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Background Sarcopenia is associated with various adverse outcomes in hemodialysis patients. However, current tools for assessing and diagnosing sarcopenia have limited applicability. In this study, we aimed to develop a simple and reliable nomogram to predict the risk of sarcopenia in hemodialysis patients that could assist physicians identify high-risk patients early. Methods A total of 615 patients undergoing hemodialysis at the First Affiliated Hospital College of Medicine Zhejiang University between March to June 2021 were included. They were randomly divided into either the development cohort (n = 369) or the validation cohort (n = 246). Multivariable logistic regression analysis was used to screen statistically significant variables for constructing the risk prediction nomogram for Sarcopenia. The line plots were drawn to evaluate the effectiveness of the nomogram in three aspects, namely differentiation, calibration, and clinical net benefit, and were further validated by the Bootstrap method. Results The study finally included five clinical factors to construct the nomogram, including age, C-reactive protein, serum phosphorus, body mass index, and mid-upper arm muscle circumference, and constructed a nomogram. The area under the ROC curve of the line chart model was 0.869, with a sensitivity and specificity of 77% sensitivity and 83%, the Youden index was 0.60, and the internal verification C-statistic was 0.783. Conclusions This study developed and validated a nomogram model to predict the risk of sarcopenia in hemodialysis patients, which can be used for early identification and timely intervention in high-risk groups.

Immunotherapy has gradually emerged as the most promising anticancer therapy. In addition to conventional anti-PD-1/PD-L1 therapy, anti-CTLA-4 therapy, CAR-T therapy, etc., immunotherapy can also be induced by stimulating the maturation of immune cells or inhibiting negative immune cells, regulating the tumor immune microenvironment and cancer vaccines. Lipid nanovesicle drug delivery system includes liposomes, cell membrane vesicles, bacterial outer membrane vesicles, extracellular vesicles and hybrid vesicles. Lipid nanovesicles can be used as functional vesicles for cancer immunotherapy, and can also be used as drug carriers to deliver immunotherapy drugs to the tumor site for cancer immunotherapy. Here, we review recent advances in five kinds of lipid nanovesicles in cancer immunotherapy and assess the clinical application prospects of various lipid nanovesicles, hoping to provide valuable information for clinical translation in the future.

Background In our previous study, we demonstrated that Sirtuin 6 (SIRT6) is upregulated and associated with papillary thyroid cancer (PTC) progression (Qu et al. in Int J Oncol 50(5):1683–92, 2017). This study examined whether SIRT6 promotes epithelial–mesenchymal transition (EMT) of papillary thyroid cancer through hypoxia inducible factor-1α (HIF-1α). Methods SIRT6-upregulated TPC-1 and B-CPAP cells were generated by lentivirus. Western blotting, RT-qPCR, immunofluorescence was performed to detect the following EMT associated markers: E-cadherin, Vimentin, Snail, and TWIST. Cell proliferation was detected by CCK8, and cell invasion and migration were detected by transwell and wound healing assays, respectively. HIF-1α expression was further detected by western blotting in both normoxia and hypoxia conditions. A HIF-1α inhibitor was then used to block HIF-1α expression in SIRT6-upregulated PTC cells. The same parameters were then assessed and compared with control HIF-1α cells. Results E-cadherin was significantly decreased, whereas Vimentin, Snail, and TWIST were increased in SIRT6-upregulated PTC cells. Additionally, SIRT6 promoted the invasion and migration of PTC cells. We found that SIRT6 enhanced HIF-1α stability and synthesis and prolonged the protein half-life. The changes in the EMT associated markers and in the invasion and migration ability were rescued after inhibition of HIF-1α expression. Furthermore, we found that SIRT6 increased PTC resistance to HIF-1α inhibitor-mediated proliferation changes. Conclusion These results confirm that the SIRT6/HIF-1α axis promotes papillary thyroid cancer progression by inducing EMT.

