Differential diagnosis between hepatic alveolar echinococcosis and intrahepatic cholangiocarcinoma with conventional ultrasound and contrast-enhanced ultrasound.

BACKGROUND: Misclassifications of hepatic alveolar echinococcosis (HAE) as intrahepatic cholangiocarcinoma (ICC) may lead to inappropriate treatment strategies. The aim of this study was to explore the differential diagnosis with conventional ultrasound and contrast-enhanced ultrasound (CEUS). METHODS: Sixty HAE lesions with 60 propensity score-matched ICC lesions were retrospectively collected. The 120 lesions were randomly divided into a training set (n = 80) and a testing set (n = 40). In the training set, the most useful independent conventional ultrasound and CEUS features was selected for differentiating between HAE and ICC. Then, a simplified US scoring system for diagnosing HAE was constructed based on selected features with weighted coefficients. The constructed US score for HAE was validated in both the training set and the testing set, and diagnostic performance was evaluated. RESULTS: Compared with ICC lesions, HAE lesions were mostly located in the right lobe and had mixed echogenicity, a pseudocystic appearance and foci calcifications on conventional ultrasound. On CEUS, HAE lesions showed more regular rim-like enhancement than ICC lesions and had late washout with a long enhancement duration. The simplified US score consisted of echogenicity, pseudocystic/calcification, bile duct dilatation, enhancement pattern, enhancement duration, and marked washout. In the testing set, the sensitivity, specificity, LR+, LR- and the area under the ROC curve for the score to differentiate HAE from ICC were 80.0, 81.3%, 4.27, 0.25 and 0.905, respectively. CONCLUSIONS: The US score based on typical features from both conventional ultrasound and CEUS could accurately differentiate HAE from ICC.

Prevalence and composition of CHD at different altitudes in Tibet: a cross-sectional study.

BACKGROUND: The prevalence of CHD has been well described worldwide except in Tibet. This study aimed to illustrate the prevalence and composition of CHD in Tibetan children according to altitude. Methods and results In the first part, we prospectively recruited 7088 unselected Tibetan children (4-17 years) from south-west Tibet. The total prevalence of CHD increased from 4.6/1000 below 4200 m to 13.4/1000 above 4700 m, with a female-to-male ratio of 1.3:3.1. The total prevalence and female prevalence of patent ductus arteriosus increased more than 10-fold. Females living above 4700 m had exceptionally high prevalence of patent ductus arteriosus (14.9/1000). The prevalence of atrial septal defect was comparable among different altitudes (3.3-3.8/1000). The prevalence of ventricular septal defect was 1.3/1000 below 4700 m, and no cases were found above this altitude. In the second part, we retrospectively reviewed the clinical data of 383 CHD children in Tibet and 73 children at lower altitudes. The percentage of isolated ventricular septal defect decreased from 54.8 to 3.1%, and the percentage of isolated patent ductus arteriosus increased from 8.2 to 68.4% with elevation. Children living below 4200 m (10.4-13.7%) had a larger proportion of complex CHD than those above this altitude (2.0-3.1%). Of the 20 Tibetan children with complex CHD, 14 (70.0%) lived below 4200 m. CONCLUSIONS: A wide variation in CHD prevalence and composition existed in Tibetan children among different altitudes.

Enhanced upconversion luminescence from ZnO/Zn hybrid nanostructures induced on a Zn foil by femtosecond laser ablation.

ZnO/Zn hybrid nanostructures including nanowires and nanonets were induced on a Zn foil by using 400-nm femtosecond (fs) laser pulses with a low repetition rate of 1 kHz and duration of 100 fs. The laser fluence was chosen to be slightly above the ablation threshold of Zn. The luminescence of the formed ZnO/Zn hybrid nanostructures was examined by using fs laser pulses with a high repetition rate of 76 MHz and duration of ~130 fs through both single-photon and multiphoton excitation. While the luminescence spectrum under the single-photon excitation exhibited a single peak at ~480 nm, a broadband upconversion luminescence with many ripples was observed under the multiphoton excitation. More interestingly, the upconversion luminescence of the ZnO/Zn hybrid nanostructures was significantly enhanced by the underlying Zn nanostructures which induced strongly localized electric field. The enhancement of the upconversion luminescence was verified by the short lifetime of only ~79 ps observed for the ZnO/Zn hybrid nanostructures, which is nearly one order of magnitude smaller as compared with the luminescence lifetime of the ZnO nanorods synthesized by using the chemical coprecipitation method. The localization of electric field in the ZnO/Zn hybrid nanostructures was confirmed by the numerical simulations based the finite-difference time-domain technique.

