Inhibition of Nogo-B reduces the progression of pancreatic cancer by regulation NF-κB/GLUT1 and SREBP1 pathways.

Pancreatic cancer (PC) is a lethal disease and associated with metabolism dysregulation. Nogo-B is related to multiple metabolic related diseases and types of cancers. However, the role of Nogo-B in PC remains unknown. In vitro, we showed that cell viability and migration was largely reduced in Nogo-B knockout or knockdown cells, while enhanced by Nogo-B overexpression. Consistently, orthotopic tumor and metastasis was reduced in global Nogo knockout mice. Furthermore, we indicated that glucose enhanced cell proliferation was associated to the elevation expression of Nogo-B and nuclear factor κB (NF-κB). While, NF-κB, glucose transporter type 1 (GLUT1) and sterol regulatory element-binding protein 1 (SREBP1) expression was reduced in Nogo-B deficiency cells. In addition, we showed that GLUT1 and SREBP1 was downstream target of NF-κB. Therefore, we demonstrated that Nogo deficiency inhibited PC progression is regulated by the NF-κB/GLUT1 and SREBP1 pathways, and suggested that Nogo-B may be a target for PC therapy.

Evaluation of the DGT passive samplers for integrating fluctuating concentrations of pharmaceuticals in surface water.

Diffusive gradients in thin films (DGTs) have been well-documented for the measurement of a broad range of organic pollutants in surface water. However, the performance has been challenged by the inherent periodic concentration fluctuations for most organic pollutants. Therefore, there is an urgent need to assess the true time-weighted average (TWA) concentration based on fluctuating concentration profiles. The study aimed to evaluate the responsiveness of DGT and accuracy of TWA concentrations, considering various concentration fluctuating scenarios of 20 pharmaceuticals in surface water. The reliability and accuracy of the TWA concentrations measured by the DGT were assessed by comparison with the sum of cumulative mass of DGT exposed at different stages over the deployment period. The results showed that peak concentration duration (1-5 days), peak concentration fluctuation intensity (6-20 times), and occurrence time of peak concentration fluctuation (early, middle, and late stages) have minimal effect on DGT's response to most target pharmaceutical concentration fluctuations (0.8 < CDGT/CTWA < 1.2). While the downward-bent accumulations of a few pharmaceuticals on DGT occur as the sampling time increases, which could be accounted for by capacity effects during a long-time sampling period. Additionally, the DGT device had good sampling performance in recording short fluctuating concentrations from a pulse event returning to background concentrations with variable intensity and duration. This study revealed a satisfactory capacity for the evaluation of the TWA concentration of pharmaceuticals integrated over the period of different pulse deployment for DGT, suggesting that this passive sampler is ideally suited as a monitoring tool for field application. This study represents the first trial for evaluating DGT sampling performance for pharmaceuticals with multiple concentration fluctuating scenarios over time, which would be valuable for assessing the pollution status in future monitoring campaign.

[Effect of CircCCND1 on the Malignant Biological Behaviors of H446 Lung Cancer Cells by Regulating the MiR-340-5p/TGIF1 Axis].

BACKGROUND: Lung cancer is a common malignant tumor of the lung. To explore the molecular mechanism of the occurrence and development of lung cancer is a hot topic in current research. Cyclic RNA D1 (CircCCND1) is highly expressed in lung cancer and may be a potential target for the treatment of lung cancer. The aim of this study was to investigate the effect of CircCCND1 on the malignant biological behaviors of lung cancer cells by regulating the miR-340-5p/transforming growth factor ß-induced factor homeobox 1 (TGIF1) axis. METHODS: The expression of CircCCND1, miR-340-5p, and TGIF1 mRNA in human normal lung epithelial cells BEAS-2B and human lung cancer H446 cells were detected. H446 cells cultured in vitro were randomly divided into control group, CircCCND1 siRNA group, miR-340-5p mimics group, negative control group, and CircCCND1 siRNA+miR-340-5p inhibitor group. Cell proliferation, mitochondrial membrane potential, apoptosis, migration, and invasion were detected, and the expressions of CircCCND1, miR-340-5p, TGIF1 mRNA, BCL2-associated X protein (Bax), cleaved Caspase-3, N-cadherin, E-cadherin, and TGIF1 proteins in each group were detected. The targeting relationship of miR-340-5p with CircCCND1 and TGIF1 was verified. RESULTS: Compared with BEAS-2B cells, CircCCND1 and TGIF1 mRNA were increased in H446 cells, and miR-340-5p expression was decreased (P<0.05). Knocking down CircCCND1 or up-regulating the expression of miR-340-5p inhibited the proliferation, migration and invasion of H446 cells, decreased the expression of TGIF1 mRNA and TGIF1 protein, and promoted cell apoptosis. Down-regulation of miR-340-5p could antagonize the inhibitory effect of CircCCND1 knockdown on the malignant biological behavior of H446 lung cancer cells. CircCCND1 may target the down-regulation of miR-340-5p, and miR-340-5p may target the down-regulation of TGIF1. CONCLUSIONS: Knocking down CircCCND1 can inhibit the malignant behaviors of lung cancer H446 cells, which may be achieved through the regulation of miR-340-5p/TGIF1 axis.

