Identification and characterization of nucleotide metabolism and neuroendocrine regulation-associated modification patterns in stomach adenocarcinoma with auxiliary prognostic assessment and immunotherapy response prediction

BackgroundThe significance of nucleotide metabolism and neuroendocrine in cellular immune response and cancer is becoming more well-established. However, the mechanisms underlying nucleotide metabolism and neuroendocrine involvement in stomach adenocarcinoma (STAD) remain unclear.MethodsFirst, a pan-cancer overview of nucleotide metabolism and neuroendocrine-related genes (NMNGs) was explored through the integration of expression profiles, prognostic values, mutation information, methylation levels, and pathway-regulation relationships. We next extensively assessed variations in prognosis and tumor microenvironment (TME) features across the various modification patterns, based on an extensive analysis of the NMNG modification patterns of 808 STAD samples based on 46 NMNGs. Utilizing principal component analysis methodologies, the NMNGscore was developed to measure NMNG alteration patterns of individual tumors.ResultsPan-cancer analysis shows that NMNGs mostly act as risk genes in multiple cancer types, especially in STAD. Based on the NMNGs we detected two different NMNG modification patterns in STAD. Both patterns showed distinct immune cell infiltration features and biological behavior, with NMNGcluster A exhibiting a worse prognosis and a larger amount of immune infiltration. Differentially expressed genes with prognostic relevance were used to classify the STAD samples into three genomic subgroups. Analysis of survival rates revealed that cluster B genes were associated with longer life expectancy than clusters A and C. Individual STAD patients’ NMNG alteration patterns were analyzed by analyzing their NMNGscore signatures. NMNGscore and immune cells showed a statistically significant adverse correlation with each other. Increased longevity, a higher incidence of mutations, and a better response to immunotherapy were associated with patients’ NMNG scores.ConclusionsOur findings provide a personalized prediction tool for prognosis and immunotherapy sensitivity in patients, as well as a promising knowledge of nucleotide metabolism and neuroendocrine in STAD

Totally thoracoscopic closure of ventricular septal defect without a robotically assisted surgical system: A summary of 119 cases

ObjectivesTo summarize the clinical outcomes of totally thoracoscopic closure of a ventricular septal defect (VSD).MethodsTotally thoracoscopic VSD closure was performed in 119 patients (66 boys; mean age, 7.1 ± 3.6 years). An additional 35 patients undergoing open-chest VSD closure were selected as a control group. Using 3 port incisions in the right chest, pericardiotomy, bicaval occlusion, atriotomy, and VSD closure were performed by thoracoscopy without the aid of a robotically assisted surgical system.ResultsCardiopulmonary bypass and aortic crossclamp times were 42.2 ± 9.8 and 32.5 ± 7.3 minutes, respectively. There were no deaths but 1 patient required insertion of a permanent pacemaker as a result of postoperative atrioventricular conduction block. The length of stay in the intensive care unit (11.0 ± 2.6 vs 22.9 ± 4.9 hours, P < .01) or postoperative hospital stay (4.2 ± 1.1 vs 6.6 ± 2.1 days, P < .03) in the thoracoscopic group were shorter than in the control group. The percentage of patients who required postoperative opioid analgesics in the thoracoscopic group was lower than in the control group (31.9% vs 74.2%, P < .001). Rate of blood transfusion during the operation (17.6% vs 65.7%, P = .001) and the postoperative use of opioid analgesics (31.9% vs 74.3%, P = .003) in the thoracoscopic group was lower than in the control group. Transesophageal echocardiographic analysis 4.6 ± 2.3 months after the operation showed complete closure of the defect.ConclusionsTotally thoracoscopic closure of VSD through a 3-port entry was safe and effective

Strong and Electromagnetic Decays of X(1835) as a Baryonium State

With the assumption that the recently observed X(1835) is a baryonium state we have studied the strong decays of $X(1835) \to \eta^{(\prime)} \pi^+ \pi^-, \eta^{(\prime)} \pi^0 \pi^0$ and the electromagnetic decay of $X(1835) \to 2\gamma$ in the framework of effective Lagrangian formalism. In the present investigation we have included the contributions from the iso-singlet light scalar resonances but we have not included the isospin violating effect. Our result for the strong decay of $X(1835) \to \eta^{\prime} \pi^+ \pi^-$ is smaller than the observed data. The decay width for the radiative decay of $X(1835) \to 2\gamma$ is consistent with the assumption that it decays through the glueball. In addition, the width for the strong decay of $X(1835) \to \eta \pi^+ \pi^-$ is larger than that of the strong decay of $X(1835) \to \eta^{\prime} \pi^+ \pi^-$ due to the large phase space and coupling constant $g_{N\bar{N}\eta}$. From our investigation, it is not possible to interpret X(1835) as a baryonium.Comment: Corrected typo

The Mediating Effect of Depression on the Relation Between Interpersonal Needs and Suicidal Ideation Among Chinese Transgender Women

