Generation of iPSC-derived human venous endothelial cells for the modeling of vascular malformations and drug discovery.

Venous malformations (VMs) represent prevalent vascular anomalies typically attributed to non-inherited somatic mutations within venous endothelial cells (VECs). The lack of robust disease models for VMs impedes drug discovery. Here, we devise a robust protocol for the generation of human induced VECs (iVECs) through manipulation of cell-cycle dynamics via the retinoic signaling pathway.

Integrative Single Cell Atlas Revealed Intratumoral Heterogeneity Generation from an Adaptive Epigenetic Cell State in Human Bladder Urothelial Carcinoma.

Intratumor heterogeneity (ITH) of bladder cancer (BLCA) contributes to therapy resistance and immune evasion affecting clinical prognosis. The molecular and cellular mechanisms contributing to BLCA ITH generation remain elusive. It is found that a TM4SF1-positive cancer subpopulation (TPCS) can generate ITH in BLCA, evidenced by integrative single cell atlas analysis.

Host genetic regulation of human gut microbial structural variation.

Although the impact of host genetics on gut microbial diversity and the abundance of specific taxa is well established, little is known about how host genetics regulates the genetic diversity of gut microorganisms. Here we conducted a meta-analysis of associations between human genetic variation and gut microbial structural variation in 9,015 individuals from four Dutch cohorts. Strikingly, the presence rate of a structural variation segment in Faecalibacterium prausnitzii that harbours an N-acetylgalactosamine (GalNAc) utilization gene cluster is higher in individuals who secrete the type A oligosaccharide antigen terminating in GalNAc, a feature that is jointly determined by human ABO and FUT2 genotypes, and we could replicate this association in a Tanzanian cohort.

KMT2D deficiency drives lung squamous cell carcinoma and hypersensitivity to RTK-RAS inhibition.

Lung squamous cell carcinoma (LUSC) represents a major subtype of lung cancer with limited treatment options. KMT2D is one of the most frequently mutated genes in LUSC (>20%), and yet its role in LUSC oncogenesis remains unknown. Here, we identify KMT2D as a key regulator of LUSC tumorigenesis wherein Kmt2d deletion transforms lung basal cell organoids to LUSC.

Rare, convergent antibodies targeting the stem helix broadly neutralize diverse betacoronaviruses.

Humanity has faced three recent outbreaks of novel betacoronaviruses, emphasizing the need to develop approaches that broadly target coronaviruses. Here, we identify 55 monoclonal antibodies from COVID-19 convalescent donors that bind diverse betacoronavirus spike proteins. Most antibodies targeted an S2 epitope that included the K814 residue and were non-neutralizing.

Preclinical safety assessment of MV-s-NAP, a novel oncolytic measles virus strain armed with an immunostimulatory bacterial transgene.

Despite recent therapeutic advances, metastatic breast cancer (MBC) remains incurable. Engineered measles virus (MV) constructs based on the attenuated MV Edmonston vaccine platform have demonstrated significant oncolytic activity against solid tumors. The neutrophil-activating protein (NAP) is responsible for the robust inflammatory reaction in gastroduodenal mucosa during bacterial infection.

Effects of Bonding Materials on Optical-Thermal Performances and High-Temperature Reliability of High-Power LED.

The die-bonding layer between chips and substrate determinates the heat conduction efficiency of high-power LED. Sn-based solder, AuSn20 eutectic, and nano-Ag paste were widely applied to LED interconnection. In this paper, the optical-thermal performances and high-temperature reliability of LED with these bonding materials have systematically compared and studied.

A Fully Automated Segmentation and Morphometric Parameter Estimation System for Assessing Corneal Endothelial Cell Images.

Purpose: To develop a fully automated segmentation and morphometric parameter estimation system for assessing corneal endothelial cells from in vivo confocal microscopy images.

Design: Artificial intelligence (neural network) study.

Methods: First, a fully automated deep learning system for assessing corneal endothelial cells was developed using the development set (from 99 subjects).

Post-Covid-19-vaccination adverse events and healthcare utilization among individuals with or without previous SARS-CoV-2 infection.

