The Value of PSMA-RADS Version 2.0 in the Assessment of Pulmonary Metastases in Patients With Prostate Cancer and the Improvement of Differential Diagnosis Efficiency by PSMA PET/CT Parameters.

PURPOSE: The aim of this study was to investigate the application of PSMA-RADS version 2.0 in assessment of pulmonary metastases in patients with prostate cancer and whether PSMA PET/CT parameters provide incremental value. PATIENTS AND METHODS: From October 2016 to July 2023, PC patients with pulmonary opacities (including pulmonary metastases, lung cancer, and pulmonary benign opacities) who underwent Al18F-PSMA-BCH PET/CT scans were retrospectively analyzed. CT imaging characteristics, including the longest diameter, density, smoothness, lobulation, pleural retraction, and vacuole sign, as well as PET parameters including SUVmax and tumor-to-background ratio, were measured and analyzed. Additionally, the pulmonary PSMA-RADS score for each patient was determined. Independent predictors of pulmonary metastases were identified through univariate analysis and multivariate logistic regression analysis, which were utilized to construct a parallel diagnostic test. The differential diagnostic performances were evaluated using receiver operating characteristic analysis. RESULTS: A total of 148 pulmonary opacities from 96 patients were retrospectively included. The number of pulmonary benign opacities, lung cancer, and pulmonary metastases were 48 (32.4%), 20 (13.5%), and 80 (54.1%), respectively. The number of opacities across different PSMA-RADS scores from 2 to 5 was 8 (5.4%), 88 (59.5%), 7 (4.7%), and 45 (30.4%). SUVmax and smooth edges were independent predictors of pulmonary metastases (both P < 0.05), and the AUC of the parallel test for these 2 parameters was 0.86 (95% confidence interval: 0.79, 0.94; P < 0.001). Furthermore, the diagnostic accuracy of the parallel test across PSMA-RADS score from 2 to 5 was 85.7%, 79.6%, 100%, and 92.9%, respectively. CONCLUSIONS: Al18F-PSMA-BCH PET/CT parameters were helpful in differentiating pulmonary metastases in PC patients and provided incremental value when integrated with PSMA-RADS version 2.0.

Polyphenol Compound 18a Modulates UCP1-Dependent Thermogenesis to Counteract Obesity.

Recent studies increasingly suggest that targeting brown/beige adipose tissues to enhance energy expenditure offers a novel therapeutic approach for treating metabolic diseases. Brown/beige adipocytes exhibit elevated expression of uncoupling protein 1 (UCP1), which is a thermogenic protein that efficiently converts energy into heat, particularly in response to cold stimulation. Polyphenols possess potential anti-obesity properties, but their pharmacological effects are limited by their bioavailability and distribution within tissue. This study discovered 18a, a polyphenol compound with a favorable distribution within adipose tissues, which transcriptionally activates UCP1, thereby promoting thermogenesis and enhancing mitochondrial respiration in brown adipocytes. Furthermore, in vivo studies demonstrated that 18a prevents high-fat-diet-induced weight gain and improves insulin sensitivity. Our research provides strong mechanistic evidence that UCP1 is a complex mediator of 18a-induced thermogenesis, which is a critical process in obesity mitigation. Brown adipose thermogenesis is triggered by 18a via the AMPK-PGC-1α pathway. As a result, our research highlights a thermogenic controlled polyphenol compound 18a and clarifies its underlying mechanisms, thus offering a potential strategy for the thermogenic targeting of adipose tissue to reduce the incidence of obesity and its related metabolic problems.

TNFR2 promotes pancreatic cancer proliferation, migration, and invasion via the NF-κB signaling pathway.

PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignant disease with low overall survival; chemotherapy and immunotherapy have limited efficacy. Tumor necrosis factor receptor 2 (TNFR2), a type II transmembrane protein, contributes to the development and progression of several tumors. In this study, we elucidated the effect and molecular mechanisms of TNFR2. METHOD: We used The Cancer Genome Atlas and the Genotype-Tissue Expression database to compare the expression of the TNFR2 gene between normal and malignant pancreatic tissue. Using immunohistochemical staining, we divided the patients into high and low-expression groups, then investigated clinicopathologic data and survival curves of pancreatic cancer patients. We measured TNFR2 protein expression in PANC-1 and ASPC-1 pancreatic cancer cells subjected to TNFR2 small interfering RNA or negative control treatment. We performed proliferation, invasion, and migration assays to study the biological effects of TNFR2 in PDAC. The molecular mechanisms were validated using western blotting. RESULTS: TNFR2 was more highly expressed in PDAC cells and tissues than controls. Abundant expression of TNFR2 was associated with aggressive clinicopathologic characteristics and poor outcomes. Overexpression of TNFR2 promoted PDAC cell proliferation, migration, and invasion in vitro. Mechanistically, TNFR2 binds to TNF-α and activates the NF-κB signaling pathway. CONCLUSION: TNFR2 is a prognostic marker that facilitates the proliferation, migration, and invasion of PDAC via the NF-κB signaling pathway. TNFR2 may become a therapeutic target.

Superiority of [68Ga]Ga-DOTA-FAPI-04 PET/CT to [18F]FDG PET/CT in the evaluation of thymic epithelial tumours.

PURPOSE: The purpose of this study is to compare the ability of [68Ga]Ga-DOTA-FAPI-04 PET/CT and [18F]FDG PET/CT to stratify the malignancy and invasiveness of thymic epithelial tumours (TETs). METHODS: From April 2021 to November 2022, participants with suspected TETs confirmed by histopathology or follow-up imaging were prospectively analysed. All participants underwent [18F]FDG and [68Ga]Ga-DOTA-FAPI-04 PET/CT within 1 week. Clinical characteristics, CT features, and metabolic parameters (maximum standardized uptake value [SUVmax] and tumour-to-mediastinum ratio [TMR]) of subjects with different pathological types and stages were compared. The diagnostic capacities of [18F]FDG and [68Ga]Ga-DOTA-FAPI-04 PET/CT were compared using receiver operating characteristic (ROC) curves and McNemar's test. RESULTS: Fifty-seven participants were included. [68Ga]Ga-DOTA-FAPI-04 PET/CT was superior to [18F]FDG PET/CT in differentiating thymomas from thymic carcinomas (TCs) (AUC: 0.99 vs. 0.90, P = 0.02). Logistic regression revealed that SUVmax-FAPI (P = 0.04) was a significant predictive factor for TCs. SUVmax-FAPI and TMR-FAPI showed an excellent ability to differentiate low-risk thymomas (types A, AB, and B1), high-risk thymomas (types B2 and B3), and TCs (both P < 0.001). In thymomas, only SUVmax-FAPI (P < 0.001), TMR-FAPI (P < 0.001), and nonsmooth edges (P = 0.02) were significantly higher in the advanced-stage (Masaoka-Koga [MK] stage III/IV) group than in the early-stage group (MK stage I/II). Compared with [18F]FDG PET/CT, [68Ga]Ga-DOTA-FAPI-04 PET/CT showed significantly higher specificity (67% [46 of 69] vs. 93% [64 of 69], P < 0.001) in the detection of lymph node metastases and higher sensitivity (49% [19 of 39] vs. 97% [38 of 39], P < 0.001) in evaluating distant metastases. Both SUVmax-FAPI and TMR-FAPI were correlated with FAP expression (both r = 0.843, P < 0.001). CONCLUSION: [68Ga]Ga-DOTA-FAPI-04 PET/CT was superior to [18F]FDG PET/CT in evaluating the World Health Organization (WHO) classification, MK staging, and metastatic status of TETs. TRIAL REGISTRATION: ChiCTR2000038080, registration date 2020-09-09, https://www.chictr.org.cn/com/25/showproj.aspx?proj=61192.

Effect of an inactivated coronavirus disease 2019 vaccine, CoronaVac, on blood coagulation and glucose: a randomized, controlled, open-label phase IV clinical trial.

