A Fused-Ring Electron Acceptor with Phthalimide-Based Ending Groups for Efficient Ternary Organic Solar Cells.

The ternary strategy has been widely applied and recognized to be a valid strategy to enhance the organic photovoltaics' (OPVs) performance. Here, a new fused-ring electron acceptor, BTP-PIO, is designed and synthesized, whose ending groups were replaced by a phthalimide-based group (2-butylcyclopenta[f]isoindole-1,3,5,7(2H,6H)-tetraone) from traditional 2-(3-oxo-2,3-dihydro-1H-inden-1-ylidene)malononitrile. The phthalimide-based ending groups endow BTP-PIO with the highest lowest unoccupied molecular orbital (LUMO) level and wider band gap than those of Y6. The ternary device based on PM6:Y6 with BTP-PIO as a guest electron acceptor achieved an elevated open-circuit voltage (VOC) of 0.848 V, a short-circuit current density (JSC) of 27.31 mA cm-2, and a fill factor (FF) of 73.9%, generating a remarkable power conversion efficiency (PCE) of 17.10%, which is superior to the PM6:Y6 binary device of 16.08%. The ternary device exhibited improved charge transfer, suppressed carrier recombination, and lower energy loss. BTP-PIO exhibited a good miscibility with Y6, and an alloy phase between BTP-PIO and Y6 was formed in the ternary bulk heterojunction, leading to better phase separation and molecular packing. This research reveals that ending group modification of Y6 derivatives is a feasible way to produce highly efficient ternary devices.

Inflammatory microenvironment in gastric premalignant lesions: implication and application.

Gastric precancerous lesions (GPL) are a major health concern worldwide due to their potential to progress to gastric cancer (GC). Understanding the mechanism underlying the transformation from GPL to GC can provide a fresh insight for the early detection of GC. Although chronic inflammation is prevalent in the GPL, how the inflammatory microenvironment monitored the progression of GPL-to-GC are still elusive. Inflammation has been recognized as a key player in the progression of GPL. This review aims to provide an overview of the inflammatory microenvironment in GPL and its implications for disease progression and potential therapeutic applications. We discuss the involvement of inflammation in the progression of GPL, highlighting Helicobacter pylori (H. pylori) as a mediator for inflammatory microenvironment and a key driver to GC progression. We explore the role of immune cells in mediating the progression of GPL, and focus on the regulation of inflammatory molecules in this disease. Furthermore, we discuss the potential of targeting inflammatory pathways for GPL. There are currently no specific drugs for GPL treatment, but traditional Chinese Medicine (TCM) and natural antioxidants, known as antioxidant and anti-inflammatory properties, exhibit promising effects in suppressing or reversing the progression of GPL. Finally, the challenges and future perspectives in the field are proposed. Overall, this review highlights the central role of the inflammatory microenvironment in the progression of GPL, paving the way for innovative therapeutic approaches in the future.

MicroRNA expression profile of human umbilical vein endothelial cells in response to coxsackievirus A10 infection reveals a potential role of miR-143-3p in maintaining the integrity of the blood-brain barrier.