The introduction of second-generation antipsychotics (SGAs) over the past 2 decades generated considerable optimism that better antipsychotic treatments for schizophrenia and bipolar disorder were possible. SGAs offer several tolerability benefits over first-generation antipsychotics (FGAs), particularly with respect to extrapyramidal symptoms. However, SGAs can induce serious metabolic dysregulations, especially in drug-naive, first-episode, and child and adolescent populations, with olanzapine and clozapine having the highest propensity to cause these abnormalities. In this context, newer SGAs were developed to further improve the adverse effect burden of available agents. However, until now, the metabolic risk profile of the newly approved SGAs - asenapine, iloperidone, lurasidone and paliperidone (paliperidone extended release and paliperidone palmitate) - has not been compared.The objective of this systematic review and exploratory meta-analysis was to assess the effects of asenapine, iloperidone, lurasidone and paliperidone on body weight and other metabolic parameters (cholesterol, triglycerides and glucose), as this information is relevant to guide clinical decision making.A systematic literature search (1966-March 2012), using the Cochrane Central Register of Controlled Trials and MEDLINE, CINAHL and EMBASE databases, was conducted for randomized, placebo-controlled and head-to-head clinical trials of asenapine, iloperidone, lurasidone and paliperidone. Published and unpublished data on changes in body weight and glucose and lipid metabolism parameters were extracted. For placebo-controlled, short-term (≤12 weeks) and longer-term (12 weeks) trials with available data on ≥7% weight increase compared with pre-treatment weight, or mean weight change with standard deviation, a formal meta-analysis was performed, estimating the pooled effect size (represented as relative risk [RR], numbers-needed-to-harm [NNH] and weighted mean difference [WMD]). An exploratory meta-analysis was also performed for the other metabolic variables (cholesterol, triglycerides and glucose). Data from active- and placebo-controlled studies were used for a pooled comparison of simple mean changes in weight, cholesterol, triglyceride and glucose levels.Fifty-six trials (n = 21 691) in schizophrenia (N = 49, n = 19 299) or bipolar disorder (N = 7, n = 2392) were identified (asenapine: N = 9, iloperidone: N = 11, lurasidone: N = 8, paliperidone: N = 28). Most of the trials (64.3%) were of ≤12 weeks' duration. In the short-term trials, compared with placebo, a ≥7% weight increase was statistically significantly (p 0.05) most prevalent for asenapine (5 trials, n = 1360, RR = 4.09, 95% confidence interval [CI] 2.25, 7.43, NNH = 17), followed by iloperidone (4 trials, n = 1931, RR = 3.13, 95% CI 2.08, 4.70, NNH = 11) and paliperidone (12 trials, n = 4087, RR = 2.17, 95% CI 1.64, 2.86, NNH = 20). The effect of lurasidone on body weight (6 trials, n = 1793, RR = 1.42, 95% CI 0.87, 2.29) was not statistically significant. Short-term weight gain was statistically significantly (p 0.001) greater than placebo with iloperidone (1 trial, n = 300, +2.50 kg, 95% CI 1.92, 3.08), paliperidone (15 trials, n = 3552, +1.24 kg, 95% CI 0.91, 1.57), asenapine (3 trials, n = 751, +1.16 kg, 95% CI 0.83, 1.49), as well as with lurasidone (5 trials, n = 999, +0.49 kg, 95% CI 0.17, 0.81, p 0.01). Sufficient meta-analysable, longer-term, weight change data were only available for asenapine and paliperidone, showing statistically significantly (p 0.001) greater weight gain versus placebo for both drugs (asenapine, 3 trials, n = 311, +1.30 kg, 95% CI 0.62, 1.98; paliperidone, 6 trials, n = 1174, +0.50 kg, 95% CI 0.22, 0.78). Although statistically significant, in general, no clinically meaningful differences were observed between the four newly approved SGAs and placebo regarding the mean change from baseline to endpoint in cholesterol levels in short-term trials, with the exception of iloperidone for total cholesterol (1 trial, n = 300, +11.60 mg/dL, 95% CI 4.98, 18.22, p ≤ 0.001), high-density cholesterol (1 trial, n = 300, +3.6 mg/dL, 95% CI 1.58, 5.62, p 0.001) and low-density cholesterol (1 trial, n = 300, +10.30 mg/dL, 95% CI 4.94, 15.66, p 0.001) and with the exception of lurasidone for high-density cholesterol (5 trials, n = 1004, +1.50 mg/dL, 95% CI 0.56, 2.44, p 0.01). Asenapine increased total cholesterol statistically significantly (p 0.05) during longer-term treatment (1 trial, n = 194, +6.53 mg/dL, 95% CI 1.17, 11.89). Regarding triglycerides, only short-term (3 trials, n = 1152, +1.78 mg/dL, 95% CI 0.40, 3.17, p 0.01) and longer-term treatment with paliperidone (4 trials, n = 791, -0.20 mg/dL, 95% CI -0.40, -0.01, p 0.05) had a statistically, but not clinically, significant effect. Statistically significant changes in glucose levels were noticed during short-term treatment with asenapine (2 trials, n = 379, -3.95 mg/dL, 95% CI -7.37, -0.53, p 0.05) and iloperidone (1 trial, n = 300, +6.90 mg/dL, 95% CI 2.48, 11.32, p 0.01), and during long-term treatment with paliperidone (6 trials, n = 1022, +3.39 mg/dL, 95% CI 0.42, 6.36, p 0.05).While preliminary data suggest the lowest weight gain potential with lurasidone and potentially relevant short-term metabolic effects for asenapine and iloperidone, data are still too sparse to comprehensively evaluate the metabolic safety of the newly approved SGAs. Therefore, there is a clear need for further controlled studies to evaluate whether these agents are less problematic regarding treatment-emergent weight gain and metabolic disturbances than other currently available antipsychotics.

