High-Performance Ultraviolet Photodetectors Based on Nanoporous GaN with a Ga2O3 Single-Crystal Layer.

The utilization of a nanoporous (NP) GaN fabricated by electrochemical etching has been demonstrated to be effective in the fabrication of a high-performance ultraviolet (UV) photodetector (PD). However, the NP-GaN PD typically exhibits a low light-dark current ratio and slow light response speed. In this study, we present three types of UV PDs based on an unetched GaN, NP-GaN distributed Bragg reflector (DBR), and NP-GaN-DBR with a Ga2O3 single-crystal film (Ga2O3/NP-GaN-DBR). The unetched GaN PD does not exhibit a significant photoresponse. Compared to the NP-GaN-DBR PD device, the Ga2O3/NP-GaN-DBR PD demonstrates a larger light-dark current ratio (6.14 × 103) and higher specific detectivity (8.9 × 1010 Jones) under 365 nm at 5 V bias due to its lower dark current (3.0 × 10-10 A). This reduction in the dark current can be attributed to the insertion of the insulating Ga2O3 between the metal and the NP-GaN-DBR, which provides a thicker barrier thickness and higher barrier height. Additionally, the Ga2O3/NP-GaN-DBR PD device exhibits shorter rise/decay times (0.33/0.23 s) than the NP-GaN-DBR PD, indicating that the growth of a Ga2O3 layer on the DBR effectively reduces the trap density within the NP-GaN DBR structure. Although the device with a Ga2O3 layer presents low photoresponsivity (0.1 A/W), it should be feasible to use Ga2O3 as a dielectric layer based on the above-mentioned reasons.

Efficacy of cardiopulmonary rehabilitation nursing in enhancing pulmonary function, sleep quality, and living ability in COVID-19 patients.

OBJECTIVE: The purpose of this study was to elucidate the impact of cardiopulmonary rehabilitation nursing on the pulmonary function, sleep quality, and living ability of patients afflicted with Coronavirus Disease 2019 (COVID-19). METHODS: A total of 98 patients with COVID-19 treated at The People's Hospital of Guang'an between September 2021 and January 2023 were retrospectively collected as the research subjects. Among them, 48 patients who received standard nursing care from September 2021 to September 2022 were set as the control group, and 50 patients who underwent cardiopulmonary rehabilitation nursing from October 2022 to January 2023 were set as the research group. The pulmonary function indicators [including Forced Expiratory Volume in 1 second (FEV1) and Left Ventricular Ejection Fraction (LVEF)], sleep quality [evaluated using the Pittsburgh Sleep Quality Index (PSQI)], and living ability [assessed by the 36-Item Short Form Survey (SF-36) scale] pre- and post-intervention were compared between the two groups. RESULTS: Pre-intervention, FEV1, LVEF, PSQI scores, inflammatory factor levels [C-reactive protein (CRP), procalcitonin (PCT)], and SF-36 scores showed no significant differences between the two groups (P>0.05). Post-intervention, the research group exhibited notably enhanced FEV1 and LVEF, lower PSQI scores, lower CRP and PCT, and higher SF-36 scores compared with the control group, with statistical significance (P<0.05). Multifactorial logistic regression analysis showed that non-receipt of cardiopulmonary rehabilitation, age ≥60 years, concurrent respiratory failure, coexistent heart failure, and acid-base imbalance were independent risk factors of adverse outcomes in COVID-19 patients (P<0.05). CONCLUSION: Application of cardiopulmonary rehabilitation nursing in COVID-19 patients can significantly improve pulmonary function, sleep quality, and overall quality of life, and relieve the inflammatory state of the patients, thereby enhancing prognosis. This approach has certain value of popularization and application.

Efficient generation of induced pluripotent stem cell lines from healthy donors' peripheral blood mononuclear cells of different genders.

Peripheral blood mononuclear cell (PBMC) are recognized as a conveniently collected reprogramming resource. Several methods are available in academia to reprogram PBMC into induced pluripotent stem cells (iPSC). In this research, we reprogrammed PBMC of different genders by using non-integrative non-viral liposome electrotransfer containing the reprogramming factors OCT4, SOX2, KLF4, and c-MYC. The three obtained iPSC cell lines were karyotypically normal and showed significant tritiated differentiation potential in vitro and in vivo. Our study provided an efficient procedure for reprogramming PBMC into iPSC and obtained three well-functioning iPSC, that may contribute to advance personalized cell therapy in the future.

