mRNA therapy is a novel anticancer strategy based on
transcription (IVT), which has potential for the treatment of malignant tumors. The outbreak of the COVID-19 pandemic in the early 21st century ...has promoted the application of mRNA technologies in SARS-CoV-2 vaccines, and there has been a great deal of interest in the research and development of mRNA cancer vaccines. There has been progress in a number of key technologies, including mRNA production strategies, delivery systems, antitumor immune strategies, etc. These technologies have accelerated the progress and clinical applications of mRNA therapy, overcoming problems encountered in the past, such as instability, inefficient delivery, and weak immunogenicity of mRNA vaccines. This review provides a detailed overview of the production, delivery systems, immunological mechanisms, and antitumor immune response strategies for mRNA cancer vaccines. We list some mRNA cancer vaccines that are candidates for cancer treatment and discuss clinical trials in the field of tumor immunotherapy. In addition, we discuss the immunological mechanism of action by which mRNA vaccines destroy tumors as well as challenges and prospects for the future.
The coronavirus disease 2019 (COVID-19) pandemic poses a current world-wide public health threat. However, little is known about its hallmarks compared to other infectious diseases. Here, we report ...the single-cell transcriptional landscape of longitudinally collected peripheral blood mononuclear cells (PBMCs) in both COVID-19- and influenza A virus (IAV)-infected patients. We observed increase of plasma cells in both COVID-19 and IAV patients and XIAP associated factor 1 (XAF1)-, tumor necrosis factor (TNF)-, and FAS-induced T cell apoptosis in COVID-19 patients. Further analyses revealed distinct signaling pathways activated in COVID-19 (STAT1 and IRF3) versus IAV (STAT3 and NFκB) patients and substantial differences in the expression of key factors. These factors include relatively increase of interleukin (IL)6R and IL6ST expression in COVID-19 patients but similarly increased IL-6 concentrations compared to IAV patients, supporting the clinical observations of increased proinflammatory cytokines in COVID-19 patients. Thus, we provide the landscape of PBMCs and unveil distinct immune response pathways in COVID-19 and IAV patients.
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•We generated a single-cell atlas of PBMCs in both COVID-19 and influenza patients•Plasma cells increase significantly in both COVID-19 and influenza patients•COVID-19 is featured with XAF1-, TNF-, and FAS-induced T cell apoptosis•COVID-19 activates distinct pathway (STAT1/IRF3) versus influenza (STAT3/NFκB)
COVID-19 and influenza are both respiratory infections with cytokine release syndrome. Zhu et al. use single-cell RNA sequencing of longitudinally collected PBMCs in both patients to reveal distinct immune response landscapes of the two diseases and identify virus-specific cell composition and immune response pathways.
Circular RNAs (circRNAs) are emerging as essential regulators of various biological and disease processes. To comprehensively understand the diversity of circRNAs and prioritize their importance, we ...present a large-scale study of circRNA repertoires from multiple tissues from human, macaque, and mouse. We discovered totals of 104,388, 96,675, and 82,321 circRNAs from the three species, respectively, with an average of 72.6% being successfully assembled into full-length transcripts for each species. Using these full-length circRNAs, we identified thousands of evolutionarily conserved circRNAs that were valuable for functional screening and prioritization. By constructing both species-specific and conserved gene co-expression networks, we inferred circRNA functions on a global scale and prioritized promising functional candidates. To illustrate how well-established prior knowledge facilitates to screen functional candidates, we used the circRNA co-expression networks to prioritize circRNAs that may be involved in liver tumorigenesis and experimentally validated their functions.
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•RNA-seq libraries and data from 44 normal tissues of human, macaque, and mouse•CircAtlas is the most comprehensive catalog of circRNAs from normal tissues•72.6% of circRNAs have been assembled into full-length circular transcripts•Prioritized a new subset of circRNAs, overlapped orthologous circRNAs
Ji et al. present a large-scale study of circRNA repertoires from multiple tissues of human, macaque, and mouse and propose a new approach to annotate and prioritize functional circRNAs.
Infectious diseases have always threatened human life, but with the development of vaccines, effective strategies for preventing and controlling these diseases have become available. The global ...outbreak of COVID-19 ushered in the advent of mRNA vaccine technologies, which quickly led to the introduction of mRNA vaccines effective against SARS-CoV-2. The success of this approach has stimulated research into the use of mRNA vaccines in the fight against other emerging as well as remerging infectious diseases. This review examines the constructive strategies and delivery systems used in mRNA vaccines and provides an overview of current clinical trials of those vaccines in the prevention of infectious diseases. The underlying mechanisms of mRNA vaccines are also discussed, including the double-edged sword of the innate immune response. Finally, the challenges but also the potential of mRNA vaccines are considered.