Background: Post-marketing pharmacovigilance data are scant on the safety of Covid-19 vaccines among people with previous SARS-CoV-2 infection compared with ordinary vaccine recipients. We compared the post-vaccination adverse events of special interests (AESI), accident and emergency room (A&E) visit, and hospitalization between these two groups.

Methods: We conducted a retrospective cohort study using a territory-wide public healthcare database with population-based vaccination records in Hong Kong.

Deep learning for distinguishing normal versus abnormal chest radiographs and generalization to two unseen diseases tuberculosis and COVID-19.

Chest radiography (CXR) is the most widely-used thoracic clinical imaging modality and is crucial for guiding the management of cardiothoracic conditions. The detection of specific CXR findings has been the main focus of several artificial intelligence (AI) systems. However, the wide range of possible CXR abnormalities makes it impractical to detect every possible condition by building multiple separate systems, each of which detects one or more pre-specified conditions.

A brief review of reporter gene imaging in oncolytic virotherapy and gene therapy.

Reporter gene imaging (RGI) can accelerate development timelines for gene and viral therapies by facilitating rapid and noninvasive studies to determine the biodistribution, magnitude, and durability of viral gene expression and/or virus infection. Functional molecular imaging systems used for this purpose can be divided broadly into deep-tissue and optical modalities. Deep-tissue modalities, which can be used in animals of any size as well as in human subjects, encompass single photon emission computed tomography (SPECT), positron emission tomography (PET), and functional/molecular magnetic resonance imaging (f/mMRI).

Construction of specific Smo lentivirus and expression of infected pancreatic cancer cells positive for CD24CD44 surface antibody.

This study aimed to construct a vector lentivirus carrying the Smo gene and transfect pancreatic cancer cells positive for CD24CD44 surface antibody and detect the infectivity. A lentivirus carrying a specific Smo fragment was designed and synthesized, and its functionality was tested. An overexpression group, inhibitory group, and negative control group were used for subsequent experimental research and comparison.

Retargeted and Stealth-Modified Oncolytic Measles Viruses for Systemic Cancer Therapy in Measles Immune Patients.

Measles viruses (MV) are rapidly inactivated by anti-measles neutralizing antibodies, which has limited their clinical performance as oncolytic agents. Here, by substituting the H and F surface glycoproteins of MV with those from the homologous canine distemper virus (CDV) and engineering the CDV H attachment protein to target EGFR or CD38, we generated a fully retargeted MV capable of resisting neutralization by measles-immune human serum. The resultant recombinant MVs encoding retargeted CDV envelope glycoproteins had similar growth kinetics as the control MV, showed the expected engineered receptor specificities for cell entry, intercellular fusion, and target cell killing, and were blind to native CDV receptors.

CRISPR/Cas9-mediated introduction of the sodium/iodide symporter gene enables noninvasive in vivo tracking of induced pluripotent stem cell-derived cardiomyocytes.

Techniques that enable longitudinal tracking of cell fate after myocardial delivery are imperative for optimizing the efficacy of cell-based cardiac therapies. However, these approaches have been underutilized in preclinical models and clinical trials, and there is considerable demand for site-specific strategies achieving long-term expression of reporter genes compatible with safe noninvasive imaging. In this study, the rhesus sodium/iodide symporter (NIS) gene was incorporated into rhesus macaque induced pluripotent stem cells (RhiPSCs) via CRISPR/Cas9.

A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19.

Background: No therapeutics have yet been proven effective for the treatment of severe illness caused by SARS-CoV-2.

Methods: We conducted a randomized, controlled, open-label trial involving hospitalized adult patients with confirmed SARS-CoV-2 infection, which causes the respiratory illness Covid-19, and an oxygen saturation (Sao) of 94% or less while they were breathing ambient air or a ratio of the partial pressure of oxygen (Pao) to the fraction of inspired oxygen (Fio) of less than 300 mm Hg. Patients were randomly assigned in a 1:1 ratio to receive either lopinavir-ritonavir (400 mg and 100 mg, respectively) twice a day for 14 days, in addition to standard care, or standard care alone.

Mapping of Ion and Substrate Binding Sites in Human Sodium Iodide Symporter (hNIS).