Global, regional, and national burden of chronic kidney disease attributable to high fasting plasma glucose from 1990 to 2019: a systematic analysis from the global burden of disease study 2019.

Purpose: Given the rising prevalence of high fasting plasma glucose (HFPG) over the past three decades, it is crucial to assess its global, national, and regional impact on chronic kidney disease (CKD). This study aims to investigate the burden of CKD attributed to HFPG and its distribution across various levels. Methods and materials: The data for this research was sourced from the Global Burden of Diseases Study 2019. To estimate the burden of CKD attributed to HFPG, we utilized DisMod-MR 2.1, a Bayesian meta-regression tool. The burden was measured using age-standardized mortality rate (ASMR) and age-standardized disability-adjusted life years (DALYs) rate. Correlation analysis was performed using the Spearman rank order correlation method. Temporal trends were analyzed by estimating the estimated annual percentage change (EAPC). Results: Globally in 2019, there were a total of 487.97 thousand deaths and 13,093.42 thousand DALYs attributed to CKD attributed to HFPG, which represent a substantial increase of 153.8% and 120%, respectively, compared to 1990. Over the period from 1990 to 2019, the burden of CKD attributable to HFPG increased across all regions, with the highest increases observed in regions with high socio-demographic index (SDI) and middle SDI. Regions with lower SDI exhibited higher ASMR and age-standardized DALYs (ASDR) compared to developed nations at the regional level. Additionally, the EAPC values, which indicate the rate of increase, were significantly higher in these regions compared to developed nations. Notably, high-income North America, belonging to the high SDI regions, experienced the greatest increase in both ASMR and ASDR over the past three decades. Furthermore, throughout the years from 1990 to 2019, males bore a greater burden of CKD attributable to HFPG. Conclusion: With an increasing population and changing dietary patterns, the burden of CKD attributed to HFPG is expected to worsen. From 1990 to 2019, males and developing regions have experienced a more significant burden. Notably, the EAPC values for both ASMR and ASDR were higher in males and regions with lower SDI (excluding high-income North America). This emphasizes the pressing requirement for effective interventions to reduce the burden of CKD attributable to HFPG.

Occurrence, Source Apportionment, and Ecological Risk of Typical Pharmaceuticals in Surface Waters of Beijing, China.

Various studies have shown that the heavy use of pharmaceuticals poses serious ecological risks, especially in metropolitan areas with intensive human activities. In this study, the spatial distribution, sources, and ecological risks of 29 pharmaceuticals in 82 surface waters collected from the North Canal Basin in Beijing were studied. The results showed that the pharmaceutical concentrations ranged from not detected to 193 ng/L, with ampicillin being undetected while ofloxacin had a 100% detection frequency, which indicates the widespread occurrence of pharmaceutical pollution in the North Canal Basin. In comparison with other freshwater study areas, concentrations of pharmaceuticals in the North Canal Basin were generally at moderate levels. It was found that pharmaceutical concentrations were always higher in rivers that directly received wastewater effluents. Source analysis was conducted using the positive matrix factorization model. Combining the spatial pollution patterns of pharmaceuticals, it has been found that wastewater effluents contributed the most to the loads of pharmaceuticals in the studied basin, while in suburban areas, a possible contribution of untreated wastewater was demonstrated. Risk assessment indicated that approximately 55% of the pharmaceuticals posed low-to-high ecological risks, and combining the results of risk analyses, it is advised that controlling WWTP effluent is probably the most cost-effective measure in treating pharmaceutical pollution.

