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.

Intensive Ambulance-Delivered Blood-Pressure Reduction in Hyperacute Stroke.

Background: Treatment of acute stroke, before a distinction can be made between ischemic and hemorrhagic types, is challenging. Whether very early blood-pressure control in the ambulance improves outcomes among patients with undifferentiated acute stroke is uncertain.

Methods: We randomly assigned patients with suspected acute stroke that caused a motor deficit and with elevated systolic blood pressure (≥150 mm Hg), who were assessed in the ambulance within 2 hours after the onset of symptoms, to receive immediate treatment to lower the systolic blood pressure (target range, 130 to 140 mm Hg) (intervention group) or usual blood-pressure management (usual-care group).

Diagnostic Performance of Carotid Ring Sign on CT-Angiography in Internal Carotid True Occlusion.

Background: To differentiate between pseudo occlusion (PO) and true occlusion (TO) of internal carotid artery (ICA) is important in thrombectomy treatment planning for patients with acute ischemic stroke. Although delayed contrast filling has been differentiated carotid PO from TO, its application has been limited by the implementations of multiphasic computed tomography angiography. In this study, we hypothesized that carotid ring sign, which is readily acquired from single-phasic CTA, can sufficiently differentiate carotid TO from PO.

Fluorogenic CRISPR for genomic DNA imaging.

Genomic DNA exhibits high heterogeneity in terms of its dynamic within the nucleus, its structure and functional roles. CRISPR-based imaging approaches can image genomic loci in living cells. However, conventional CRISPR-based tools involve expressing constitutively fluorescent proteins, resulting in high background and nonspecific nucleolar signal.

Development of a highly sensitive aptamer-based electrochemical sensor for detecting saxitoxin based on KFe(CN) regulated silver nanoparticles.

Background: Saxitoxin (STX) is the most toxic marine toxin, which can pose several adverse effects on human health. High sensitivity, fast response, and low-cost detection of STX contamination are of significance to reducing the fishery and seafood industries' loss. Among the various types of biosensors, the electrochemical biosensors have been extensively studied in the detection of STX, but the electrode surface modification material is easy to fall off, resulting in unstable electrochemical signals and poor reproducibility.

[Clinical features and genetic analysis of two fetuses with ring chromosome 21 mosaicism].

Objective: To investigate the perinatal clinical phenotype and genetic characteristics of two fetuses with ring chromosome 21 mosaicisms.

Methods: Two fetuses who were diagnosed at the Xiamen Maternal and Child Health Care Hospital in November 2021 were selected as the study subjects. Clinical data of the two fetuses were collected.

Self-Enhanced Antibacterial and Antifouling Behavior of Three-Dimensional Porous CuO Nanoparticles Functionalized by an Organic-Inorganic Hybrid Matrix.

CuO is currently an important protective material for domestic engineering and equipment used to exploit marine resources. Cu is considered to have more effective antibacterial and antifouling activities than Cu. However, disproportionation of Cu in the natural environment leads to its reduced bioavailability and weakened reactivity.

HRD effects on first-line adjuvant chemotherapy and PARPi maintenance therapy in Chinese ovarian cancer patients.

Homologous recombination deficiency (HRD) testing has been approved by FDA for selecting epithelial ovarian cancer (EOC) patients who may benefit from the first-line poly (ADP-ribose) polymerase inhibitor (PARPi) maintenance therapy. However, the effects of HRD on the clinical outcomes of first-line chemotherapy and first-line PARPi maintenance therapy have not been rigorously evaluated in Chinese EOC patients. Here, we developed an HRD assay and applied it to two large retrospectively collected Chinese EOC patient cohorts.

Quantitative analysis of low content polymorphic impurities in canagliflozin tablets by PXRD, NIR, ATR-FITR and Raman solid-state analysis techniques combined with stoichiometry.

Canagliflozin (CFZ) was a commercially new class of anti-diabetic drug, which had various anhydrate crystal forms and two hydrate crystal forms (Canagliflozin hemihydrate (Hemi-CFZ) and Canagliflozin monohydrate (Mono-CFZ) crystal form). Commercially available CFZ tablets' active pharmaceutical ingredient (API) was Hemi-CFZ, which was easy conversion to CFZ or Mono-CFZ under the influence of temperature, pressure, humidity and other factors in tablets processing, storage, and transportation, thus affected bioavailability and efficacy of tablets. Therefore, quantitative analysis low content of CFZ and Mono-CFZ in tablets was essential to control tablets' quality.

