B-Cell Maturation Antigen/CD19 Dual-Targeting Immunotherapy in Newly Diagnosed Multiple Myeloma.

Importance: Patients with high-risk newly diagnosed multiple myeloma (NDMM) often have poor outcomes with standard treatments, necessitating novel effective frontline therapies to enhance clinical outcomes. GC012F, a B-cell maturation antigen/CD19 dual-targeting chimeric antigen receptor (CAR) T-cell therapy, has been developed on the novel FasTCAR platform. Notably, its use as a frontline therapy for patients with high-risk NDMM who are eligible for transplant has not been thoroughly explored. Objective: To examine the safety, pharmacokinetics, and patient health and survival outcomes associated with GC012F in individuals with NDMM. Design, Setting, and Participants: Patients were enrolled in this single-arm, open-label phase 1 cohort study between June 28, 2021, and June 1, 2023 (the data cutoff date). All patients included in this study were treated at a single center, Shanghai Changzheng Hospital. The patients in the efficacy evaluation were followed up for a minimum period of 3 months. Intervention: Patients underwent 2 cycles of induction therapy, followed by GC012F infusion (at 1 × 105 cells/kg, 2 × 105 cells/kg, or 3 × 105 cells/kg). Main Outcomes and Measures: The primary goals were to assess the safety, efficacy, and pharmacokinetics of GC012F at various dose levels. Results: Of 22 patients receiving GC012F treatment, 6 experienced mild to moderate cytokine release syndrome (grade 1-2) and none experienced neurotoxic effects. Nineteen patients were included in the efficacy evaluation, and all 19 patients showed stringent complete responses and achieved minimal residual disease negativity. The treatment's effectiveness was consistent across different dose levels. GC012F demonstrated a rapid response, with a median time to first stringent complete response of 84 days (range, 26-267 days) and achieving minimal residual disease negativity within 28 days (range, 23-135 days). The CAR T-cell expansion was robust, with a median peak copy number of 60 652 copies/µg genomic DNA (range, 8754-331 159 copies/µg genomic DNA), and the median time to median peak copy number was 10 days (range, 9-14 days). Conclusions and Relevance: The findings of this single-arm, open-label phase 1 cohort study suggest that GC012F may be a safe treatment associated with positive health and survival outcomes for patients with high-risk NDMM eligible for transplant. Owing to the small sample size, further studies with larger cohorts and longer follow-up durations are needed.

Nitrogen doped biomass derived carbon dots as a fluorescence dual-mode sensing platform for detection of tetracyclines in biological and food samples.

Nitrogen-doped carbon dots (N-CDs) were synthesized hydrothermally using abundantly accessible pitaya peel and 1,2-ethylenediamine as precursors. N-CDs exhibited favorable photostability, which can serve as a multifunctional nano-sensor for detection of three tetracycline antibiotics (TCs) based on fluorescence (FL) dual-mode sensing strategy. The FL intensity of N-CDs could be rapidly quenched by tetracycline (TC) and oxytetracycline (OTC) based on bandgap transition, inner filter effect (IFE), static quenching (SQ) and electrostatic interaction. While a new finding that FL of N-CDs demonstrated a remarkable enhancement in the presence of chlortetracycline (CTC) with the same detection mechanisms as TC and OTC, also including the aggregation-induced emission (AIE). Furthermore, an easily extensible fluorescence sensor array was developed based on multiple CDs for identifying multiple TCs in real samples. Therefore, the constructed N-CDs provides a new perspective for choosing extensive natural biomass to synthesize CDs, further developing a novel sensor to realize their versatile sensing application.

A facile fluorescence platform for chromium and ascorbic acid detection based on "on-off-on" strategy.

In this paper, a facile and rapid fluorescence "on-off-on" strategy for the detection of chromium (Cr(VI)) and ascorbic acid (AA) was developed, which was based on the water-soluble carbon dots (CDs). The CDs was synthesized by a microwave-assisted treatment of L-tartaric acid, citric acid, and urea. The CDs have many advantages, such as high fluorescence quantum yield (20.5%) and good fluorescence stability. Based on inner filter effect (IFE) and static quenching, the fluorescence of the CDs can be quenched by Cr(VI) quickly; while the reduction of IFE and reducing action can make the fluorescence of the CDs recover by AA efficiently. Moreover, under the optimal experimental conditions, the CDs had a good detection performance for Cr(VI) in the range of 0.8 âˆ¼ 189 µM with the limit of detection (LOD) of 0.16 µM. The linear detection for AA was ranged from 0.43 to 25.7 µM with a LOD of 0.1 µM. More importantly, the as-constructed fluorescence detecting platform was successfully applied for Cr(VI) and AA detection in the environmental samples and fruit samples, respectively. In addition, the application potential of the CDs in fluorescent films and anti-counterfeiting materials was further discussed in detail. This work will provide a novel idea for designing a portable sensor based on the CDs to quickly and sensitively detect Cr(VI) and AA.