A novel double suction shaft-less mini pump was developed for heat control of small energy systems in this study. The mini pump impeller with an exit diameter of 40 mm was combined with the motor rotor supported by the hybrid dynamic bearing. The specific speed of the pump was 125 min−1 m3 min−1 m. The hydraulic performance of the pump was investigated experiment- tally under four rotational speeds. From the test results, it was recognized that the pump could provide a flow discharge of 5 L/min and head of 1.5 m, which are applicable for the heat control system of a 3 kW fuel cell. A three-dimensional turbulent flow simulation in the pump was also conducted near the design point. The numerical results showed that the average hydraulic performance of the mini pump was predicted reasonably. From the internal flow simulation, it was revealed that the favorable inflow condition upstream of impeller inlet could be attained by applying the double suction shaft-less design for the mini pump.

Assessment of renal masses with conventional imaging may be challenging. Anti-1-amino-3-[(18)F]fluorocyclobutane-1-carboxylic acid (anti-[18F]FACBC) is a synthetic L: -leucine analog with relatively little renal excretion. The present study examines anti-[(18)F]FACBC positron emission tomography uptake in patients with renal masses.Six patients with seven renal lesions were imaged dynamically for 2 h after injection of 10-10.9 mCi (370-403 MBq) anti-[(18)F]FACBC. Lesions were evaluated qualitatively and quantitatively and correlated with histology.Four clear cell and one Rosai-Dorfman lesion were hypo/isointense to normal cortex; two papillary lesions in the same patient were hyperintense. Mean SUV(max) +/- SD at 30 min was 2.8 +/- 0.24 for clear cell carcinomas and 4.5 +/- 1.7 for papillary cell lesions. Mean SUV(max)/SUV(mean) ratios +/- SD of lesion to normal cortex at 30 min was 1.15 +/- 0.19 for the clear cell carcinomas and 2.3 +/- 0.84 for papillary cell.In this small patient sample, relative amino acid transport compared with renal cortex is elevated in renal papillary cell carcinoma but not in clear cell carcinoma.

This research treats the effect of impeller inlet geometry on performance improvement for a boiler feed pump, who is a centrifugal pump having specific speed of 183 m·m3min−1·min−1 and close type impeller with exit diameter of 450 mm. The hydraulic performance and cavitation performance of the pump have been tested experimentally. In order to improve the pump, five impellers have been considered by extending the blade leading edge or applying much larger blade angle at impeller inlet compared with the original impeller. The 3-D turbulent flow inside those pumps has been analyzed basing on RNG k-ɛ turbulence model and VOF cavitation model. It is noted that the numerical results are fairly good compared with the experiments. Based on the experimental test and numerical simulation, the following conclusions can be drawn: (1) Impeller inlet geometry has important influence on performance improvement in the case of centrifugal pump. Favorite effects on performance improvement have been achieved by both extending the blade leading edge and applying much larger blade angle at impeller inlet; (2) It is suspected that the extended leading edge have favorite effect for improving hydraulic performance, and the much larger blade angle at impeller inlet have favorite effect for improving cavitation performance for the test pump; (3) Uniform flow upstream of impeller inlet is helpful for improving cavitation performance of the pump.

