Liquid biopsies, based on cell free DNA (cfDNA) and proteins, have shown the potential to detect early stage cancers of diverse tissue types. However, most of these studies were retrospective, using ...individuals previously diagnosed with cancer as cases and healthy individuals as controls. Here, we developed a liquid biopsy assay, named the hepatocellular carcinoma screen (HCCscreen), to identify HCC from the surface antigen of hepatitis B virus (HBsAg) positive asymptomatic individuals in the community population. The training cohort consisted of individuals who had liver nodules and/or elevated serum α-fetoprotein (AFP) levels, and the assay robustly separated those with HCC from those who were non-HCC with a sensitivity of 85% and a specificity of 93%. We further applied this assay to 331 individuals with normal liver ultrasonography and serum AFP levels. A total of 24 positive cases were identified, and a clinical follow-up for 6–8 mo confirmed four had developed HCC. No HCC cases were diagnosed from the 307 test-negative individuals in the follow-up during the same time-scale. Thus, the assay showed 100% sensitivity, 94% specificity, and 17% positive predictive value in the validation cohort. Notably, each of the four HCC cases was at the early stage (<3 cm) when diagnosed. Our study provides evidence that the use of combined detection of cfDNA alterations and protein markers is a feasible approach to identify early stage HCC from asymptomatic community populations with unknown HCC status.
Nasopharyngeal carcinoma (NPC) is etiologically associated with Epstein–Barr virus (EBV) infection and is known to be highly vascularized. Previous studies have suggested that EBV oncoproteins ...contribute to NPC angiogenesis. However, the regulatory network of EBV in angiogenesis still remains elusive. Herein, we reveal a novel mechanism of EBV‐induced angiogenesis in NPC. First, we showed that EBV‐infected NPC cell lines generated larger tumors with more microvessels in mouse xenograft models. Subsequent proteomic analysis revealed that EBV infection increased the expression of a series of angiogenic factors, including chemokine (C‐C motif) ligand 5 (CCL5). We then proved that CCL5 was a target of EBV in inducing tumor angiogenesis and growth. Further investigation through transcriptome analysis indicated that the pro‐angiogenic function of CCL5 might be mediated by the PI3K/AKT pathway. Furthermore, we confirmed that activation of the PI3K/AKT and hypoxia‐inducible factor‐1α pathways was essential for CCL5‐promoted angiogenesis. Finally, the immunohistochemical analysis of human NPC specimens also showed that CCL5 was correlated with angiogenesis. Taken together, our study identifies CCL5 as a key EBV‐regulated molecular driver that promotes NPC angiogenesis, suggesting it as a potential therapeutic target.
Our study revealed that EBV infection promotes the production of CCL5, which increases VEGF expression and NPC angiogenesis by interacting with the PI3K/AKT and HIF‐1α pathways.
Health-care waste (HCW) management is a high priority public health and environmental concern particularly in developing countries. The decision to select an optimal technology for the disposal of ...HCW is a complicated multi-criteria decision analysis problem involving both qualitative and quantitative factors. Evaluating HCW treatment technologies may be based on imprecise information or uncertain data. Moreover, there can be significant dependence and feedbacks between the different dimensions and criteria. However, most existing decision models for HCW cannot capture these complex interrelationships. In response, this paper proposes a novel hybrid multi-criteria decision making (MCDM) model by integrating the 2-tuple DEMATEL technique and fuzzy MULTIMOORA method for selection of HCW treatment alternatives. It makes use of modified 2-tuple DEMATEL for obtaining the relative weights of criteria and fuzzy MULTIMOORA for assessing the alternatives according to each criterion. Specifically, an empirical case in Shanghai, one of the largest cities in China, is provided to illustrate the potential of the new model. Results show that the proposed framework for evaluating HCW treatment technologies is effective and provides meaningful implications for engineering designers to refer.
Traditional desiccant-based dehumidification systems suffer from low energy efficiency due to the desiccant’s fixed affinity to water, meaning it has a single moisture adsorption isotherm regardless ...of the temperature. We modeled a novel thermo-responsive desiccant with temperature-dependent isotherms in a desiccant wheel model for three representative dehumidification scenarios. These cases show remarkable improvement in moisture removal efficiency of this material because of its switchable water affinity below/above the critical temperature. Our work discusses how to apply and tune the thermo-responsive desiccants for further enhancement in dehumidification performance, depending on application.
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•Developed a thermo-responsive desiccant wheel model for air dehumidification.•Demonstrated how and why thermo-responsiveness improves dehumidification efficiency.•Quantified thermo-responsive desiccants’ improvement in dehumidification efficiency.•Provided guidance on desiccant material and system design for air dehumidification.
The desiccant wheel is a promising technology for energy-efficient humidity control. However, its overall efficiency—hindered by the desiccant materials’ properties—remains low because traditional desiccants (e.g., silica gels) have a single isotherm regardless of their adsorption temperature. Thermo-responsive materials have been proposed to break this fixed affinity to water vapor, with drastically different adsorption isotherms depending on temperature. Its potential for improving dehumidification efficiency, however, has not been addressed. In this paper, we model the potential of a thermo-responsive interpenetrating polymer network (IPN) desiccant with temperature-dependent adsorption isotherms for energy-efficient dehumidification via a validated transient desiccant wheel model for humidity control of buildings. Thermo-responsive desiccants can improve the dehumidification performance due to their thermo-responsive switchable hydrophilicity below/above the lower critical solution temperature. Our analysis shows that thermo-responsive IPN desiccants can potentially reduce energy consumption by up to 30% compared to silica gels. The savings depend strongly on the critical temperature of the thermo-responsive desiccant and should be higher when the inlet temperatures are expected to be higher.