This study investigates the potential of the plate-shaped Zn-22 wt.% Al (Zn-22Al) alloy as an innovative energy dissipation material for seismic damping devices, since plate-shaped material is more ...suitable to fabricate large-scale devices for building structures. The research begins with the synthesis of Zn-22Al alloy, given its unavailability in the commercial market. Monotonic tensile tests and low-cycle fatigue tests are performed to analyze material properties and fatigue performance of plate-shaped specimens. Monotonic tensile curves and cyclic stress-strain curves, along with SEM micrographs for microstructure and fracture surface analysis, are acquired. The combined cyclic hardening material model is calibrated to facilitate finite element analysis. Experimental results reveal exceptional ductility in Zn-22Al alloy, achieving a fracture strain of 200.37% (1.11 fracture strain). Fatigue life ranges from 1126 to 189 cycles with increasing strain amplitude (±0.8% to ±2.5%), surpassing mild steel by at least 6 times. The cyclic strain-life relationships align well with the Basquin-Coffin-Manson relationship. The combined kinematic/isotropic hardening model in ABAQUS accurately predicts the hysteretic behavior of the material, showcasing the promising potential of Zn-22Al alloy for seismic damping applications.
•Rapid combustion by turbulent jet ignition (TJI) was optically studied.•Volume is a key parameter for optimizing the TJI.•TJI is more suitable for engine combustion under lean conditions.•TJI ...increases the knock tendency and knock intensity under high load conditions.
Recently the turbulent jet ignition (TJI) configured by pre-chamber has been paid more attention as it can effectively achieve rapid combustion thus high thermal efficiency. In this work, using a single-cylinder optical engine with high compression ratios, the effects of turbulent jet ignition on lean burning and engine knocking were comprehensively investigated, with the conventional spark-ignition scenarios for comparisons. The results show that the pre-chamber with larger volume results in stronger flame jets and a higher promoting effect on the combustion. However, due to the higher heat dissipation and throttling loss, the pre-chamber with larger volume results in lower IMEP. For lean combustion, the optimized TJI (small volume) can reduce the combustion instability and improve the thermal efficiency when compared to spark ignition. The main reason is that TJI can increase the in-cylinder flame speed and achieve a concentrated HRR. For knocking combustion, TJI increases the knock tendency and knock intensity. The main reason is that the accelerated flame advances the auto-ignition and induces a high energy density. In summary, the effect of TJI on engine performance differs under different load conditions and the TJI strategy should be optimized especially under heavy load conditions.
Abstract
Spatially resolved transcriptomics provides genetic information in space toward elucidation of the spatial architecture in intact organs and the spatially resolved cell-cell communications ...mediating tissue homeostasis, development, and disease. To facilitate inference of spatially resolved cell-cell communications, we here present SpaTalk, which relies on a graph network and knowledge graph to model and score the ligand-receptor-target signaling network between spatially proximal cells by dissecting cell-type composition through a non-negative linear model and spatial mapping between single-cell transcriptomic and spatially resolved transcriptomic data. The benchmarked performance of SpaTalk on public single-cell spatial transcriptomic datasets is superior to that of existing inference methods. Then we apply SpaTalk to STARmap, Slide-seq, and 10X Visium data, revealing the in-depth communicative mechanisms underlying normal and disease tissues with spatial structure. SpaTalk can uncover spatially resolved cell-cell communications for single-cell and spot-based spatially resolved transcriptomic data universally, providing valuable insights into spatial inter-cellular tissue dynamics.
Reliably prediction models for coronary artery abnormalities (CAA) in children aged >5 years with Kawasaki disease (KD) are still lacking. This study aimed to develop a nomogram model for predicting ...CAA at 4 to 8 weeks of illness in children with KD older than 5 years.
A total of 644 eligible children were randomly assigned to a training cohort (n = 450) and a validation cohort (n = 194). The least absolute shrinkage and selection operator (LASSO) analysis was used for optimal predictors selection, and multivariate logistic regression was used to develop a nomogram model based on the selected predictors. Area under the receiver operating characteristic curve (AUC), calibration curves, Hosmer-Lemeshow test, Brier score, and decision curve analysis (DCA) were used to assess model performance.
Neutrophil to lymphocyte ratio, intravenous immunoglobulin resistance, and maximum baseline z-score ≥ 2.5 were identified by LASSO as significant predictors. The model incorporating these variables showed good discrimination and calibration capacities in both training and validation cohorts. The AUC of the training cohort and validation cohort were 0.854 and 0.850, respectively. The DCA confirmed the clinical usefulness of the nomogram model.
A novel nomogram model was established to accurately assess the risk of CAA at 4–8 weeks of onset among KD children older than 5 years, which may aid clinical decision-making.
Since March 2013, the emergence of an avian-origin influenza A (H7N9) virus has raised concern in China. Although most infections resulted in respiratory illness, some severe cases resulted in acute ...respiratory distress syndrome (ARDS), which is a severe form of acute lung injury (ALI) that further contributes to morbidity. To date, no effective drugs that improve the clinical outcome of influenza A (H7N9) virus-infected patients have been identified. Angiotensin-converting enzyme (ACE) and ACE2 are involved in several pathologies such as cardiovascular functions, renal disease, and acute lung injury. In the current study, we report that ACE2 could mediate the severe acute lung injury induced by influenza A (H7N9) virus infection in an experimental mouse model. Moreover, ACE2 deficiency worsened the disease pathogenesis markedly, mainly by targeting the angiotensin II type 1 receptor (AT1). The current findings demonstrate that ACE2 plays a critical role in influenza A (H7N9) virus-induced acute lung injury, and suggest that might be a useful potential therapeutic target for future influenza A (H7N9) outbreaks.
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