Bivalent CD47 Immunotoxin for Targeted Therapy of T-Cell Acute Lymphoblastic Leukemia.

CD47 is overexpressed on the surface of many types of cancer cells, including T-cell acute lymphoblastic leukemia (T-ALL) cells. In this study, we have developed a diphtheria toxin-based bivalent anti-human CD47 immunotoxin (bi-CD47-IT) for the targeted therapy of CD47+ cancers using a unique diphtheria toxin-resistant yeast Pichia pastoris expression system. Bi-CD47-IT demonstrated compelling in vivo efficacy in multiple T-ALL cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) mouse models.

Structural Comparisons, Fluorescence Properties, and Glass-to-Crystal Transformations of Heat-Cooled and Melt-Quenched Zeolitic Imidazolate Framework Glass.

As a representative of zeolitic imidazolate framework glass, agZIF-62 has been reported to be synthesized using a melt-quenching method in which the ZIF-62 crystal is heated to a temperature above the melting point. Interestingly, we unexpectedly found that agZIF-62 can also be synthesized by simple heating at temperatures lower than the melting point, which may be assisted by the release of encapsulated solvent molecules. The structural differences between melt-quenched agZIF-62 (MQ-agZIF-62) and heat-cooled agZIF-62 (HC-agZIF-62) were investigated.

[Air Pollutant Spatiotemporal Evolution Characteristics and Effects on Human Health in Xi'an City].

Xi'an is the political, economic, and cultural center of northwest China with a developed industry. Air pollution incidents have brought great challenges to the high-quality development of the social economy. It is vital to study air pollution characteristics and clarify their impact on human health.

Mowing aggravates the adverse effects of nitrogen addition on soil acid neutralizing capacity in a meadow steppe.

Soil acidification induced by reactive nitrogen (N) inputs is a major environmental issue in grasslands, as it lowers the acid neutralizing capacity (ANC). The specific impacts of different N compound forms on ANC remain unclear. Grassland management practices like mowing and grazing can remove a considerable amount of soil N and other nutrients, potentially mitigating soil acidification by removing N from the ecosystem or aggravating it by removing base cations.

Design of Bionic Foot Inspired by the Anti-Slip Cushioning Mechanism of Yak Feet.

In recent years, legged robots have been more and more widely used on non-structured terrain, and their foot structure has an important impact on the robot's motion performance and stability. The structural characteristics of the yak foot sole with a high outer edge and low middle, which has excellent soil fixation ability and is an excellent bionic prototype, can improve the friction between the foot and the ground. At the same time, the foot hooves can effectively alleviate the larger impact load when contacting with the ground, which is an excellent anti-slip buffer mechanism.

Associations between serum 25-hydroxyvitamin D and prognosis of chronic kidney disease: a prospective cohort study.

Background And Objectives: 25-hydroxyvitamin D [25(OH)D] deficiency is prevalent in patients with chronic kidney disease (CKD), the associations between serum 25(OH)D levels and mortality in patients with CKD remain unclear, and this study aimed to explore these associations further.

Methods: 4989 participants with CKD were enrolled in the study, and the Cox regression model was used to assess the effects of serum 25(OH)D concentrations on mortality risk. A restricted cubic spline model was used to explore the dose-response relationships, and threshold effect analysis was performed based on inflection points identified by a two-piecewise linear regression model.

Synthesis of Chiral 1,2-Amino Alcohol-Containing Compounds Utilizing Ruthenium-Catalyzed Asymmetric Transfer Hydrogenation of Unprotected α-Ketoamines.

Herein, we disclose a facile synthetic strategy to access an important class of drug molecules that contain chiral 1,2-amino alcohol functionality utilizing highly effective ruthenium-catalyzed asymmetric transfer hydrogenation of unprotected α-ketoamines. Recently, the COVID-19 pandemic has caused a crisis of shortage of many important drugs, especially norepinephrine and epinephrine, for the treatment of anaphylaxis and hypotension because of the increased demand. Unfortunately, the existing technologies are not fulfilling the worldwide requirement due to the existing lengthy synthetic protocols that require additional protection and deprotection steps.

cMPL-Based Purification and Depletion of Human Hematopoietic Stem Cells: Implications for Pre-Transplant Conditioning.

The transplantation of gene-modified autologous hematopoietic stem and progenitor cells (HSPCs) offers a promising therapeutic approach for hematological and immunological disorders. However, this strategy is often limited by the toxicities associated with traditional conditioning regimens. Antibody-based conditioning strategies targeting cKIT and CD45 antigens have shown potential in mitigating these toxicities, but their long-term safety and efficacy in clinical settings require further validation.

FedEYE: A scalable and flexible end-to-end federated learning platform for ophthalmology.