Coxsackievirus A10 (CV-A10) has been one of the main etiologies of hand, foot, and mouth disease (HFMD) epidemics in recent years and can cause mild to severe illness and even death. Most of these severe and fatal cases were closely associated with neurological impairments, but the potential mechanism of neuropathological injury triggered by CV-A10 infection has not been elucidated. MicroRNAs (miRNAs), implicated in the regulation of gene expression in a post-transcriptional manner, play a vital role in the pathogenesis of various central nervous system (CNS) diseases; therefore, they serve as diagnostic biomarkers and are emerging as novel therapeutic targets for CNS injuries. To gain insights into the CV-A10-induced regulation of host miRNA-processing machinery, we employed high-throughput sequencing to identify differentially expressed miRNAs in CV-A10-infected human umbilical vein endothelial cells (HUVECs) and further analyzed the potential functions of these miRNAs during CV-A10 infection. The results showed that CV-A10 infection could induce 189 and 302 significantly differentially expressed miRNAs in HUVECs at 24 and 72 hpi, respectively, compared with the uninfected control. Moreover, the expression of four selected miRNAs and their relevant mRNAs was determined to verify the sequencing data by quantitative reverse transcription-polymerase chain reaction (RT-qPCR) methods. After that, gene target prediction and functional annotation revealed that the targets of these dysregulated miRNAs were mostly enriched in cell proliferation, signal transduction, cAMP signalling pathway, cellular response to interleukin-6, ventral spinal cord interneuron differentiation, negative regulation of glial cell differentiation, neuron migration, positive regulation of neuron projection development, etc., which were primarily involved in the processes of basic physiology, host immunity, and neurological impairments and further reflected vital regulatory roles of miRNA in viral pathogenicity. Finally, the construction of a miRNA-regulated network also suggested that the complex regulatory mechanisms mediated by miRNAs might be involved in viral pathogenesis and virus-host interactions during CV-A10 infection. Furthermore, among these dysregulated miRNAs, miR-143-3p was demonstrated to be involved in the maintenance of blood-brain barrier (BBB) integrity.

Soluble perinone isomers as electron transport materials for p-i-n perovskite solar cells.

We synthesized three soluble perinone isomers as electron transport materials in p-i-n perovskite solar cells. The cis-isomer BBIN-2 possesses higher LUMO level and electron mobility than the trans-isomers. The BBIN-2 devices showed the highest power conversion efficiency of 19.36%, demonstrating the potential of perinone dyes in perovskite solar cells.

Current Advances and Outlook in Gastric Cancer Chemoresistance: A Review.

BACKGROUND: Surgical resection of the lesion is the standard primary treatment of gastric cancer. Unfortunately, most patients are already in the advanced stage of the disease when they are diagnosed with gastric cancer. Alternative therapies, such as radiation therapy and chemotherapy, can achieve only very limited benefits. The emergence of cancer drug resistance has always been the major obstacle to the cure of tumors. The main goal of modern cancer pharmacology is to determine the underlying mechanism of anticancer drugs. OBJECTIVES: Here, we mainly review the latest research results related to the mechanism of chemotherapy resistance in gastric cancer, the application of natural products in overcoming the chemotherapy resistance of gastric cancer, and the new strategies currently being developed to treat tumors based on immunotherapy and gene therapy. CONCLUSION: The emergence of cancer drug resistance is the main obstacle in achieving alleviation and final cure for gastric cancer. Mixed therapies are considered to be a possible way to overcome chemoresistance. Natural products are the main resource for discovering new drugs specific for treating chemoresistance, and further research is needed to clarify the mechanism of natural product activity in patients.

Clinical Characteristics of Bloodstream Infection in Immunosuppressed Patients: A 5-Year Retrospective Cohort Study.

Introduction: Immunosuppressed patients with bloodstream infection are at risk of mortality. Our objective was to assess the independent risk factors of bloodstream infection with mortality in immunosuppressive states. Methods: The medical data of a total of 896 patients who were hospitalized in our hospital were collected from January 2015 to December 2019. Evaluation of the independent risk factors of mortality was done by univariate and multivariate logistic regression analyses. Results: Of the 896 immunosuppressed patients with bloodstream infection, 698 had over 60-day survivals and 198 had 60-day mortality. In our study, PCT (mean ±; standard: 11.40 ±; 31.89 µg/l vs. 62.45 ±; 17.10 µg/l, p = 0.007) and presence of age >60 years (40% vs. 14.19%, p = 0.001) were significantly different between situations with and without 60-day survivals in both univariate and multivariate logistic regression analyses. Age >60 years and PCT could be used as indicators for bloodstream infection with 60-day death in immunosuppressive states; the OR (95% CI) were 1.532 (1.099-2.135) and 2.063 (1.413-3.013), respectively. In different subgroups, PCT and age were also independent risk factors of blood system diseases, Klebsiella pneumoniae infection, diabetes, and ICU-stay subgroups. Conclusions: Age and PCT were independently associated with mortality in immunosuppressive states, which may help to identify the highly risky situation of bloodstream infection in immunosuppressive states.

