Structural insights into the calcium-coupled zinc export of human ZnT1.

Cellular zinc (Zn) homeostasis is essential to human health and is under tight regulations. Human zinc transporter 1 (hZnT1) is a plasma membrane-localized Zn exporter belonging to the ZnT family, and its functional aberration is associated with multiple diseases. Here, we show that hZnT1 works as a Zn/Ca exchanger.

Outcomes of Second Anti-CD19 CAR T-Cell Therapy (CART2) in Acute B Lymphoblastic Leukemia and the Impact of Allo-HSCT on Efficacy.

For patients exhibiting a suboptimal response to the first chimeric antigen receptor (CAR) T-cell therapy (CART1) or relapse after remission, secondary CAR T-cell therapy (CART2) for the same target may be an option. We retrospectively analyzed patients with acute B-cell lymphoblastic leukemia (B-ALL) receiving CD19 CART1 at our center (n = 84) to report the clinical outcomes of CART2 and to identify the factors that may influence the outcomes. Twenty-six patients received CART2 for suboptimal response or relapse post-CART1.

Longitudinal Serum Proteomics Characterization of CD19-CAR-T Cell Therapy for B-Cell Malignancies.

Chimeric antigen receptor (CAR)-modified T cells have demonstrated remarkable efficacy in treating B-cell leukemia. However, treated patients may potentially develop side effects, such as cytokine release syndrome (CRS), the mechanisms of which remain unclear. Here, we collected 43 serum samples from eight patients with B-cell acute lymphoblastic leukemia (B-ALL) before and five time points after CD19-specific CAR-T cell treatment.

WPD-Enhanced Deep Graph Contrastive Learning Data Fusion for Fault Diagnosis of Rolling Bearing.

Rolling bearings are crucial mechanical components in the mechanical industry. Timely intervention and diagnosis of system faults are essential for reducing economic losses and ensuring product productivity. To further enhance the exploration of unlabeled time-series data and conduct a more comprehensive analysis of rolling bearing fault information, this paper proposes a fault diagnosis technique for rolling bearings based on graph node-level fault information extracted from 1D vibration signals.

Lysosomal K channel TMEM175 promotes apoptosis and aggravates symptoms of Parkinson's disease.

Lysosomes are degradative organelles and play vital roles in a variety of cellular processes. Ion channels on the lysosomal membrane are key regulators of lysosomal function. TMEM175 has been identified as a lysosomal potassium channel, but its modulation and physiological functions remain unclear.

[Clinical Study on Dynamic Detection of Minimal Residual Disease in Acute Myeloid Leukemia by Multiparameter Flow Cytometry].

Objective: To investigate the prognostic significance of dynamic detection of minimal residual disease (MRD) in patients with acute myeloid leukemia (AML) by 8-color flow cytometry.

Methods: MRD of 282 AML patients who achieved remission after initial therapy was detected by 8-color flow cytometry. MRD threshold for predicting recurrence was determined by receiver operating characteristic (ROC) curve, and time from MRD-positive to clinical recurrence was analyzed.

Impact of Consolidative Unrelated Cord Blood Transplantation on Clinical Outcomes of Patients With Relapsed/Refractory Acute B Lymphoblastic Leukemia Entering Remission Following CD19 Chimeric Antigen Receptor T Cells.

Background: While chimeric antigen receptor (CAR)-T cell therapy is becoming widely used in hematological malignancies with remarkable remission rate, their high recurrence remains an obstacle to overcome. The role of consolidative transplantation following CAR-T cell-mediated remission remains controversial. We conducted a retrospective study to explore whether bridging to unrelated cord blood transplantation (UCBT) could improve the prognosis of patients entering remission after CAR-T therapy with different characteristics through subgroup analyses.

Standard-Intensity Induction and Intermediate/High-Dose Cytarabine Consolidation Can Improve Survival for Elderly Patients with Newly Diagnosed Acute Myeloid Leukemia: A Retrospective Cohort Study.

Background: There is great uncertainty in the treatment of elderly patients with acute myeloid leukemia (AML), which leads to great challenges in treatment decision. The aim of this study is to find more suitable induction therapy and consolidation therapy for elderly AML patients.

Methods: A total of 149 consecutive newly diagnosed elderly AML patients (aged ≥60 years) who received induction chemotherapy in our medical center from January 2015 to December 2019 were retrospectively analyzed.

Zkscan3 affects erythroblast development by regulating the transcriptional activity of GATA1 and KLF1 in mice.

ZKSCAN3 encodes a zinc-finger transcription factor that regulates the expression of important genes and plays a significant role in tumor development, pathogenesis, and metastasis. However, its biological functions under normal physiological conditions remain largely unknown. In our previous studies, using flow cytometry, we found that the deletion of Zkscan3 may cause abnormal erythropoiesis.

Chimeric antigen receptor T cells self-neutralizing IL6 storm in patients with hematologic malignancy.

IL6 is one of the most elevated cytokines during chimeric antigen receptor (CAR) T cell cytokine release syndrome (CRS), and IL6R blockade by Tocilizumab has successfully relieved the most life-threatening aspects of CRS in patients. In addition, latest studies demonstrated the essential role of IL1 in driving CART induced neurotoxicity in mouse models. Here we present a clinical investigation (ChiCTR2000032124; ChiCTR2000031868) of anti-CD19 and anti-BCMA CART (41BBζ) secreting an anti-IL6 scFv and IL1 receptor antagonist (IL1RA) in treating patients with hematologic malignancy.

