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Skin malignant melanoma is one of the most aggressive skin tumors. Superficial spreading melanoma (SSM) is the most common histological type, which can originate from different body skin sites, and some patients can still accumulate regional lymph nodes and even have distant metastasis in some cases. This study used the relevant data from the monitoring, epidemiology and results database of the National Cancer Institute database to study the overall survival (OS) and cancer-specific survival (CSS) of SSM patients and established an SSM nomogram to evaluate the prognosis of patients. A total of 13,922 patients were collected from the monitoring, epidemiology and results database of the National Cancer Institute and randomly divided into a training cohort (8353 cases) and a validation cohort (5569 cases). Univariate and multivariate Cox regression analysis were used to determine prognostic factors, and these factors were used to construct OS and CSS nomograms for patients with SSM. Finally, the discrimination and consistency of the nomogram model were evaluated by the consistency index (C-index), area under the curve (AUC) and calibration curve. Multivariate Cox regression analysis suggested that age, sex, tumor site, the American joint committee on cancer T stage and the first primary melanoma were independent predictors of OS and CSS in patients with SSM and that the American joint committee on cancer N stage was also an independent predictor of CSS in patients with SSM. Based on the above prognostic factors, this study constructed a predictive model. The C-index of the model OS and CSS for this training cohort was 0.805 [95% CI: 0.793-0.817] and 0.896 [95% CI: 0.878-0.913], respectively. The AUC values for 1-, 3-, and 5-year OS were 0.822, 0.820, and 0.821, respectively, and the AUC values for CSS were 0.914, 0.922, and 0.893, respectively. The data indicated that both nomograms showed better predictive accuracy. The calibration curves of the training cohort and the validation cohort were in good agreement. The nomogram has superior predictive performance in predicting 1-, 3-, and 5-year OS and CSS prognosis in patients with SSM and can provide a reference for individualized treatment and clinical counseling of SSM.

Background It is important to determine the severity of inhalation injury in severely burned patients. The oxygenation index PaO2/FiO2(PF) ratio is a key clinical indicator of inhalation injury. Sequential organ failure assessment (SOFA) is developed to assess the acute incidence of critical illness in the population. We hope to provide an assessment of survival or prognostic factor for severely burned patients with inhalation injury based on the respiratory SOFA score. Methods This is a retrospective cohort study of all admissions to Department of Burn and Plastic Surgery at West China Hospital of Sichuan University from July 2010 to March 2021. Data was analyzed using Cox regression models to determine significant predictors of mortality. Survival analysis with time to death event was performed using the Kaplan–Meier survival curve with the log-rank test. All potential risk factors were considered independent variables, while survival was considered the risk dependent variable. Results One hundred eighteen severe burn patients with inhalation injury who met the inclusion and exclusion criteria were admitted, including men accounted for 76.3%. The mean age and length of stay were 45.9 (14.8) years and 44.3 (38.4) days. Flame burns are the main etiology of burn (74.6%). Patients with the respiratory SOFA score greater than 2 have undergone mechanical ventilation. Univariate Kaplan–Meier analysis identified age, total body surface area burned (TBSA), ICU admission and the respiratory SOFA score as significant factors on survival. Cox regression analysis showed that TBSA and the respiratory SOFA score were associated with patient survival (p p = 0.175). Conclusion The study indicates that a high respiratory system SOFA score was identified as a strong and independent predictor of severely burned patients with inhalation injury during hospitalization. When combined with TBSA, the respiratory SOFA scores can dynamically assess the severity of the patient's lung injury and improve the predictive level.

Bone age assessment using hand-wrist X-ray images is fundamental when diagnosing growth disorders of a child or providing a more patient-specific treatment. However, as clinical procedures are a subjective assessment, the accuracy depends highly on the doctor’s experience. Motivated by this, a deep learning-based computer-aided diagnosis method was proposed for performing bone age assessment. Inspired by clinical approaches and aimed to reduce expensive manual annotations, informative regions localization based on a complete unsupervised learning method was firstly performed and an image-processing pipeline was proposed. Subsequently, an image model with pre-trained weights as a backbone was utilized to enhance the reliability of prediction. The prediction head was implemented by a Multiple Layer Perceptron with one hidden layer. In compliance with clinical studies, gender information was an additional input to the prediction head by embedded into the feature vector calculated from the backbone model. After the experimental comparison study, the best results showed a mean absolute error of 6.2 months on the public RSNA dataset and 5.1 months on the additional dataset using MobileNetV3 as the backbone.

Cisplatin nephrotoxicity has been considered as serious side effect caused by cisplatin‐based chemotherapy. Recent evidence indicates that renal tubular cell apoptosis and inflammation contribute to the progression of cisplatin‐induced acute kidney injury (AKI). Hepatocyte nuclear factor 1β (HNF1β) has been reported to regulate the development of kidney cystogenesis, diabetic nephrotoxicity, etc However, the regulatory mechanism of HNF1β in cisplatin nephrotoxicity is largely unknown. In the present study, we examined the effects of HNF1β deficiency on the development of cisplatin‐induced AKI in vitro and in vivo. HNF1β down‐regulation exacerbated cisplatin‐induced RPTC apoptosis by indirectly inducing NF‐κB p65 phosphorylation and nuclear translocation. HNF1β knockdown C57BL/6 mice were constructed by injecting intravenously with HNF1β‐interfering shRNA and PEI. The HNF1β scramble and knockdown mice were treated with 30 mg/kg cisplatin for 3 days to induce acute kidney injury. Cisplatin treatment caused increased caspase 3 cleavage and p65 phosphorylation, elevated serum urea nitrogen and creatinine, and obvious histological damage of kidney such as fractured tubules in control mice, which were enhanced in HNF1β knockdown mice. These results suggest that HNF1β may ameliorate cisplatin nephrotoxicity in vitro and in vivo, probably through regulating NF‐κB signalling pathway.

