Background and Aim
Coronavirus disease 2019 (COVID‐19) has attracted increasing worldwide attention. While diabetes is known to aggravate COVID‐19 severity, it is not known whether nondiabetic ...patients with metabolic dysfunction are also more prone to more severe disease. The association of metabolic associated fatty liver disease (MAFLD) with COVID‐19 severity in nondiabetic patients was investigated here.
Methods
The study cohort comprised 65 patients with (i.e. cases) and 65 patients without MAFLD (i.e. controls). Each case was randomly matched with one control by sex (1:1) and age (±5 years). The association between the presence of MAFLD (as exposure) and COVID‐19 severity (as the outcome) was assessed by binary logistic regression analysis.
Results
In nondiabetic patients with COVID‐19, the presence of MAFLD was associated with a four‐fold increased risk of severe COVID‐19; the risk increased with increasing numbers of metabolic risk factors. The association with COVID‐19 severity persisted after adjusting for age, sex, and coexisting morbid conditions.
Conclusion
Health‐care professionals caring for nondiabetic patients with COVID‐19 should be cognizant of the increased likelihood of severe COVID‐19 in patients with MAFLD.
Liver injury is common in patients with COVID‐19, but little is known about its clinical presentation and severity in the context of liver transplant. We describe a case of COVID‐19 in a patient who ...underwent transplant 3 years ago for hepatocellular carcinoma. The patient came to clinic with symptoms of respiratory disease; pharyngeal swabs for severe acute respiratory syndrome coronavirus 2 were positive. His disease progressed rapidly from mild to critical illness and was complicated by several nosocomial infections and multiorgan failure. Despite multiple invasive procedures and rescue therapies, he died from the disease. The management of COVID‐19 in the posttransplant setting presents complex challenges, emphasizing the importance of strict prevention strategies.
This report presents the clinic features, treatment, and fatal outcome in a liver transplant recipient with COVID‐19.
Abstract
Background
The emergence of coronavirus disease 2019 (COVID-19) is a major healthcare threat. The current method of detection involves a quantitative polymerase chain reaction (qPCR)–based ...technique, which identifies the viral nucleic acids when present in sufficient quantity. False-negative results can be achieved and failure to quarantine the infected patient would be a major setback in containing the viral transmission. We aim to describe the time kinetics of various antibodies produced against the 2019 novel coronavirus (SARS-CoV-2) and evaluate the potential of antibody testing to diagnose COVID-19.
Methods
The host humoral response against SARS-CoV-2, including IgA, IgM, and IgG response, was examined by using an ELISA-based assay on the recombinant viral nucleocapsid protein. 208 plasma samples were collected from 82 confirmed and 58 probable cases (qPCR negative but with typical manifestation). The diagnostic value of IgM was evaluated in this cohort.
Results
The median duration of IgM and IgA antibody detection was 5 (IQR, 3–6) days, while IgG was detected 14 (IQR, 10–18) days after symptom onset, with a positive rate of 85.4%, 92.7%, and 77.9%, respectively. In confirmed and probable cases, the positive rates of IgM antibodies were 75.6% and 93.1%, respectively. The detection efficiency by IgM ELISA is higher than that of qPCR after 5.5 days of symptom onset. The positive detection rate is significantly increased (98.6%) when combining IgM ELISA assay with PCR for each patient compared with a single qPCR test (51.9%).
Conclusions
The humoral response to SARS-CoV-2 can aid in the diagnosis of COVID-19, including subclinical cases.
The time kinetics of humoral responses against the novel coronavirus (SARS-CoV-2) are characterized in patients with COVID-19 by nucleocapsid-based enzyme-linked immunosorbent assay. The antibody testing can aid in the diagnosis of COVID-19 when combined with quantitative polymerase chain reaction, including in subclinical cases.