Discovery of 6-Acylamino/Sulfonamido Benzoxazolone with IL-6 Inhibitory Activity as Promising Therapeutic Agents for Ulcerative Colitis.

Ulcerative colitis has been widely concerned for its persistent upward trend, and the sustained overproduction of pro-inflammatory cytokines such as IL-6 remains a crucial factor in the development of UC. Therefore, the identification of new effective drugs to block inflammatory responses is an urgent and viable therapeutic strategy for UC. In our research, twenty-three 6-acylamino/sulfonamido benzoxazolone derivatives were synthesized, characterized, and evaluated for anti-inflammatory activity against NO and IL-6 production in LPS-induced RAW264.7 cells. The results demonstrated that most of the target compounds were capable of reducing the overexpression of NO and IL-6 to a certain degree. For the most active compounds 3i, 3j and 3 l, the inhibitory activities were superior or equivalent to those of the positive drug celecoxib with a dose-dependent relationship. Furthermore, animal experiments revealed that active derivatives 3i, 3j and 3 l exhibited definitive therapeutical effect on DSS induced ulcerative colitis in mice by mitigating weight loss and DAI score while decreasing levels of pro-inflammatory cytokines such as IL-6 and IFN-γ, simultaneously increasing production of anti-inflammatory cytokines IL-10. In addition, compounds 3i, 3j and 3 l could also inhibit the oxidative stress to alleviate ulcerative colitis by decreasing MDA and MPO levels. These finding demonstrated that compounds 3i, 3j and 3 l hold significant potential as novel therapeutic agents for ulcerative colitis.

First-line sugemalimab with chemotherapy for advanced esophageal squamous cell carcinoma: a randomized phase 3 study.

Although antiprogrammed death 1 antibody plus chemotherapy has recently been approved for first-line esophageal squamous cell carcinoma (ESCC), antiprogrammed death-ligand 1 antibody may offer another combination option in this setting. In this multicenter, randomized, double-blinded phase 3 trial a total of 540 adults (aged 18-75 years) with unresectable, locally advanced, recurrent or metastatic ESCC and who had not received systemic treatment were enrolled. All patients were randomized at 2:1 to receive either sugemalimab (an anti-PD-L1 antibody; 1,200 mg) or placebo every 3 weeks for up to 24 months, plus chemotherapy (cisplatin 80 mg m-2 on day 1 plus 5-fluorouracil 800 mg m-2 day-1 on days 1-4) every 3 weeks for up to six cycles. At the prespecified interim analysis this study had met dual primary endpoints. With a median follow-up of 15.2 months, the prolongation of progression-free survival was statistically significant with sugemalimab plus chemotherapy compared with placebo plus chemotherapy (median 6.2 versus 5.4 months, hazard ratio 0.67 (95% confidence interval 0.54-0.82), P = 0.0002) as assessed by blinded independent central review. Overall survival was also superior with sugemalimab chemotherapy (median 15.3 versus 11.5 months, hazard ratio 0.70 (95% confidence interval 0.55-0.90, P = 0.0076). A significantly higher objective response rate (60.1 versus 45.2%) as assessed by blinded independent central review was observed with sugemalimab chemotherapy. The incidence of grade 3 or above treatment-related adverse events (51.3 versus 48.4%) was comparable between the two groups. Sugemalimab plus chemotherapy significantly prolonged progression-free survival and overall survival in treatment-naïve patients with advanced ESCC, with no unexpected safety signal. The ClinicalTrials.gov identifier is NCT04187352 .

CD36 inhibition reduces non-small-cell lung cancer development through AKT-mTOR pathway.