Background: Billions of doses of coronavirus disease 2019 (COVID-19) vaccines have been administered and several cases of thrombocytopenia with thrombosis syndrome (TTS) have been reported after the administration of adenoviral vector vaccines. However, the effects of an inactivated COVID-19 vaccine, CoronaVac, on coagulation are not well understood. Methods: In this randomized, controlled, open-label phase IV clinical trial, 270 participants including 135 adults aged 18-59 years and 135 adults aged 60 years or older, were enrolled and randomized to the CoronaVac group or to the control group in a 2:1 ratio and received two doses of CoronaVac or one dose of the 23-valent pneumococcal polysaccharide vaccine and one dose of inactivated hepatitis A vaccine on days 0 and 28, respectively. Adverse events were collected for 28 days after each dose. Blood samples were taken on days 0, 4, 14, 28, 32, 42, and 56 after the first dose to evaluate neutralizing antibody titers and laboratory parameters of coagulation function and blood glucose. Results: Fourteen days after the second dose of CoronaVac, the seroconversion rates of neutralizing antibodies against the prototype strain and beta, gamma, and delta variants of concern (VOC) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) reached peak values of 89.31%, 23.3%, 45.3%, and 53.5%, respectively. The incidence of adverse reactions was 43.6% and 52.2% in the CoronaVac group and in the control group, respectively. All were mild or moderate in severity. For the laboratory parameters, there was no difference in the means of any parameter between the two groups at any time point, except for the D-dimer on day 14. However, the D-dimer in the CoronaVac group decreased on day 14 compared to the value at baseline, while a higher D-dimer value, instead of a decreased D-dimer value, was a risk factor for TTS. Conclusion: CoronaVac showed a good safety profile and could induce a humoral response against the prototype and VOCs of SARS-CoV-2 in adults 18 years or older, with no abnormal effects on laboratory parameters of blood glucose and coagulation function.

Enabling Specific Benzene Oxidation by Tuning the Adsorption Behavior on Au Loaded MgAl Layered Double Hydroxides.

Direct and selective oxidation of benzene to phenol is a long-term goal in industry. Although great efforts have been made in homogenous catalysis, it still remains a huge challenge to drive this reaction via heterogeneous catalysts under mild conditions. Herein, a single-atom Au loaded MgAl-layered double hydroxide (Au1 -MgAl-LDH) with a well-defined structure, in which the Au single atoms are located on the top of Al3+ with Au-O4 coordination as revealed by extended x-ray-absorption fine-structure (EXAFS)and density-functional theory (DFT)calculation is reported. The photocatalytic results prove the Au1 -MgAl-LDH is capable of driving benzene oxidation reaction with O2 in water, and exhibits a high selectivity of 99% for phenol. While contrast experiment shows a ≈99% selectivity for aliphatic acid with Au nanoparticle loaded MgAl-LDH (Au-NP-MgAl-LDH). Detailed characterizations confirm that the origin of the selectivity difference can be attributed to the profound adsorption behavior of substrate benzene with Au single atoms and nanoparticles. For Au1 -MgAl-LDH, single Au-C bond is formed in benzene activation and result in the production of phenol. While for Au-NP-MgAl-LDH, multiple AuC bonds are generated in benzene activation, leading to the crack of CC bond.

Application of artificial neural network algorithm in pathological diagnosis and prognosis prediction of digestive tract malignant tumors. / äººå·¥ç¥žç»ç½‘ç»œç®—æ³•åœ¨æ¶ˆåŒ–é“æ¶æ€§è‚¿ç˜¤ç— ç†è¯Šæ–­åŠæ‚£è€ é¢„åŽé¢„æµ‹ä¸­çš„åº”ç”¨.

The application of artificial neural network algorithm in pathological diagnosis of gastrointestinal malignant tumors has become a research hotspot. In the previous studies, the algorithm research mainly focused on the model development based on convolutional neural networks, while only a few studies used the combination of convolutional neural networks and recurrent neural networks. The research contents included classical histopathological diagnosis and molecular typing of malignant tumors, and the prediction of patient prognosis by utilizing artificial neural networks. This article reviews the research progress on artificial neural network algorithm in the pathological diagnosis and prognosis prediction of digestive tract malignant tumors.

Harmonization of standard uptake values across different positron emission tomography/computed tomography systems and different reconstruction algorithms: validation in oncology patients.