Sequence analysis of mitochondrial ND1 gene can reveal the genetic structure and origin of Bactrocera dorsalis s.s.

BACKGROUND: The oriental fruit fly, Bactrocera dorsalis s.s., is one of the most important quarantine pests in many countries, including China. Although the oriental fruit fly has been investigated extensively, its origins and genetic structure remain disputed. In this study, the NADH dehydrogenase subunit 1 (ND1) gene was used as a genetic marker to examine the genetic diversity, population structure, and gene flow of B. dorsalis s.s. throughout its range in China and southeast Asia. RESULTS: Haplotype networks and phylogenetic analysis indicated two distinguishable lineages of the fly population but provided no strong support for geographical subdivision in B. philippinensis. Demographic analysis revealed rapid expansion of B. dorsalis s.s. populations in China and Southeast Asia in the recent years. The greatest amount of genetic diversity was observed in Manila, Pattaya, and Bangkok, and asymmetric migration patterns were observed in different parts of China. The data collected here further show that B. dorsalis s.s. in Yunnan, Guangdong, and Fujian Provinces, and in Taiwan might have different origins within southeast Asia. CONCLUSIONS: Using the mitochondrial ND1 gene, the results of the present study showed B. dorsalis s.s. from different parts of China to have different genetic structures and origins. B. dorsalis s.s. in China and southeast Asia was found to have experienced rapid expansion in recent years. Data further support the existence of two distinguishable lineages of B. dorsalis s.s. in China and indicate genetic diversity and gene flow from multiple origins.The sequences in this paper have been deposited in GenBank/NCBI under accession numbers KC413034-KC413367.

Formation of 100-nm periodic structures on a titanium surface by exploiting the oxidation and third harmonic generation induced by femtosecond laser pulses.

Periodic surface structures with periods as small as about one-tenth of the irradiating femtosecond (fs) laser light wavelength were created on the surface of a titanium (Ti) foil by exploiting laser-induced oxidation and third harmonic generation (THG). They were achieved by using 100-fs laser pulses with a repetition rate of 1 kHz and a wavelength ranging from 1.4 to 2.2 µm. It was revealed that an extremely thin TixOy layer was formed on the surface of the Ti foil after irradiating fs laser light with a fluence smaller than the ablation threshold of Ti, leading to a significant enhancement in THG which may exceed the ablation threshold of TixOy. As compared with Ti, the maximum efficacy factor for TixOy appears at a larger normalized wavevector in the direction perpendicular to the polarization of the fs laser light. As a result, the THG-dominated laser ablation of TixOy induces 100-nm periodic structures parallel to the polarization of the fs laser light. The depth of the periodic structures was found to be ~10 nm by atomic force microscopy and the formation of the thin TixOy layer was verified by energy dispersive X-ray spectroscopy.

Referral by outreach specialist reduces hospitalisation costs of rural patients with digestive tract cancer: a report from medical consortium in China.

INTRODUCTION: The authors examined the effect of referrals from outreach specialists on total hospitalisation costs of rural Chinese patients receiving surgical treatment for digestive tract cancer at a tertiary hospital within a vertically integrated medical consortium. METHODS: A retrospective cohort study was conducted within the Taiyuan Central Hospital medical consortium between January 2008 and December 2010. This consortium consists of Taiyuan Central Hospital (a tertiary hospital) and three county hospitals in Taiyuan city, the capital of Shanxi province in China. Patients admitted for surgery to treat digestive tract cancer (N=359) were assigned to control (direct admission without referral), referral by local doctor (RL), or referral by outreach specialist (RO) groups according to referral type. Length of stay (LOS) and hospitalisation costs were examined. Regression-adjusted costs were estimated by a multivariate model that controlled for gender, age, type of cancer, Charlson Comorbidity Index (CCI) score, and referral type. RESULTS: Significant differences were found between the three groups (p<0.001) for LOS and total hospitalisation costs. Both were highest for the control group, followed by RL and then the RO groups (LOS: 28.3 ± 4.9, 24.2 ± 5.9, and 19.2 ± 3.7 days; hospitalisation cost: Chinese yuan (CNY)35,087.87 ± 6208.30, 32,853.38 ± 5195.40, and 29,794.56 ± 5250.20). CONCLUSION: A strong association was found between RO and substantially reduced hospitalisation costs in patients receiving digestive tract cancer surgery within the medical consortium as compared to RL. This finding suggests that the strengthened collaboration between outreach specialists and local doctors, herein referred to as the green referral channel, is the key factor leading to reduced hospitalisation costs.