Lung cancer is the most common cause of cancer-related deaths worldwide and is caused by multiple factors, including high-fat diet (HFD). CD36, a fatty acid receptor, is closely associated with metabolism-related diseases, including cardiovascular disease and cancer. However, the role of CD36 in HFD-accelerated non-small-cell lung cancer (NSCLC) is unclear. In vivo, we fed C57BL/6J wild-type (WT) and CD36 knockout (CD36-/-) mice normal chow or HFD in the presence or absence of pitavastatin 2 weeks before subcutaneous injection of LLC1 cells. In vitro, A549 and NCI-H520 cells were treated with free fatty acids (FFAs) to mimic HFD situation for exploration the underlying mechanisms. We found that HFD promoted LLC1 tumor growth in vivo and that FFAs increased cell proliferation and migration in A549 and NCI-H520 cells. The enhanced cell or tumor growth was inhibited by the lipid-lowering agent pitavastatin, which reduced lipid accumulation. More importantly, we found that plasma soluble CD36 (sCD36) levels were higher in NSCLC patients than those in healthy ones. Compared to that in WT mice, the proliferation of LLC1 cells in CD36-/- mice was largely suppressed, which was further repressed by pitavastatin in HFD group. At the molecular level, we found that CD36 inhibition, either with pitavastatin or plasmid, reduced proliferation- and migration-related protein expression through the AKT/mTOR pathway. Taken together, we demonstrate that inhibition of CD36 expression by pitavastatin or other inhibitors may be a viable strategy for NSCLC treatment.

Methionine redox regulation of actin-interacting proteins primarily governs antioxidative signaling and response to the salvianolic acid B treatment in EA.hy926 cells.

Actin-interacting proteins are important molecules for filament assembly and cytoskeletal signaling within vascular endothelium. Disruption in their interactions causes endothelial pathogenesis through redox imbalance. Actin filament redox regulation remains largely unexplored, in the context of pharmacological treatment. This work focused on the peptidyl methionine (M) redox regulation of actin-interacting proteins, aiming at elucidating its role on governing antioxidative signaling and response. Endothelial EA.hy926 cells were subjected to treatment with salvianolic acid B (Sal B) and tert-butyl-hydroperoxide (tBHP) stimulation. Mass spectrometry was employed to characterize redox status of proteins, including actin, myosin-9, kelch-like erythroid-derived cap-n-collar homology-associated protein 1 (Keap1), plastin-3, prelamin-A/C and vimentin. The protein redox landscape revealed distinct stoichiometric ratios or reaction site transitions mediated by M sulfoxide reductase and reactive oxygen species. In comparison with effects of tBHP stimulation, Sal B treatment prevented oxidation at actin M325, myosin-9 M1489/1565, Keap1 M120, plastin-3 M592, prelamin-A/C M187/371/540 and vimentin M344. For Keap1, reaction site was transitioned within its scaffolding region to the actin ring. These protein M oxidation regulations contributed to the Sal B cytoprotective effects on actin filament. Additionally, regarding the Keap1 homo-dimerization region, Sal B preventive roles against M120 oxidation acted as a primary signal driver to activate nuclear factor erythroid 2-related factor 2 (Nrf2). Transcriptional splicing of non-POU domain-containing octamer-binding protein was validated during the Sal B-mediated overexpression of NAD(P)H dehydrogenase [quinone] 1. This molecular redox regulation of actin-interacting proteins provided valuable insights into the phenolic structures of Sal B analogs, showing potential antioxidative effects on vascular endothelium.

Predictive value of HTS grade in patients with intrahepatic cholangiocarcinoma undergoing radical resection: a multicenter study from China.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a highly malignant tumor with a poor prognosis. This study aimed to investigate whether Hemoglobin, Albumin, Lymphocytes, and Platelets (HALP) score and Tumor Burden Score (TBS) serves as independent influencing factors following radical resection in patients with ICC. Furthermore, we sought to evaluate the predictive capacity of the combined HALP and TBS grade, referred to as HTS grade, and to develop a prognostic prediction model. METHODS: Clinical data for ICC patients who underwent radical resection were retrospectively analyzed. Univariate and multivariate Cox regression analyses were first used to find influencing factors of prognosis for ICC. Receiver operating characteristic (ROC) curves were then used to find the optimal cut-off values for HALP score and TBS and to compare the predictive ability of HALP, TBS, and HTS grade using the area under these curves (AUC). Nomogram prediction models were constructed and validated based on the results of the multivariate analysis. RESULTS: Among 423 patients, 234 (55.3%) were male and 202 (47.8) were aged ≥ 60 years. The cut-off value of HALP was found to be 37.1 and for TBS to be 6.3. Our univariate results showed that HALP, TBS, and HTS grade were prognostic factors of ICC patients (all P < 0.05), and ROC results showed that HTS had the best predictive value. The Kaplan-Meier curve showed that the prognosis of ICC patients was worse with increasing HTS grade. Additionally, multivariate regression analysis showed that HTS grade, carbohydrate antigen 19-9 (CA19-9), tumor differentiation, and vascular invasion were independent influencing factors for Overall survival (OS) and that HTS grade, CA19-9, CEA, vascular invasion and lymph node invasion were independent influencing factors for recurrence-free survival (RFS) (all P < 0.05). In the first, second, and third years of the training group, the AUCs for OS were 0.867, 0.902, and 0.881, and the AUCs for RFS were 0.849, 0.841, and 0.899, respectively. In the first, second, and third years of the validation group, the AUCs for OS were 0.727, 0.771, and 0.763, and the AUCs for RFS were 0.733, 0.746, and 0.801, respectively. Through the examination of calibration curves and using decision curve analysis (DCA), nomograms based on HTS grade showed excellent predictive performance. CONCLUSIONS: Our nomograms based on HTS grade had excellent predictive effects and may thus be able to help clinicians provide individualized clinical decision for ICC patients.