[Clinical Research of Dendritic Cell-Mediated Tumor-Associated Antigen-Specific Cytotoxic T Lymphocytes in the Treatment of Multiple Myeloma and Non-Hodgkin Lymphoma].

Objective: To investigate the safety and efficacy of tumor-associated antigen-specific cytotoxic T lympho- cytes (TAA-CTL) in the treatment of multiple myeloma (MM) and non-Hodgkin lymphoma (NHL).

Methods: Peripheral blood mononuclear cells (PBMNC)of patients were collected. Dendritic cells (DC) were loaded with multiple tumor-associated antigens (TAA) (NY-ESO-1, MAGE-A3, MAGE-A4, WT1, Survivin, PRAME, LMP1 and LMP2A), then co-cultured with PBMNC to induce cytotoxic T lymphocytes (CTL).

[Killing Effect of A CD7 Chimeric Antigen Receptor-Modified NK-92MI Cell Line on CD7-Positive Hematological Malignant Cells].

Objective: To investigate the killing effect of NK-92MI cells modified by chimeric antigen receptor (CD7-CAR) and specifically targeting CD7 to CD7 hematological malignant cells.

Methods: Three types of hematological malignant tumor cells, including 5 cases of CD7 acute T-lymphoblastic leukemia (T-ALL), 10 cases of acute myeloid leukemia (AML) and 6 cases of T-cell lymphoma were collected, centrifuged, cultured and used to detect the expression levels of tumor cell surface targets; 7-AAD, CD56-APC, CD3-FITC, IgG Fc-PE flow cytometry were used to detected the transfection efficiency of NK-92MI and CD7-CAR-NK-92MI cells, killing efficiencies of CD7-CAR-NK-92MI cells to CD7 hematological tumor cells in vitro were determined by flow cytometry using PE Annexin V Apoptosis Detection Kit. Secretion differences of NK-92MI and CD7-CAR-NK-92MI cytokines interleukin (IL)-2, interferon (IFN)-γ, and granzyme B detection were estimated by using CBA kit.

[Expression of Lysosomal Membrane Proteins LAMP1, TPC1 and TPC2 in Acute Myeloid Leukemia Cells and Its Clinical Significance].

Objective: To investigate the relationship between the expression of lysosomal membrane proteins LAMP1, TPC1 and TPC2 in acute myeloid leukemia (AML) cells and clinical indications of AML and to explore the possible role in the genesis and development of AML and clinical significance.

Methods: Real-time quantitative PCR was used to detect the mRNA expression of LAMP1, TPC1 and TPC2 in AML cell lines (HL-60, NB4) and 57 patients with acute myeloid leukemia (including 44 initially treated patients and 13 relapsed and refractory patients). The relationship of mRNA expression levels with clinical indicators and post-chemotherapy remission was analyzed.

T cells targeting multiple tumor-associated antigens as a postremission treatment to prevent or delay relapse in acute myeloid leukemia.

Background: Relapse is a major problem in acute myeloid leukemia (AML) and adversely affects survival. Tumor-associated antigen-specific cytotoxic T lymphocyte (TAA-CTLs)-based therapy was introduced and increasingly used clinically to kill tumor cells via tumor antigen activation.

Method: In this study, we expanded autologous lymphocytes reactive to five TAA (NY-ESO-1, MAGE-A3, WT1, Survivin, and PRAME) and evaluated its safety and efficacy in 9 patients with AML at high risk of relapse.

Decitabine enhances cytotoxic effect of T cells with an anti-CD19 chimeric antigen receptor in treatment of lymphoma.

CD19-directed chimeric antigen receptor (CAR) T cells have substantial benefit in the treatment of patients with B-cell malignancies. However, despite encouraging therapeutic efficiency, there is limited overall response rate when anti-CD19 CAR-T cells are used to treat patients with relapsed and refractory (R/R) B cell lymphomas. Therefore, it further investigation is urgently needed to improve treatment efficacy.

Retrospective cohort study comparing the outcomes of intravenous busulfan vs. total-body irradiation after single cord blood transplantation.

Limited to inadequate stem-cell doses, cord blood transplantation (UCBT) is accompanied by increased graft failure and delayed haematopoietic recovery. The conditioning regimen is critically important for engraftment, and numerous trials have been undertaken comparing the outcomes of IV Bu and TBI, but there are no comparative data for UCBT. We conducted a retrospective multicentre study to analyse the outcomes of IV Bu and TBI in UCBT patients with haematologic malignancies.

MicroRNA‑155 targets myosin light chain kinase to inhibit the migration of human bone marrow‑derived mesenchymal stem cells.

Toll‑like receptors (TLRs) are expressed in human bone marrow‑derived mesenchymal stromal cells (BM‑MSCs). The activation of TLRs is important in the proliferation, differ-entiation, migration and hematopoiesis‑supporting functions of BM‑MSCs. MicroRNAs (miRNAs) are involved in various biological functions by mediating mRNA degradation or inhibiting the translation of target genes.

[Effect of MiR-99a-5p on the Differential Ability of Human Bone Marrow Mesenchymal Stem Cells].

Objective: To investigate the effect of microRNA-99a-5p (miR-99a-5p) on differentiation ability of human bone marrow mesenchymal stem cells (BM-MSC).

Methods: BM-MSC was cultured and then transfected with miR-99a-5p mimics or inhibitors. The transfection efficiency was detected by real-time quantitative PCR.