The Prognostic Factors of Bloodstream Infection in Immunosuppressed Elderly Patients: A Retrospective, Single-center, Five-year Cohort Study.

Introduction: Elderly patients with immunosuppressive status may have increased risk of mortality. At present, few studies have explored the clinical characteristics of the elderly immunosuppressed population with bloodstream infection. Our objectives were to evaluate the prognostic factors in immunosuppressed elderly patients with bloodstream infection. Methods: Three hundred and seventy-six elderly patients who were diagnosed with bloodstream infection in immunosuppressive status while receiving treatment in our hospital were selected from 2015 to 2019. The demographic data, underlying diseases, comorbidity, inducement, complications, pathogen sources, etiologies and the antibiotic therapy were analyzed between 90-day survival groups and 90-day mortality groups. The prognostic factors of 90-day mortality were evaluated by univariate logistic regression analysis and multivariate logistic regression analysis. Results: The clinical characteristics of 376 immunosuppressed elderly people diagnosed with bloodstream infection were analyzed, and among those people about 111 were 90-day mortality. By univariate logistic regression analysis and multivariate logistic regression analysis, we found ICU admission (OR: 2.052, 95%CI: 1.088-3.871, p=0.026), the decrease in BMI (OR: 0.307, 95%CI: 0.130-0.723, p=0.007), coronary heart disease (OR: 2.028, 95%CI: 1.078-3.816, p=0.028), biliary infection (OR: 4.406, 95%CI: 1.794-10.821, p=0.001) and the use of tigecycline (OR: 2.480, 95%CI: 1.195-5.147, p=0.015) were significantly different between the 90-day survival and 90-day mortality groups. Conclusion: ICU admission, coronary heart disease, biliary infection, and the use of tigecycline were the independent prognostic risk factors of 90-day mortality in immunosuppressed elderly people, and the decrease in BMI was the protective factor, which would have the benefit of discriminating the prognostic factors in immunosuppressed elderly people with bloodstream infection.

Mechanism of N-Methyl-N-Nitroso-Urea-Induced Gastric Precancerous Lesions in Mice.

Early diagnosis and treatment of gastric precancerous lesions (GPL) are key factors for reducing the incidence and morbidity of gastric cancer. The study is aimed at examining GPL in mice induced by N-methyl-N-nitroso-urea (MNU) and to illustrate the underlying mechanisms of tumorigenesis. In this study, we utilized an in vivo MNU-induced GPL mouse model, and histopathological changes of the gastric mucosa were observed by hematoxylin and eosin (H&E-stain) and alcian blue (AB-PAS-stain). The level of miR-194-5p in the gastric mucosa was determined by real-time polymerase chain reaction. We used transmission electron microscopy to observe the effects of MNU on gastric chief cells and parietal cells. We performed immunohistochemical detection of HIF-1α, vWF, Ki-67, and P53, while the changes in the protein expression of key genes in LKB1-AMPK and AKT-FoxO3 signaling pathways were detected by western blot analysis. We demonstrated that the miR-194-5p expression was upregulated under hypoxia in GPL gastric tissues, and that a high miR-194-5p expression level closely related with tumorigenesis. Mechanistically, miR-194-5p exerted the acceleration of activities related to metabolic reprogramming through LKB1-AMPK and AKT-FoxO3 pathways. Furthermore, similar to miR-194-5p, high expression levels of AMPK and AKT were also related to the metabolic reprogramming of GPL. Moreover, we revealed the correlation between the expression levels of miR-194-5p, p-AMPKα, p-AKT, and FoxO3a. These findings suggest that miR-194-5p/FoxO3 pathway is important for the reversal of metabolic reprogramming in GPL. Thus, exploring strategies to regulate the miR-194-5p/FoxO3a pathway may provide an efficient strategy for the prevention and treatment of GPL.