Toripalimab plus nab-paclitaxel in metastatic or recurrent triple-negative breast cancer: a randomized phase 3 trial.

The combination of immune-checkpoint blockade with chemotherapy for the first-line treatment of advanced triple-negative breast cancer (TNBC) has generated mixed results. TORCHLIGHT is a randomized, double-blinded phase 3 trial evaluating the efficacy and safety of first-line toripalimab and nab-paclitaxel (nab-P) (n = 353; experimental arm) versus placebo and nab-P (n = 178; control arm) for the treatment of women with metastatic or recurrent TNBC. The primary end point was progression-free survival (PFS) assessed by a blinded independent central review in the PD-L1-positive and intention-to-treat populations. The secondary end points included overall survival and safety. Overall, 200 and 100 patients, in the toripalimab and placebo arm respectively had PD-L1-positive TNBC. At the prespecified interim analysis, a statistically significant improvement in PFS assessed by a blinded independent central review was demonstrated in the experimental arm in the PD-L1-positive population (median PFS 8.4 versus 5.6 months; hazard ratio (HR) = 0.65, 95% confidence interval (CI) 0.470-0.906, P = 0.0102). The median overall survival was 32.8 versus 19.5 months (HR = 0.62, 95% CI 0.414-0.914, P = 0.0148). Similar incidences of treatment-emergent adverse events (AEs) (99.2% versus 98.9%), grade ≥3 treatment-emergent AEs (56.4% versus 54.3%) and fatal AEs (0.6% versus 3.4%) occurred in the experimental and control arms. The addition of toripalimab to nab-P provided a significant improvement in PFS for PD-L1-positive patients with metastatic or recurrent TNBC with an acceptable safety profile. ClinicalTrial.gov identifier NCT03777579 .

Depth-dependent variations of physicochemical properties of sedimentary dissolved organic matter and the influence on the elimination of typical pharmaceuticals.

Sedimentary dissolved organic matter (DOM) could exert a significant influence on the transformation of trace organic contaminants. However, the variations of sedimentary DOM properties with depth and their impact on trace organic contaminants biodegradation remain unclear. In this study, the qualitative changes in DOM properties with depth were assessed using spectral techniques. Specifically, within the sediment range of 0-30 cm, humic acid and fulvic acid fractions exhibited higher degrees of humification and aromatization at 10-20 cm, while hydrophilic fractions showed higher degrees of humification and aromatization at 20-30 cm. Furthermore, electrochemical methods were employed to quantitatively assess the electron transfer capacity of sedimentary DOM at different depths, which displayed consistent variation trend with humification and aromatization degree. The high degree of humification and aromatization, along with strong electron-accepting capability of DOM, significantly enhanced the biodegradation rates of tetracycline and ritonavir. To gain deeper insights into the influence of molecular composition of DOM on its properties, two-dimensional gas chromatography-quadrupole mass spectrometry analysis revealed that quinones and phenolic hydroxyl compounds govern the redox reactivity of DOM. Simulated experiment of DOM-mediated biodegradation of typical pharmaceuticals confirmed the role of quinones and phenolic hydroxyl groups in the redox reactivity of DOM.

The pterostilbene-dihydropyrazole derivative Ptd-1 ameliorates vascular calcification by regulating inflammation.

