CD7 targeted "off-the-shelf" CAR-T demonstrates robust in vivo expansion and high efficacy in the treatment of patients with relapsed and refractory T cell malignancies.

T-cell acute lymphoblastic leukemia (T-ALL) represents an area of highly unmet medical needs. Once relapsed, patients have limited treatment options and poor prognosis. T-ALL antigens such as CD7 is extensively expressed in normal T cells and natural killer (NK) cells, and extending the success of CAR-T therapy to T cell malignancies was challenged by CAR-T cell fratricide, high production cost, and potential product contaminations.

Next-day manufacture of a novel anti-CD19 CAR-T therapy for B-cell acute lymphoblastic leukemia: first-in-human clinical study.

To improve clinical outcomes and shorten the vein-to-vein time of chimeric antigen receptor T (CAR-T) cells, we developed the FasT CAR-T (F-CAR-T) next-day manufacturing platform. We report the preclinical and first-in-human clinical studies evaluating the safety, feasibility, and preliminary efficacy of CD19 F-CAR-T in B-cell acute lymphoblastic leukemia (B-ALL). CD19 F-CAR-T cells demonstrated excellent proliferation with a younger cellular phenotype, less exhaustion, and more effective tumor elimination compared to conventional CAR-T cells in the preclinical study.

Novel CD19 chimeric antigen receptor T cells manufactured next-day for acute lymphoblastic leukemia.

Chimeric antigen receptor-engineered T (CAR-T) cells have shown promising efficacy in patients with relapsed/refractory B cell acute lymphoblastic leukemia (R/R B-ALL). However, challenges remain including long manufacturing processes that need to be overcome. We presented the CD19-targeting CAR-T cell product GC007F manufactured next-day (FasTCAR-T cells) and administered to patients with R/R B-ALL.

Social Force Model-Based Safety Evaluation of Intersections in Arterials Considering the Pedestrian Yield Rule.

To enhance the safety of pedestrians crossing the street, a series of new regulations regarding pedestrian yield has been proposed and widely implemented across cities. In this study, we first made some improvements to the social force model, in which pedestrian crossing at the intersection, drivers' psychology of giving way, vehicle yield to pedestrians, vehicle yield in different directions, the influence of pedestrians crossing boundaries, and signal lamp groups on pedestrian behavior were considered. Furthermore, pedestrian crossing and vehicle yield safety models were established, based on which the comprehensive safety evaluation model of intersections in arterials was established, in which two indices-(1) the safety degree of pedestrian crossings and (2) vehicle acceleration interference-were combined with the entropy weight method.

Phase I study of CAR-T cells with PD-1 and TCR disruption in mesothelin-positive solid tumors.

Programmed cell death protein-1 (PD-1)-mediated immunosuppression has been proposed to contribute to the limited clinical efficacy of chimeric antigen receptor T (CAR-T) cells in solid tumors. We generated PD-1 and T cell receptor (TCR) deficient mesothelin-specific CAR-T (MPTK-CAR-T) cells using CRISPR-Cas9 technology and evaluated them in a dose-escalation study. A total of 15 patients received one or more infusions of MPTK-CAR-T cells without prior lymphodepletion.

RF Thermal Plasma Synthesis of Ultrafine ZrB-ZrC Composite Powders.

Ultrafine ZrB-ZrC composite powders were synthesized via a radiofrequency (RF) thermal plasma process. Numerical simulation and thermodynamic analysis were conducted to predict the synthesis process, and experimental work was performed accordingly to demonstrate its feasibility. The as-prepared samples were characterized by XRD, FESEM, particle size analyzer, nitrogen/oxygen analyzer, Hall flowmeter, and the Brunner-Emmet-Teller (BET) measurements.

Eradication of T-ALL Cells by CD7-targeted Universal CAR-T Cells and Initial Test of Ruxolitinib-based CRS Management.

Purpose: Although chimeric antigen receptor T-cell (CAR-T) therapy development for B-cell malignancies has made significant progress in the last decade, broadening the success to treating T-cell acute lymphoblastic leukemia (T-ALL) has been limited. We conducted two clinical trials to verify the safety and efficacy of GC027, an "off-the-shelf" allogeneic CAR-T product targeting T-cell antigen, CD7. Here, we report 2 patients as case reports with relapsed/refractory T-ALL who were treated with GC027.

Ghrelin inhibits IKKβ/NF-κB activation and reduces pro-inflammatory cytokine production in pancreatic acinar AR42J cells treated with cerulein.

Background: Previous studies have provided conflicting results regarding whether the serum ghrelin concentration can reflect the severity of acute pancreatitis (AP). The present study examined the correlation between the serum ghrelin concentration and AP severity in animal models and investigated whether altered ghrelin expression in pancreatic acinar cells influences IKKβ/NF-κB signaling and pro-inflammatory cytokine production.

