An mpox quadrivalent mRNA vaccine elicits sustained and protective immunity in mice against lethal vaccinia virus challenge.

Assessing the long-term efficacy of MPXV vaccine candidates is crucial for the global response to the ongoing mpox epidemic. Built upon our previous study of the mpox quadrivalent mRNA vaccine, herein we reported that MPXV-1103 could elicit sustained humoral and cellular immunity in mice, including the induction of MPXV A35/B6/A29/M1-specific IgG antibodies, VACV neutralizing antibodies and activated cytotoxic CD8T cells, which provides 100% protection against lethal VACV challenge even at 280 days after the first vaccination. Our results provide critical insights for orthopoxvirus vaccine development.

A Systematic Method to Detect Next-Generation Sequencing-Based Microsatellite Instability in Plasma Cell-Free DNA: plasmaMSI.

Microsatellite instability (MSI) detection using tumor tissue is a well-established prognostic and predictive biomarker for certain types of cancers. However, tumor tissue samples are less convenient to obtain than blood plasma samples. The main challenge facing next-generation sequencing-based MSI detection in blood plasma samples is the ultralow signal/noise ratio in plasma cell-free DNA (cfDNA).

Integrated omics profiling reveals systemic dysregulation and potential biomarkers in the blood of patients with neuromyelitis optica spectrum disorders.

Background: Neuromyelitis optica spectrum disorders (NMOSD) are autoimmune conditions that affect the central nervous system. The contribution of peripheral abnormalities to the disease's pathogenesis is not well understood.

Methods: To investigate this, we employed a multi-omics approach analyzing blood samples from 52 NMOSD patients and 46 healthy controls (HC).

RNA Helicase DDX5 Maintains Cardiac Function by Regulating Alternative Splicing.

Background: Heart failure (HF) is a leading cause of morbidity and mortality worldwide. RNA-binding proteins are identified as regulators of cardiac disease; DDX5 (dead-box helicase 5) is a master regulator of many RNA processes, although its function in heart physiology remains unclear.

Methods: We assessed DDX5 expression in human failing hearts and a mouse HF model.

Orphan Nuclear Receptor NR4A3 Promotes Vascular Calcification via Histone Lactylation.

Background: Medial arterial calcification is a chronic systemic vascular disorder distinct from atherosclerosis and is commonly observed in patients with chronic kidney disease, diabetes, and aging individuals. We previously showed that NR4A3 (nuclear receptor subfamily 4 group A member 3), an orphan nuclear receptor, is a key regulator in apo (apolipoprotein) A-IV-induced atherosclerosis progression; however, its role in vascular calcification is poorly understood.

Methods: We generated NR4A3 mice and 2 different types of medial arterial calcification models to investigate the biological roles of NR4A3 in vascular calcification.

Producing high-quantity and high-quality recombinant adeno-associated virus by low-cis triple transfection.

Recombinant adeno-associated virus (rAAV)-based gene therapy is entering clinical and commercial stages at an unprecedented pace. Triple transfection of HEK293 cells is currently the most widely used platform for rAAV manufacturing. Here, we develop low-cis triple transfection that decreases transgene plasmid use by 10- to 100-fold and overcomes several major limitations associated with standard triple transfection.

Testing Conditional Independence Between Latent Variables by Independence Residuals.

Conditional independence (CI) testing is an important problem, especially in causal discovery. Most testing methods assume that all variables are fully observable and then test the CI among the observed data. Such an assumption is often untenable beyond applications dealing with, e.

Citric acid/chitosan adhesive with viscosity-controlled for wood bonding through supramolecular self-assembly.

Developing bio-based sustainable wood adhesives is significant as a substitute for petroleum-derived adhesives. However, the existing bio-based adhesives have disadvantages of complex fabrication, uncontrollable viscosity, and poor water resistance. Herein, we developed a citric acid/chitosan adhesive with viscosity-controlled and water-resistant features by one-step dissolution at room temperature based on the supramolecular self-assembly strategy.

The association of global vessel width with cognitive decline and cerebral small vessel disease burden in the KaiLuan study.

Background: As the retinal microvasculature shares similarities with the cerebral microvasculature, numerous studies have shown that retinal vascular is associated with cognitive decline. In addition, several population-based studies have confirmed the association between retinal vascular and cerebral small vessel disease (CSVD) burden. However, the association of retinal vascular with CSVD burden as well as cognitive function has not been explored simultaneously.

Olgotrelvir, a dual inhibitor of SARS-CoV-2 M and cathepsin L, as a standalone antiviral oral intervention candidate for COVID-19.