Vascular calcification is an independent risk factor for cardiovascular disease. However, there is still a lack of adequate treatment. This study aimed to examine the potential of (E)-1-(5-(2-(4-fluorobenzyloxy)Styryl)-4,6-dimethoxyphenyl)-3-methyl-4,5-dihydro-1H-pyrazole-1-yl) ethyl ketone (Ptd-1) to alleviate vascular calcification. ApoE-deficient mice were fed a high-fat diet for 12/16 weeks to induce intimal calcification, and wild-type mice were induced with a combination of nicotine and vitamin D3 to induce medial calcification. Human aortic smooth muscle cells (HASMCs) and aortic osteogenic differentiation were induced in vitro with phosphate. In the mouse model of atherosclerosis, Ptd-1 significantly ameliorated the progression of atherosclerosis and intimal calcification, and there were significant reductions in lipid deposition and calcium salt deposition in the aorta and aortic root. In addition, Ptd-1 significantly improved medial calcification in vivo and osteogenic differentiation in vitro. Mechanistically, Ptd-1 reduced the levels of the inflammatory factors IL-1ß, TNFα and IL-6 in vivo and in vitro. Furthermore, we demonstrated that Ptd-1 could attenuate the expression of p-ERK1/2 and ß-catenin, and that the levels of inflammatory factors were elevated in the presence of ERK1/2 and ß-catenin agonists. Interestingly, we determined that activation of the ERK1/2 pathway promoted ß-catenin expression, which further regulated the IL-6/STAT3 signaling pathway. Ptd-1 blocked ERK1/2 signaling, leading to decreased expression of inflammatory factors, which in turn improved vascular calcification. Taken together, our study reveals that Ptd-1 ameliorates vascular calcification by regulating the production of inflammatory factors, providing new ideas for the treatment of vascular calcification.

Construction and validation of a novel prognostic model for intrahepatic cholangiocarcinoma based on a combined scoring system of systemic immune-inflammation index and albumin-bilirubin: a multicenter study.

Background: The degree of inflammation and immune status is widely recognized to be associated with intrahepatic cholangiocarcinoma (ICC) and is closely linked to poor postoperative survival. The purpose of this study was to evaluate whether the systemic immune-inflammatory index (SII) and the albumin bilirubin (ALBI) grade together exhibit better predictive strength compared to SII and ALBI separately in patients with ICC undergoing curative surgical resection. Methods: A retrospective analysis was performed on a cohort of 374 patients with histologically confirmed ICC who underwent curative surgical resection from January 2016 to January 2020 at three medical centers. The cohort was divided into a training set comprising 258 patients and a validation set consisting of 116 patients. Subsequently, the prognostic predictive abilities of three indicators, namely SII, ALBI, and SII+ALBI grade, were evaluated. Independent risk factors were identified through univariate and multivariate analyses. The identified independent risk factors were then utilized to construct a nomogram prediction model, and the predictive strength of the nomogram prediction model was assessed through Receiver Operating Characteristic (ROC) survival curves and calibration curves. Results: Univariate analysis of the training set, consisting of 258 eligible patients with ICC, revealed that SII, ALBI, and SII+ALBI grade were significant prognostic factors for overall survival (OS) and recurrence-free survival (RFS) (p < 0.05). Multivariate analysis revealed the independent significance of SII+ALBI grade as a risk factor for postoperative OS and RFS (p < 0.05). Furthermore, we conducted an analysis of the correlation between SII, ALBI, SII+ALBI grade, and clinical features, indicating that SII+ALBI grade exhibited stronger associations with clinical and pathological characteristics compared to SII and ALBI. We constructed a predictive model for postoperative survival in ICC based on SII+ALBI grade, as determined by the results of multivariate analysis. Evaluation of the model's predictive strength was performed through ROC survival curves and calibration curves in the training set and validation set, revealing favorable predictive performance. Conclusion: The SII+ALBI grade, a novel classification based on inflammatory and immune status, serves as a reliable prognostic indicator for postoperative OS and RFS in patients with ICC.

SENP1-mediated SUMOylation of SIRT1 affects glioma development through the NF-κB pathway.