Efficacy of dupilumab and risk factors for dupilumab-induced hypereosinophilia in severe asthma: a preliminary study from China.

OBJECTIVE: Dupilumab has been approved for the treatment of severe asthma with type 2 inflammation by inhibiting interleukin (IL)-4 and IL-13 signaling. However, dupilumab-induced hypereosinophilia (HE) has been reported and should not be ignored. The aim of this study was to investigate the efficacy of dupilumab in Chinese patients with severe asthma, whether HE affects its efficacy, and the possible risk factors for HE. METHODS: 20 patients with severe asthma who received dupilumab treatment for at least 12 months in the First Affiliated Hospital of Guangzhou Medical University from 2019 to 2022 were included. We compared clinical data and laboratory tests results before dupilumab treatment and at 4 and 12 months after treatment. Based on whether dupilumab treatment triggers HE defined as blood eosinophil count (BEC) ≥ 1.5 × 109 cells/L, the patients were allocated into non-HE and HE groups. RESULTS: The patients showed a significant increase in asthma control test (ACT) scores, a decrease in the number of exacerbations, a decrease in the proportion of patients taking an oral corticosteroid (OCS) and in the dose, and a significant improvement in the pulmonary function parameters FEV1/FVC (%) and FEV1 (% predicted) after 4 and 12 months of treatment with dupilumab. For type 2 inflammatory biomarkers, the levels of fractional concentration of exhaled nitric oxide (FeNO), sputum eosinophil count percentage (SEC%) and total immunoglobulin E (TIgE) decreased significantly, whereas BEC were higher after 4 months of treatment, but returned to baseline levels after 12 months. 8 patients (40%) developed asymptomatic HE after dupilumab, and the efficacy was not significantly different between the HE and non-HE groups. The earliest BEC elevation appeared at 1 month after treatment, but most of them declined after 6 months, and basically returned to the baseline level around 12 months of treatment. In addition, we further found that when patients had FeNO ≥ 60 ppb, food allergens positive and combined eosinophilic otitis media (EOM), their BEC increased significantly more than that of the control group after 4 months as well as 12 months of treatment. CONCLUSIONS: This study demonstrated that dupilumab was efficacious in Chinese patients with severe asthma, and some patients developed asymptomatic, self-limited HE, which did not affect its efficacy. Additionally, FeNO ≥60 ppb, food allergens positive, and co-morbidities with EOM may be the risk factors for developing HE.

Soluble CD80 oral delivery by recombinant Lactococcus suppresses tumor growth by enhancing antitumor immunity.

CD80 is an important co-stimulatory molecule that participates in the immune response. Soluble CD80 can induce T cell activation and overcome PDL1-mediated immune suppression. In this study, we aimed to construct recombinant Lactococcus lactis for oral delivery of the soluble CD80 (hsCD80) protein or the fusion protein containing the cholera toxin B subunit (CTB) and hsCD80 (CTB-hsCD80) under the control of the nisin-inducible expression system. The recombinant L. lactis expressed and secreted hsCD80 or CTB-hsCD80 fusion proteins after induction by nisin in vitro and in the enteric cavity. Additionally, the CTB-hsCD80 fusion protein showed uptake by intestinal epithelial cells, was cleaved by the furin protease, and was released as free hsCD80 protein into the blood circulation. Orally administered hsCD80 and CTB-hsCD80 containing L. lactis increased the proportion of activated T cells in the spleen and intestinal epithelium, inhibited tumor growth, and prolonged the survival of tumor-bearing mice. The hsCD80-containing L. lactis showed greater therapeutic effects on primary colonic adenoma in APCmin/- mice and completely suppressed tumor growth. Further, recombinant CTB-hsCD80 in L. lactis was more efficient than hsCD80-containing bacteria in inhibiting the growth of xenografted colon cancer and melanoma cells. hsCD80 engineered probiotics may serve as a promising new approach for antitumor immunotherapy, especially for colorectal cancer.

Reduction of peritoneal cavity B1a cells in adult Slc7a5 knockdown mice via dysregulating the mTOR pathway.