BACKGROUND: EQ.PET is a software package that overcomes the reconstruction-dependent variation of standard uptake values (SUV). In this study, we validated the use of EQ.PET for harmonizing SUVs between different positron emission tomography/computed tomography (PET/CT) systems and reconstruction algorithms. METHODS: In this retrospective study, 49 patients with various cancers were scanned on a Biograph mCT (mCT) or Gemini TF 16 (Gemini) after [18F]FDG injections. Three groups of patient data were collected: Group 1, patients scanned on mCT or Gemini with data reconstructed using two parameters; Group 2, patients scanned twice on different PET scanners (interval between two scans, 68.9 ± 41.4 days); and Group 3, patients scanned twice using mCT with data reconstructed using different algorithms (interval between two scans, 109.5 ± 60.6 days). The SUVs of the lesions and background were measured, and the tumor-to-background ratios (TBRs) were calculated. In addition, the consistency between the two reconstruction algorithms and confounding factors were evaluated. RESULTS: In Group 1, the consistency of SUV and TBR between different reconstruction algorithms improved when the EQ.PET filter was applied. In Group 2, by comparing ΔSUV, ΔSUV%, ΔTBR, and ΔTBR% with and without the EQ.PET, the results showed significant differences (P < 0.05). In Group 3, Bland-Altman analysis of ΔSUV with EQ.PET showed an improved consistency relative to that without EQ.PET. CONCLUSIONS: EQ.PET is an efficient tool to harmonize SUVs and TBRs across different reconstruction algorithms. Patients could benefit from the harmonized SUV, ΔSUV, and ΔSUV% for therapy responses and follow-up evaluations.

Initial stage of carbonization of iron during hydrocarbons dissociation: a molecular dynamics study.

The carbonization of iron is a very important early phenomenon in the field of heterogeneous catalysis and the petrochemical industry, but the mechanism is still controversial. In this work, the carbonization mechanism and carbonization structure of iron nanoparticles by different carbon sources (CH4, C2H6, C2H4, C2H2) were systematically investigated using the reactive molecular dynamics method. The results show that saturated alkanes are dehydrogenated while adsorbed, but unsaturated olefins and alkynes undergo bond-breaking while adsorbed. The C-H bond is more likely to break than the C-C bond. Hydrocarbons with high carbon content have a strong ability to carbonize Fe nanoparticles under the same conditions. For C2H4 and C2H2, the C atoms generated from dissociation form a large number of long carbon chains intertwined with branched chains and multiple carbon rings. The C2 species formed by C2H2 after complete dehydrogenation diffuse rapidly to the interior of the nanoparticles, releasing the surface active sites and accelerating the carbonization process. Carbon-rich iron carbides (FeCx) with different Fe/C ratios were obtained by carbonization with different carbon sources. In addition, the Fe(110) surface exhibits the strongest carburizing ability. These findings provide systematic insights into the initial stages of metal Fe carburization.

Fabrication of Epitaxially Grown Mg2Al-LDH-Modified Nanofiber Membranes for Efficient and Sustainable Separation of Water-in-Oil Emulsion.

Efficient separation of water-in-oil emulsion is of great importance but remains highly challenging since such emulsion contains stable tiny droplets with a diameter less than 20 µm. Herein, we reported the fabrication of a modular fibrous functional membrane using an "in situ growth and covalent functionalization" strategy. The as-prepared PAN@LDH@OTS (PAN = polyacrylonitrile; LDH = layered double hydroxides; and OTS = octadecyltrichlorosilane) membrane possessed an interlaced rough nanostructured surface with intriguing superhydrophobic/superlipophilic properties. When applied for the separation of surfactant-stabilized water-in-oil emulsion (SSE), the PAN@LDH@OTS membrane exhibited an ultrahigh permeation flux of up to 4.63 × 104 L m-2 h-1 with an outstanding separation efficiency of >99.92%, outperforming most of the state-of-the-art membranes. In addition, the membrane can maintain a stable permeation flux and superhydrophobic/superlipophilic properties after 20 times of use. Detailed characterization demonstrated that the demulsification of the SSE process was as follows: first, the droplets can be easily adsorbed to the PAN@LDH@OTS membrane due to the improved intermolecular interactions between OTS and the surfactants (Span 80); second, the droplets can be deformed by the electropositive LDH laminate; and third, the deformed tiny emulsion droplets coalesced into large droplets and floated up, and as a result, efficient separation of SSE can be achieved.

