CRISPR/Cas9-engineered universal CD123/B7-H3 tandem CAR-T cell for the treatment of acute myeloid leukemia.

Background: Autologous chimeric antigen receptor T (CAR-T) cell therapy has demonstrated efficacy in the treatment of acute myeloid leukemia (AML). Nevertheless, the intrinsic characteristics of autologous therapy, such as extended manufacturing timelines and patient-specific limitations, contribute to delays in treatment availability. More critically, relapse due to antigen escape following single-targeted CAR-T therapy constitutes a significant clinical obstacle.

A fc-engineered NKG2D × B7-H3 bispecific antibody enhances the antitumor activity by orchestrating cytotoxic lymphocytes.

B7-H3, an immune-checkpoint molecule that is overexpressed in several cancer types, has been identified as a promising immunotherapy target. However, most immunotherapy approaches against B7-H3 tumor cells focus on manipulating the T cells. Natural killer (NK) cells, another important part of the cellular immune system, also exhibit anti-tumor properties and play complementary roles in tumor eradication with T cells.

A20 attenuates oxidized self-DNA-mediated inflammation in acute kidney injury.

The ubiquitin-editing enzyme A20 is known to regulate inflammation and maintain homeostasis, but its role in self-DNA-mediated inflammation in acute kidney injury (AKI) is not well understood. Here, our study demonstrated that oxidized self-DNA accumulates in the serum of AKI mice and patients. This oxidized self-DNA exacerbates the progression of AKI by activating the cGAS-STING pathway and NLRP3 inflammasome.

Myeloid-derived suppressor cell-targeted virus-like particles synergistically activate innate immune response for cancer immunotherapy.

The importance of the tumor microenvironment in dynamically modulating neoplastic process, fostering proliferation, survival and migration is now widely appreciated. Therapeutics directed to various components of tumor microenvironment, especially tumor-associated macrophages and myeloid-derived suppressor cells (MDSCs), have become an attractive avenue for cancer immunotherapy. Virus-like particles (VLPs) derived from cowpea chlorotic mottle viruses (CCMV) have been used extensively in biotechnology and are ideal platforms for the targeted delivery of therapeutic drugs for cancer immunotherapy.

Development and Characterization of a Lysosome-Targeting SLC3A2/PD-L1 Bispecific Antibody-Drug Conjugate for Enhanced Antitumor Efficacy in Solid Tumors.

Bispecific antibodies (BsAb) and antibody-drug conjugates (ADC) have shown significant promise in cancer treatment, enhancing drug selectivity and therapeutic efficacy as demonstrated in multiple clinical studies. Bispecific antibody-drug conjugates (BsADC), which combine the targeting capabilities of BsAbs with the cytotoxic potential of ADCs, offer a novel approach to overcoming several challenges associated with ADCs, including limited internalization, off-target toxicity, and drug resistance. In this study, we identified solute carrier family 3 member 2 (SLC3A2) as a highly expressed protein in a variety of solid tumors, making it a promising therapeutic target.

Flotation separation of pyrite and carbonate minerals from a carlin-type gold deposit in Guizhou by a new combined collector and its adsorption mechanism.

Flotation is the most common method for effective separation of pyrite and carbonate minerals from Carlin-type gold deposits. The effect of conventional xanthate collector on flotation of a Carlin-type gold mine in Guizhou province is poor, and it can not effectively remove carbonate minerals. In this paper, butyl xanthoxanthate and benzohydroxamic acid (BHA) were used as a new combined collector for the flotation separation of a Carlintype gold mine in Guizhou Province.

mRNA-Engineered CD5-CAR-γδT Cells for the Immunotherapy of T-Cell Acute Lymphoblastic Leukemia.

Clinical trials of Chimeric Antigen Receptor T-cell (CAR-T) therapy have demonstrated remarkable success in treating both solid tumors and hematological malignancies. Nanobodies (Nbs) have emerged as promising antigen-targeting domains for CARs, owing to their high specificity, robust stability, and strong affinity, leading to significant advancements in the field of Nb-CAR-T. In the realm of T-cell acute lymphoblastic leukemia (T-ALL) targets, CD5 stands out as a potentially excellent candidate for T-cell-based CAR therapy, due to its distinct expression on the surface of malignant T-ALL cells.

Systemic delivery of oncolytic herpes virus using CAR-T cells enhances targeting of antitumor immuno-virotherapy.