Uric acid crystal is known to activate the NLRP3 inflammasome and to cause tissue damages, which can result in many diseases, such as gout, chronic renal injury and myocardial damage. Meanwhile, soluble uric acid (sUA), before forming crystals, is also related to these diseases. This study was carried out to investigate whether sUA could also activate NLRP3 inflammasome in cardiomyocytes and to analyse the mechanisms. The cardiomyocyte activity was monitored, along with the levels of mature IL‐1β and caspase‐1 from H9c2 cells following sUA stimulus. We found that sUA was able to activate NLRP3 inflammasome, which was responsible for H9c2 cell apoptosis induced by sUA. By elevating TLR6 levels and then activating NF‐κB/p65 signal pathway, sUA promoted NLRP3, pro‐caspase 1 and pro‐IL‐1β production and provided the first signal of NLRP3 inflammasome activation. Meanwhile, ROS production regulated by UCP2 levels also contributed to NLRP3 inflammasome assembly and subsequent caspase 1 activation and mature IL‐1β secretion. In addition, the tlr6 knockdown rats suffering from hyperuricemia showed the lower level of IL‐1β and an ameliorative cardiac function. These findings suggest that sUA activates NLRP3 inflammasome in cardiomyocytes and they may provide one therapeutic strategy for myocardial damage induced by sUA.

Fuel cells are considered renewable and clean energy sources to replace the dwindling fossil fuel resources. However, the sluggish reaction kinetics of the anodic fuel oxidation and cathodic oxygen reduction reactions hinder the wide commercialization of fuel cells. The Pt/C material is still the most efficient electrocatalyst; however, its high price and poor stability severely impede its large-scale application. Recently, transition metal nitrides (TMNs) have been regarded as promising electrocatalyst materials owing to their unique physical, chemical, and electronic properties, e.g., thermal stability, metallic conductivity, great hardness, and corrosion resistance. Herein, the advances pertaining to TMN-based catalyst materials for fuel cells are reviewed, ranging from their structures, properties, and synthesis to their applications. TMNs can act as catalysts or supports in electrocatalytic processes. Briefly, as catalysts, TMNs are grouped into free-standing TMNs (including binary and ternary TMNs) and TMN/carbon composites. Moreover, as supports, TMNs can be categorized as pure TMNs supports and hybrid supports to anchor noble metals. Finally, the challenges and perspectives of TMN-based catalyst materials for high-performance fuel cell systems are discussed.

Acute myocardial infarction (AMI) is associated with high morbidity and mortality. An effective therapeutic strategy is to rescue cardiomyocytes from death. Apoptosis is a key reason of cardiomyocyte death that can be prevented. In this study, we investigated the role of TNF-related apoptosis-inducing ligand (TRAIL) in initiating apoptosis by binding to death receptor 5 (DR5), and this procession is inhibited by soluble DR5 (sDR5) in rats after AMI. First, we found that the level of TRAIL in serum was down-regulated in AMI patients. Then, TRAIL and DR5 expression was analysed in the myocardium of rats after AMI, and their expression was up-regulated. sDR5 treatment reduced the myocardial infarct size and the levels of CK-MB and cTn-I in serum. The expression of caspase 3 and PARP is decreased, but the anti-apoptotic factor Bcl-2 was increased in sDR5 treatment rats after AMI. DR5 expression was also analysed after sDR5 treatment and it was down-regulated, and a low level of DR5 expression seemed to be beneficial for the myocardium. Overall, our findings indicated that sDR5 decreases myocardial damage by inhibiting apoptosis in rat after AMI. We expect to observe the potential therapeutic effects of sDR5 on AMI in the future.

The sluggish kinetics of sulfur conversion in the cathode and the nonuniform deposition of lithium metal at the anode result in severe capacity decay and poor cycle life for lithium-sulfur (Li-S) batteries. Resolving these deficiencies is the most direct route toward achieving practical cells of this chemistry. Herein, a vertically aligned wood-derived carbon plate decorated with Co

Lithium–sulfur batteries (LSBs) are considered one of the most promising candidates for next-generation energy storage owing to their large energy capacity. Tremendous effort has been devoted to overcoming the inherent problems of LSBs to facilitate their commercialization, such as polysulfide shuttling and dendritic lithium growth. Pouch cells present additional challenges for LSBs as they require greater electrode active material utilization, a lower electrolyte–sulfur ratio, and more mechanically robust electrode architectures to ensure long-term cycling stability. In this review, the critical challenges facing practical Li–S pouch cells that dictate their energy density and long-term cyclability are summarized. Strategies and perspectives for every major pouch cell component—cathode/anode active materials and electrode construction, separator design, and electrolyte—are discussed with emphasis placed on approaches aimed at improving the reversible electrochemical conversion of sulfur and lithium anode protection for high-energy Li–S pouch cells.