Slc7a5 is an important amino acid transporter that is highly expressed in metabolically active and rapidly proliferating cells. To explore the effect of Slc7a5 on adult B cell development, we conditionally deleted Slc7a5 in murine B cells and observed a significant reduction of B1a cells. In contrast to PI3K-Akt pathway activation, activity of the mTOR pathway was decreased. This may result from intracellular amino acid starvation in Slc7a5 knockdown (Slc7a5 KD) bone marrow B cells, thereby dampening B1a development. RNA-seq analysis demonstrated increased translation and reduced proliferation in Slc7a5 KD bone marrow B cells. Overall, the results of our study highlight the importance of Slc7a5 in peritoneal B1a cell development.

Efficient generation of induced pluripotent stem cell lines from peripheral blood mononuclear cells.

Peripheral blood mononuclear cells (PBMCs) have been widely considered as a more convenient and almost unlimited reprogramming resource, while the reprogramming procedure and efficiency still need to be improved. We reprogrammed the PBMCs by using non-integrative non-viral vectors liposome electrotransfer containing the reprogramming factors OCT4, SOX2, KLF4, and c-MYC. The iPSC lines exhibited a normal karyotype with their corresponding PBMCs and exhibited significant cellular pluripotency. Teratoma formation assay revealed that the iPSCs we generated could differentiate into three embryonic germ layers. Our study provides a more effective procedure for peripheral blood monocyte reprogramming to iPSC, and promotes its future application.

iNOS contributes to heart failure with preserved ejection fraction through mitochondrial dysfunction and Akt S-nitrosylation.

INTRODUCTION: Despite the high morbidity and mortality of heart failure with preserved fraction (HFpEF), there are currently no effective therapies for this condition. Moreover, the pathophysiological basis of HFpEF remains poorly understood. OBJECTIVE: The aim of the present study was to investigate the role of inducible nitric oxide synthase (iNOS) and its underlying mechanism in a high-fat diet and Nω-nitro-L-arginine methyl ester-induced HFpEF mouse model. METHODS: The selective iNOS inhibitor L-NIL was used to examine the effects of short-term iNOS inhibition, whereas the long-term effects of iNOS deficiency were evaluated using iNOS-null mice. Cardiac and mitochondrial function, oxidative stress and Akt S-nitrosylation were then measured. RESULTS: The results demonstrated that both pharmacological inhibition and iNOS knockout mitigated mitochondrial dysfunction, oxidative stress and Akt S-nitrosylation, leading to an ameliorated HFpEF phenotype in mice. In vitro, iNOS directly induced Akt S-nitrosylation at cysteine 224 residues , leading to oxidative stress, while inhibiting insulin-mediated glucose uptake in myocytes. CONCLUSION: Altogether, the present findings suggested an important role for iNOS in the pathophysiological development of HFpEF, indicating that iNOS inhibition may represent a potential therapeutic strategy for HFpEF.

Elevated DLL3 in stomach cancer by tumor-associated macrophages enhances cancer-cell proliferation and cytokine secretion of macrophages.

Background: The notch signal pathway is important in the development of both tumor-associated macrophages (TAMs) and stomach cancer, but how Notch signaling affects TAMs in stomach cancer is barely understood. Methods: The expressions of Notch1, Notch2, Notch3, Notch4, hes family bHLH transcription factor 1 (Hes1), and delta-like canonical Notch ligand 3 (DLL3) were detected by Western blot and the expressions of interleukin (IL)-10, IL-12, and IL1-ß were detected using enzyme-linked immunosorbent assay after the co-culture of macrophages and stomach-cancer cells. The proliferation and migration of cancer cells were detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and scratch assay, respectively, and the cell cycle was detected using Annexin V/propidium iodide assay. The protein interactions with DLL3 were detected using co-immunoprecipitation and mass spectrometry. Results: The co-culture of macrophages and stomach-cancer cells MKN45 and BGC823 could enhance cell proliferation accompanied by the activation of Notch1/Notch2 signaling and upregulation of DLL3. Notch signaling gamma-secretase inhibitor (DAPT) blocked this process. The overexpression of DLL3 in stomach-cancer cells could promote the proliferation of cancer cells, enhance the activation of Notch1/Notch2 signaling, induce the expression of IL-33, lead to the degradation of galectin-3-binding protein (LG3BP) and heat shock cognate 71 kDa protein (HSPA8), and result in elevated IL-1ß, IL-12, and IL-10 secretion by macrophages. Higher expression of DLL3 or IL-33 could lead to a lower survival rate based on University of California, Santa Cruz Xena Functional Genomics Explorer and The Cancer Genome Atlas data set. Conclusions: This is evidence that DLL3 regulates macrophages in stomach cancer, suggesting that DLL3 may be a novel and potential target for stomach-cancer therapy.

