.026-95.869) and current drinkers (OR = 4.450, 95% CI: 2.556-7.746) are more likely to be current smokers. On the contrary, current smokers are also more likely to be exposed to secondhand smoke (OR = 4.269, 95% CI: 2.330-7.820) and have a higher risk of chronic respiratory disease (OR = 4.955, 95% CI: 1.669-14.706). Conclusion: Cigarette smoking is highly prevalent among the Dulong people in Southwest China. An appropriate and effective tobacco control strategy is an urgent need for this population.

Protrudent electron transfer channels on kaolinite modified iron oxide QDs/N vacancy graphitic carbon nitride driving superior catalytic oxidation.

Optimizing electron transfer channels and sufficiently exposing active sites to trigger an efficient Fenton-like reaction are vital for manipulating catalytic properties of water treatment. Herein, Fe2O3 quantum dots were prepared and integrated with composites of g-C3N4 and kaolinite with nitrogen (N) vacancies (FONGK-10) for bisphenol A (BPA) removal in a peroxymonosulfate (PMS)/visible light (Vis) system. X-ray absorption near-edge structures and extended X-ray absorption fine structures demonstrated interface's combined properties. In particular, the tight interfacial contact and introduction of N vacancies resulted in the formation of effective electron channels, which caused more effective separation of electron-hole pairs and an extended response time of 1.5 × 10-4 s. Furthermore, the introduction of kaolinite reduced the Fe2O3 particle size and accelerated PMS consumption. The k value in FONGK-10/PMS/Vis system was 4.5 times that of the FONGK-10/PMS and 27.5 times that of the FONGK-10/Vis system, and the synergetic system exhibited superior consecutive catalytic performance in a fluidized-bed catalytic unit, degrading ~100% of BPA in 200 min. The exposed electron channels significantly maintained the Fe(III)/Fe(II) stable dynamic cycle, thereby enhancing the activation of PMS and photocatalysis performance.

Effects of La2O3contents on microstructure and properties of laser-cladded 5 wt% CaB6/HA bioceramic coating.

In the present work, 5 wt% CaB6/hydroxyapatite (HA) bioceramic coatings with different La2O3contents (0-0.6 wt%) have been fabricated by a laser cladding technique on Ti-6Al-4V. The effects of La2O3contents on microstructure and properties of the laser-cladded 5 wt% CaB6/HA coatings have been carefully investigated. The results show that the microstructure is obviously refined, and the structure is relatively uniform after doping 0.2-0.4 wt% La2O3. As the La2O3content increases, the corrosion resistance are found to increase firstly and then gradually decrease. The x-rays diffraction analysis confirms that the amount of HA and TCP (calcium phosphate) in the coating reaches maximum after doping 0.2 wt% La2O3. The La2O3-doped coatings show a significantly higher bone-like apatite precipitation after immersion in simulated body fluid compared with La2O3-free coating. In vitro experiment also shows that 5 wt% CaB6/HA bioceramic coatings with 0.2-0.4 wt% La2O3are more suitable for the attachment and proliferation of MG63 cells, exhibiting superior bioactivity and biocompatibility.

Construction of BiOCl/Clinoptilolite Composite Photocatalyst for Boosting Formaldehyde Removal.

Binary composite was synthesized via coupling BiOCl with alkali leached natural clinoptilolite (40B0/CN), which showed retarded recombination of photo-generated carriers. The clinoptilolite was pretreated with alkali leaching, resulting in a larger pore size and high cation exchange capacity. The modified clinoptilolite was more feasible for the growth of BiOCl and to promote the adsorption ability for formaldehyde (HCHO). In addition, the cation exchange capacity was conducive to anchor Bi3+, further leading to the reduction of the particle size of BiOCl. The carrier effect of alkali leached natural clinoptilolite promoted the amorphous transformation of BiOCl at low temperature, which simultaneously produced more distortions and defects in the BiOCl lattice. The 40B0/CN composite exhibited the superior light absorption ability with a narrower band gap. The photocatalytic degradation rate for HCHO of 40B0/CN under solar light reached 87.7%, and the reaction rate constant was 0.0166 min-1, which was 1.6 times higher than that of BiOCl. This paper gave a deep insight into photocatalytic technology to efficiently degrade formaldehyde.

Cerebellar artery infarction with sudden hearing loss and vertigo as initial symptoms: A case report.