Background: Transgender women are at high risk of depression and suicidal ideation. The interpersonal theory of suicide proposes that suicidal ideation could be a consequence of high interpersonal needs (thwarted belongingness and perceived burdensomeness). The current study tests this theory and investigates whether depression could mediate the relationship between interpersonal needs and suicidal ideation among transgender women in Shenyang, China. Methods: A total of 198 transgender women were recruited by snowball sampling. A cross-sectional study was conducted through a structured questionnaire. Suicidal ideation, depression, and interpersonal needs were assessed. Path analysis was used to carry out the research goals and the mediating effect of depression was tested. Results: There were nearly 37% of the participants reported lifetime suicidal ideation. Suicidal ideation was positively correlated with thwarted belongingness (t = −5.53, p \u3c 0.01) and perceived burdensomeness (t = −5.02, p \u3c 0.01). The direct effect from thwarted belongingness to suicidal ideation via depression was statistically significant (Std. β = 0.232, p \u3c 0.01). Depression could also mediate the indirect path from perceived burdensomeness to suicidal ideation through depression (Std. β = 0.222, p \u3c 0.01) although the direct path between them was not significant (Std. β = 0.046, p = 0.693). Conclusions: Depression fully mediated the relationship between perceived burdensomeness and suicidal ideation, and partially mediate the relationship between thwarted belongingness and suicidal ideation. To reduce the risk of suicidal ideation among transgender women, interventions targeting thwarted belongingness, perceived burdensomeness, and depression are needed

Intratumoral Delivery of a PD-1-blocking scFv encoded in Oncolytic HSV-1 Promotes Antitumor Immunity and Synergizes with TIGIT Blockade

恶性肿瘤已严重威胁人类健康和生命，现有的治疗手段远远未能满足临床需求。厦门大学研究团队联合浙江养生堂生物科技有限公司、养生堂有限公司进行协同攻关，研制出新一代肿瘤免疫治疗药物——“注射用重组人PD-1抗体单纯疱疹病毒”。研究发现，重组表达PD-1单链抗体的溶瘤病毒具有“双药合一”抗肿瘤的突出优势，提高肿瘤治愈率。相关成果于2020年3月3日以研究论文形式在线发表于Cancer Immunology Research（《癌症免疫学研究》）期刊，为指导新型溶瘤病毒的升级改造和突破肿瘤免疫耐受提供了新的思路，为重组表达PD-1单链抗体的溶瘤病毒药物运用于肿瘤临床治疗奠定了坚实的理论基础。 厦门大学公共卫生学院夏宁邵教授和黄承浩助理教授为该论文的共同通讯作者，博士生林超龙和任文峰为该论文的共同第一作者。【Abstract】Oncolytic virotherapy can lead to systemic antitumor immunity, but the therapeutic potential of oncolytic viruses (OVs) in humans is limited due to their insufficient ability to overcome the immunosuppressive tumor microenvironment (TME). Here, we showed that locoregional oncolytic virotherapy upregulated the expression of PD-L1 in the TME, which was mediated by virus-induced type I and type II interferons (IFNs). To explore PD-1/PD-L1 signaling as a direct target in tumor tissue, we developed a novel immunotherapeutic herpes simplex virus (HSV), OVH-aMPD-1, that expressed a single-chain variable fragment (scFv) against PD-1 (aMPD-1 scFv). The virus was designed to locally deliver aMPD-1 scFv in the TME to achieve enhanced antitumor effects. This virus effectively modified the TME by releasing damage associated molecular patterns (DAMPs), promoting antigen cross-presentation by dendritic cells, and enhancing the infiltration of activated T cells; these alterations resulted antitumor T cell activity which led to reduced tumor burdens in a liver cancer model. Compared with OVH, OVH-aMPD-1 promoted the infiltration of myeloid-derived suppressor cells (MDSCs),resulting in significantly higher percentages of CD155+ G-MDSCs and M-MDSCs in tumors. In combination with TIGIT blockade, this virus enhanced tumor-specific immune responses in mice with implanted subcutaneous tumors or invasive tumors. These findings highlighted that intratumoral immunomodulation with an OV expressing aMPD-1 scFv could be an effective standalone strategy to treat cancers or drive maximal efficacy of a combination therapy with other immune checkpoint inhibitors.This work was supported by grant 2018ZX10301404-001-002 from the National Science and Technology Major Project and grant 81571990 from the National Natural Science Foundation of China.该研究获得了国家自然科学基金、国家科技重大专项的资助

Ultra-Sensitive, Deformable and Transparent Triboelectric Tactile Sensor based on Micro-Pyramid Patterned Ionic Hydrogel for Interactive Human-Machine Interfaces

Rapid advances in wearable electronics and mechno-sensational human-machine interfaces impose great challenges in developing flexible and deformable tactile sensors with high efficiency, ultra-sensitivity, environment-tolerance and self-sustainability. Herein, we report a tactile hydrogel sensor (THS) based on micro-pyramid-patterned double-network (DN) ionic organohydrogels to detect subtle pressure changes by measuring the variations of triboelectric output signal without an external power supply. By the first time of pyramidal-patterned hydrogel fabrication method and laminated PDMS encapsulation process, the self-powered THS shows the advantages of remarkable flexibility, good transparency (~85), and excellent sensing performance, including extraordinary sensitivity (45.97 mV Pa-1 ), fast response (~20 ms), very low limit of detection (50 Pa) as well as high stability (36000 cycles). Moreover, with the LiBr immersion treatment method, the THS possesses excellent long-term hyper antifreezing and anti-dehydrating properties, broad environment tolerance (-20 to 60 ℃), and instantaneous peak power density of 20 μW cm-2 , providing reliable contact outputs with different materials and detecting very slight human motions. The THS shows no apparent output decline under the extreme environments of −29℃, 60℃ and even the vacuum conditions, demonstrating the excellent application potential in the field of harsh environments. By integrating the signal acquisition/process circuit, the THS with excellent self-power sensing ability is utilized as a switching button to control electric appliances and robotic hands by simulating human finger gestures, offering its great potentials for wearable and multi-functional electronic applications