Lack of Association of FLT3 rs2504235 and Absence of SLITRK1 var321 in Patients with Tic Disorders from Guangdong Province, China.

OBJECTIVE: Tic disorders (TDs) are highly polygenic and heritable neurodevelopmental disorders characterized by the presence of movements (motor tics) and/or vocalizations (phonic tics). SLITRK1 is a pathogenic variation of TD, and in a recent genome-wide association study in those of European ancestry, a single-nucleotide polymorphism (rs2504235) in the FLT3 gene was significantly associated with TDs/Tourette's syndrome. However, these results need to be proved in different populations. This study aimed to determine whether these two genetic variants were also associated with TD patients in south China. METHODS: A total of 116 child TD patients and 114 healthy controls were included. All children underwent peripheral blood sampling for genomic DNA extraction. Gene fragments with two single-nucleotide polymorphisms were amplified by PCR and sequenced by Sanger chain termination before genotype analysis. RESULTS: SLITRK1 var321 was not observed in any of the TD patients or controls. No significant difference was observed in allelic frequencies or genotypic distributions of rs2504235 between TD patients and controls. CONCLUSION: Our results provide no evidence to support the previous conclusion that SLITRK1 var321 plays a major role in TDs, and FLT3 rs2504235 was not significantly associated with TDs in our cohort.

Lonicerin attenuates house dust mite-induced eosinophilic asthma through targeting Src/EGFR signaling.

Eosinophilic asthma is the predominant phenotype of asthma, and although these patients are sensitive to glucocorticoid therapy, they also experience many side effects. Lonicerin is a kind of bioflavonoid isolated from the Chinese herb Lonicera japonica Thunb, which has anti-inflammatory and immunomodulatory effects. The aim of this study was to elucidate the effects of lonicerin on eosinophilic asthma and its potential mechanisms. Here, we established a house dust mite (house dust mite)-induced eosinophilic asthma model in BALB/c mouse, and evaluated the effects of lonicerin on it. Our results showed that lonicerin significantly reduced airway hyperresponsiveness the number of inflammatory cells (especially eosinophils) and the elevation of interleukin (IL)-4, IL-5, IL-13 and eotaxin in bronchoalveolar lavage fluid (BALF) supernatants of mice. Additionally, lonicerin also eminently blunted inflammatory infiltration and mucus secretion, as well as mRNA levels of Mucin 5AC (MUC5AC) in lung tissue. Furthermore, results of network pharmacology and molecular docking revealed that Src kinase and epidermal growth factor receptor may be the potential targets responsible for the effects of lonicerin. Finally, in vivo experiments confirmed that lonicerin inhibited activation of the Src/EGFR pathway by decreasing their phosphorylation. Taken together, the present study demonstrated that lonicerin could suppress HDM-induced eosinophilic asthma in mice through inhibiting the activation of Src/EGFR pathway, which also provides a basis for further research as a new potentially therapeutic agent for eosinophilic asthma and its underlying mechanisms in the future.

Notch Signaling Ligand Jagged1 Enhances Macrophage-Mediated Response to Helicobacter pylori.