Recent studies have indicated that combining oncolytic viruses with CAR-T cells in therapy has shown superior anti-tumor effects, representing a promising approach. Nonetheless, the localized delivery method of intratumoral injection poses challenges for treating metastatic tumors or distal tumors that are difficult to reach. To address this obstacle, we employed HSV-1-infected CAR-T cells, which systemically delivery HSV into solid tumors.

A novel SLC3A2-targeting antibody-drug conjugate exerts potent antitumor efficacy in head and neck squamous cell cancer.

The development of innovative therapeutic strategies for head and neck squamous cell carcinoma (HNSCC) is a critical medical requirement. Antibody-drug conjugates (ADC) targeting tumor-specific surface antigens have demonstrated clinical effectiveness in treating hematologic and solid malignancies. Our investigation revealed high expression levels of SLC3A2 in HNSCC tissue and cell lines.

Improved antitumor effects elicited by an oncolytic HSV-1 expressing a novel B7H3nb/CD3 BsAb.

Oncolytic viruses have emerged as a promising modality for cancer treatment due to their unique abilities to directly destroy tumor cells and modulate the tumor microenvironment. Bispecific T-cell engagers (BsAbs) have been developed to activate and redirect cytotoxic T lymphocytes, enhancing the antitumor response. To take advantage of the specific infection capacity and carrying ability of exogenous genes, we generated a recombinant herpes simplex virus type 1 (HSV-1), HSV-1-B7H3nb/CD3 or HSV-1-B7H3nb/mCD3, carrying a B7H3nb/CD3 or B7H3nb/mCD3 BsAb that replicates and expresses BsAb in tumor cells in vitro and in vivo.

Delivery of CD47-SIRPα checkpoint blocker by BCMA-directed UCAR-T cells enhances antitumor efficacy in multiple myeloma.

In the treatment of relapsed or refractory multiple myeloma patients, BCMA-directed autologous CAR-T cells have showed excellent anti-tumor activity. However, their widespread application is limited due to the arguably cost and time-consuming. Multiple myeloma cells highly expressed CD47 molecule and interact with the SIRPα ligand on the surface of macrophages, in which evade the clearance of macrophages through the activation of "don't eat me" signal.

Study on synergistic inhibition and mechanism of flotation separation of fluorite and calcite by tannin and sodium humate.

At present, the separation technology of fluorite and calcite is still immature, and the research in this paper can promote the improvement of the separation technology of fluorite and calcite. The selective inhibition mechanism of tannin and humate sodium on calcite was studied by means of actual ore flotation test, single mineral flotation test, Zeta potential measurement and FT-IR spectroscopy. The results show that the mixture of tannin and sodium humate inhibitor has a good inhibitory effect on carbonate under weak alkaline condition.

Supramolecular nanoparticles based on elastin-like peptides modified capsid protein as drug delivery platform with enhanced cancer chemotherapy efficacy.

Cancer, a prevalent disease posing significant threats to human health and longevity, necessitates effective therapeutic interventions. Chemotherapy has emerged as a primary strategy following surgical procedures for combating most malignancies. Despite the considerable efficacy of conventional chemotherapeutic agents against cancer cells, their utility is hindered by profound challenges such as multidrug resistance and deleterious toxic side effects, thereby limiting their systemic application.

Acupotomy for knee osteoarthritis: A systematic review protocol.

Background: Knee osteoarthritis (KOA) is the most common form of arthritis, leading to pain disability in seniors and increased health care utilization. Acupotomy has been widely used to treat KOA. But its efficiency has not been scientifically and methodically evaluated.

Remote Evaluation of Rotational Velocity Using a Quadrant Photo-Detector and a DSC Algorithm.

This paper presents an approach to remotely evaluate the rotational velocity of a measured object by using a quadrant photo-detector and a differential subtraction correlation (DSC) algorithm. The rotational velocity of a rotating object is determined by two temporal-delay numbers at the minima of two DSCs that are derived from the four output signals of the quadrant photo-detector, and the sign of the calculated rotational velocity directly represents the rotational direction. The DSC algorithm does not require any multiplication operations.

First characterization of bacterial pathogen, Vibrio alginolyticus, for Porites andrewsi White syndrome in the South China Sea.

Background: White syndrome, a term for scleractinian coral disease with progressive tissue loss, is known to cause depressed growth and increased morality of coral reefs in the major oceans around the world, and the occurrence of this disease has been frequently reported in the past few decades. Investigations during April to September in both 2010 and 2011 identified widespread Porites andrewsi White syndrome (PAWS) in Xisha Archipelago, South China Sea. However, the causes and etiology of PAWS have been unknown.