Data-driven machine learning, as a promising approach, possesses the capability to build high-quality, exact, and robust models from ophthalmic medical data. Ophthalmic medical data, however, presently exist across disparate data silos with privacy limitations, making centralized training challenging. While ophthalmologists may not specialize in machine learning and artificial intelligence (AI), considerable impediments arise in the associated realm of research.

Toxicology, pharmacokinetics, and immunogenicity studies of CCR4-IL2 bispecific immunotoxin in rats and minipigs.

We have developed a diphtheria toxin-based recombinant human CCR4-IL2 bispecific immunotoxin (CCR4-IL2-IT) for targeted therapy of cutaneous T-cell lymphoma (CTCL). CCR4-IL2-IT demonstrated superior efficacy in an immunodeficient mouse CTCL model. Recently, we have compared the in vivo efficacy of CCR4-IL2-IT versus Brentuximab (FDA approved leading drug in CTCL market) in the same immunodeficient mouse CTCL model.

Genetic factors associated with acquired phenotypic drug resistance and its compensatory evolution during tuberculosis treatment.

Objectives: We elucidated the factors, evolution, and compensation of antimicrobial resistance (AMR) in Mycobacterium tuberculosis (MTB) isolates under dual pressure from the intra-host environment and anti-tuberculosis (anti-TB) drugs.

Methods: This retrospective case-control study included 337 patients with pulmonary tuberculosis from 15 clinics in Tianjin, China, with phenotypic drug susceptibility testing results available for at least two time points between January 1, 2009 and December 31, 2016. Patients in the case group exhibited acquired AMR to isoniazid (INH) or rifampicin (RIF), while those in the control group lacked acquired AMR.

Spatial distribution, ecological risk and health risk assessment of heavy metals in agricultural soil from Ankang basin, Shaanxi Province.

In order to assess the heavy metal pollution features, ecological dangers, and health risk status posed to human beings by soils in the Ankang Basin, a study was conducted. This involved the collection of 38 surface soil samples, followed by the determination of elemental levels of arsenic, mercury, copper, cadmium, lead, chromium, nickel, and zinc. The concentrations of arsenic, mercury, copper, cadmium, lead, chromium, nickel, and zinc were quantified through the collection of 38 surface soil samples.

Short-term legacy effects of long-term nitrogen and water addition on soil chemical properties and micro-bial characteristics in a temperate grassland.

Nitrogen deposition and summer precipitation in eastern Inner Mongolia are predicted to increase in recent decades. However, such increases in nitrogen inputs and precipitation may not be continuous under the future new patterns of global change, with the direction and magnitude of which may change or weaken. The legacy effects of nitrogen and water addition after cessation on ecosystems are still unclear.

Design and Discovery of Water-Soluble Benzooxaphosphole-Based Ligands for Hindered Suzuki-Miyaura Coupling Reactions with Low Catalyst Load.

We report a new class of highly effective, benzooxaphosphole-based, water-soluble ligands in the application of Suzuki-Miyaura cross-coupling reactions for sterically hindered substrates in aqueous media. The catalytic activities of the coupling reactions were greatly enhanced by the addition of catalytic amounts of organic phase transfer reagents, such as tetraglyme and tetrabutylammonium bromide. The optimized general protocol can be conducted with a low catalyst load, thereby providing a practical solution for these reactions.

CCR4-IL2 bispecific immunotoxin is more effective than brentuximab for targeted therapy of cutaneous T-cell lymphoma in a mouse CTCL model.

Cutaneous T-cell lymphoma (CTCL) encompasses two main subtypes: mycosis fungoides and Sezary syndrome. Global response rates for the systemic treatment of mycosis fungoides and Sezary syndrome are approximately 30%, and none of these treatments are thought to be curative. C-C chemokine receptor type 4 (CCR4) and CD25 are encouraging targets for the treatment of CTCL and are individually targeted by mogamulizumab and denileukin diftitox, respectively.

Deep-Learning-Enhanced Diffusion Imaging Assay for Resolving Local-Density Effects on Membrane Receptors.

G-protein-coupled receptor (GPCR) density at the cell surface is thought to regulate receptor function. Spatially resolved measurements of local-density effects on GPCRs are needed but technically limited by density heterogeneity and mobility of membrane receptors. We now develop a deep-learning (DL)-enhanced diffusion imaging assay that can measure local-density effects on ligand-receptor interactions in the plasma membrane of live cells.

Near-Infrared Blinking Carbon Dots Designed for Quantitative Nanoscopy.