Helicobacter pylori (H. pylori) is one of the gram-negative bacteria that mainly colonize the stomach mucosa and cause many gastrointestinal diseases, such as gastritis, peptic ulcer, and gastric cancer. Macrophages play a key role in eradicating H. pylori. Recent data have shown that Notch signaling could modulate the activation and bactericidal activities of macrophages. However, the role of Notch signaling in macrophages against H. pylori remains unclear. In the present study, in the co-culture model of macrophages with H. pylori, the inhibition of Notch signaling using γ-secretase decreased the expression of inducible nitric oxide synthase (iNOS) and its product, nitric oxide (NO), and downregulated the secretion of pro-inflammatory cytokine and attenuated phagocytosis and bactericidal activities of macrophages to H. pylori. Furthermore, we identified that Jagged1, one of Notch signaling ligands, was both upregulated in mRNA and protein level in activated macrophages induced by H. pylori. Clinical specimens showed that the number of Jagged1+ macrophages in the stomach mucosa from H. pylori-infected patients was significantly higher than that in healthy control. The overexpression of Jagged1 promoted bactericidal activities of macrophages against H. pylori and siRNA-Jagged1 presented the opposite effect. Besides, the addition of exogenous rJagged1 facilitated the pro-inflammatory mediators of macrophages against H. pylori, but the treatment of anti-Jagged1 neutralizing antibody attenuated it. Taken together, these results suggest that Jagged1 is a promoting molecule for macrophages against H. pylori, which will provide insight for exploring Jagged1 as a novel therapeutic target for the control of H. pylori infection.

Notch 1 Is Involved in CD4+ T Cell Differentiation Into Th1 Subtype During Helicobacter pylori Infection.

Helicobacter pylori infection induces CD4+ T differentiation cells into IFN-γ-producing Th1 cells. However, the details of mechanism underlying this process remain unclear. Notch signal pathway has been reported to regulate the differentiation of CD4+ T cells into Th1 subtype in many Th1-mediated inflammatory disorders but not yet in H. pylori infection. In the present study, the mRNA expression pattern of CD4+ T cells in H. pylori-infected patients differed from that of healthy control using Human Signal Transduction Pathway Finder RT2 Profiler PCR Array, and this alteration was associated with Notch signal pathway, as analyzed by Bioinformation. Quantitative real-time PCR showed that the mRNA expression of Notch1 and its target gene Hes-1 in CD4+ T cells of H. pylori-infected individuals increased compared with the healthy controls. In addition, the mRNA expression of Th1 master transcription factor T-bet and Th1 signature cytokine IFN-γ was both upregulated in H. pylori-infected individuals and positively correlated with Notch1 expression. The increased protein level of Notch1 and IFN-γ were also observed in H. pylori-infected individuals confirmed by flow cytometry and ELISA. In vitro, inhibition of Notch signaling decreased the mRNA expression of Notch1, Hes-1, T-bet, and IFN-γ, and reduced the protein levels of Notch1 and IFN-γ and the secretion of IFN-γ in CD4+ T cells stimulated by H. pylori. Collectively, this is the first evidence that Notch1 is upregulated and involved in the differentiation of Th1 cells during H. pylori infection, which will facilitate exploiting Notch1 as a therapeutic target for the control of H. pylori infection.

Novel Lactobacillus reuteri HI120 Affects Lipid Metabolism in C57BL/6 Obese Mice.

Intestinal probiotics are a primary focus area of current medical research. Probiotics such as bifidobacteria and lactobacilli can positively impact obesity and other metabolic diseases by directly or indirectly affecting lipid metabolism. However, the precise mechanisms of these effects remain unclear. In our previous work, the novel strain Lactobacillus reuteri HI120 was isolated and identified. HI120 expresses high levels of linoleic isomerase, resulting in the production of large amounts of conjugated linoleic acid (CLA) when mixed with linoleic acid (LA). As HI120 can efficiently transform LA into CLA, the effect of HI120 on the lipid metabolism in C57BL/6 obese mice was studied and the underlying molecular mechanism was explored in vitro. The results revealed no significant change in the diet, body weight, and serum triglyceride levels in mice. However, serum cholesterol levels were significantly decreased. The underlying mechanism may involve a CLA-mediated reduction in the gene expression levels of NPC1L1, SREBP-2, and HMG-CR, resulting in reduced cholesterol synthesis and absorption. Thus, HI120 can be developed as a potential probiotic formulation. After oral administration, LA from certain food sources can be converted into CLA in the human intestine to contribute to the prevention and treatment of obesity and hyperlipidemia.

Method of calculating porosity based on M44 element images of the Mueller matrix.