Inundative practice for screening siRNA management candidates against a notorious predatory beetle using olfactory silencing.

Calosoma maximoviczi, a predatory pest beetle, poses a significant threat to wild silk farm production due to its predation on wild silkworms. Given the coexistence of this species with beneficial silkworms in the farm orchards, chemical pesticides are not an ideal solution for controlling its population. In this study, we employed a comprehensive multi-target RNA interference (RNAi) approach to disrupt the olfactory perception of C. maximoviczi through independently silencing 16 odorant receptors (ORs) in the respective genders. Specifically, gene-specific siRNAs were designed to target a panel of ORs, allowing us to investigate the specific interactions between odorant receptors and ligands within this species. Our investigation led to identifying four candidate siOR groups that effectively disrupted the beetle's olfactory tracking of various odorant ligands associated with different trophic levels. Furthermore, we observed sex-specific differences in innate RNAi responses reflected by subsequent gene expression, physiological and behavioral consequences, underscoring the complexity of olfactory signaling and emphasizing the significance of considering species/sex-specific traits when implementing pest control measures. These findings advance our understanding of olfactory coding patterns in C. maximoviczi beetles and establish a foundation for future research in the field of pest management strategies.

Exploring 0D lead-free metal halide with highly efficient blue light emission and high-sensitivity photodetection.

Environmentally friendly and highly efficient blue luminescent materials are an unremitting pursuit in the optoelectronic field. Herein, we assembled a new 0D lead-free metal halide of (F-PPA)ZnBr4, which exhibits narrow blue light emission with a remarkable PLQY of 50.15%, high stability and high detection sensitivity toward UV light. These results indicate the potential for the application of low-dimensional zinc-based halides in multiple optoelectronic devices.

Prognostic value of neutrophil/lymphocyte, platelet/lymphocyte, lymphocyte/monocyte ratios and Glasgow prognostic score in osteosarcoma: A meta-analysis.

BACKGROUND: Some studies investigated the prognostic role of several blood biomarkers, including the neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), lymphocyte/monocyte ratio (LMR) and Glasgow prognostic score (GPS), in osteosarcoma, but their results were inconsistent with each other. AIM: To identify the prognostic value of NLR, PLR, LMR and GPS in osteosarcoma patients through reviewing relevant studies. METHODS: The PubMed, EMBASE, Web of Science and CNKI databases were searched up to October 2, 2021. The primary and second outcomes were overall survival (OS) and disease-free survival (DFS), respectively. The hazard ratios (HRs) with 95% confidence intervals (CIs) were combined to assess the association between these indicators and prognosis of osteosarcoma patients. RESULTS: A total of 13 studies involving 2087 patients were eventually included. The pooled results demonstrated that higher NLR and GPS were significantly associated with poorer OS (HR = 1.88, 95%CI: 1.38-2.55, P < 0.001; HR = 2.19, 95%CI: 1.64-2.94, P < 0.001) and DFS (HR = 1.67, 95%CI: 1.37-2.04, P < 0.001; HR = 2.50, 95%CI: 1.39-4.48, P < 0.001). However, no significant relationship of PLR and LMR and OS (P = 0.085; P = 0.338) and DFS (P = 0.396; P = 0.124) was observed. CONCLUSION: Higher NLR and GPS were related with worse prognosis and might serve as novel prognostic indicators for osteosarcoma patients.

CS1 promotes multiple myeloma cell adhesion, clonogenic growth, and tumorigenicity via c-maf-mediated interactions with bone marrow stromal cells.