RRR-alpha-tocopherol ether linked acetic acid analog (alpha-TEA), is a potential chemotherapeutic agent for ovarian cancer. Pro-death and pro-life signaling pathways were studied to understand the anti-cancer actions of alpha-TEA on cisplatin-sensitive (A2780S) and -resistant (A2780/cp70R) human ovarian cancer cells. Both cell lines were refractory to Fas; whereas, alpha-TEA sensitized them to Fas signaling. alpha-TEA increased levels of Fas message, protein and membrane-associated Fas. Neutralizing antibodies to Fas or Fas L partially blocked alpha-TEA-induced apoptosis. alpha-TEA induced prolonged activation of c-Jun N-terminal kinase (JNK) and its substrate c-Jun; Bax conformational change; and cleavage of Bid and caspases-8, -9 and -3. Chemical inhibitors of JNK, and caspases blocked alpha-TEA-induced apoptosis. alpha-TEA decreased phosphorylation of protein kinase B (Akt/PKB) and extracellular signal-regulated kinase (ERK1/2), as well as cellular FLICE-like inhibitory protein (c-FLIP) and Survivin protein levels. Knockdown of Akt and ERK activity using phosphoinositide- 3-kinase (PI3K) and mitogen-activated protein kinase kinase (MKK1) inhibitors enhanced alpha-TEA-induced apoptosis. Over-expression of constitutively active Akt2 and MKK1 blocked alpha-TEA-induced apoptosis. Collectively, data show alpha-TEA to be a potent apoptotic inducer of both cisplatin-sensitive and -resistant human ovarian cancer cells via activating death receptor Fas signaling and suppressing anti-apoptotic AKT and ERK targets.

Study objective: To asses the association between alcohol consumption and the risk of colorectal cancer (CRC) in the Chinese population. Design: A population-based prospective cohort study was initiated from the colorectal cancer screening population in Jiashan County in 1989–1990. The drinking habits of individuals were investigated with demographic information. Setting: A cohort study was followed-up from 1st May 1990 to 1st January 2001 and censored at the date of diagnosis of CRC, at death from any causes, or at 1st January 2001, whichever came first, and the person-time was computed. Participants: Two hundred and forty two CRC patients were diagnosed during the study period and 64,100 individuals finished the follow-up. Results: The distribution of sex, smoking status, occupation, education level and marital status were all significantly different among different drinking habits at baseline. When the above factors were adjusted, no significant association was observed between alcohol consumption and the risk of CRC. Exclusion of individuals diagnosed cancer less than 1 year after the examination date did not alter the strength of an alcohol–CRC relationship. Further analysis in sex strata also did not show a significant relationship. Conclusions: Alcohol drinking may not be associated with a higher risk of CRC in the Chinese population.

Vitamin E is a collective term used to refer to a number of structurally and functionally different compounds. Although some vitamin E compounds are popular supplements marketed for their potential beneficial antioxidant effects for a number of chronic diseases including various forms of cancer, a recent report by the National Academy of Sciences Food and Nutrition Board concluded that too little is known at present to provide definitive answers regarding whether taking larger doses of dietary antioxidants will help prevent chronic diseases. Recent reviews of epidemiological data suggest that dietary source vitamin E may provide some protection against breast cancer, while vitamin E supplements do not. A majority of studies investigating the protective effects of certain types of vitamin E in animal models of mammary cancer prevention conclude that there is little or no effect. The study of vitamin E is complex, and the vitamin E field faces many scientific challenges.

A novel method to prepare ceramic coatings has been developed by making use of plasma energy produced from the pulsed discharge between electric conductor and aqueous electrolyte. A ZrO2-8%Y2O3, coating was obtained by this method, which had excellent adhesion with substrate, smooth surface and good resistance to high temperature oxidation.