BACKGROUND: Sudden hearing loss (SHL) is associated with serious systematic conditions such as neoplasms, vascular events, autoimmune diseases, infections, and iatrogenic injury. Some authors report that SHL can be an early warning sign of impending vertebrobasilar ischemic stroke. It is important to distinguish stroke from benign disease. CASE SUMMARY: A 48-year-old male patient presented with SHL and vertigo as first symptoms. Diffusion-weighted imaging revealed high signal intensity in the left posterior inferior cerebellar artery territory of the cerebellar hemisphere and high signal intensity in the right pons and bridge cerebellar arm, confirming that the patient had cerebral infarction. Treatment with antiplatelet drugs, steroid anti-inflammatory drugs, and neurotrophic nerve therapy promoted blood circulation and removed blood stasis, and the symptoms of the patient were significantly improved. CONCLUSION: SHL and vertigo could be the initial symptoms of vertebrobasilar ischemic stroke.

Pharmacologic Treatment of Restless Legs Syndrome.

Restless legs syndrome (RLS)/Willis-Ekbom disease is a neurologic disorder characterized by a strong desire to move when at rest (usually in the evening) and paraesthesia in their lower legs. The most widely used therapies for first-line treatment of RLS are dopaminergic drugs; however, their long-term use can lead to augmentation. α2δ Ligands, opioids, iron, glutamatergic drugs, adenosine, and sleep aids have been investigated as alternatives. The pathogenesis of RLS is not well understood. Despite the efficacy of dopaminergic drugs in the treatment of this disorder, unlike in Parkinson's disease dopaminergic cell loss in the substantia nigra has not been observed in RLS. The etiology of RLS is likely complex, involving multiple neural pathways. RLS-related genes identified in genome-wide association studies can provide insight into the mechanistic basis and pathophysiology of RLS. Here we review the current treatments and knowledge of the mechanisms underlying RLS.

Anti-Rheumatic Properties of Gentiopicroside Are Associated With Suppression of ROS-NF-κB-NLRP3 Axis in Fibroblast-Like Synoviocytes and NF-κB Pathway in Adjuvant-Induced Arthritis.

Rheumatoid arthritis (RA) is among the most prevalent forms of autoimmunity. Gentiopicroside (Gent) is an iridoid glucoside derived from the Gentiana Macrophylla Pall which is used in traditional Chinese medicine to treat RA. The present study was designed to explore the ability of Gent to combat RA and to explore the molecular basis for such anti-RA activity both in vitro using tumor necrosis factor alpha (TNF-α)-stimulated human RA fibroblast-like synoviocytes (RA-FLS) and in vivo using a rat adjuvant-induced arthritis (AIA) model. We found that Gent was able to significantly reduce the swelling of joints and arthritic index scores, with corresponding reductions in synovial inflammatory cell infiltration, synovial hyperplasia, and bone erosion in treated AIA rats. Importantly, Gent 200 mg/kg reduced thymus index in AIA rats, but had no effect on spleen index and body weight, it revealed that Gent was relatively safe at the dose we chose. We further found that Gent was able to suppress the TNF-α-induced proliferation and migration of RA-FLS cells. This suppression was attributed to the ability of Gent to block NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), and caspase-1, thereby disrupting the activation of the NLRP3 inflammasome. Consistent with such suppression, Gent led to a significant decrease in IL-1ß secretion by treated cells. Furthermore, this reduction in NLRP3 inflammasome activation was also associated with decreases in the activation of nuclear factor (NF-κB), the production of reactive oxygen species (ROS), and the expression of inflammatory IL-6. Together these findings indicate that Gent can suppress the ROS-NF-κB-NLRP3 axis to alleviate RA symptoms. CHEMICAL COMPOUNDS STUDIED IN THIS ARTICLE: Gentiopicroside (PubChem CID: 88708).

Low percolation threshold carbon-black/ nitrile-butadiene-rubber composites and their electromagnetic shielding effects.

Nitrile-butadiene-rubber composites, filled with super conducting carbon black, are successfully prepared with low percolation threshold, high conductivity and electromagnetic shielding effectiveness. Percolation theory is used to represent the system's conductivity, and the corresponding result is close to the experimental value. The fitting curve also gives the weight fraction threshold and conductivity exponent of the conducting polymer. The percolation threshold of the composite is 9.2 phr, which is much smaller than previous homologous findings and lower than the value of short carbon fiber counterparts reported. The volume resistivity becomes 3.17 omega x cm for the 20 phr sample and decreases to 0.66 omega x cm for the 40 phr sample. At 1.8 GHz for 40 phr sample, the shielding effectiveness is -43 dB.