CS1 is highly expressed on tumor cells from the majority of multiple myeloma (MM) patients regardless of cytogenetic abnormalities or response to current treatments. Furthermore, CS1 is detected in MM patient sera and correlates with active disease. However, its contribution to MM pathophysiology is undefined. We here show that CS1 knockdown using lentiviral short-interfering RNA decreased phosphorylation of ERK1/2, AKT, and STAT3, suggesting that CS1 induces central growth and survival signaling pathways in MM cells. Serum deprivation markedly blocked survival at earlier time points in CS1 knockdown compared with control MM cells, associated with earlier activation of caspases, poly(ADP-ribose) polymerase, and proapoptotic proteins BNIP3 and BIK. CS1 knockdown further delayed development of MM tumor and prolonged survival in mice. Conversely, CS1 overexpression promoted myeloma cell growth and survival by significantly increasing myeloma adhesion to bone marrow stromal cells (BMSCs) and enhancing myeloma colony formation in semisolid culture. Moreover, CS1 increased c-maf-targeted cyclin D2-dependent proliferation, -integrin beta7/alphaE-mediated myeloma adhesion to BMSCs, and -vascular endothelial growth factor-induced bone marrow angiogenesis in vivo. These studies provide direct evidence of the role of CS1 in myeloma pathogenesis, define molecular mechanisms regulating its effects, and further support novel therapies targeting CS1 in MM.

Aberrant expression of the von Hippel-Lindau gene in human endometrial hyperplasia and endometrial carcinoma.

INTRODUCTION: The purpose of this study was to determine whether aberrant expression of the von Hippel-Lindau (VHL) gene in human hyperplastic and malignant endometrial tissues was involved in endometrial carcinogenesis. METHODS: Fresh tissue samples of endometrial hyperplasia consisting of simple (n = 26), complex (n = 23), and atypical hyperplasia (n = 20); endometrial carcinoma (n = 17); and normal endometrium (n = 40) were measured using Western blotting and real-time reverse transcription polymerase chain reaction. Paraffin-embedded sections of endometrial hyperplasia (n = 90), endometrial carcinoma (n = 30), and normal endometrium (n = 60) were detected by immunohistochemical method. RESULTS: Von Hippel-Lindau staining was present in the cytoplasm of epithelial cells and stroma. A decreased expression of VHL mRNA in endometrial hyperplasia from simple, complex, to atypical hyperplasia was observed. There were statistical differences on VHL messenger RNA (mRNA) levels among simple, complex, and atypical hyperplasia (P < 0.01). The VHL mRNA levels in endometrial carcinoma were significantly lower than those in normal endometrium, simple hyperplasia, or complex hyperplasia (P < 0.01) but similar to those in atypical hyperplasia (P > 0.05). Von Hippel-Lindau protein levels by Western blotting and staining intensity by immunohistochemistry were coincident with the VHL mRNA levels. CONCLUSIONS: Aberrant expression of the VHL gene is associated with the risk of endometrial hyperplasia progressing to endometrial carcinoma, and its expression levels are useful as a predictive indicator for endometrial carcinoma.

Anti-CS1 humanized monoclonal antibody HuLuc63 inhibits myeloma cell adhesion and induces antibody-dependent cellular cytotoxicity in the bone marrow milieu.

Currently, no approved monoclonal antibody (mAb) therapies exist for human multiple myeloma (MM). Here we characterized cell surface CS1 as a novel MM antigen and further investigated the potential therapeutic utility of HuLuc63, a humanized anti-CS1 mAb, for treating human MM. CS1 mRNA and protein was highly expressed in CD138-purified primary tumor cells from the majority of MM patients (more than 97%) with low levels of circulating CS1 detectable in MM patient sera, but not in healthy donors. CS1 was expressed at adhesion-promoting uropod membranes of polarized MM cells, and short interfering RNA (siRNA) targeted to CS1 inhibited MM cell adhesion to bone marrow stromal cells (BMSCs). HuLuc63 inhibited MM cell binding to BMSCs and induced antibody-dependent cellular cytotoxicity (ADCC) against MM cells in dose-dependent and CS1-specific manners. HuLuc63 triggered autologous ADCC against primary MM cells resistant to conventional or novel therapies, including bortezomib and HSP90 inhibitor; and pretreatment with conventional or novel anti-MM drugs markedly enhanced HuLuc63-induced MM cell lysis. Administration of HuLuc63 significantly induces tumor regression in multiple xenograft models of human MM. These results thus define the functional significance of CS1 in MM and provide the preclinical rationale for testing HuLuc63 in clinical trials, either alone or in combination.