Previous studies have shown that treatment of avian reticuloendotheliosis virus-transformed RECC-UTC4-1 (C4-1) lymphoblastoid cells with 10 microg/ml (18.8 microM) of RRR-alpha-tocopheryl succinate (vitamin E succinate, VES) for 3 days induced approximately 50% of the cells to undergo apoptosis. Elevated and prolonged expression of c-jun mRNA and protein was temporally correlated with VES-induced cell death. Data presented in this paper show that the elevated and prolonged expression of c-jun message and protein are not accounted for by enhanced stability, and show the involvement of c-Jun in VES-induced apoptosis in this lymphoblastoid cell type. C4-1 cells infected with a virus carrying a dominant, negatively acting mutant form of c-Jun, supjun-1, exhibited: (i) 71% reduction in VES-induced apoptosis, (ii) a 2.0-2.5-fold decrease in wildtype, endogenous c-Jun expression, and (iii) a 2.4-2.6-fold reduction in AP-1 binding activity. Additionally, cells co-treated with VES plus RRR-alpha-tocopherol, exhibited a 70% reduction in apoptosis, a marked reduction in c-Jun expression and a 1.6-fold reduction in AP-1 binding activity. These studies suggest that c-Jun plays a crucial role in VES-induced apoptosis in C4-1 cells, and add to our understanding of mechanisms of action involved in VES-mediated tumor cell growth inhibition.

An analytical model of hardness has been developed. Four major indentation tests, namely indentation by cones, wedges, spheres, and flat-ended, axisymmetric cylinders have been analyzed based on the model. Analytical relationships among hardness, yield stress, elastic modulus, Poisson's ratio, and indenter geometries have been found. These results enable hardness to be calculated in terms of uniaxial material properties and indenter geometries for a wide variety of elastic and plastic materials. These relationships can also be used for evaluating other mechanical properties through hardness measurements and for converting hardness from one type of hardness test into those of a different test. Comparison with experimental data and numerical calculations is excellent.

Introduction Successful treatment of p53 mutant, triple-negative breast cancers (TNBC) remains a daunting challenge. Doxorubicin (DOXO) and cisplatin (CDDP) are standard-of-care treatments for TNBC, but eventually fail due to acquired drug resistance and toxicity. New treatments for overcoming drug resistance and toxicity in p53 mutant, TNBC are therefore badly needed. Unlike p53, p73 - a member of the p53 family - is usually not mutated in cancers and has been shown to regulate p53-mediated apoptotic signaling in p53-deficient cancers. Therefore, identification of anticancer agents that can activate p73 in p53-deficient cancers may provide a chemotherapeutic approach for treatment of p53 mutant cancers. Here we report on the reconstitution of the p53 tumor suppressor pathway in a p53-independent manner via p73 with combination treatments of α-TEA, a small bioactive lipid, plus DOXO or CDDP. Methods p53 mutant, TNBC cell lines MDA-MB-231, BT-20 and MDA-MB-468 were used to evaluate the anticancer effect of chemotherapeutic drugs and α-TEA using annexin V (FITC)/PI staining, western blot analyses, RT-PCR and siRNA knockdown techniques. Results Combination treatments of α-TEA plus DOXO or CDDP act cooperatively to induce apoptosis, caspase-8 and caspase-9 cleavage, p73, phospho-c-Ab1 and phospho-JNK protein expression, and increase expression of p53 downstream mediators; namely, death receptor-5, CD95/APO-1 (Fas), Bax and Noxa, as well as Yap nuclear translocation - plus reduce expression of Bcl-2. Knockdown of p73, c-Abl, JNK or Yap using siRNAs shows that p73 plays a critical role in combination treatment-enhanced apoptosis and the expression of pro-apoptotic and anti-apoptotic mediators, and that c-Abl, JNK and Yap are upstream mediators of p73 in combination treatment responses. Conclusions Data show that α-TEA in combination with DOXO or CDDP synergistically enhances apoptosis in TNBC via targeting p53-mediated genes in a p73-dependent manner, and that p73 responses are downstream of c-Abl, JNK and Yap.