Vertical measurements of stable nitrogen and oxygen isotope composition of fine particulate nitrate aerosol in Guangzhou city: Source apportionment and oxidation pathway.

Nowadays, the emission source and formation mechanism of fine particulate nitrate (pNO) in China are mired in controversy. In this study, the stable nitrogen isotope (δN-NO) and triple oxygen isotope (ΔO-NO) were determined for the pNO samples collected at three heights under different atmospheric oxidation capacity (AOC) (O = O + NO: 107 ± 29 μg m at ground, 102 ± 28 μg m at 118 m, 122 ± 23 μg m at 488 m) conditions during the sampling period based on the Canton Tower, Guangzhou, China. The Bayesian mixing model showed that coal combustion was the largest contributor to pNO in this city, followed by biomass burning, vehicle exhaust, and soil emission.

SAR study of 1,2-benzisothiazole dioxide compounds that agonize HIF-2 stabilization and EPO production.

Benzisothiazole dioxide compound was reported to agonize HIF-2 stabilization and improve EPO production, thus conceiving a potential strategy to treat disease with chronic hypoxia exemplified by renal anemia. Herein, on the bases of multiple molecular and cellular assays, a series of benzisothiazole derivatives have been synthesized and their structure-activity relationship was evaluated. The SAR and molecular docking studies have revealed the structural insights on the rational design of HIF-2 agonist and discovered a more potential 5-bromine substituted analogue, which showed 2-4 times improvement of HIF-2 downstream gene transcriptions, including EPO production.

Small Interfering RNA to Reduce Lipoprotein(a) in Cardiovascular Disease.

Background: Lipoprotein(a) is a presumed risk factor for atherosclerotic cardiovascular disease. Olpasiran is a small interfering RNA that reduces lipoprotein(a) synthesis in the liver.

Methods: We conducted a randomized, double-blind, placebo-controlled, dose-finding trial involving patients with established atherosclerotic cardiovascular disease and a lipoprotein(a) concentration of more than 150 nmol per liter.

Long Noncoding RNA TPRG1-AS1 Suppresses Migration of Vascular Smooth Muscle Cells and Attenuates Atherogenesis via Interacting With MYH9 Protein.

Background: Migration of human aortic smooth muscle cells (HASMCs) contributes to the pathogenesis of atherosclerosis. This study aims to functionally characterize long noncoding RNA TPRG1-AS1 (tumor protein p63 regulated 1, antisense 1) in HASMCs and reveal the underlying mechanism of TPRG1-AS1 in HASMCs migration, neointima formation, and subsequent atherosclerosis.

Methods: The expression of TPRG1-AS1 in atherosclerotic plaques was verified a series of in silico analysis and quantitative real-time polymerase chain reaction analysis.

Purification and Identification of Flavonoid Molecules from Waste Extracts and Evaluation of Antioxidant, Antiproliferative and Antimicrobial Activities.

is widely used in the essential oil industry and generates large amounts of waste annually. The purpose of this research is the recycling of bioactive flavonoids from rose waste biomass to develop high-value products. Resin screening and adsorption/desorption dynamic analysis showed that HP20 resin was suitable to purify the flavonoids from waste extracts.

Health Benefits, Food Applications, and Sustainability of Microalgae-Derived N-3 PUFA.

Today's consumers are increasingly aware of the beneficial effects of n-3 PUFA in preventing, delaying, and intervening various diseases, such as coronary artery disease, hypertension, diabetes, inflammatory and autoimmune disorders, neurodegenerative diseases, depression, and many other ailments. The role of n-3 PUFA on aging and cognitive function is also one of the hot topics in basic research, product development, and clinical applications. For decades, n-3 PUFA, especially EPA and DHA, have been supplied by fish oil and seafood.

Production, Processing, and Protection of Microalgal n-3 PUFA-Rich Oil.