Association between promoter DNA methylation and gene expression in the pathogenesis of ischemic stroke.

To assess DNA methylation sites as well as gene expression related to ischemic stroke (IS) and comprehensively reveal their correlation and possible pathological mechanisms, we implemented (1) genome-wide DNA methylation profiling from the GEO repository related to IS with and without symptoms; (2) identification of differentially methylation positions (DMPs) and genes (DMGs), functional enrichment analysis along with DMG regulatory network construction; (3) validation tests of 2 differential methylation positions of interest as well as analogous gene expression in other datasets and in IS patients and controls; and (4) correlation analysis of DNA methylation and mRNA expression data. In total, 870 DMPs were physically located within 693 DMGs. After disease ontology (DO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, gene ontology (GO), protein-protein interaction (PPI) network construction as well as module analysis, HLA-DRB1 and HLA-DQB1 were identified. Their expression was validated in 4 other datasets but was significant in only 1, and the expression was lower in the IS group (P < 0.05). After validation in IS patients and controls, we found that these two genes showed more hypermethylation and lower expression levels in the IS group (P < 0.001). The methylation of genes was negatively associated with their expression (P < 0.05). The current study recognized a connection among DNA methylation and gene expression and emphasized the prominence of HLA-DRB1 and HLA-DQB1 in IS pathogenesis.

c­Jun N­terminal kinase inhibition attenuates early brain injury induced neuronal apoptosis via decreasing p53 phosphorylation and mitochondrial apoptotic pathway activation in subarachnoid hemorrhage rats.

Early brain injury (EBI)­induced neuronal apoptosis is primarily responsible for the subsequent complications of aneurysmal subarachnoid hemorrhage (aSAH), which may increase the risk of mortality in patients with aSAH. c­Jun N­terminal kinase (JNK) has been demonstrated to be a promoter of EBI­induced cell apoptosis, although the mechanism has yet to be fully elucidated. The present study aimed to explore whether the role of JNK1 is associated with tumor protein p53 (p53), which is one of the most important factor that triggers cell apoptosis. JNK1 expression was downregulated via in vivo small interfering RNA transfection in an aSAH rat model in order to assess differences in the behavior, survival times, morphology and genetics of the experimental animals. The results revealed that JNK1 inhibition improved the neurological scores and survival times of SAH rats by interrupting cascaded neuronal apoptosis. The interruption of EBI­induced neuronal apoptosis may originate from a decrease in the level of p53 phosphorylation and deactivation of the downstream mitochondrial apoptotic pathway. Taken together, these results suggest that JNK1 may be a promising target for improving the prognosis of patients with aSAH.

Effects of soil warming on soil microbial extracellular enzyme activities with different depths in a young Chinese fir (Cunninghamia lanceolata)plantation of subtropics.

Extracellular enzyme activitie (EEAs) are a sensitive indicator of microbial function and soil organic matter decomposition in response to climate warming. Up to now, most studies of climate warming and their effects on EEAs have been restricted on the relatively carbon rich topsoil (the upper 20 cm of the soil), whereas little is known about EEAs in subsoil (below 30 cm depth). This study focused on the responses of EEAs to soil warming in a subtropical forest at depths of 0-10 cm, 10-20 cm, 20-40 cm and 40-60 cm. The examined extracellular enzymes included ß-glucosidase (BG), cellobiohydrolase (CBH), phenoloxidase (PHO) and peroxidase (PEO), all being involved in the C-cycle. The results showed that, 1) warming significantly increased all EEAs (18%-69%) at the depth of 0-10 cm and 10-20 cm. Below the depth of 20 cm, warming did no affect or suppressed EEAs (13%-31%), except increasing PHO (10%) at 20-40 cm. 2) Results from the redundancy analysis showed that the EEAs were mainly driven by ammonium nitrogen (NH4+-N) and soil moisture (M) in organic carbon rich topsoil. Warming enhanced nutrient competition between soil microorganisms and plants. Thus, it increased EEAs to meet NH4+-N demands of microorganisms. In subsoil with relatively low substrate availability, the EEAs were dominated by dissolved organic matter and microbial biomass (MBC). Warming increased dissolved organic matter and thus provided more substrates for microorganisms, which relieved the dependence of microbes on EEAs. Consequently, warming diminished EEAs in subsoils. Our results suggested that EEAs at the four depths showed different responses to warming. In addition, environmental factors accounting for the variances in EEAs under soil warming condition were different at topsoil and subsoil. Paying more attention to microbes at different soil depths has important implications to precisely predict ecosystem C cycling in response to global warming.