Non-reciprocal devices, which allow non-reciprocal signal routing, serve as fundamental elements in photonic and microwave circuits and are crucial in both classical and quantum information ...processing. The radiation-pressure-induced coupling between light and mechanical motion in travelling-wave resonators has been exploited to break the Lorentz reciprocity, enabling non-reciprocal devices without magnetic materials. Here, we experimentally demonstrate a reconfigurable non-reciprocal device with alternative functions as either a circulator or a directional amplifier via optomechanically induced coherent photon-phonon conversion or gain. The demonstrated device exhibits considerable flexibility and offers exciting opportunities for combining reconfigurability, non-reciprocity and active properties in single photonic devices, which can also be generalized to microwave and acoustic circuits.
This study aimed to establish an effective prognostic nomogram with or without plasma Epstein-Barr virus DNA (EBV DNA) for nondisseminated nasopharyngeal carcinoma (NPC).
The nomogram was based on a ...retrospective study of 4630 patients who underwent radiotherapy with or without chemotherapy at Sun Yat-sen University Cancer Center from 2007 to 2009. The predictive accuracy and discriminative ability of the nomogram were determined by a concordance index (C-index) and calibration curve and were compared with EBV DNA and the current staging system. The results were validated using bootstrap resampling and a prospective cohort study on 1819 patients consecutively enrolled from 2011 to 2012 at the same institution. All statistical tests were two-sided.
Independent factors derived from multivariable analysis of the primary cohort to predict recurrence were age, sex, body mass index (BMI), T stage, N stage, plasma EBV DNA, pretreatment high sensitivity C-reactive protein (hs-CRP), lactate dehydrogenase (LDH), and hemoglobin level (HGB), which were all assembled into the nomogram with (nomogram B) or without EBV DNA (nomogram A). The calibration curve for the probability of recurrence showed that the nomogram-based predictions were in good agreement with actual observations. The C-index of nomogram B for predicting recurrence was 0.728 (P < .001), which was statistically higher than the C-index values for nomogram A (0.690), EBV DNA (0.680), and the current staging system (0.609). The C-index of nomogram B (0.730) and nomogram A (0.681) remained higher for predicting recurrence among patients treated with intensity-modulated radiotherapy (P < .001). The results were confirmed in the validation cohort.
The proposed nomogram with or without plasma EBV DNA resulted in more accurate prognostic prediction for NPC patients.
The successful treatment of cancer has significantly improved as a result of targeted therapy and immunotherapy. However, during chemotherapy, cancer cells evolve and can acquire “multidrug ...resistance” (MDR), which significantly limits the efficacy of cancer treatment and impacts patient survival and quality of life. Among the approaches to reverse MDR, modulating reactive oxidative species (ROS) may represent a strategy to kill MDR cancer cells that are mechanistically diverse. ROS in cancer cells play a central role in regulating and inducing apoptosis, thereby modulating cancer cells proliferation, survival and drug resistance. The levels of ROS and the activity of scavenging/anti-oxidant enzymes in drug resistant cancer cells are typically increased compared to non-MDR cancer and normal cells. Consequently, MDR cancer cells may be more susceptible to alterations in ROS levels. Numerous studies suggest that compounds modulating cellular ROS levels can enhance MDR cancer cell death and sensitize MDR cancer cells to certain chemotherapeutic drugs.
In the current review, we discuss the critical and targetable redox-regulating enzymes, including mitochondrial electron transport chain (ETC) complexes, NADPH oxidases (NOXs), enzymes related to glutathione metabolism, glutamate/cystine antiporter xCT, thioredoxin reductases (TrxRs), nuclear factor erythroid 2-related factor 2 (Nrf2), and their roles in regulating cellular ROS levels, drug resistance as well as their clinical significance. We also discuss and summarize the findings in the past decade regarding the efficacy of ROS modulators for the treatment of MDR cancer alone or as sensitizing compounds. Compounds that are efficacious in modulating ROS generation represent a prominent class of drug candidates that warrants evaluation in clinical trials for patients harboring MDR cancers.