Background Cutaneous malignant melanoma (CMM) is one of the most aggressive skin tumors. Sentinel lymph node biopsy (SLNB) is an important test before thorough treatment of melanoma. The aim of this study was to investigate cancer-specific survival (CSS) in patients with head and neck CMM after negative SLNB and to analyze predictors of decreased survival. Methods Based on the Surveillance, Epidemiology and End Results (SEER) database, a study was conducted using data from patients with head and neck CMM after negative SLNB. The demographic, clinical, and pathological characteristics of the case population were analyzed. Cox univariate, Kaplan–Meier analysis, and multivariate Cox regression models were used to explore predictors of decreased survival; propensity score matching (PSM) analysis was used to reduce confounding bias, and outcomes were compared between the wide margin excision and narrow margin excision groups. Results A total of 1597 confirmed head and neck CMM patients with SLNB-negative were found. A Breslow>4.0 mm was the highest independent risk predictor for patients (HR 3.82, 95% CI 2.04-7.16, P < .001), and significant risk independent predictors also included a high mitotic rate >4 (HR 1.54, 95% CI 1.06-2.25, P = .023). Age< 60 years old was a significant survival predictor (HR 0.56, 95% CI .37-.85, P = .007), and not scalp and neck CMM were also important factors for longer survival (auricle skin: HR .51, 95% CI .29-.90, P = .02; unspecified parts of face: HR .59, 95% CI .40-.87, P = .007). After harmonizing baseline data by PSM, it was found that the extent of surgical resection did not affect patient survival. Conclusion This study analyzed the risk factors affecting CSS in patients with CMM of the head and neck region with SLNB-negative and observed a statistically significant difference in the prognosis of patients with CMM in different aesthetic subunits of the head and neck region. Close clinical follow-up for this population is necessary, and periodic medical examinations should be carried out.

Lithium metal batteries with polyethylene oxide (PEO) electrolytes are considered as one of the ideal candidates for next generation power sources. However, the low ambient operation capability and conventional solvent-based fabrication process of PEO limit their large-scale application. In this work, a comb-like quasi-solid polymer electrolyte (QPE) reinforced with polyethylene glycol terephthalate nonwoven is fabricated. Combining the density functional theory calculation analysis and polymer structure design, optimized and synergized ion conductive channels are established by copolymerization of tetrahydrofurfuryl acrylate and introduction of plasticizer tetramethyl urea. Additionally, a unique two-stage solventless UV polymerization strategy is utilized for rheology tuning and electrolyte fabrication. Compared with the conventional one-step UV process, this strategy is ideally suited for the roll-to-roll continuous coating fabrication process with environmental friendliness. The fabricated QPE exhibits high ionic conductivity of 0.40 mS cm

Zhizeng Wang,1,* Qianqwen Zhou,1,* Yafei Guo,2,* Hangzhan Hu,1 Zhi Zheng,1 Shulian Li,1 Yaohui Wang,1 Yuanfang Ma1 1Joint National Laboratory for Antibody Drug Engineering, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, People’s Republic of China; 2School of Laboratory, Sanquan college of Xinxiang Medical University, Xinxiang, Henan, 453003, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yaohui Wang; Yuanfang MaJoint National Laboratory for Antibody Drug Engineering, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, People’s Republic of ChinaTel +86 18237816739; +86 13803786139Email wangyaohui2001@sina.com; mayf@henu.edu.cnPurpose: The purpose of this study was to establish a lateral flow immunoassay using selenium nanoparticles (Se-NPs) as a probe to detect ractopamine (RAC) and salbutamol (SAL) in swine urine.Methods: SDS and PEG were used as templates to prepare Se-NPs; anti-RAC monoclonal antibodies or anti-SAL monoclonal antibodies were labelled with Se-NPs; and rapid detection kits were prepared. The sensitivity, specificity, and stability were measured, and actual samples were analysed.Results: The Se-NPs were spherical with a diameter of 40.63 ± 5.91 nm, and were conjugated successfully with an anti-RAC antibody to give a total diameter of 82.33 ± 17.91 nm. The detection limit of a RAC kit in swine urine was 1 ng/mL, and that of a SAL kit was 3 ng/mL. Both procedures could be completed within 5 minutes. No cross-reaction occurred with clenbuterol, bambuterol and phenylethanolamine A. Samples were tested consistently across different batches of kits for swine urine. The results of the kits were identical to those of actual clinical samples analysed by ELISA, and the coincidence rate was 100%.Conclusion: The assay kit does not require any special device for reading the results, and the readout is a simple colour change that can be evaluated with the naked eye. It is easy to operate, sensitive, specific, and stable This kit is suitable for the rapid and real-time detection of RAC and SAL residues in swine urine samples.Clinical Trial Registration: Swine urines samples were used under approval from the Experimental Animal Ethics committee of the Joint National Laboratory for Antibody Drug Engineering, Henan University.Keywords: ractopamine, salbutamol, lateral flow, selenium nanoparticles

