Low-Powered Photodetector Based on Two-Dimensional InS0.3Se0.7/WS2 Heterostructure

Photodetectors based on two-dimensional (2D) materials have great potential applications in the field of new energy, such as fuel cells, solar cells, and other fields. Van der Waals (vdW) heterojunction photodiodes are expected to be one of the promising applications of two-dimensional materials due to the photoelectric properties without consideration of lattice mismatch. High-efficiency photoelectric sensors based on two-dimensional materials have great significance to reducing the energy consumption of devices. Here, we build a complex vdW heterostructure by combining InS0.3Se0.7 with another suitable 2D material WS2. Few-layer graphite was used as electrodes to enhance the optoelectronic performance of indium monochalcogenides. Evident photocurrent is observed in the InS0.3Se0.7/WS2 vdW heterostructure device arising from the formed p–n junction at the interface. The uniformity and photoresponse of the InS0.3Se0.7/WS2 vdW heterostructure has been further investigated by the photocurrent mapping. It shows that the entire photovoltaic current was originated from the InS0.3Se0.7/WS2 vdW heterojunction by scanning photocurrent microscope images. Furthermore, the response speed is enhanced at small bias voltage. The transient photoresponse can be well reproduced in almost 100 cycles, indicating the good repeatable optoelectronic performance. Our study indicates that the as-prepared InS0.3Se0.7/WS2 vdW heterostructures are attractive building blocks for photodetectors application. Our findings will open up a new way to further develop high-performance, low-power, and energy-efficient photodetectors based on indium monochalcogenides

Low-Powered Photodetector Based on Two-Dimensional InS0.3Se0.7/WS2 Heterostructure

Photodetectors based on two-dimensional (2D) materials have great potential applications in the field of new energy, such as fuel cells, solar cells, and other fields. Van der Waals (vdW) heterojunction photodiodes are expected to be one of the promising applications of two-dimensional materials due to the photoelectric properties without consideration of lattice mismatch. High-efficiency photoelectric sensors based on two-dimensional materials have great significance to reducing the energy consumption of devices. Here, we build a complex vdW heterostructure by combining InS0.3Se0.7 with another suitable 2D material WS2. Few-layer graphite was used as electrodes to enhance the optoelectronic performance of indium monochalcogenides. Evident photocurrent is observed in the InS0.3Se0.7/WS2 vdW heterostructure device arising from the formed p–n junction at the interface. The uniformity and photoresponse of the InS0.3Se0.7/WS2 vdW heterostructure has been further investigated by the photocurrent mapping. It shows that the entire photovoltaic current was originated from the InS0.3Se0.7/WS2 vdW heterojunction by scanning photocurrent microscope images. Furthermore, the response speed is enhanced at small bias voltage. The transient photoresponse can be well reproduced in almost 100 cycles, indicating the good repeatable optoelectronic performance. Our study indicates that the as-prepared InS0.3Se0.7/WS2 vdW heterostructures are attractive building blocks for photodetectors application. Our findings will open up a new way to further develop high-performance, low-power, and energy-efficient photodetectors based on indium monochalcogenides.</jats:p

An empirical study on the underpricing phenomenon of initial public offerings in Singapore and its association with corporate governance mechanisms.

Effects of corporate governance mechanisms on underpricing have been investigated to see whether corporate governance mechanisms serve as a signal of the quality of the investment in a given IPO to the investors

Autologous CD7-targeted CAR T-cell therapy for refractory or relapsed T-cell acute lymphoblastic leukemia/lymphoma.