99mTc-Rituximab sentinel lymph node mapping and biopsy, the effective technique avoids axillary dissection and predicts prognosis in 533 cutaneous melanoma.

OBJECTIVE: To evaluate the efficiency of a novel lymph node radiotracer 99mTc-rituximab in sentinel lymph node (SLN) lymphoscintigraphy and SLN biopsy (SLNB), and the influence of SLNB results on the prognosis of cutaneous malignant melanoma (CMM) patients. METHODS: A retrospective study was performed on 533 patients with CMM who underwent lymphoscintigraphy and SLNB. All patients received a preoperative peritumoral injection of 11.1-18.5 MBq of 99mTc-rituximab 0.5 to 1 h before lymphoscintigraphy and SLNB. RESULTS: The detection rate of lymphoscintigraphy and SLNB was both 99.81% (532/533), and the average number of detected SLNs was 2.1 (range 1 to 8) and 2.7 (range 1 to 11) per patient, respectively. 12.1% SLNs and 22.2% patients were found metastatic, with an average of 1.5 (range 1 to 5) metastatic SLNs per patient. The SLN metastatic rates were different in patients with different Breslow thickness, Clark levels, ulceration, mitotic counts, and HMB45 expression (p < 0.05). Ninety patients were proceeded with the regional lymph node dissection (RLND) after SLNB, and the sensitivity, specificity and accuracy of SLNB in metastatic diagnosis is 97.4, 100 and 96.7%, respectively. And SLNs with metastases was an independent prognostic factor for OS and PFS by multivariate prognostic analyses (HR was 5.9 and 4.3, p < 0.001). For patients with metastatic SLNs, the non-SLNs with metastasis and non-SLNs without metastasis in RLND, and observation groups showed different mean PFS as 14.9, 24.8 and 25.5 months (p = 0.018), but no statistically significant difference existed in the OS. CONCLUSION: The novel radiotracer 99mTc-rituximab could identify SLNs specifically in SLN lymphoscintigraphy and SLNB in CMM patients, and the pathology obtained from SLNB rather than from RLND better indicated the staging and long-term prognosis.

Evaluation of VTE, MACE, and Serious Infections Among Patients with RA Treated with Baricitinib Compared to TNFi: A Multi-Database Study of Patients in Routine Care Using Disease Registries and Claims Databases.

INTRODUCTION: The aim of this work is to evaluate baricitinib safety with respect to venous thromboembolism (VTE), major adverse cardiovascular events (MACE), and serious infection relative to tumor necrosis factor inhibitors (TNFi) in patients with rheumatoid arthritis (RA). METHODS: Patients with RA from 14 real-world data sources (three disease registries, eight commercial and three government health insurance claims databases) in the United States (n = 9), Europe (n = 3), and Japan (n = 2) were analyzed using a new user active comparator design. Propensity score matching (1:1) controlled for potential confounding. Meta-analysis of incidence rate ratios (IRR) and incidence rate differences (IRD) for each outcome, from each data source was executed using modified Poisson regression and Cochran-Mantel-Haenszel analysis. RESULTS: Of 9013 eligible baricitinib-treated patients, 7606 were propensity score-matched with TNFi-treated patients, contributing 5879 and 6512 person-years of baricitinib and TNFi exposure, respectively. Across data sources, 97 patients (56 baricitinib) experienced VTE during follow-up, 93 experienced MACE (54 baricitinib), and 321 experienced serious infection (176 baricitinib). Overall IRRs comparing baricitinib with TNFi treatment were 1.51 (95% CI 1.10, 2.08) for VTE, 1.54 (95% CI 0.93, 2.54) for MACE, and 1.36 (95% CI 0.86, 2.13) for serious infection. IRDs for VTE, MACE, and serious infection, respectively, were 0.26 (95% CI -0.04, 0.57), 0.22 (95% CI -0.07, 0.52), and 0.57 (95% CI -0.07, 1.21) per 100 person-years greater for baricitinib than TNFi. CONCLUSIONS: Overall results suggest increased risk of VTE with baricitinib versus TNFi, with consistent point estimates from the two largest data sources. A numerically greater risk was observed for MACE and serious infection when comparing baricitinib versus TNFi, with different point estimates from the two largest data sources. Findings from this study and their impact on clinical practice should be considered in context of limitations and other evidence regarding the safety and efficacy of baricitinib and other Janus kinase inhibitors. TRIAL REGISTRATION: EU PAS Register ( http://encepp.eu ), identifier #32271.