Myocardial infarction (MI) is a leading cause of death worldwide for which there is no cure. Although cardiac cell death is a well-recognized pathological mechanism of MI, therapeutic blockade of cell death to treat MI is not straightforward. Death receptor 5 (DR5) and its ligand TRAIL [tumor necrosis factor (TNF)–related apoptosis- inducing ligand] are up-regulated in MI, but their roles in pathological remodeling are unknown. Here, we report that blocking TRAIL with a soluble DR5 immunoglobulin fusion protein diminished MI by preventing cardiac cell death and inflammation in rats, pigs, and monkeys. Mechanistically, TRAIL induced the death of cardiomyocytes and recruited and activated leukocytes, directly and indirectly causing cardiac injury. Transcriptome profiling revealed increased expression of inflammatory cytokines in infarcted heart tissue, which was markedly reduced by TRAIL blockade. Together, our findings indicate that TRAIL mediates MI directly by targeting cardiomyocytes and indirectly by affecting myeloid cells, supporting TRAIL blockade as a potential therapeutic strategy for treating MI.

As a classic differentiation agent, all-trans retinoic acid (ATRA) has been widely used in the treatment of acute promyelocytic leukemia (APL). However, the clinical application of ATRA has strict limitations, for its severe side effects due to the accumulation of peripheral blood leukocytes. The scaffold protein RACK1 (Receptor for activated C kinase 1), which regulates multiple signaling pathways, has been proposed to contribute to the survival of leukemic progenitors. But it remains unclear whether it is also involved in the oncogenic growth of APL. In the present study, we demonstrate that silencing of endogenous RACK1 expression synergized with ATRA to promote the death of NB4 and HL-60 APL cells without effect on cell differentiation induced by ATRA. Interestingly, RACK1 knockdown combined with ATRA treatment mainly induces apoptosis. It is distinct to the necrotic cell death induced by idarubicin in combination with ATRA, a regimen extensively used in the clinic to prevent neutrophil accumulation. Further exploration revealed that the lysosome-autophagy pathway is likely to be responsible for the anti-apoptotic role of RACK1. Taken together, our findings indicate that RACK1 is essential in maintaining the malignant features of APL, and targeting RACK1 may have promising therapeutic implications in the treatment of APL.

NLRP3 inflammasome activation plays an important role in diabetic cardiomyopathy (DCM), which may relate to excessive production of reactive oxygen species (ROS). Gypenosides (Gps), the major ingredients of Gynostemma pentaphylla (Thunb.) Makino, have exerted the properties of anti‐hyperglycaemia and anti‐inflammation, but whether Gps improve myocardial damage and the mechanism remains unclear. Here, we found that high glucose (HG) induced myocardial damage by activating the NLRP3 inflammasome and then promoting IL‐1β and IL‐18 secretion in H9C2 cells and NRVMs. Meanwhile, HG elevated the production of ROS, which was vital to NLRP3 inflammasome activation. Moreover, the ROS activated the NLRP3 inflammasome mainly by cytochrome c influx into the cytoplasm and binding to NLRP3. Inhibition of ROS and cytochrome c dramatically down‐regulated NLRP3 inflammasome activation and improved the cardiomyocyte damage induced by HG, which was also detected in cells treated by Gps. Furthermore, Gps also reduced the levels of the C‐reactive proteins (CRPs), IL‐1β and IL‐18, inhibited NLRP3 inflammasome activation and consequently improved myocardial damage in vivo. These findings provide a mechanism that ROS induced by HG activates the NLRP3 inflammasome by cytochrome c binding to NLRP3 and that Gps may be potential and effective drugs for DCM via the inhibition of ROS‐mediated NLRP3 inflammasome activation.

The effects of structural damping to the responses of the vortex-induced vibration of solar tower should be investigated carefully to provide a reference for the structural designers. A new type of elastic test model for a 243-meter-high solar tower is particularly designed and manufactured. A core beam is designed in the test model to simulate the stiffness of the concrete structure, and a coat with baseplate (like a cup) is designed to simulate the steel structure. A structural damping ratio as low as 0.3% is realized, and four level of structural damping ratio, including 0.7%, 1.0%, 1.5% and 2.0%, can be conveniently achieved. A series wind tunnel tests are carried out to investigate the features of the wind-induced responses of the solar tower at the structural damping level of 0.3%, 0.7%, 1.0%, 1.5% and 2.0%. The results show that obvious vortex-induced vibration could be found within wind velocity range of U10 = 21.5–28.4 m/s for the structural damping ratio of 0.7%. At this time, the highest vortex-induced responses (at the wind velocity of U10 = 23.2 m/s), including acceleration at the top, base shear and base moment, are far larger than those at the design wind velocity (U10 = 41.0 m/s). Moreover, it appears that the wind-induced responses in cross-wind direction are far higher than those in the along-wind direction. The most important point is that the base shear and moment in the cross-wind direction measured from wind tunnel tests are far higher than the values obtained from the Code ACI 307–08. The wind-induced responses of the solar tower are extremely sensitive to the structural damping of the test model. For example, the highest acceleration, base shear and moment in cross-wind direction are respectively reduced by about 67%, 74%, 71% when structural damping ratio slightly increases from 0.7% to 1.0%. It seems that the vortex-induced vibration of the solar tower could be effectively mitigated if the structural damping ratio could be enhanced over 1.0%.