Background: Oral antiviral drugs with improved antiviral potency and safety are needed to address current challenges in clinical practice for treatment of COVID-19, including the risks of rebound, drug-drug interactions, and emerging resistance.

Methods: Olgotrelvir (STI-1558) is designed as a next-generation antiviral targeting the SARS-CoV-2 main protease (M), an essential enzyme for SARS-CoV-2 replication, and human cathepsin L (CTSL), a key enzyme for SARS-CoV-2 entry into host cells.

Findings: Olgotrelvir is a highly bioavailable oral prodrug that is converted in plasma to its active form, AC1115.

Safety, tolerability, and immunogenicity of a CpG/Alum adjuvanted SARS-CoV-2 recombinant protein vaccine (ZR202-CoV) in healthy adults: Preliminary report of a phase 1, randomized, double-blind, placebo-controlled, dose-escalation trial.

This was a phase 1 dose-escalation study of ZR202-CoV, a recombinant protein vaccine candidate containing a pre-fusion format of the spike (S)-protein (S-trimer) combined with the dual-adjuvant system of Alum/CpG. A total of 230 participants were screened and 72 healthy adults aged 18-59 years were enrolled and randomized to receive two doses at a 28-day interval of three different ZR202-CoV formulations or normal saline. We assessed the safety for 28 days after each vaccination and collected blood samples for immunogenicity evaluation.

Preclinical evaluation of KH631, a novel rAAV8 gene therapy product for neovascular age-related macular degeneration.

The upregulation of vascular endothelial growth factor (VEGF) is strongly associated with the development of choroidal neovascularization (CNV) in patients with neovascular age-related macular degeneration (nAMD). Currently, the standard treatment for nAMD involves frequent intravitreal injections of anti-VEGF agents, which inhibit the growth of new blood vessels and prevent leakage. However, this treatment regimen places a significant burden on patients, their families, and healthcare providers due to the need for repeated visits to the clinic for injections.

In Vivo Validation of Modulated Acoustic Radiation Force-Based Imaging in Murine Model of Abdominal Aortic Aneurysm Using VEGFR-2-Targeted Microbubbles.

Objectives: The objective of this study is to validate the modulated acoustic radiation force (mARF)-based imaging method in the detection of abdominal aortic aneurysm (AAA) in murine models using vascular endothelial growth factor receptor 2 (VEGFR-2)-targeted microbubbles (MBs).

Materials And Methods: The mouse AAA model was prepared using the subcutaneous angiotensin II (Ang II) infusion combined with the β-aminopropionitrile monofumarate solution dissolved in drinking water. The ultrasound imaging session was performed at 7 days, 14 days, 21 days, and 28 days after the osmotic pump implantation.

Tirofiban for Stroke without Large or Medium-Sized Vessel Occlusion.

Background: The effects of the glycoprotein IIb/IIIa receptor inhibitor tirofiban in patients with acute ischemic stroke but who have no evidence of complete occlusion of large or medium-sized vessels have not been extensively studied.

Methods: In a multicenter trial in China, we enrolled patients with ischemic stroke without occlusion of large or medium-sized vessels and with a National Institutes of Health Stroke Scale score of 5 or more and at least one moderately to severely weak limb. Eligible patients had any of four clinical presentations: ineligible for thrombolysis or thrombectomy and within 24 hours after the patient was last known to be well; progression of stroke symptoms 24 to 96 hours after onset; early neurologic deterioration after thrombolysis; or thrombolysis with no improvement at 4 to 24 hours.

Optimizing variant-specific therapeutic SARS-CoV-2 decoys using deep-learning-guided molecular dynamics simulations.

Treatment of COVID-19 with a soluble version of ACE2 that binds to SARS-CoV-2 virions before they enter host cells is a promising approach, however it needs to be optimized and adapted to emerging viral variants. The computational workflow presented here consists of molecular dynamics simulations for spike RBD-hACE2 binding affinity assessments of multiple spike RBD/hACE2 variants and a novel convolutional neural network architecture working on pairs of voxelized force-fields for efficient search-space reduction. We identified hACE2-Fc K31W and multi-mutation variants as high-affinity candidates, which we validated in vitro with virus neutralization assays.

A Novel SAVE Score to Stratify Decompensation Risk in Compensated Advanced Chronic Liver Disease (CHESS2102): An International Multicenter Cohort Study.

Introduction: In patients with compensated advanced chronic liver disease (cACLD), the invasive measurement of hepatic venous pressure gradient is the best predictor of hepatic decompensation. This study aimed at developing an alternative risk prediction model to provide a decompensation risk assessment in cACLD.

Methods: Patients with cACLD were retrospectively included from 9 international centers within the Portal Hypertension Alliance in China (CHESS) network.