Methods: Mild or severe AP was induced in rats by intraperitoneal injection of cerulein or retrograde cholangiopancreatic duct injection of sodium taurocholate, respectively.

β-Galactosidase gene codon optimization results in post-transcriptional enhancement of expression.

Objective: lacZ encodes for β-galactosidase within the galactose operon of bacterial cells. When used as a reporter gene, bacterial "β-galactosidase" expression is often insufficient for detection in mammalian cells. We intended to optimize the lacZ codon usage according to the most frequently used codons for the seven major proteins in cow's milk, in order to pave a way for the enhancement of transgenic genes expression in eukaryotes.

Multiscale Buffering Engineering in Silicon-Carbon Anode for Ultrastable Li-Ion Storage.

Silicon-carbon (Si-C) hybrids have been proven to be the most promising anodes for the next-generation lithium-ion batteries (LIBs) due to their superior theoretical capacity (∼4200 mAh g). However, it is still a critical challenge to apply this material for commercial LIB anodes because of the large volume expansion of Si, unstable solid-state interphase (SEI) layers, and huge internal stresses upon lithiation/delithiation. Here, we propose an engineering concept of multiscale buffering, taking advantage of a nanosized Si-C nanowire architecture through fabricating specific microsized wool-ball frameworks to solve all the above-mentioned problems.

Modeling and Selection of RF Thermal Plasma Hot-Wall Torch for Large-Scale Production of Nanopowders.

Fouling is a great problem that significantly affects the continuous operation for large-scale radio-frequency (RF) thermal plasma synthesizing nanopowders. In order to eliminate or weaken the phenomenon, numerical simulations based on FLUENT software were founded to investigate the effect of operation parameters, including feeding style of central gas and sheath gas, on plasma torches. It is shown that the tangential feeding style of central gas brings serious negative axial velocity regions, which always forces the synthesized nanopowders to "back-mix", and further leads to the fouling of the quartz tube.

Improved biosafety of a lentiviral vector by reducing cellular gene activation.

Background: Lentiviral vectors (LVs) have enhancer activity and/or transcriptional read-through (EATRT) properties that can lead to the activation of adjacent genes. Consequently, patients may be at increased risk for adverse effects if such vectors are used clinically.

Methods: In the present study, we assessed the abilities of different "pro-LV"-like constructs with respect to decreasing its EATRT, including the "pro-LV" vector bearing a chimeric ΔLTR of the human foamy virus R-U5 region replaced by that of an LV (HF).

Cav 1.2 and Cav 2.2 expression is regulated by different endogenous ghrelin levels in pancreatic acinar cells during acute pancreatitis.

Ghrelin influences pancreatic endocrine and exocrine functions, regulates intracellular calcium [Ca2+]i levels, and has an anti-inflammatory role in acute pancreatitis. This study investigated the role of endogenous ghrelin in the expression of Cav 1.2 (L-type of Ca2+ channel) and Cav 2.

Efficacy and Persistence of Allogeneic Adipose-Derived Mesenchymal Stem Cells Combined with Hyaluronic Acid in Osteoarthritis After Intra-articular Injection in a Sheep Model.

Although a number of studies have reported efficacy of autologous adipose-derived mesenchymal stem cells (AD-MSCs) in treating osteoarthritis (OA) no reliable evidences demonstrate whether allogeneic AD-MSCs can efficiently block OA progression in a large animal model. This study explored the efficacy and survival of allogeneic AD-MSCs combined with hyaluronic acid (HA) after intra-articular (IA) injection in a sheep OA model, which were conventionally established by anterior cruciate ligament resection and medial meniscectomy. Allogeneic AD-MSCs from donor sheep at high (5 × 10 cells) and low (1 × 10 cells) doses combined with HA, HA alone, or saline alone were injected into the OA sheep at 3 and 6 weeks after surgery, respectively.

Human adipose-derived mesenchymal progenitor cells engraft into rabbit articular cartilage.

Mesenchymal stem cells (MSCs) are known to have the potential for articular cartilage regeneration, and are suggested for the treatment of osteoarthritis (OA). Here, we investigated whether intra-articular injection of xenogeneic human adipose-derived mesenchymal progenitor cells (haMPCs) promoted articular cartilage repair in rabbit OA model and engrafted into rabbit articular cartilage. The haMPCs were cultured in vitro, and phenotypes and differentiation characteristics of cells were evaluated.

[Progress in improvement of lentiviral vectors' transcriptional read-through].

Four out of 10 patients of X-linked severe combined immunodeficiency (X-SCID) were finally developed leukemia after receiving the treatment of gene therapy delivered by gamma-retroviral vectors. This is due to the vector integrated to the proximity of lmo2 etc proto-oncogene promoters, leading to the activation of onco-gene expression, which raises the concern of the bio-safety of gene therapy vectors. Lentiviral vectors, especially self-inactivating lentiviral vectors, are considered to be much safer than gamma-retroviral vectors.