The sluggish kinetics of sulfur conversion in the cathode and the nonuniform deposition of lithium metal at the anode result in severe capacity decay and poor cycle life for lithium-sulfur (Li-S) batteries. Resolving these deficiencies is the most direct route toward achieving practical cells of this chemistry. Herein, a vertically aligned wood-derived carbon plate decorated with Co4 N nanoparticles host (Co4 N/WCP) is proposed that can serve as a host for both the sulfur cathode and the metallic lithium anode. This Co4 N/WCP electrode host drastically enhances the reaction kinetics in the sulfur cathode and homogenizes the electric field at the anode for the uniform lithium plating. Density functional theory calculations confirm the experimental observations that Co4 N/WCP provides a lower energy barrier for the polysulfide redox reaction in the cathode and a low adsorption energy for lithium deposition at the anode. Employing the Co4 N/WCP host at both electrodes in a S@Co4 N/WCP||Li@Co4 N/WCP full cell delivers a specific capacity of 807.9 mAh g-1 after 500 cycles at a 1 C rate. Additional experiments are performed with high areal sulfur loading of 4 mg cm-2 to demonstrate the viability of this strategy for producing practical Li-S cells.

1,25-dihydroxyvitamin D3 (1,25(OH)

The effects of Reynolds number on the wind-induced responses of a 243-m-high solar tower are modified by increasing the surface roughness of the test model. First, a series of wind tunnel t...

Magnesium hydroxide (MH) has attracted much attention as an environmentally friendly flame retardant. In this paper, high throughput preparation of high-grade MH flame retardant was successfully achieved via microreaction technology and hydrothermal treatment. The results indicated that the reactant molar ratio and reactant concentration had a significant effect on the properties of MH including the morphology, average particle size and BET specific surface area, while the flow velocity and reaction temperature had little effect. To obtain MH with desirable properties, a highly concentrated NaOH solution was added into the hydrothermal slurry. The properties of MH were remarkably influenced by hydrothermal parameters such as NaOH concentration, time, temperature and solid content. High-grade MH flame retardant can be obtained with a NaOH concentration ≥2.4 M, hydrothermal time ≥3 h, hydrothermal temperature ≥170 °C and solid content ≤6.0 wt%. On the basis of laboratory work, a microreaction system based on a stacked plate microchannel reactor with an external volume of 7 L was developed for the pilot scale preparation of MH. The production capacity of MH slurry was up to 12.6 m3 h−1, and the pressure drop of the microreaction system was kept at 1.1 bar. The average particle size and BET specific surface area of as-prepared MH were 1.0 μm and 3.4 m2 g−1, respectively, which met the requirement of high-grade flame retardant.

With the rapid development of society and the continuous deepening of reform and opening up, the current psychological pressure on college students is getting worse. Psychological counseling in colleges and universities is an important measure to improve the psychological quality of college students and maintain and enhance the mental health of college students. Under the current situation, it has gradually attracted the attention of all sectors of society. This article briefly expounds the significance and development ideas of college psychological counseling work, analyzes and discusses several issues worth noting in the process of psychological counseling work, and provides references for promoting the continuous development of college psychological counseling work.

Heat shock factor 1 (Hsf1) serves an important role in regulating the proliferation of human tumor cell lines in vitro and tissue specific tumorigenesis in certain mouse models. However, its role in viral‑oncogenesis remains to be fully elucidated. In the current study, the role of Hsf1 in fibroblastoma derived from simian virus 40/T antigen (SV40/TAG)‑transformed mouse embryonic fibroblast (MEF) cell lines was investigated. Knockout of Hsf1 inhibited MEF cell proliferation in vitro and fibroblastoma growth and metastasis to the lungs in vivo in nude mice. Knockout of Hsf1 increased the protein expression levels of p53 and phosphorylated retinoblastoma protein (pRb), however reduced the expression of heat shock protein 25 (Hsp25) in addition to the expression of the angiogenesis markers vascular endothelial growth factor, cluster of differentiation 34 and factor VIII related antigen. Furthermore, immunoprecipitation indicated that knockout of Hsf1 inhibited the association between SV40/TAG and p53 or pRb. These data suggest that Hsf1 is involved in the regulation of SV40/TAG‑derived fibroblastoma growth and metastasis by modulating the association between SV40/TAG and tumor suppressor p53 and pRb. The current study provides further evidence that Hsf1 may be a novel therapeutic target in the treatment of cancer.

A self-sustained, complete and miniaturized methanol fuel processor has been developed based on modular integration and microreactor technology. The fuel processor is comprised of one methanol oxidative reformer, one methanol combustor and one two-stage CO preferential oxidation unit. Microchannel heat exchanger is employed to recover heat from hot stream, miniaturize system size and thus achieve high energy utilization efficiency. By optimized thermal management and proper operation parameter control, the fuel processor can start up in 10 min at room temperature without external heating. A self-sustained state is achieved with H 2 production rate of 0.99 Nm 3 h −1 and extremely low CO content below 25 ppm. This amount of H 2 is sufficient to supply a 1 kW e proton exchange membrane fuel cell. The corresponding thermal efficiency of whole processor is higher than 86%. The size and weight of the assembled reactors integrated with microchannel heat exchangers are 1.4 L and 5.3 kg, respectively, demonstrating a very compact construction of the fuel processor.