As a drug carrier, the porosity of porous electrospun fiber can greatly affect its drug loading ability and stability. In this work, a method to calculate the porosity of porous electrospun fiber with a polarization micrograph is described. Different porosities of porous electrospun fibers were measured by scanning electron microscope images and transmission Mueller matrix M44 element images, respectively. Mueller matrix M44 element images were obtained after polarization micrograph and normalization. The pore areas of M44 images were extracted by region growing, and the contour parts were obtained by performing morphological operation on pore areas. The porosity calculated by the polarization microscope image is in good consistency with that measured by the scanning electron microscope. Our results will promote practical application of electrospun porous fibers in the early stage of screening a large number of porous materials in the biomedicine field.

Group B Streptococcus DNA Copy Numbers Measured by Digital PCR Correlates with Perinatal Outcomes.

Group B Streptococcus (GBS) is a one of the main causes of perinatal disease, yet the method for GBS detection, broth-enriched culture, is time-consuming and has low sensitivity and accuracy. We aimed to develop a GBS digital PCR (GBS-dPCR) assay for detecting GBS colonization. More rapid and accurate detection of GBS colonization could increase GBS diagnosis and treatment closer to delivery. A single-center, retrospective, case-controlled study was performed. A total of 182 rectovaginal swabs from pregnant women, who were undergoing prenatal screening by broth-enriched culture, were evaluated using GBS-dPCR targeting the cfb gene of GBS. Pregnant women with GBS colonization were followed up for correlation analysis between GBS DNA copy numbers and perinatal outcomes. The results of the GBS-dPCR assay were compared to those from the broth-enriched culture, which is the gold standard for GBS detection. The sensitivity and specificity of GBS-dPCR were 98% and 92.5%, respectively. By discrepant result analysis, the specificity of GBS-dPCR was raised to 97.4%. The incidence of premature rupture of membrane (PROM) and neonatal infection were statistically significantly positively correlated with GBS DNA copy numbers. GBS-dPCR has the advantage of directly detecting GBS colonization from swabs with high specificity and sensitivity, while reducing turnaround time (<4 h). Analysis of clinical samples with GBS-dPCR shows that GBS DNA copy numbers are positively correlated with the incidence of PROM and neonatal infection, suggesting that dPCR is a promising method for detection of GBS colonization during pregnancy.

High-Performance Organic Dyes with Electron-Deficient Quinoxalinoid Heterocycles for Dye-Sensitized Solar Cells under One Sun and Indoor Light.

A series of Y-shaped sensitizers incorporating quinoxaline or quinoxalinoid moieties were prepared and applied in dye-sensitized solar cells (DSSCs). By the introduction of quinoxalinoid functionalities, the absorption extinction coefficients could be enhanced. The molecular structures were modified by introducing an extra acceptor group (A) between a donor (D) and a π-bridge (D-A-π-A) and also by incorporating electron-donating substituents at various positions of the quinoxalinoid moiety. Some of the dyes and mixtures thereof were found to exhibit good light-harvesting efficiencies under both sunlight and indoor light, with efficiencies up to 7.92 % under one sun (AM 1.5G). When operated under indoor light, the efficiency could be boosted to 27.76, 28.74, and 30.45 % under 600, 1000, 2500 lux illumination, respectively. The best performance could be ascribed partly to an improved dye coverage on the TiO2 surface.

Higher notch expression implies poor survival in pancreatic ductal adenocarcinoma: A systematic review and meta-analysis.

BACKGROUND: At present, pancreatic ductal adenocarcinoma (PDAC) is a fetal disease lack of effective prognostic and therapeutic methods resulting in high mortality. The Notch signaling has been demonstrated being up- or down-regulated in many cancers, but the effects in pancreatic ductal adenocarcinoma are still controversial. Moreover, the available cases in an individual study are of small samples. Therefore, it is essential to define the effect of Notch signaling in pancreatic ductal adenocarcinoma with larger samples. METHODS: Conducted from 6 eligible studies and 463 pancreatic ductal adenocarcinoma patients, this was the first meta-analysis to analyze the correlation between the Notch signal pathway and pancreatic ductal adenocarcinoma. All data were sourced from The National Center for Biotechnology Information, Web of Science and Cochrane. The articles which matched the inclusion criteria were included. All included data were analyzed and performed by Review Manager 5.3. RESULTS: The results indicated that high expression of Notch signaling proteins was associated with poor overall survival of pancreatic ductal adenocarcinoma patients (pooled hazard ratio>2.00; P < 0.001). Moreover, poor survival was related to high expression of Notch3 (pooled hazard ratio: 2.05; confidence interval: 1.49-2.82; P < 0.001) and DLL4 (pooled hazard ratio: 2.13; confidence interval: 1.37-3.32; P < 0.001). CONCLUSIONS: This meta-analysis supports that Notch signaling proteins may be available as prognostic factors for pancreatic ductal adenocarcinoma progression and patient survival. Higher expression of Notch signaling proteins indicated poor survival of pancreatic ductal adenocarcinoma patients. Targeting Notch signaling components, especially Notch3 protein, would be beneficial for therapies.