Reduced risk of infections with the intravenous immunoglobulin, IgPro10, in patients at risk of secondary immunodeficiency-related infections.

Aim: Patients with secondary immunodeficiency (SID) are at increased risk of infections and may be treated with immunoglobulin replacement therapy (IgRT). Despite growing efficacy evidence for IgRT in infection prevention in SID, treatment guidelines are not aligned. Materials & methods: A retrospective database analysis was conducted to assess treatment patterns and infection rates in patients at risk of SID-related infections, with or without IgRT (IgPro10) exposure, to evaluate real-world effectiveness of IgRT in infection prevention. Results: Of 11,448 patients included, 222 received IgPro10. B-cell malignancies and solid organ transplants were the predominant underlying conditions. Despite being sicker at baseline, the IgPro10 cohort demonstrated fewer infections post-index than the non-IgRT cohort. Conclusion: IgPro10 may be an effective option for infection prevention in SID.

Secondary immunodeficiency (SID) occurs when the immune system is weakened by external factors, including certain medical treatments. It can leave a person with an increased risk of potentially serious or even fatal infections, as they no longer have adequate defenses against bacteria. Some patients with this condition require treatment to boost their immune system, including supplementation of their antibodies, known as immunoglobulin replacement therapy (IgRT). In this study, we explored whether: (1) patients with conditions that are at risk of SID and associated infections received IgRT; and (2) whether receiving the IgRT reduced the incidence of infections. We found that patients who had IgRT were much less likely to experience infections than those who did not receive IgRT, suggesting that IgRT may be an effective treatment option for preventing infections in patients with compromised immune systems caused by SID.

Higher accuracy of [68 Ga]Ga-DOTA-FAPI-04 PET/CT comparing with 2-[18F]FDG PET/CT in clinical staging of NSCLC.

PURPOSE: This study aimed to explore the clinical staging performance of [68 Ga]Ga-DOTA-FAPI-04 PET/CT compared with that of 2-[18F]FDG PET/CT in non-small cell lung cancer (NSCLC) patients lesion by lesion. METHODS: A total of 134 diagnosed or suspected NSCLC patients were enrolled in the prospective study (ChiCTR2000038080); they received paired 2-[18F]FDG PET/CT and [68 Ga]Ga-DOTA-FAPI-04 PET/CT. Of these patients, the retrospective analysis of 74 NSCLC patients with pathological results was conducted from primary tumor (T) diagnosis, lymph node (N), and metastatic lesion (M) staging. The imaging characteristics of the lung nodules and suspected metastases were obtained and analyzed, and the staging performance of 2-[18F]FDG PET/CT and [68 Ga]Ga-DOTA-FAPI-04 PET/CT was compared. RESULTS: For T diagnosis, [68 Ga]Ga-DOTA-FAPI-04 showed better diagnostic performance than 2-[18F]FDG in 79 lung nodules of 72 patients, especially for nonsolid and small-dimension adenocarcinoma nodules. For N staging, 98 lymph nodes (LNs) with pathological results in 37 patients were analyzed. The SUVmax of [68 Ga]Ga-DOTA-FAPI-04 in the nonmetastatic LNs was significantly lower than that in the metastatic LNs. Regarding metastatic LN identification, the calculated optimum cut-off value of [68 Ga]Ga-DOTA-FAPI-04 SUVmax was 5.5, and the diagnostic accuracy using [68 Ga]Ga-DOTA-FAPI-04 and 2-[18F]FDG criteria was 94% and 30%, respectively (P < 0.001). For M staging, [68 Ga]Ga-DOTA-FAPI-04 identified more lesions than 2-[18F]FDG (257 vs. 139 lesions) in 14 patients with multiple metastases. Overall, the staging accuracy of [68 Ga]Ga-DOTA-FAPI-04 was better than that of 2-[18F]FDG in 52 patients with different pathological stages [43/52 (82.7%) vs. 27/52 (51.9%), P = 0.001]. CONCLUSION: Compared with 2-[18F]FDG PET/CT, [68 Ga]Ga-DOTA-FAPI-04 PET/CT demonstrated better staging performance in NSCLC patients with different pathological stages, especially those with localized disease.