Gliomas are the most common primary brain tumors in adults. Although they exist in different malignant stages, most gliomas are clinically challenging because of their infiltrative growth patterns and inherent relapse tendency with increased malignancy. Epigenetic alterations have been suggested to be an important factor for glioma genesis. Using mRNA probe hybridization, we identified SUMO-specific protease 1 (SENP1) as the most significantly upregulated SUMOylation regulator in glioma. Moreover, SENP1 was overexpressed in gliomas and predicted poor prognoses. Depletion of SENP1 reduced glioma cell activity, cycle arrest, and increased apoptotic activity. Mechanistically, SENP1 inhibited the protein expression of sirtuin 1 (SIRT1) through de-SUMOylation, and SIRT1 inhibited the activity of nuclear factor kappaB (NF-κB) by deacetylation. Rescue experiments revealed that downregulation of SIRT1 reversed the inhibitory effect of sh-SENP1 on glioma cell malignant phenotype, while downregulation of NF-κB reversed the activating effect of sh-SIRT1 on glioma cell malignant phenotype. Thus, SENP1-mediated de-SUMOylation of SIRT1 might be therapeutically important in gliomas.

Continuous variable quantum key distribution based on simultaneous quantum and classical communication in the terahertz band.

Continuous variable quantum key distribution (CVQKD) based on a simultaneous quantum and classical communication (SQCC) protocol can use a single coherent communication system for multiple purposes. In this paper, we propose an inter-satellite SQCC-CVQKD scheme in the terahertz (THz) band. This scheme performs classical modulation at the sending end, followed by quantum Gaussian modulation operations. At the receiving end, an amplifier is used to amplify and demultiplex the received signal, and, finally, a homodyne detector or heterodyne detector is selected for decoding. We have demonstrated the security of the SQCC-CVQKD system in the THz band, and a performance analysis of the scheme is given in the finite-size regime. The simulation results show that this scheme has a higher secret key rate and stronger anti-interference ability in practice. This work provides an effective way to construct wireless quantum communication networks.

Arthroscopic treatment of deep gluteal syndrome and the application value of high-frequency ultrasound.

PURPOSE: This study aimed to evaluate the efficacy of arthroscopic sciatic neurolysis for treating deep gluteal syndrome (DGS) and to analyse the application value of high-frequency ultrasound during perioperative period. METHODS: Between June 2020 and February 2022, 30 patients with DGS who underwent failed conservative treatment were retrospectively analysed. Lateral arthroscopic exploration of the deep gluteal space and sciatic neurolysis were performed. In addition to pelvic X-ray, lumbar disc and hip magnetic resonance imaging (MRI), ultrasonography of the sciatic nerve was also performed in all patients. The visual analogue scale pain score (VAS), modified Harris hip score (mHHS) and Benson symptom-rating scale were used to evaluate the clinical efficacy. The correlation between preoperative sciatic nerve ultrasound and arthroscopic findings was analysed. RESULTS: The median follow-up for these patients was 13 months (range,12-21 months). Preoperative ultrasonography showed precise morphological changes in 26 sciatic nerves of patients. The VAS score decreased from 5.0 (4.0, 6.0) preoperatively to 0.5 (0, 1.0) postoperatively (p < 0.001), and the mHHS increased from 64.0 (57.0, 67.0) preoperatively to 95.0 (93.0, 97.0) postoperatively (p < 0.001). The Benson symptom score was excellent in 15 cases, good in 12 cases, fair in 2 cases, poor in 1 case; thus, the score was excellent or good in 90% of the cases. Preoperative ultrasound diagnosis and intra-operative findings matched up in all cases. There were four cases of transient numbness in the posterior thigh. CONCLUSIONS: Arthroscopic sciatic neurolysis is a safe and effective treatment option for DGS patients who fail conservative treatment. Ultrasound diagnosis matched the arthroscopic findings perfectly. Preoperative Doppler ultrasound can assist surgical decision-making, guide intraoperative release.

Fabrication of versatile polyvinyl alcohol and carboxymethyl cellulose-based hydrogels for information hiding and flexible sensors: Heat-induced adjustable stiffness and transparency.