Role of B-cell-activating factor in adhesion and growth of human multiple myeloma cells in the bone marrow microenvironment.

Recent studies have underscored the role of B-cell-activating factor (BAFF), a member of the tumor necrosis factor superfamily, in promoting the survival of malignant B cells, including human multiple myeloma. We here characterized the functional significance of BAFF in the interaction between multiple myeloma and bone marrow stromal cells (BMSC) and further defined the molecular mechanisms regulating these processes. BAFF is detected on BMSCs derived from multiple myeloma patients as evidenced by flow cytometry. BAFF secretion is 3- to 10-fold higher in BMSCs than in multiple myeloma cells, and tumor cell adhesion to BMSCs augments BAFF secretion by 2- to 5-fold, confirmed by both ELISA and immunoblotting. Adhesion of MM1S and MCCAR multiple myeloma cell lines to KM104 BMSC line transfected with a luciferase reporter vector carrying the BAFF gene promoter (BAFF-LUC) significantly enhanced luciferase activity, suggesting that nuclear factor-kappaB (NF-kappaB) activation induced by multiple myeloma adhesion to BMSCs mediates BAFF up-regulation. Moreover, BAFF (0-100 ng/mL) increases adhesion of multiple myeloma lines to BMSCs in a dose-dependent manner; conversely, transmembrane activator and calcium modulator and cyclophylin ligand interactor-Ig or B-cell maturation antigen/Fc blocked BAFF stimulation. Using adenoviruses expressing dominant-negative and constitutively expressed AKT as well as NF-kappaB inhibitors, we further showed that BAFF-induced multiple myeloma cell adhesion is primarily mediated via activation of AKT and NF-kappaB signaling. Importantly, BAFF similarly increased adhesion of CD138-expressing patient multiple myeloma cells to BMSCs. These studies establish a role for BAFF in localization and survival of multiple myeloma cells in the bone marrow microenvironment and strongly support novel therapeutics, targeting the interaction between BAFF and its receptors in human multiple myeloma.

miR-204 functions as a tumor suppressor gene, at least partly by suppressing CYP27A1 in glioblastoma.

Gliomas are the most common type of malignant primary brain tumors in adults and exhibit a spectrum of aberrantly aggressive phenotypes. Despite advances in treatments during past decades, prognosis of the disease remains poor, with a median survival time of 12-14 months. Future studies on the molecular mechanism of the disease may provide the theoretical basis to identify new targets for effective therapies. The present study revealed that in glioblastoma cells, the overexpression of cytochrome P450, family 27, subfamily A, polypeptide 1 (CYP27A1) promoted proliferation, while silencing of CYP27A1 inhibited proliferation, without affecting migration and invasion. CYP27A1 protein was upregulated in glioblastoma tissues, indicating that CYP27A1 is an oncogene. The downregulation of specific microRNAs (miRNA) may contribute to the upregulation of oncogenes in glioblastoma. A common strategy was used to predict target miRNAs of CPY27A1 using the miRanda algorithm. miR-211 and miR-204 could target the 3'untranslated region of CPY27A1 mRNA. Additional studies confirmed that the overexpression of miR-204 inhibited CPY27A1 expression in glioblastoma cells. Finally, it was identified that miR-204 was downregulated in glioblastoma and that its overexpression inhibited proliferation, migration and invasion in glioblastoma cells. Thus, it was concluded that miR-204 functions as a tumor suppressor gene, at least partly by suppressing CYP27A1 in glioblastoma.

Selective Electrochemical Reduction of Carbon Dioxide Using Cu Based Metal Organic Framework for CO2 Capture.