Perioperative alectinib in a patient with locally advanced anaplastic lymphoma kinase positive non-small cell lung cancer (NSCLC): a case report.

We reported a case of locally advanced anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC) patient who received neoadjuvant alectinib therapy. Enhanced computed tomography (CT) scan was performed after the first cycle of alectinib therapy to evaluate the efficacy of neoadjuvant alectinib. Surprisingly, the tumor shrunk 42.2% after one cycle treatment. Partial remission (PR) was achieved without any side effects, although the tumor stage didn't degrade. Then right upper lobectomy and mediastinal lymph node dissection by video assistant thoracoscopic surgery (VATS) were successfully performed after multi-disciplinary team meeting with the department of respiratory, thoracic surgery, radiotherapy (RT), pathology and radiology. Pathologic evaluation about tumor was assessed by hematoxylin and eosin staining. However, the residual viable tumor cells were 15%, which indicated that major pathologic response (MPR) was not achieved. Next, continually adjuvant alectinib and RT were given because mediastinal station 4R lymphadenectomy excluded with serious tissue adhesion and MPR status was not met. In this case, we presented neoadjuvant alectinib therapy was feasible and well tolerated in locally advanced ALK positive NSCLC, inspiring clinical studies to further assess its clinical implication in treating patients with locally advanced ALK-positive NSCLC. And we also discussed the necessary time of neoadjuvant and adjuvant alectinib in advanced ALK-positive NSCLC.

A Microbial World: Could Metagenomic Next-Generation Sequencing Be Involved in Acute Respiratory Failure?

Background: The usefulness of metagenomic next-generation sequencing (mNGS) in identifying pathogens is being investigated. We aimed to compare the power of microbial identification between mNGS and various methods in patients with acute respiratory failure. Methods: We reviewed 130 patients with respiratory failure, and 184 specimens including blood, bronchoalveolar lavage fluid (BALF), sputum, pleural effusion, ascitic fluid, and urine were tested by mNGS and conventional methods (culture, PCR). We also enrolled 13 patients to evaluate the power of mNGS and pathogen targets NGS (ptNGS) in microbial identifications. Clinical features and microbes detected were analyzed. Results: mNGS outperformed the conventional method in the positive detection rate of Mycobacterium tuberculosis (MTB) (OR, ∞; 95% CI, 1-∞; P < 0.05), bacteria (OR, 3.7; 95% CI, 2.4-5.8; P < 0.0001), fungi (OR, 4.37; 95% CI, 2.7-7.2; P < 0.0001), mycoplasma (OR, 10.5; 95% CI, 31.8-115; P = 0.005), and virus (OR, ∞; 95% CI, 180.7-∞; P < 0.0001). We showed that 20 patients (28 samples) were detected with Pneumocystis jirovecii (P. jirovecii) by mNGS, but not by the conventional method, and most of those patients were immunocompromised. Read numbers of Klebsiella pneumoniae (K. pneumoniae), Acinetobacter baumannii (A. baumannii), Pseudomonas aeruginosa (P. aeruginosa), P. jirovecii, cytomegalovirus (CMV), and Herpes simplex virus 1 (HSV1) in BALF were higher than those in other sample types, and the read number of Candida albicans (C. albicans) in blood was higher than that in BALF. We found that orotracheal intubation and type 2 diabetes mellitus (T2DM) were associated with a higher detection rate of bacteria and virus by mNGS, immunosuppression was associated with a higher detection rate of fungi and virus by mNGS, and inflammatory markers were associated with mNGS-positive detection rate of bacteria. In addition, we observed preliminary results of ptNGS. Conclusion: mNGS outperformed the conventional method in the detection of MTB, bacteria, fungi, mycoplasma, and virus. Orotracheal intubation, T2DM, immunosuppression, and inflammatory markers were associated with a higher detection rate of bacteria, fungi, and virus by mNGS. In addition, ptNGS results were consistent with the detection of abundant bacteria, fungi, and mycoplasma in our specimens.

