Intratumoral delivered novel circular mRNA encoding cytokines for immune modulation and cancer therapy.

The success of the two mRNA vaccines developed by Moderna and BioNTech during the COVID-19 pandemic increased research interest into the application of mRNA technologies. Compared with the canonical linear mRNA used in these vaccines, circular mRNA has been found to mediate more potent and durable protein expression and demands a simpler manufacturing procedure. However, the application of circular mRNA is still at the initiation stage, and proof of concept for its use as a future medicine or vaccine is required.

Microenvironment Activatable Nanoprodrug Based on Gripper-like Cyclic Phenylboronic Acid to Precisely and Effectively Alleviate Drug-induced Hepatitis.

Drug-induced hepatitis (DIH), which seriously interferes with disease treatment, is one of the most common reasons for termination of new drugs during preclinical studies or post-marketing surveillance. Although antioxidants and anti-inflammatory agents are promising, their nonspecific distribution and insolubility limit their application. Therefore, precise drug release at the disease site is an important way to alleviate DIH and avoid side effects.

Circulating SARS-CoV-2 spike N439K variants maintain fitness while evading antibody-mediated immunity.

SARS-CoV-2 can mutate and evade immunity, with consequences for efficacy of emerging vaccines and antibody therapeutics. Here, we demonstrate that the immunodominant SARS-CoV-2 spike (S) receptor binding motif (RBM) is a highly variable region of S and provide epidemiological, clinical, and molecular characterization of a prevalent, sentinel RBM mutation, N439K. We demonstrate N439K S protein has enhanced binding affinity to the hACE2 receptor, and N439K viruses have similar in vitro replication fitness and cause infections with similar clinical outcomes as compared to wild type.

Ambient Particulate Air Pollution and Daily Mortality in 652 Cities.

Background: The systematic evaluation of the results of time-series studies of air pollution is challenged by differences in model specification and publication bias.

Methods: We evaluated the associations of inhalable particulate matter (PM) with an aerodynamic diameter of 10 μm or less (PM) and fine PM with an aerodynamic diameter of 2.5 μm or less (PM) with daily all-cause, cardiovascular, and respiratory mortality across multiple countries or regions.

Author Correction: Loss of function of NCOR1 and NCOR2 impairs memory through a novel GABAergic hypothalamus-CA3 projection.

In the version of this article initially published, the Acknowledgements erroneously included a grant number that did not directly support the work in the article. The last sentence of the Acknowledgments should have read, "The authors' laboratories were supported by National Natural Science Foundation of China grants 31671222 and 31571556 (G.D.

An integrated flow cytometry-based platform for isolation and molecular characterization of circulating tumor single cells and clusters.

Comprehensive molecular analysis of rare circulating tumor cells (CTCs) and cell clusters is often hampered by low throughput and purity, as well as cell loss. To address this, we developed a fully integrated platform for flow cytometry-based isolation of CTCs and clusters from blood that can be combined with whole transcriptome analysis or targeted RNA transcript quantification. Downstream molecular signature can be linked to cell phenotype through index sorting.

H2A.Z regulates tumorigenesis, metastasis and sensitivity to cisplatin in intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is a fatal, malignant tumor of the liver; effective diagnostic biomarkers and therapeutic targets for ICC have not been identified yet. High expression of H2A histone family member Z (H2A.Z) is a high-risk factor for poor prognosis in patients with breast cancer and primary hepatocellular cancer.

Altered temporal lobe white matter lipid ion profiles in an experimental model of sporadic Alzheimer's disease.

Background: White matter is an early and important yet under-evaluated target of Alzheimer's disease (AD). Metabolic impairments due to insulin and insulin-like growth factor resistance contribute to white matter degeneration because corresponding signal transduction pathways maintain oligodendrocyte function and survival.

Methods: This study utilized a model of sporadic AD in which adult Long Evans rats administered intracerebral streptozotocin (i.

Echocardiographic Findings Predict In-Hospital and 1-Year Mortality in Left-Sided Native Valve Staphylococcus aureus Endocarditis: Analysis From the International Collaboration on Endocarditis-Prospective Echo Cohort Study.

Background: Staphylococcus aureus left-sided native valve infective endocarditis (LNVIE) has higher complication and mortality rates compared with endocarditis from other pathogens. Whether echocardiographic variables can predict prognosis in S aureus LNVIE is unknown.

Methods And Results: Consecutive patients with LNVIE, enrolled between January 2000 and September 2006, in the International Collaboration on Endocarditis were identified.

Estrogens prevent metabolic dysfunctions induced by circadian disruptions in female mice.

Circadian disruption has become a significant factor contributing to the epidemics of obesity and insulin resistance. However, interventions to treat metabolic dysfunctions induced by circadian disruptions are limited. The ovarian hormone, estrogen, produces important antiobesity and antidiabetic effects in female animals and has profound effects on daily behavioral rhythms.

Panton-Valentine leukocidin is not the primary determinant of outcome for Staphylococcus aureus skin infections: evaluation from the CANVAS studies.

The impact of Panton-Valentine leukocidin (PVL) on the severity of complicated skin and skin structure infections (cSSSI) caused by Staphylococcus aureus is controversial. We evaluated potential associations between clinical outcome and PVL presence in both methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S.

Search for a heavy particle decaying into an electron and a muon with the ATLAS detector in sqrt[s] = 7 TeV pp collisions at the LHC.

This Letter presents the first search for a heavy particle decaying into an e ± μ(-/+) final state in sqrt[s] = 7 TeV pp collisions at the LHC. The data were recorded by the ATLAS detector during 2010 and correspond to a total integrated luminosity of 35 pb(-1). No excess above the standard model background expectation is observed.

A 12-consonant confusion study on a multiple-channel cochlear implant patient.

A consonant confusion study was undertaken on a multiple-channel cochlear implant patient using a wearable speech processing device. This patient suffered from total bilateral deafness acquired postlingually. The consonants /b/, /p/, /m/, /v/, /f/, /d/, /t/, /n/, /z/, /s/, /g/, /k/ were presented in a VCV context with the vowel /a/ as in father by a male and female speaker under three conditions: lipreading alone; electrical stimulation alone using the wearable speech processor and multiple-channel cochlear implant; lipreading in conjunction with electrical stimulation.