The human sodium iodide symporter (hNIS) is a theranostic reporter gene which concentrates several clinically approved SPECT and PET radiotracers and plays an essential role for the synthesis of thyroid hormones as an iodide transporter in the thyroid gland. Development of hNIS mutants which could enhance translocation of the desired imaging ions is currently underway. Unfortunately, it is hindered by lack of understanding of the 3D organization of hNIS and its relation to anion transport.

Motschulsky (Hymenoptera, Eupelmidae): egg parasitoids of Moore (Lepidoptera, Saturniidae) in China.

Four species of Motschulsky (Hymenoptera, Eupelmidae, Eupelminae) are newly reported as egg parasitoids of the Japanese giant silkworm, Moore and, as an alternate laboratory host, the Chinese oak silk moth, (Guérin-Méneville) (Lepidoptera, Saturniidae) in China. The four species, Sheng & Wang, 1997, Chen & Zang, , Ashmead, 1904, and Sheng, 1998, were reared initially from eggs of collected in Gansu, Jilin and Liaoning provinces and subsequently cultured in the laboratory on eggs of . An illustrated key to differentiate females of the four species, and males of some of the species is provided.

Oncolytic Viruses: Priming Time for Cancer Immunotherapy.

New immuno-oncology therapies are improving cancer treatments beyond the former standard of care, as evidenced by the recent and continuing clinical approvals for immunotherapies in a broad range of indications. However, a majority of patients (particularly those with immunologically cold tumors) still do not benefit, highlighting the need for rational combination approaches. Oncolytic viruses (OV) both directly kill tumor cells and inflame the tumor microenvironment.

Deep learning versus human graders for classifying diabetic retinopathy severity in a nationwide screening program.

Deep learning algorithms have been used to detect diabetic retinopathy (DR) with specialist-level accuracy. This study aims to validate one such algorithm on a large-scale clinical population, and compare the algorithm performance with that of human graders. A total of 25,326 gradable retinal images of patients with diabetes from the community-based, nationwide screening program of DR in Thailand were analyzed for DR severity and referable diabetic macular edema (DME).

Endothelial Cells Regulate Physiological Cardiomyocyte Growth via VEGFR2-Mediated Paracrine Signaling.

Background: Heart failure, which is a major global health problem, is often preceded by pathological cardiac hypertrophy. The expansion of the cardiac vasculature, to maintain adequate supply of oxygen and nutrients, is a key determinant of whether the heart grows in a physiological compensated manner or a pathological decompensated manner. Bidirectional endothelial cell (EC)-cardiomyocyte (CMC) cross talk via cardiokine and angiocrine signaling plays an essential role in the regulation of cardiac growth and homeostasis.

Glucose-Sensitive Myokine/Cardiokine MG53 Regulates Systemic Insulin Response and Metabolic Homeostasis.

Background: Mitsugumin 53 (MG53 or TRIM72), a striated muscle-specific E3 ligase, promotes ubiquitin-dependent degradation of the insulin receptor and insulin receptor substrate-1 and subsequently induces insulin resistance, resulting in metabolic syndrome and type 2 diabetes mellitus (T2DM). However, it is unknown how MG53 from muscle regulates systemic insulin response and energy metabolism. Increasing evidence demonstrates that muscle secretes proteins as myokines or cardiokines that regulate systemic metabolic processes.

New transgenic NIS reporter rats for longitudinal tracking of fibrogenesis by high-resolution imaging.

Fibrogenesis is the underlying mechanism of wound healing and repair. Animal models that enable longitudinal monitoring of fibrogenesis are needed to improve traditional tissue analysis post-mortem. Here, we generated transgenic reporter rats expressing the sodium iodide symporter (NIS) driven by the rat collagen type-1 alpha-1 (Col1α1) promoter and demonstrated that fibrogenesis can be visualized over time using SPECT or PET imaging following activation of NIS expression by rotator cuff (RC) injury.

Author Correction: Grain Yield, Starch Content and Activities of Key Enzymes of Waxy and Non-waxy Wheat (Triticum aestivum L.).

A correction to this article has been published and is linked from the HTML version of this paper. The error has not been fixed in the paper.