Ginsenoside Rg3 Promotes Cell Growth Through Activation of mTORC1.

Ginsenoside Rg3 is a steroidal saponin isolated from Panax ginseng. Previous studies have shown that Rg3 treatment downregulates the activity of rapamycin complex 1 (mTORC1) activity and inhibits the growth of cancer cells. However, the inhibitory effect of Rg3 on cancer cells is associated with high concentrations of Rg3 that are difficult to achieve in vivo. The human cervix adenocarcinoma HeLa cells were treated with Rg3. The protein levels of AMP-activated protein kinase alpha (AMPKα), protein kinase B(Akt), ribosomal S6 protein(S6), and Erk were determined by immunoblotting analyses. We used a fluorescent probe to detect reactive oxygen species (ROS) production in living cells. The oxygen consumption rate (OCR) was examined by the Seahorse Extracellular Flux Analyzer. The content of adenosine triphosphate (ATP) was measured by ATPlite kit and Mitotracker was applied to detect the mitochondria. We showed that at lower concentrations, Rg3 activates mTORC1 independent of AKT and AMP-activated protein kinase (AMPK). Rg3 promotes mitochondrial biogenesis and function, increases the oxygen consumption of mitochondria and the content of ATP. This effect is in contrast to that of high concentrations of Rg3, which inhibits cell growth. These findings demonstrate a pro-growth activity of Rg3 that acts through mTORC1 and mitochondrial biogenesis and suggest a dose-dependent effect of Rg3 on tumor cell growth.

Blood Oxygen Accumulation Distribution Area Index Is Associated With Erectile Dysfunction in Patients With Sleep Apnea-Results From a Cross-sectional Study.

INTRODUCTION: Obstructive sleep apnea (OSA) has been linked with erectile dysfunction (ED), but the relatively independent polysomnography (PSG) outcomes of apnea and nocturnal hypoxia may not effectively assess the physiological impairment of OSA well. AIM: To propose a new calculation method, the blood oxygen accumulation distribution area index (BOADAI), for evaluating the association between OSA and ED. METHODS: In this study, 502 male participants with suspected OSA were enrolled. Clinical questionnaire, physical measurements, and PSG outcomes were obtained by 2 respiratory physicians. ED was assessed by a urologist using the International Index of Erectile Function-5 (IIEF-5). Whole pulse oxygen saturation curves during the sleep time were compressed into a fixed scale image, and the distribution area of oxygen saturation curves was outlined. We then calculated the value of the outlined area and normalized it by total sleep time. The least absolute shrinkage and selection operator logistic regression model was used for selecting the optimal variable associated with ED and model construction. The clinical net benefit of the BOADAI and its related modules was estimated and compared by decision curve analysis. MAIN OUTCOME MEASURE: ED and OSA were assessed using the IIEF-5, clinical questionnaire, physical measurements, and PSG outcomes. RESULTS: The frequency of ED in patients with OSA was significantly greater than that in the no-OSA group. Meanwhile, the new BOADAI was negatively correlated with the IIEF-5 score (r = -0.2525, P = .0000). Moreover, the least absolute shrinkage and selection operator method retained BOADAI but not the other PSG parameters such as respiratory disorder index and lowest SaO2. Finally, logistic regression analysis revealed that older age, lips with cyanochroia, systemic hypertension, and BOADAI were independently associated with ED, and decision curve analysis indicated the clinical usefulness of the BOADAI module. CONCLUSION: This study revealed novel evidence that OSA is a risk factor for ED. Meanwhile, the BOADAI could act as a potential clinical characteristic to evaluate ED in patients with OSA and to provide clinical treatment recommendations. Zheng W, Chen X, Huang J, et al. Blood Oxygen Accumulation Distribution Area Index Is Associated With Erectile Dysfunction in Patients With Sleep Apnea-Results From a Cross-sectional Study. Sex Med 2019; 8:36-44.