The conversion efficiency and product selectivity of the electroreduction of carbon dioxide have been largely limited by the low CO2 solubility in aqueous solution. To relieve this problem, Cu3(BTC)2 (Cu-MOF) as CO2 capture agent was introduced into a carbon paper based gas diffusion electrode (GDE) in this study. The faradaic efficiencies (FEs) of CH4 on GDE with Cu-MOF weight ratio in the range of 7.5-10% are 2-3-fold higher than that of GDE without Cu-MOF addition under negative potentials (-2.3 to -2.5 V vs SCE), and the FE of the competitive hydrogen evolution reaction (HER) is reduced to 30%. This work paves the way to develop GDE with high catalytic activity for ERC.

Immunomodulatory drug lenalidomide (CC-5013, IMiD3) augments anti-CD40 SGN-40-induced cytotoxicity in human multiple myeloma: clinical implications.

SGN-40, a humanized immoglobulin G1 (IgG1) anti-CD40 monoclonal antibody, mediates cytotoxicity against human multiple myeloma (MM) cells via suppression of interleukin (IL)-6-induced proliferative and antiapoptotic effects as well as antibody-dependent cell-mediated cytotoxicity (ADCC). Here, we studied the clinical significance of an immunomodulatory drug lenalidomide on SGN-40-induced cytotoxicity against CD138(+)CD40(+) MM lines and patient MM cells. Pretreatment with lenalidomide sensitized MM cells to SGN-40-induced cell death. Combined lenalidomide and SGN-40 significantly induced MM apoptosis, evidenced by enhanced cleavage of caspase-3/8/poly(ADP-ribose)polymerase and increased sub-G(0) cells, compared with either single agent at the same doses. Pretreatment of effector cells with lenalidomide augmented SGN-40-induced MM cell lysis, associated with an increased number of CD56(+)CD3(-) natural killer (NK) cells expressing CD16 and LFA-1. Importantly, pretreatment with lenalidomide or lenalidomide and SGN-40 markedly enhanced NK-cell-mediated lysis of autologous patient MM cells triggered by SGN-40. Lenalidomide also up-regulated CD40L on CD56(+)CD3(-) NK cells, facilitating IL-2-mediated activation of NK cells. In addition, lenalidomide induced the CD56(dim) NK subset, which are more potent mediators of ADCC against target MM cells than the CD56(bright) NK subset. Finally, pretreatment of both effector and target MM cells with lenalidomide markedly enhanced SGN-40-mediated ADCC against CD40-expressing MM cells. These studies, therefore, show that the addition of lenalidomide to SGN-40 enhances cytotoxicity against MM cells, providing the framework for combined lenalidomide and SGN-40 in a new treatment paradigm to both target MM cells directly and induce immune effectors against MM.

Transthoracic contrast echocardiography using vitamin B6 and sodium bicarbonate as contrast agents for the diagnosis of patent foramen ovale.

To evaluate the utility of transthoracic contrast echocardiography (cTTE) using vitamin B6 and sodium bicarbonate as contrast agents for diagnosing right-to-left shunt (RLS) caused by patent foramen ovale (PFO) compared to that of transesophageal echocardiography (TEE). We investigated 125 patients admitted to our neurology department with unexplained cerebral infarction and migraine. All patients underwent cTTE using vitamin B6 and sodium bicarbonate as contrast agents, after which they underwent transthoracic echocardiography. The Doppler signal was recorded during the Valsalva maneuver, and TEE examinations were performed. The feasibility, diagnostic sensitivity, and safety of cTTE and TEE for PFO recognition were compared. Evidence of PFO was found in 49 (39.20%) patients with cTTE, more than were detected with TEE (39, 31.20%) (χ2=5.0625, P=0.0244). cTTE had a sensitivity of 92.31% and a specificity of 84.88% for diagnosing PFO, showing high concordance with TEE for PFO recognition (κ=0.72). Further, results of a semi-quantitative evaluation of PFO-RLS by cTTE were better than those with TEE (Z=-2.011, P=0.044). No significant adverse reaction was discovered during cTTE examination. cTTE using vitamin B6 and sodium bicarbonate as contrast agents has relatively good sensitivity and specificity for diagnosing RLS caused by PFO when compared with those for TEE. Using vitamin B6 and sodium bicarbonate as contrast agents to perform cTTE is recommended for detecting and diagnosing the PFO due to its simplicity, non-invasive character, low cost, and high feasibility.