Microalgae have been increasingly considered as a sustainable "biofactory" with huge potentials to fill up the current and future shortages of food and nutrition. They have become an economically and technologically viable solution to produce a great diversity of high-value bioactive compounds, including n-3 polyunsaturated fatty acids (PUFA). The n-3 PUFA, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), possess an array of biological activities and positively affect a number of diseases, including cardiovascular and neurodegenerative disorders.

A defective viral genome strategy elicits broad protective immunity against respiratory viruses.

RNA viruses generate defective viral genomes (DVGs) that can interfere with replication of the parental wild-type virus. To examine their therapeutic potential, we created a DVG by deleting the capsid-coding region of poliovirus. Strikingly, intraperitoneal or intranasal administration of this genome, which we termed eTIP1, elicits an antiviral response, inhibits replication, and protects mice from several RNA viruses, including enteroviruses, influenza, and SARS-CoV-2.

Ethacridine inhibits SARS-CoV-2 by inactivating viral particles.

The respiratory disease COVID-19 is caused by the coronavirus SARS-CoV-2. Here we report the discovery of ethacridine as a potent drug against SARS-CoV-2 (EC50 ~ 0.08 μM).

Pareto-Optimal Data Compression for Binary Classification Tasks.

The goal of lossy data compression is to reduce the storage cost of a data set while retaining as much information as possible about something () that you care about. For example, what aspects of an image contain the most information about whether it depicts a cat? Mathematically, this corresponds to finding a mapping X → Z ≡ f ( X ) that maximizes the mutual information I ( Z , Y ) while the entropy H ( Z ) is kept below some fixed threshold. We present a new method for mapping out the Pareto frontier for classification tasks, reflecting the tradeoff between retained entropy and class information.

Ethacridine inhibits SARS-CoV-2 by inactivating viral particles in cellular models.

SARS-CoV-2 is the coronavirus that causes the respiratory disease COVID-19, which is now the third-leading cause of death in the United States. The FDA has recently approved remdesivir, an inhibitor of SARS-CoV-2 replication, to treat COVID-19, though recent data from the WHO shows little to no benefit with use of this anti-viral agent. Here we report the discovery of ethacridine, a safe antiseptic use in humans, as a potent drug for use against SARS-CoV-2 (EC ~ 0.

Residue-Orientation-Dependent Dynamics and Selectivity of Active Pocket in Microbe Class I Terpene Cyclases.

Microbe class I terpene cyclases (TPCs) are responsible for deriving numerous functionally and structurally diverse groups of terpenoid natural products. The conformational change of their active pockets from "open" state to "closed" state upon substrate binding has been clarified. However, the key structural basis relevant to this active pocket dynamics and its detailed molecular mechanism are still unclear.

Modular supramolecular dimerization of optically tunable extended aryl viologens.

Cucurbit[8]uril (CB[8]) mediated assembly of extended aryl viologens (EVs) into optically tunable dimers is reported for the first time. We show that the modular design and synthesis of a new class of π-conjugated viologen derivatives with rigid aromatic or heteroaromatic bridging units as well as electron donating molecular recognition motifs enable their self-assembly into 2 : 2 complexes with CB[8]. The quantitative dimerization process involving these two molecular components in an aqueous solution enables excimer-like interactions between closely packed charged guests giving rise to distinct spectroscopic behavior.

Lymph Node Metastasis Prediction from Primary Breast Cancer US Images Using Deep Learning.

Background Deep learning (DL) algorithms are gaining extensive attention for their excellent performance in image recognition tasks. DL models can automatically make a quantitative assessment of complex medical image characteristics and achieve increased accuracy in diagnosis with higher efficiency. Purpose To determine the feasibility of using a DL approach to predict clinically negative axillary lymph node metastasis from US images in patients with primary breast cancer.

Leptin Induces Hypertension Acting on Transient Receptor Potential Melastatin 7 Channel in the Carotid Body.

Rationale: Obesity leads to resistant hypertension and mechanisms are poorly understood, but high plasma levels of leptin have been implicated. Leptin increases blood pressure acting both centrally in the dorsomedial hypothalamus and peripherally. Sites of the peripheral hypertensive effect of leptin have not been identified.