Molecular representation for small molecules has been routinely used in QSAR/SAR, virtual screening, database search, ranking, drug ADME/T prediction and other drug discovery processes. To facilitate ...extensive studies of drug molecules, we developed a freely available, open-source python package called chemoinformatics in python (ChemoPy) for calculating the commonly used structural and physicochemical features. It computes 16 drug feature groups composed of 19 descriptors that include 1135 descriptor values. In addition, it provides seven types of molecular fingerprint systems for drug molecules, including topological fingerprints, electro-topological state (E-state) fingerprints, MACCS keys, FP4 keys, atom pairs fingerprints, topological torsion fingerprints and Morgan/circular fingerprints. By applying a semi-empirical quantum chemistry program MOPAC, ChemoPy can also compute a large number of 3D molecular descriptors conveniently.
The python package, ChemoPy, is freely available via http://code.google.com/p/pychem/downloads/list, and it runs on Linux and MS-Windows.
Supplementary data are available at Bioinformatics online.
Background
An association between a nonmedicinal herbal diet and nasopharyngeal carcinoma (NPC) has often been hypothesized but never thoroughly investigated.
Methods
This study enrolled a total of ...2469 patients with incident NPC and 2559 population controls from parts of Guangdong and Guangxi Provinces in southern China between 2010 and 2014. Questionnaire information was collected on the intake of traditional herbal tea and herbal soup as well as the specific herbal plants used in soups and other potentially confounding lifestyle factors. Multivariate logistic regression models were used to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for the NPC risk in association with herbal tea and soup intake.
Results
Ever consumption of herbal tea was not associated with NPC risk (OR, 1.03; 95% CI, 0.91‐1.17). An inverse association was observed for NPC among ever drinkers of herbal soup (OR, 0.78; 95% CI, 0.67‐0.90) but without any monotonic trend with an increasing frequency or duration of herbal soup consumption. Inverse associations with NPC risk were detected with 9 herbal plants used in herbal soup, including Ziziphus jujuba, Fructus lycii, Codonopsis pilosula, Astragalus membranaceus, Semen coicis, Smilax glabra, Phaseolus calcaratus, Morinda officinalis, and Atractylodes macrocephala (OR range, 0.31‐0.79).
Conclusions
Consuming herbal soups including specific plants, but not herbal tea, was inversely associated with NPC. If replicated, these results might provide potential for NPC prevention in endemic areas.
Consuming herbal soups is inversely associated with nasopharyngeal carcinoma in the endemic region of southern China. Nine herbal types are identified as responsible for this inverse association.
Stimulator of interferon genes (STING), a major adaptor protein in antiviral innate immune signaling, is considered as one of the most important regulators of antiviral and antitumor immunity. ...Although STING agonists are now intensively studied in clinical trials as a new class of adjuvants to boost cancer immunotherapy, the tumor-intrinsic role of the STING pathway in shaping the tumor microenvironment remains controversial. Here, we discovered that STING plays a vital role in regulation of myeloid-derived suppressor cell (MDSC) differentiation and antitumor immunity in Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC). Mechanistic analyses reveal that STING represses NPC-derived MDSC induction by enhancing SOCS1 expression in both tumor cells and MDSCs. SOCS1 physically interacts with STAT3 through its SH2 domain to prevent STAT3 phosphorylation and dimerization, resulting in reduced MDSC induction via inhibition of GM-CSF and IL-6 production. Notably, reduced tumoral STING expression was found to be significantly associated with a poor prognosis for NPC patients. Our findings reveal a novel mechanism linking STING to tumor microenvironmental cytokine production and MDSC induction.
Yi outlines the demographic trends of population aging and the academic and public health needs for interdisciplinary research on healthy aging. The concept of healthy aging not only means surviving ...to old ages in good physical/mental health and with active social participation (individual life processes) but also refers to how societies can age healthily (societal processes) with sound policy and intervention program supports. Populations worldwide are aging rapidly, with an extraordinary increase of the oldest-old. The much more dramatic increase of the oldest-old in both developed and developing countries deserves serious attention because the oldest-old consume services and medical care at a much higher rate than the young-old.
We previously observed enhanced immunoglobulin A (IgA) responses in severe COVID‐19, which might confer damaging effects. Given the important role of IgA in immune and inflammatory responses, the aim ...of this study was to investigate the dynamic response of the IgA isotype switch factor TGF‐β1 in COVID‐19 patients. We observed, in a total of 153 COVID‐19 patients, that the serum levels of TGF‐β1 were increased significantly at the early and middle stages of COVID‐19, and correlated with the levels of SARS‐CoV‐2‐specific IgA, as well as with the APACHE II score in patients with severe disease. In view of the genetic association of the TGF‐β1 activator THBS3 with severe COVID‐19 identified by the COVID‐19 Host Genetics Initiative, this study suggests TGF‐β1 may play a key role in COVID‐19.
Traditional Chinese medicines (TCMs) bring a great challenge in quality control and evaluating the efficacy because of their complexity of chemical composition. Chemometric techniques provide a good ...opportunity for mining more useful chemical information from TCMs. Then, the application of chemometrics in the field of TCMs is spontaneous and necessary. This review focuses on the recent various important chemometrics tools for chromatographic fingerprinting, including peak alignment information features, baseline correction and applications of chemometrics in metabolomics and modernization of TCMs, including authentication and evaluation of the quality of TCMs, evaluating the efficacy of TCMs and essence of TCM syndrome. In the conclusions, the general trends and some recommendations for improving chromatographic metabolomics data analysis are provided.
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