Blinking carbon dots (CDs) have attracted attention as a probe for single molecule localization microscopy (SMLM), yet quantitative analysis is limited because of inept blinking and low signal-to-noise ratio (SNR). Here we report the design and synthesis of near-infrared (NIR) blinking CDs with a maximum emission of around 750 nm by weaving a nitrogen-doped aromatic backbone with surplus carboxyl groups on the surface. The NIR-CDs allow conjugation to monovalent antibody fragments for labeling and imaging of cellular receptors as well as afford increases of 52% in SNR and 33% in localization precision over visible CDs.

EGF‑IL2 bispecific and bivalent EGF fusion toxin efficacy against syngeneic head and neck cancer mouse models.

The epidermal growth factor receptor (EGFR) remains one of the best molecules for developing targeted therapy for multiple human malignancies, including head and neck squamous cell carcinoma (HNSCC). Small molecule inhibitors or antibodies targeting EGFR have been extensively developed in recent decades. Immunotoxin (IT)‑based therapy, which combines cell surface binding ligands or antibodies with a peptide toxin, represents another cancer treatment option.

The Limb Kinetics of Goat Walking on the Slope with Different Angles.

The study aimed to assess the gait adjustment techniques of limbs on different slopes and investigate the relationship between forelimb and hindlimb kinetics and the center of mass (COM) during the uphill movement of a specific Boer goat using a pressure-sensitive walkway (PSW). During the uphill and downhill movements at a comfortable walking speed, we measured the ground reaction force (GRF) of the forelimbs and hindlimbs on the slope, the change in the included angle of the propulsive force direction of the forelimbs and hindlimbs, and the impulse relationship between GRF and propulsive force. According to the study, since the forelimbs of the goat were nearer the COM, they were primarily adjusted during the movement on the slope.

CD3e-immunotoxin spares CD62L Tregs and reshapes organ-specific T-cell composition by preferentially depleting CD3e T cells.

CD3-epsilon(CD3e) immunotoxins (IT), a promising precision reagent for various clinical conditions requiring effective depletion of T cells, often shows limited treatment efficacy for largely unknown reasons. Tissue-resident T cells that persist in peripheral tissues have been shown to play pivotal roles in local and systemic immunity, as well as transplant rejection, autoimmunity and cancers. The impact of CD3e-IT treatment on these local cells, however, remains poorly understood.

4,7-Didehydro-neophysalin B Protects Rat Lung Epithelial Cells against Hydrogen Peroxide-Induced Oxidative Damage through Nrf2-Mediated Signaling Pathway.

The administration of 4,7-didehydro-neophysalin B is expected to be a promising strategy for mitigating oxidative stress in respiratory diseases. This study was aimed at investigating the efficacy of 4,7-didehydro-neophysalin B for apoptosis resistance of rat lung epithelial cells (RLE-6TN) to oxidative stress and evaluating its underlying mechanism of action. The RLE-6TN cells treated with hydrogen peroxide (HO) were divided into five groups, and 4,7-didehydro-neophysalin B was administered into it.

Comparison of CD3e Antibody and CD3e-sZAP Immunotoxin Treatment in Mice Identifies sZAP as the Main Driver of Vascular Leakage.

Anti-CD3-epsilon (CD3e) monoclonal antibodies (mAbs) and CD3e immunotoxins (ITs) are promising targeted therapy options for various T-cell disorders. Despite significant advances in mAb and IT engineering, vascular leakage syndrome (VLS) remains a major dose-limiting toxicity for ITs and has been poorly characterized for recent "engineered" mAbs. This study undertakes a direct comparison of non-mitogenic CD3e-mAb (145-2C11 with Fc-silent murine IgG1: S-CD3e-mAb) and a new murine-version CD3e-IT (saporin-streptavidin (sZAP) conjugated with S-CD3e-mAb: S-CD3e-IT) and identifies their distinct toxicity profiles in mice.

Characterization of Fluoroquinolone-Resistant and Multidrug-Resistant Isolates Using Whole-Genome Sequencing in Tianjin, China.

Objective: Tuberculosis (TB) caused by remains a global concern. This study aimed to determine the molecular characteristics of fluoroquinolone-resistant and multidrug-resistant strains using whole-genome sequencing to predict drug resistance in in Tianjin, China, which has not been established previously.

Methods: Twenty-one fluoroquinolone-resistant and multidrug-resistant strains were isolated from sputum samples.

A Review of Ultrafine-Grained Magnetic Materials Prepared by Using High-Pressure Torsion Method.

High-pressure torsion (HPT) is a severe plastic deformation technique where a sample is subjected to torsional shear straining under a high hydrostatic pressure. The HPT method is usually employed to create ultrafine-grained nano-structures, making it widely used in processing many kinds of materials such as metals, glasses, biological materials, and organic compounds. Most of the published HPT results have been focused on the microstructural development of non-magnetic materials and their influence on the mechanical properties.