Realizing Simultaneous Detrimental Reactions Suppression and Multiple Benefits Generation from Nickel Doping toward Improved Protonic Ceramic Fuel Cell Performance.

Anode-supported protonic ceramic fuel cells (PCFCs) are highly promising and efficient energy conversion systems. However, several challenges need to be overcome before these systems are used more widely, including the poor sintering of recently developed proton-conducting oxides and the decreased proton conductivity due to detrimental reactions between the nickel from anode and the electrolyte occurring during high-temperature co-sintering. Herein, a Ni doping strategy to increase the electrolyte sintering, suppress the detrimental phase reactions, and generate stable Ni nanoparticles for enhanced performance is proposed. A nickel-doped perovskite oxide is developed with the nominal composition of Ba(Zr0.1 Ce0.7 Y0.1 Yb0.1 )0.95 Ni0.05 O3- δ . Acting as a sintering aid, such a small amount of nickel effectively improves the sintering of the electrolyte. Concomitantly, reactions between nickel and the Ni-doped ceramic phase are suppressed, turning detrimental phase reactions into benefits. The nickel doping further promotes the formation of Ni nanoparticles, which enhance the electrocatalytic activity of the anode toward the hydrogen oxidation reaction and improve the charge transfer across the anode-electrolyte interface. As a result, highly efficient PCFCs are developed. The innovative anode developed in this work also shows favorable activity toward ammonia decomposition, making it highly promising for use in direct ammonia fuel cells.

Promoter CAG is more efficient than hepatocyte­targeting TBG for transgene expression via rAAV8 in liver tissues.

The recombinant adeno­associated virus 8 (rAAV8) vector is a widely used tool in basic research and clinical trials. The cytomegalovirus immediate­early enhancer/chicken ß­actin (CAG) promoter is a synthetic promoter used in adenoviral constructs with a wide spectrum and notable efficiency. The thyroxine binding globulin (TBG) promoter is a liver­specific promoter, which directs transgene expression in hepatocytes. However, the transduction efficiency of the rAAV vector is dependent on both the administration routes and the promoter elements. In the present study, the transduction efficiency in the liver following intraperitoneal (IP) and intravenous (IV) injections of rAAV8 with the CAG, TBG669 and TBG410 promoters was compared. Enhanced green fluorescent protein (EGFP) expression was used as the biomarker to indicate efficiency. Among the three different promoters, CAG exhibited the highest efficiency from both IV and IP injections. Following IV administration, EGFP expression, induced by the CAG promoter, was 67­fold higher compared with that in the TBG410 promoter group and 26­fold higher compared with that in the TBG669 promoter group. EGFP protein expression was higher with IV injection compared with that for IP injection for both the CAG and TBG669 promoters (P<0.05). With the CAG promoter, EGFP protein expression was 1.5­fold higher with the use of IV injection than with IP injection. With the TBG410 promoter, no differences were observed between the two administrations. In conclusion, these findings demonstrated that the CAG promoter was much more efficient at driving gene expression in the liver compared with that for the TBG promoters in rAAV8. In addition, IP administration produced comparable efficiency for gene delivery via the rAAV8 vector, particularly with the promoter TBG410.

Gene co-expression analysis identifies modules related to insufficient sleep in humans.

BACKGROUND: Insufficient sleep and circadian rhythm disruption may cause cancer, obesity, cardiovascular disease, and cognitive impairment. The underlying mechanisms need to be elucidated. METHOD: Weighted gene co-expression network analysis (WGCNA) was used to identify co-expressed modules. Connectivity Map tool was used to identify candidate drugs based on top connected genes. R ptestg package was utilized to detected module rhythmicity alteration. A hypergeometric test was used to test the enrichment of insomnia SNP signals in modules. Google Scholar was used to validate the modules and hub genes by literature. RESULTS: We identified a total of 45 co-expressed modules. These modules were stable and preserved. Eight modules were correlated with sleep restriction duration. Module rhythmicity was disrupted in sleep restriction subjects. Hub genes that involve in insufficient sleep also play important roles in sleep disorders. Insomnia GWAS signals were enriched in six modules. Finally, eight drugs associated with sleep disorders were identified. CONCLUSION: Systems biology method was used to identify sleep-related modules, hub genes, and candidate drugs. Module rhythmicity was altered in sleep insufficient subjects. Thiamphenicol, lisuride, timolol, and piretanide are novel candidates for sleep disorders.