HSF1-mediated heat shock response is activated in most tumors and plays important roles in regulating tumor homeostasis. However, the signals underlying HSF1 activation is still not completely understood. In this paper, we find that glucose, the dominant tumor energy supplement, participates in regulating HSF1's activation in HCC cell lines. The immunoblotting results indicate that the phosphorylation of HSF1/S326, a hallmark of HSF1 activation, varies between the HCC cell lines (e.g., SMMC7721, HapG2, plc/prf5, and Chang-liver). Glucose, but not 2D-glucose, can induce the phosphorylation of HSF1 at S326 and upregulate the expression of HSF1's downstream alpha B-crystallin and Hsp70 as well as the none-heat shock proteins CSK2 and RBM23 in two tested hepatocellular carcinoma cell lines (prl/prf5 and SMMC7721). Rapamycin, an inhibitor of mTOR, can suppress the glucose-induced phosphorylation of HSF1/S326 and the expression of alpha B-crystallin. Knockdown of HSF1 with shRNA enhances the glucose-depletion-mediated inhibition of plc/prf5 cell proliferation. Our data reveal that HSF1 can be activated by glucose-mTOR pathway, providing an alternative pathway for targeting HSF1 in tumor therapy.

The interplay between Hsf4 and Hsf1 plays an important role in the regulation of lens homeostasis. However, the mechanism of the intermolecular association involved is still unclear. In this paper, we find that reconstitution of Hsf4b into Hsf4−/− lens epithelial (mLEC/Hsf4−/−) cells can simultaneously downregulate Hsp70 expression and upregulate the expression of small heat shock proteins Hsp25 and αB-crystallin at both RNA and protein levels. ChIP assay results indicate Hsf4b, which binds to the promoters of Hsp90α, Hsp70.3, Hsp25 and αB-crystallin but not Hsp70.1, can inhibit Hsf1 binding to Hsp70.3 promoter and the heat shock mediated Hsp70 promoter activity by reducing Hsf1 protein expression. Hsf4b N-terminal hydrophobic region can interact with Hsf1 N-terminal hydrophobic region. Their interaction impairs Hsf1's intramolecular interaction between the N- and C-terminal hydrophobic regions, leading to Hsf1's cytosolic retention and protein degradation. Both lysosome inhibitors (chloroquine, pepstatin A plus E64d) and proteasome inhibitor MG132 can inhibit Hsf4-mediated Hsf1 protein degradation, but MG132 can induce Hsf1 activation as well. Upregulation of Hsf4b can significantly inhibit cisplatin and staurosporine induced lens epithelial cell apoptosis through direct upregulation of Hsp25 and αB-crystallin expression. Taken together, our results imply that upregulation of Hsf4b modulates the expression pattern of heat shock proteins in lens tissue by either directly binding to their promoters or promoting Hsf1 protein degradation. Moreover, upregulation of Hsf4b protects lens cell survival by upregulating anti-apoptotic pathways. These studies reveal a novel regulatory mechanism between Hsf1 and Hsf4b in modulating lens epithelial cell homeostasis.

Tumor necrosis factor-related apoptosis-inducing ligand can induce apoptosis in many tumor cell lines. This apoptotic effect is mediated by interaction of TRAIL and its receptors, which include Death Receptor 4 (DR4) and Death Receptor 5 (DR5). Some antibodies to DR4 or DR5 do not have anti-tumor ability without cross-linking but exhibit anti-tumor ability in the presence of a cross-linking reagent. Here, we suggest that the tetravalent anti-DR5 antibody can induce apoptosis of cancer cells independent of cross-linking reagent. The single-chain variable fragment of the anti-DR5 antibody, HSA (human serum albumin) – p53 gene, comprising residues 490–513 of HSA and the tetramerization domain of human p53 were assembled into the tetravalent antibody by an overlapping PCR. Results of size exclusion HPLC indicated that the purified protein exhibited a major peak (tetramer) and a minor peak (dimer). MTT assay demonstrated the tetravalent antibody without cross-linking could inhibit survival of Jurkat and EC9706 cells in a dose-dependent manner while the monovalent antibody could not inhibit survival of Jurkat and EC9706 cells. IC50 of Jurkat cell was 3.2 mg/L and IC50 of EC9706 cell was 3.9 mg/L. Furthermore, the Annexin V/PI assay and the Hoechst 33258 staining showed that the tetravalent antibody could efficiently induce apoptosis of Jurkat and EC9706 cells. Therefore, the tetravalent anti-DR5 antibody can act as a direct agonistic antibody, and initiate efficient apoptotic independent of cross-linking reagent. Thus, the tetravalent anti-DR5 antibody will be a new kind of candidate for potential cancer therapeutics.