Identification of Two Lpp20 CD4+ T Cell Epitopes in Helicobacter pylori-Infected Subjects.

Antigen-specific CD4+ T cells play an essential role in effective immunity against Helicobacter pylori (H. pylori) infection. Lpp20, a conserved lipoprotein of H. pylori, has been investigated as one of major protective antigens for vaccination strategies. Our previous study identified two H-2d-restricted CD4+ T cell epitopes within Lpp20 and an epitope vaccine based on these epitopes was constructed, which protected mice in prophylactic and therapeutic vaccination against H. pylori infection. Immunodominant CD4+ T cell response is an important feature of antiviral, antibacterial, and antitumor cellular immunity. However, while many immunodominant HLA-restricted CD4+ T cell epitopes of H. pylori protective antigens have been identified, immunodominant HLA-restricted Lpp20 CD4+ T cell epitope has not been elucidated. In this study, a systematic method was used to comprehensively evaluate the immunodominant Lpp20-specific CD4+ T cell response in H. pylori-infected patients. Using in vitro recombinant Lpp20 (rLpp20)-specific expanded T cell lines from H. pylori-infected subjects and 27 18mer overlapping synthetic peptides spanned the whole Lpp20 protein, we have shown that L55-72 and L79-96 harbored dominant epitopes for CD4+ T cell responses. Then the core sequence within these two 18mer dominant epitopes was screened by various extended or truncated 13mer peptides. The immunodominant epitope was mapped to L57-69 and L83-95. Various Epstein-Barr virus (EBV) transformed B lymphoblastoid cell lines (B-LCLs) with different HLA alleles were used as antigen presenting cell (APC) to present peptides to CD4+ T cells. The restriction molecules were determined by HLA class-antibody blocking. L57-69 was restricted by DRB1-1501 and L83-95 by DRB1-1602. The epitopes were recognized on autologous dendritic cells (DCs) loaded with rLpp20 but also those pulsed with whole cell lysates of H. pylori (HP-WCL), suggesting that these epitopes are naturally processed and presented by APC. CD4+ T cells were isolated from H. pylori-infected patients and stimulated with L57-69 and L83-95. These two epitopes were able to stimulate CD4+ T cell proliferation. This study may be of value for the future development of potential H. pylori vaccine.

Novel AgNWs-PAN/TPU membrane for point-of-use drinking water electrochemical disinfection.

The safety of drinking water remains a major challenge in developing countries and point-of-use (POU) drinking water treatment device plays an important role in decentralised drinking water safety. In this study, a novel material, i.e. a silver nanowires-polyacrylonitrile/thermoplastic polyurethane (AgNWs-PAN/TPU) composite membrane, was fabricated via electrospinning and vacuum filtration deposition. Morphological and structural characterisation showed that the PAN/TPU fibres had uniform diameters and enhanced mechanical properties. When added to these fibres, the AgNWs formed a highly conductive network with good physical stability and low silver ion leaching (<100 ppb). A POU device equipped with a AgNWs-PAN/TPU membrane displayed complete removal of 105 CFU/mL bacteria, which were inactivated by silver ions released from the AgNWs within 6 h. Furthermore, under a voltage of 1.5 V, the bacteria were completely inactivated within 20-25 min. Inactivation efficiency in 5 mM NaCl solution was higher than those in Na2SO4 and NaNO3 solutions. We concluded that a strong electric field was formed at the AgNW tips. Additionally, silver ions and chlorine compounds worked synergistically in the disinfection process. This study provides a scientific basis for research and development of silver nanocomposite membranes, with high mechanical strength and high conductivity, for POU drinking water disinfection.