Multicomponent Self-Assembly of a Giant Heterometallic Polyoxotungstate Supercluster with Antitumor Activity.

The hierarchical aggregation of molecular nanostructures from multiple components is a grand synthetic challenge, which requires highly selective linkage control. We demonstrate how two orthogonal linkage groups, that is, organotin and lanthanide cations, can be used to drive the aggregation of a giant molecular metal oxide superstructure. The title compound {[(Sn(CH3 )2 )2 O]4 {[CeW5 O18 ] [TeW4 O16 ][CeSn(CH3 )2 ]4 [TeW8 O31 ]4 }2 }46- (1 a) features dimensions of ca. 2.2×2.3×3.4 nm3 and a molecular weight of ca. 25 kDa. Structural analysis shows the hierarchical aggregation from several independent subunits. Initial biomedical tests show that 1 features an inhibitory effect on the proliferation of HeLa cells based on an apoptosis pathway. In vivo experiments in mice reveal the antiproliferative activity of 1 and open new paths for further development of this new compound class.

High performance polypyrrole/SWCNTs composite film as a promising organic thermoelectric material.

Conducting polymer thermoelectric (TE) materials have received great attention due to their unique properties. In this work, polypyrrole (PPy)/single-walled carbon nanotubes (SWCNTs) composite films with improved TE performance have been prepared by chemical interfacial polymerization at the cyclohexane/water interface under a controlled temperature. Attributed to the smooth surface, higher conjugation length and more ordered molecular structure of the interfacial polymerized PPy film, the electrical conductivity can be as high as ∼500 S cm-1. To further enhance the TE properties of PPy, SWCNT was added to construct a PPy/SWCNTs composite. Due to the synergistic effect between the two phases and the energy filtering effect at the interfaces between PPy and SWCNTs, the Seebeck coefficient of the composite enhanced significantly with the increase SWCNTs content. The composite shows an optimal power factor of 37.6 ± 2.3 µW mK-2 when the content of SWCNTs is 0.8 mg. This value is one of the largest values among the reported PPy based composites fabricated by the chemical polymerization method. The results indicate that interfacial polymerization under a controlled temperature is a promising way to improve the TE performance of conducting polymer based composite materials.

Safety and Efficacy of Through-the-Scope Placement of Colonic Self-expandable Metal Stents Without Fluoroscopic Guidance: A Retrospective Cohort Study.

BACKGROUND: Colonic self-expandable metal stents (SEMSs) are usually placed through an endoscope under fluoroscopic guidance. In this retrospective study, we measured the safety and efficacy of through-the-scope colonic stent placement without fluoroscopic guidance. MATERIALS AND METHODS: We included consecutive patients with malignant colonic obstruction who underwent SEMS placement through the endoscope without fluoroscopic guidance (NF group) from 2016 to June 2019 in a single tertiary medical center. Technical and clinical success rates and complication rates were compared with those of a historical control group consisting of consecutive patients who underwent stent placement through the endoscope under fluoroscopic guidance (F group) from 2012 to 2015. RESULTS: Of 136 patients analyzed, 67 were in the NF group and 69 were in the F group. For the NF and F groups, technical success rates were 97.0% and 95.7%, respectively (P=0.763); clinical success rates were 92.5% and 89.9%, respectively (P=0.581). Major complications included perforation (NF group, 1.5%; F group, 1.4%), stent migration (NF group, 0; F group, 1.4%), and stent occlusion (NF group, 1.5%; F group, 2.9%) (P=0.425). The median procedure time was significantly lower in the NF group (25.90±18.68 min) than in the F group (44.23±20.40 min) (P<0.001). CONCLUSIONS: Colonic SEMS placement without fluoroscopy is as safe and effective as the conventional fluoroscopically guided approach. This new method significantly reduced the procedure time.