Heat shock factor 1 (HSF1) is associated with tissue-specific tumorigenesis in a number of mouse models, and has been used a as prognostic marker of cancer types, including breast and prostatic cancer. However, its role in human hepatocellular carcinoma (HCC) is not well understood. Using immunoblotting and immunohistochemical staining, it was identified that HSF1 and its serine (S) 326 phosphorylation, a biomarker of HSF1 activation, are significantly upregulated in human HCC tissues and HCC cell lines compared with their normal counterparts. Cohort analyses indicated that upregulation of the expression of HSF1 and its phospho-S326 is significantly correlated with HCC progression, invasion and patient survival prognosis (P

Hsf4b, a key regulator of postnatal lens development, is subjected to posttranslational modifications including phosphorylation. However, the phosphorylation sites in Hsf4b and their biological effects on the transcription activity of Hsf4b are poorly understood. Here we examined 17 potential phosphorylation residues in Hsf4b with alanine-scanning assays and found that a T472A mutation diminished Hsf4b-mediated expression of Hsp25 and alphaB-crystallin. In contrast, the phosphomimetic mutation of T472D enhanced their expression. Further investigation demonstrated that Hsf4b could interact with nuclear-transporter importin beta-1 and Hsc70 via amino acids 246-320 and 320-493, respectively. T472A mutation reduced Hsf4bs interaction with importin beta-1, while enhancing its interaction with Hsc7O, resulting in Hsf4b cytosolic re-localization, protein instability and transcription activity attenuation. At the upstream, MEK6 was found to interact with Hsf4b and enhance Hsf4b's nuclear translocation and transcription activity, probably by phosphorylation at sites such as T472. Taken together, our results suggest that phosphotylation of Hsf4b at T472 by protein kinases such as MEI(6 regulates Hsf4b interaction with the importin V I -Hsc7O complex, resulting in blockade of its nuclear translocation and transcriptional activity of Hsf4b.

Mercapto-silica (SiO2-SH) microspheres were prepared via direct hydrolysis of 3-mercaptopropyltrimethoxysilane (MPS) in a basic aqueous solution. The content of surface thiol group (SH) of SiO2-SH microspheres was measured by Ellman's reagent method and X-ray photoelectron spectroscopy (XPS) and the content of surface thiol group of SiO2-SH microspheres is strongly dependent on the reaction conditions. The thermal stability of SiO2-SH microspheres was evaluated by thermogravimetric (TG) analysis, which tended to reduce with the increase of content of surface thiol groups. SiO2-SH microspheres can be easily modified with reduced glutathione (GSH) to generate SiO2-GSH microspheres for the affinity separation of Glutathione S-transferase (GST). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was performed to examine the validity of the separation procedure. The results showed that SiO2-GSH microspheres were efficient in GST affinity separation from mixed proteins.

Drilling fluids used for accessing unconventional reservoirs need new focus because the fluids used to exploit conventional reservoirs need without some modifications or new formulations. New smart-fluid formulations were developed and optimized using nano-materials. Three nano-materials were added to the generic water-based fluids. Scanning electronic microscope tests were performed to check the size quality of the nano-materials. Rheology properties, pH and filtration tests were performed to evaluate the smart drilling fluids. Mud cakes formed by each smart drilling fluid were collected and scanned. For practical field applications, the smart drilling fluids were tested against two rock samples by performing dispersion, barite sag and aging (stability) tests. The rocks were characterized using scanning electronic microscope (SEM), cation exchange capacity (CEC) and adsorption tests. Results showed that the developed fluids exhibited excellent rheological properties and the filtration losses were reduced after adding nano-materials. Mud cakes formed by each smart drilling fluid were collected and scanned. Thin, tight, and well textured mud cakes were formed. The mud cakes' thicknesses were reduced significantly after adding nano materials. The barite sag tests indicated the fluids to be excellent for cutting suspension. No sedimentation was observed after aging for three days, which indicated a good cleaning and suspension of drilled cuttings. The rheology and filtration properties of smart drilling fluid system remained stable under static condition after three days of aging. Results showed reduced shale dispersion, excellent suspension capacity, and stability. The cost comparison between the developed smart drilling fluids with nano-materials and base (generic) drilling fluids shows that that the smart fluids are relatively inexpensive even though they are excellent for preventing wellbore instability and for used in the environmentally sensitive areas.

The dimethyl ether steam reforming (DME SR) was carried out over the composite catalyst of ZnO–Cr 2 O 3 coupled with Al 2 O 3 , TiO 2 or TiO 2 –Al 2 O 3 in the microreactor. The results showed that the catalytic activities were greatly enhanced over the composite catalyst of ZnO–Cr 2 O 3 combined with TiO 2 –Al 2 O 3 (ZnCr–TiAl) in comparison to those combined with Al 2 O 3 or TiO 2 in DME SR. By evaluating the catalytic activity of solid acids in DME hydrolysis, it was proposed that the better performance of TiO 2 –Al 2 O 3 in DME hydrolysis contributed to the superior activity of ZnCr–TiAl in DME SR, indicating a higher DME hydrolysis activity favored DME SR. In view of the characterization of N 2 physisorption, scanning electron microscope, X-ray diffraction and NH 3 temperature-programmed desorption, the promotion effect of TiO 2 on both DME hydrolysis and steam reforming was discussed in terms of the modification effect of TiO 2 on the acid properties of Al 2 O 3 surface. The acid strength or total acid amount was enhanced by the addition of different TiO 2 content. In the 150 h medium stability test, there was no obvious deactivation for ZnCr–TiAl catalyst with the H 2 production rate of 345 mol h − 1 k g cat − 1 and the CO selectivity in the dry reformate remained below 6%. The characterization results of the used catalyst revealed that no change in the crystalline phase and size occurred on the spent catalyst.

