An antibody cocktail targeting two different CD73 epitopes enhances enzyme inhibition and tumor control.

CD73, an ectoenzyme responsible for adenosine production, is often elevated in immuno-suppressive tumor environments. Inhibition of CD73 activity holds great promise as a therapeutic strategy for CD73-expressing cancers. In this study, we have developed a therapeutic anti-human CD73 antibody cocktail, HB0045.

Radiological features on high-resolution MR imaging predicts successful recanalization in patients with symptomatic chronic intracranial large artery occlusion.

Rationale And Objectives: Endovascular recanalization has been attempted in patients with symptomatic chronic intracranial large artery occlusion (CILAO), however, the heterogeneity of recanalization outcomes present challenges for the clinical application.

Objective: To determine the radiological features on high-resolution MR imaging (HR-MRI) for predicting successful recanalization of symptomatic CILAO.

Methods: Seventy-three patients with symptomatic CILAO who underwent endovascular recanalization at our center were retrospectively analyzed.

Effect of Delayed Remote Ischemic Preconditioning on Acute Kidney Injury and Outcomes in Patients Undergoing Cardiac Surgery: A Randomized Clinical Trial.

Background: Remote ischemic preconditioning (RIPC) has 2 time windows for organ protection: acute and delayed. Previous studies have mainly focused on the organoprotective effects of acute RIPC. We aimed to determine whether delayed RIPC can reduce the occurrence of acute kidney injury (AKI) and postoperative complications in patients undergoing cardiac surgery.

Safety and immunogenicity of a skin- and neuro-attenuated live vaccine for varicella: a randomized, double-blind, controlled, dose-escalation and age de-escalation phase 1 clinical trial.

Background: Despite the success in decreasing varicella-related disease burden, live-attenuated Oka vaccine strain of varicella-zoster virus (vOka) remains neuro-virulence and may establish latency and reactivate, raising safety concerns. Here we aimed to evaluate the safety and immunogenicity of a skin- and neuro-attenuated varicella vaccine candidate (v7D).

Methods: This is a randomized, double-blind, placebo-controlled, dose-escalation and age de-escalation phase 1 clinical trial conducted in Liuzhou, China (ChiCTR1900022284).

Preferential Hematopoietic Differentiation in Induced Pluripotent Stem Cells Derived From Human Umbilical Cord Arterial Endothelial Cells.

Background: The major obstacle for applications of human induced pluripotent stem cells (hiPSCs) is efficient and controlled lineage-specific differentiation. Hence, a deeper understanding of the initial populations of hiPSCs is required to instruct proficient lineage commitment.

Methods: hiPSCs were generated from somatic cells by transduction of 4 human transcription factors (OCT4, SOX2, KLF4, and C-MYC) using Sendai virus vectors.

Early-Life Cardiovascular Risk Factor Trajectories and Vascular Aging in Midlife: A 30-Year Prospective Cohort Study.

Background: Vascular aging, as assessed by structural and functional arterial properties, is an independent predictor of cardiovascular outcomes. We aimed to explore the associations of individual cardiovascular risk factors from childhood to midlife and their accumulation over a 30-year span with vascular aging in midlife.

Methods: Using data from the ongoing cohort of Hanzhong Adolescent Hypertension study, 2180 participants aged 6 to 18 years at baseline were followed for over 30 years.

Endovascular Recanalization of Symptomatic Chronic ICA Occlusion: Procedural Outcomes and Radiologic Predictors.

Background And Purpose: Endovascular recanalization has been attempted in patients with symptomatic chronic ICA occlusion, however, the heterogeneity of recanalization outcomes and the perioperative complications present challenges for the clinical application. Our aim was to evaluate the safety and efficacy of endovascular recanalization for symptomatic chronic ICA occlusion and identify potential predictors for successful recanalization.

Materials And Methods: This study included 47 consecutive patients with symptomatic chronic ICA occlusion who underwent endovascular recanalization at our institution.

Automated Estimation of Quantitative Lesion Water Uptake as a Prognostic Biomarker for Patients with Ischemic Stroke and Large-Vessel Occlusion.

Background And Purpose: Net water uptake is qualified as an imaging marker of brain edema. We aimed to investigate the ability of net water uptake to predict 90-day functional outcome in patients with acute ischemic stroke and large-vessel occlusion.

Materials And Methods: A total of 295 consecutive patients were retrospectively enrolled.

COVID-19 vaccination boosts the potency and breadth of the immune response against SARS-CoV-2 among recovered patients in Wuhan.

The immunity of patients who recover from coronavirus disease 2019 (COVID-19) could be long lasting but persist at a lower level. Thus, recovered patients still need to be vaccinated to prevent reinfection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or its mutated variants. Here, we report that the inactivated COVID-19 vaccine can stimulate immunity in recovered patients to maintain high levels of anti-receptor-binding domain (RBD) and anti-nucleocapsid protein (NP) antibody titers within 9 months, and high neutralizing activity against the prototype, Delta, and Omicron strains was observed.

Mitochondrial genome sequencing with short overlapping amplicons on MiSeq FGx system.

With the development and maturation of massively parallel sequencing (MPS) technology, the mitochondrial genome (mitogenome) sequencing is increasingly applied in the forensic field. In this study, we employed the strategy of short overlapping amplicons for the whole mitogenome, library preparation with tagmentation using the Nextera® XT DNA Library Preparation Kit, sequencing on the MiSeq FGx Forensic Genomics System and analyzing data using the mitochondrial(mtDNA) MSR Plug-in and the mtDNA Variant Analyzer. A total of 27 libraries and 56 libraries were sequenced in a run using MiSeq Reagent Kit v2 and v3, respectively.