The development of multidrug resistance (MDR) to chemotherapy remains a major challenge in the treatment of cancer. Numerous mechanisms have been recognized that cause MDR, but one of the most ...important mechanisms is overexpression of adenosine triphosphate (ATP)-binding cassette (ABC) transporters, through which the efflux of various anticancer drugs against their concentration gradients is powered by ATP. In recent years, small molecular tyrosine kinase inhibitors (TKIs) have been developed for treatment in various human cancers overexpressing epidermal growth factor receptor (EGFR). At the same time, some TKIs have been shown to be capable of inhibiting ABC transporter-mediated MDR. Dacomitinib (PF-00299804) is a second generation, irreversible TKI, which has shown positive anticancer activities in some preclinical and clinical trials. As many TKIs are substrates or inhibitors of ABC transporters, this study investigates whether dacomitinib could interact with ABC subfamily members that mediate MDR, including ABCB1 (P-gp), ABCG2 (BCRP) and ABCC1 (MRP1). The results showed that dacomitinib at 1.0 μM significantly reversed drug resistance mediated by ABCB1 and ABCG2, but not ABCC1, doing so by antagonizing the drug efflux function in ABCB1- and ABCG2-overexpressing cell lines. The reversal effect on ABCB1-overexpressing cells is more potent than that on ABCG2-overexpressing cells. In addition, dacomitinib at reversal concentration affected neither the protein expression level nor the localization of ABCB1 and ABCG2. Therefore, the mechanisms of this modulating effect are likely to be the following: first, as an inhibitor of ABCB1 or ABCG2 transporters, dacomitinib binds to drug-substrate site in transmembrane domains (TMD) stably in a noncompetitive manner; or second, dacomitinib inhibits ATPase activity and maintains the stability of TMD conformation in a concentration-dependent manner thereby inhibiting the drug efflux function of ABCB1 or ABCG2 transporter. This study provides a useful combinational therapeutic strategy with dacomitinib and substrates of ABCB1 and/or ABCG2 transporters in ABCB1- or ABCG2-overexpressing cancers.
•Dacomitinib, a selective and irreversible inhibitor of EGFR has advanced to several Phase III clinical trials for the treatment of non-small-cell lung carcinoma (NSCLC).•Dacominitib significantly enhanced the chemotherapeutic potential of anticancer drugs by blocking the function of ABCB1 and ABCG2 transporters.•Molecular docking analysis suggests that Dacomitinib interacts with ABCB1 within its large cavity located in the transmembrane region.•Combination of Dacomitinib and anticancer drugs can overcome ABCB1- or ABCG2-mediated drug resistance which is of great clinical interest.
This study aims to provide a better understanding of the autogenous shrinkage of slag and fly ash-based alkali-activated materials (AAMs) cured at ambient temperature. The main reaction products in ...AAMs pastes are C-A-S-H type gel and the reaction rate decreases when slag is partially replaced by fly ash. Due to the chemical shrinkage and the fine pore structure of AAMs pastes, drastic drop of internal relative humidity is observed and large pore pressure is generated. The pore pressure induces not only elastic deformation but also a large creep of the paste. Besides the pore pressure, other driving forces, like the reduction of steric-hydration force due to the consumption of ions, also cause a certain amount of shrinkage, especially in the acceleration period. Based on the mechanisms revealed, a computational model is proposed to estimate the autogenous shrinkage of AAMs. The calculated autogenous shrinkage matches well with the measured results.
Plasmon-coupled circular dichroism has emerged as a promising approach for ultrasensitive detection of biomolecular conformations through coupling between molecular chirality and surface plasmons. ...Chiral nanoparticle assemblies without chiral molecules present also have large optical activities. We apply single-particle circular differential scattering spectroscopy coupled with electron imaging and simulations to identify both structural chirality of plasmonic aggregates and plasmon-coupled circular dichroism induced by chiral proteins. We establish that both chiral aggregates and just a few proteins in interparticle gaps of achiral assemblies are responsible for the ensemble signal, but single nanoparticles do not contribute. We furthermore find that the protein plays two roles: It transfers chirality to both chiral and achiral plasmonic substrates, and it is also responsible for the chiral three-dimensional assembly of nanorods. Understanding these underlying factors paves the way toward sensing the chirality of single biomolecules.
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