With the growing demand for wearable electronics, designing biocompatible hydrogels that combine self-repairability, wide operating temperature and precise sensing ability offers a promising scheme. Herein, by interpenetrating naturally derived carboxymethyl cellulose (CMC) into a polyvinyl alcohol (PVA) gel matrix, a novel hydrogel is successfully developed via simple coordination with calcium chloride (CaCl2). The chelation of CMC and Ca2+ is applied as a second crosslinking mechanism to stabilize the hydrogel at relatively high temperature (95 °C). In particular, it has unique heat-induced healing behavior and unexpected tunable stiffness & transparency. Like the sea cucumber, the gel can transform between a stiffened state and a relaxed state (nearly 23 times modulated stiffness from 453 to 20 kPa) which originates from the reconstruction of the crystallites. The adjustable transparency enables the hydrogel to become an excellent information hiding material. Due to the presence of Ca2+, the hydrogels show favorable conductivity, anti-freezing and long-term stability. Based on the advantages, a self-powered sensor, where chemical energy is converted to electrical energy, is assembled for human motion detection. The low-cost, environmentally friendly strategy, at the same time, complies to the "green" chemistry concept with the full employment of the biopolymers. Therefore, the proposed hydrogel is deemed to find potential use in wearable sensors.

Novel pterostilbene derivatives ameliorate heart failure by reducing oxidative stress and inflammation through regulating Nrf2/NF-κB signaling pathway.

Pterostilbene is a demethylated resveratrol derivative with attractive anti-inflammatory, anti-tumor and anti-oxidative stress activities. However, the clinical use of pterostilbene is limited by its poor selectivity and druggability. Heart failure is a leading cause of morbidity and mortality worldwide, which is closely related to enhanced oxidative stress and inflammation. There is an urgent need for new effective therapeutic drugs that can reduce oxidative stress and inflammatory responses. Therefore, we designed and synthesized a series of novel pterostilbene chalcone and dihydropyrazole derivatives with antioxidant and anti-inflammatory activities by the molecular hybridization strategy. The preliminary anti-inflammatory activities and structure-activity relationships of these compounds were evaluated by nitric oxide (NO) inhibitory activity in lipopolysaccharide (LPS)-treated RAW264.7 cells, and compound E1 exhibited the most potent anti-inflammatory activities. Furthermore, pretreatment with compound E1 decreased reactive oxygen species (ROS) generation both in RAW264.7 and H9C2 cells by increasing the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), as well as downstream antioxidant enzymes superoxide dismutase 1 (SOD1), catalase (CAT) and glutathione peroxidase 1 (GPX1). In addition, compound E1 also significantly inhibited LPS or doxorubicin (DOX)-induced inflammation in both RAW264.7 and H9C2 cells through reducing the expression of inflammatory cytokines by inhibiting nuclear factor-κB (NF-κB) signaling pathway. Moreover, we found that compound E1 improved DOX-induced heart failure by inhibiting inflammation and oxidative stress in mouse model, which is mediated by the potential of antioxidant and anti-inflammatory activities. In conclusion, this study demonstrated the novel pterostilbene dihydropyrazole derivative E1 was identified as a promising agent for heart failure treatment.

6-Methyl flavone inhibits Nogo-B expression and improves high fructose diet-induced liver injury in mice.

Excessive fructose consumption increases hepatic de novo lipogenesis, resulting in cellular stress, inflammation and liver injury. Nogo-B is a resident protein of the endoplasmic reticulum that regulates its structure and function. Hepatic Nogo-B is a key protein in glycolipid metabolism, and inhibition of Nogo-B has protective effects against metabolic syndrome, thus small molecules that inhibit Nogo-B have therapeutic benefits for glycolipid metabolism disorders. In this study we tested 14 flavones/isoflavones in hepatocytes using dual luciferase reporter system based on the Nogo-B transcriptional response system, and found that 6-methyl flavone (6-MF) exerted the strongest inhibition on Nogo-B expression in hepatocytes with an IC50 value of 15.85 µM. Administration of 6-MF (50 mg· kg-1 ·d-1, i.g. for 3 weeks) significantly improved insulin resistance along with ameliorated liver injury and hypertriglyceridemia in high fructose diet-fed mice. In HepG2 cells cultured in a media containing an FA-fructose mixture, 6-MF (15 µM) significantly inhibited lipid synthesis, oxidative stress and inflammatory responses. Furthermore, we revealed that 6-MF inhibited Nogo-B/ChREBP-mediated fatty acid synthesis and reduced lipid accumulation in hepatocytes by restoring cellular autophagy and promoting fatty acid oxidation via the AMPKα-mTOR pathway. Thus, 6-MF may serve as a potential Nogo-B inhibitor to treat metabolic syndrome caused by glycolipid metabolism dysregulation.