A series of ZnO–Al2O3 catalysts with various ZnO/(ZnO + Al2O3) molar ratios have been developed for hydrogen production by dimethyl ether (DME) steam reforming within microchannel reactor. The catalysts were characterized by N2 adsorption-desorption, X-ray diffraction and temperature programmed desorption of NH3. It was found that the catalytic activity was strongly dependent on the catalyst composition. The overall DME reforming rate was maximized over the catalyst with ZnO/(ZnO + Al2O3) molar ratio of 0.4, and the highest H2 space time yield was 315 mol h−1·kgcat−1 at 460 °C. A bi-functional mechanism involving catalytic active site coupling has been proposed to account for the phenomena observed. An optimized bi-functional DME reforming catalyst should accommodate the acid sites and methanol steam reforming sites with a proper balance to promote DME steam reforming, whereas all undesired reactions should be impeded without sacrificing activity. This work suggests that an appropriate catalyst composition is mandatory for preparing good-performance and inexpensive ZnO–Al2O3 catalysts for the sustainable conversion of DME into H2-rich reformate.

Objective The aim of our study was to detect whether Vitamin E Succinic Acid (VES) could regulate the expression level of DR5 in the cells and further elucidate the potential mechanisms involving that VES enhances the effect of mDRA-6 to eradicate leukemia Raji and K562 cells.

In this study, a series of ZnO-Al2O3 catalysts with various ZnO/(ZnO + Al2O3) molar ratios have been evaluated for the high-temperature steam reforming of methanol, and the optimizing catalyst composition consists in the range of 0.50-0.67. The catalysts were characterized by N-2 adsorption-desorption, X-ray diffraction and UV-vis spectra. In the case of ZnO/(ZnO + Al2O3)> 0.5, a significant proportion of Zn could dissolve in ZnAl2O4, resulting in Zn-rich non-stoichiometric spine!, in which the Zn2+ ions located both at the tetrahedral and octahedral sites. It was noticed that such a coordination of Zn2+ ions in the octahedral position brought about a higher CO selectivity. Further investigation illuminated water gas shift and methanol decomposition reaction were both involved in the formation of CO. There was no noticeable deactivation for ZnO-Al2O3 with the ZnO/(ZnO+ Al2O3) molar ratio of 0.50 during the 200h continuous operation (GHSV= 17930 h(-1), T=420 degrees C). The H-2 space time yield is 55 Lh(-1)g(cat)(-1) and the concentration of CO in the dry gaseous products was lower than 0.8%. (C) 2010 Elsevier B.V. All rights reserved.

Heat shock factor 4 (Hsf4b) has been identified as a novel cataractogenic protein whose mutation has been closely associated with hereditary cataracts in humans and animals. It acts both as a transcription activator and a transcription inhibitor in the regulation of its downstream targets during lens development. However, the signaling factors that regulate Hsf4b transcription activity are still not completely defined. Here, we found that Hsf4b, not Hsf4a (another isoform of Hsf4), acts as the inhibitor of CMV promoter as well as the activator of Hsp25 in the Hsf4-/- mouse lens epithelial cell line (mLEC/hsf4-/-). Hsf4b inhibits CMV-promoter activity by directly binding to TTCC (HSE motif) at 173-176bps in the CMV promoter. The phosphorylation of Hsf4b/S299 in the PDSM motif, which is absent in Hsf4a, participates in the negative regulation of the CMV promoter. The transcriptional inhibition of Hsf4b is associated with transcriptional inhibitor Daxx. Hsf4b can interact and co-localize with Daxx in the nucleus, and their association is regulated by the phosphorylation of Hsf4b/S299. In addition, we found that Hsf4a and Hsf1 were also associated with Daxx. However, in contrast to activating Hsf1, Daxx can repress Hsf4b-induced expression of Hsp25 in the mLEC/hsf4-/- cell line. Our results demonstrate that the transcription-inhibitory function of Hsf4b is regulated by the phosphorylation of Hsf4b/S299 and phosphorylation-dependent association with Daxx.

The aim of this work was to evaluate anti-tumor effects of mDRA-6 plus nimesulide on a human hepatocellular cancer cell line, SMMC-7721, and study the main mechanisms. The DR5 receptor of SMMC-7721 cells was detected by flow cytometry (FCM). For further experimental application, SMMC-7721 cells were treated with proper dose of mDRA-6, nimesulide, or mDRA-6 plus 200 μmol/L nimesulide; untreated SMMC-7721 cells were comparably set as control. Cytotoxicity was tested by MTT assay; cell morphology was examined using Hoechst 33258 staining; and apoptosis was determined by FCM. The positive rate of DR5 on SMMC-7721 was 95.0%. Either mDRA-6 or nimesulide alone induces SMMC-7721 cell death in a dose-dependent manner. Treatment of 1,600 ng/mL mDRA-6 for 12h led to a cell-death rate of 35.0%, while an increased cell-death rate (91.1%) was found under the same condition of mDRA-6 treatment supplemented with 200 μmol/L nimesulide. Hoechst 33258 and Annexin V/PI staining confirmed apoptosis as the main cause of this anti-tumor response. Both mDRA-6 and nimesulide can induce apoptosis of SMMC-7721 cells, and they have synergistic anti-tumor activities against SMMC-7721.