Potent Anti-SARS-CoV-2 Efficacy of COVID-19 Hyperimmune Globulin from Vaccine-Immunized Plasma.

Coronavirus disease 2019 (COVID-19) remains a global public health threat. Hence, more effective and specific antivirals are urgently needed. Here, COVID-19 hyperimmune globulin (COVID-HIG), a passive immunotherapy, is prepared from the plasma of healthy donors vaccinated with BBIBP-CorV (Sinopharm COVID-19 vaccine).

Associations of Long-Term Visit-to-Visit Blood Pressure Variability With Subclinical Kidney Damage and Albuminuria in Adulthood: a 30-Year Prospective Cohort Study.

Background: Recent evidence indicates that long-term visit-to-visit blood pressure variability (BPV) may be associated with risk of cardiovascular disease. We, therefore, aimed to determine the potential associations of long-term BPV from childhood to middle age with subclinical kidney damage (SKD) and albuminuria in adulthood.

Methods: Using data from the ongoing cohort of Hanzhong Adolescent Hypertension study, which recruited children and adolescents aged 6 to 18 years at baseline, we assessed BPV by SD and average real variability (ARV) for 30 years (6 visits).

Development of a BCL-xL and BCL-2 dual degrader with improved anti-leukemic activity.

PROteolysis-TArgeting Chimeras (PROTACs) have emerged as an innovative drug development platform. However, most PROTACs have been generated empirically because many determinants of PROTAC specificity and activity remain elusive. Through computational modelling of the entire NEDD8-VHL Cullin RING E3 ubiquitin ligase (CRL)/PROTAC/BCL-xL/UbcH5B(E2)-Ub/RBX1 complex, we find that this complex can only ubiquitinate the lysines in a defined band region on BCL-xL.

PCSK9 (Proprotein Convertase Subtilisin/Kexin 9) Enhances Platelet Activation, Thrombosis, and Myocardial Infarct Expansion by Binding to Platelet CD36.

Background: PCSK9 (proprotein convertase subtilisin/kexin 9), mainly secreted by the liver and released into the blood, elevates plasma low-density lipoprotein cholesterol by degrading low-density lipoprotein receptor. Pleiotropic effects of PCSK9 beyond lipid metabolism have been shown. However, the direct effects of PCSK9 on platelet activation and thrombosis, and the underlying mechanisms, as well, still remain unclear.

Elevated Methylation of FOXP3 (Forkhead Box P3)-TSDR (Regulatory T-Cell-Specific Demethylated Region) Is Associated With Increased Risk for Adverse Outcomes in Patients With Acute Coronary Syndrome.

Demethylation of the forkhead box P3 (FOXP3) corresponds with stability of FOXP3 expression and immunosuppressive function of regulatory T cells (Tregs). Previous studies have demonstrated that reduction in Tregs is associated with acute coronary syndrome (ACS). The aim of this study was to establish the relationship between methylation level of FOXP3-TSDR (Treg-specific demethylated region) and clinical outcomes of ACS.

Cannulation of Occluded Inferior Petrosal Sinuses for the Transvenous Embolization of Cavernous Sinus Dural Arteriovenous Fistulas: Usefulness of a Frontier-Wire Probing Technique.

Background And Purpose: Pursuing an alternative access route for transvenous embolization of cavernous sinus dural arteriovenous fistulas can be challenging in patients with an occluded inferior petrosal sinus. We found that cannulation of even a completely occluded inferior petrosal sinus is feasible, especially when using a standard hydrophilic-polymer-jacketed 0.035-inch guidewire as a frontier-wire for probing.

The red bayberry genome and genetic basis of sex determination.

Morella rubra, red bayberry, is an economically important fruit tree in south China. Here, we assembled the first high-quality genome for both a female and a male individual of red bayberry. The genome size was 313-Mb, and 90% sequences were assembled into eight pseudo chromosome molecules, with 32 493 predicted genes.

Localized Marked Elongation of the Distal Internal Carotid Artery with or without PHACE Syndrome: Segmental Dolichoectasia of the Distal Internal Carotid Artery.

Background And Purpose: Segmental intracranial dolichoectasia of the distal ICA is a feature of PHACE syndrome or a sporadic phenomenon. We evaluated the relationship between intracranial dolichoectasia of the distal ICA and PHACE syndrome and illustrated the characteristic radiologic findings of the lesions.

Materials And Methods: Intracranial dolichoectasia of the distal ICA was identified in 20 patients at our institution from 2005 to 2016 through a review of diagnostic cerebral angiography results.

Treatment of supratentorial spontaneous intracerebral hemorrhage using image-guided minimally invasive surgery: Initial experiences of a flat detector CT-based puncture planning and navigation system in the angiographic suite.

Background And Purpose: The intracerebral hemorrhage drainage through minimally invasive approach is emerging as an alternative for traditional craniotomy, due to its improved survival rate and reduced complication rate. In this study, we investigated the feasibility and safety of a flat detector CT-based puncture planning and navigation system for minimally invasive hematoma drainage on patients with intracerebral hemorrhage.

Materials And Methods: The minimally invasive hematoma drainage was performed on 21 hypertensive patients with intracerebral hemorrhage in the angiographic suite with the guidance of a flat detector CT-based puncture planning and navigation system.

Correlation between bacterial biofilms and osteitis in patients with chronic rhinosinusitis.

Objectives/hypothesis: Bacterial biofilms (BBF) and osteitis are potential contributors to the local inflammatory load in chronic rhinosinusitis (CRS). This study investigated the relationship between BBF and osteitis status in CRS patients.

Study Design: Prospective cohort study.