7035 Background: Refractory or relapsed (r/r) T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) has a poor prognosis. Our previous report showed that donor-derived CD7 CAR-T cell therapy could induce remission of r/r T-ALL, but graft-versus-host disease (GVHD) occurred in some patients (Pan et al. J Clin Oncol 2021;39:3340-3351). We recently conducted a phase I trial to evaluate autologous CD7 CAR-T therapy in r/r T-ALL/LBL, which may avoid GVHD while showing the efficacy; here we report the early result with the approval of the Data and Safety Monitoring Committee and Institutional Review Board (IRB). Methods: The patients who had CD7+ r/r T-ALL/LBL and no leukemia cells in peripheral blood were eligible for this phase I trial (NCT04840875). The CD7 CAR construct included an endoplasmic reticulum anchor domain fused to a CD7 binding domain to prevent CD7 expression on cell surface, which contributed to minimize CAR T cell fratricide. CAR T product was checked to ensure lack of tumor contamination before infusion. The trial followed a “3+3” dose escalation process. Adverse events and efficacy were primary and secondary endpoints. Results: A total of 5 patients (Pt1-5), with a median age of 3.8 years (range, 1.9-13), were enrolled between Sept 2021 and Jan 2022. At enrollment, Pt1 had mediastinal mass and blasts in pleural fluid; Pt4 was in central nervous system (CNS)-3 status; Pt2, 3 and 5 had marrow disease with a median burden of 1.35% (range, 0.07%-7.31%). Pt1, 2 and 3 received 5×105 (±20%) cells/kg; Pt5 received 1×106 (±20%) cells/kg; Pt4 received cells below the target dose. Three patients had cytokine release syndrome (CRS), including one grade 3; the median onset was on day 5 (range, 1-9) with the median duration of 4 days (range, 3-14). No patient had neurotoxicity, GVHD or infection. Grade 3-4 hematological toxicity occurred in all five patients, which recovered to grade 2 within 30 days. On one month post-infusion, four patients achieved complete remission, and one patient (Pt4) still had leukemia cells in the cerebrospinal fluid. With the median follow-up time of 62 days (range, 35-136), one patient (Pt1) underwent stem cell transplantation (SCT) on 2.9 months post-infusion, and had a CD7- relapse on 1.4 months post-SCT; the other three responders remained in MRD- CR. In the four patients who received target dose, the median peak CAR T cell count in peripheral blood was 4.27×102/uL (range, 2.49-5.61) by flow cytometry, and all five patients had detectable CAR transgene by PCR on their last visits. There was a decrease of CD7-positive normal T cells and an increase of CD7-negative counterparts in all responders. Conclusions: Autologous CD7 CAR T cell therapy was safe and effective in the induction of remission in r/r T-ALL/LBL patients, without signs of GVHD. Longer follow-up time of more cases will be used to further evaluate this therapy. Clinical trial information: NCT04840875. </jats:p

Low-intensity pulsed ultrasound inhibits fibroblast-like synoviocyte proliferation and reduces synovial fibrosis by regulating Wnt/β-catenin signaling

Objective: Synovial fibrosis is a characteristic symptom of osteoarthritis (OA), which is closely associated with joint pain and stiffness. Previous studies have reported that low-intensity pulsed ultrasound (LIPUS) can alleviate cartilage degradation in OA. However, the functions and mechanisms of LIPUS in OA synovial fibrosis are still unknown. Methods: The destabilization of the medial meniscus (DMM) mouse model of OA was established in C57 male mice and fibroblast-like synoviocytes (FLS) were isolated from synovial tissue of OA patients. The knee joint diameter, Masson's trichrome (MT) and Hematoxylin-eosin (HE) staining were used to evaluate synovial fibrosis and hyperplasia. The Immunohistochemistry (IHC) staining was performed to detected the expression of synovial fibrosis makers and the activation of Wnt/β-catenin signaling in vivo. FLS were treated with TGF-β1 to serve as an in vitro model of synovial fibrosis, Wnt3a was used to activate the Wnt/β-catenin signaling in cells. Cell proliferation was detected by using EdU assay, cell viability was performed by CCK8 assay. The protein levels of α-SMA, CTGF, Col Ⅰ, β-catenin, active β-catenin, c-Myc and cyclin D1 were examined by western blot and immunofluorescence staining. Results: Two weeks after the LIPUS treatment, the synovial fibrosis, synovial hyperplasia and synoviocyte proliferation in the DMM model were significantly decreased. In vitro, LIPUS directly inhibited the TGF-β1-induced fibrotic response and proliferation of FLS. Meanwhile, LIPUS suppressed Wnt/β-catenin signaling in the synovium of DMM mice and cultured FLS. More importantly, we found that the synovial fibrosis makers, Wnt/β-catenin pathway downstream proteins and FLS proliferation were significantly decreased in Wnt3a-stimulated FLS following LIPUS treatment. Conclusions: Our results present a novel role of LIPUS in OA-related synovial fibrosis, which is associated with its ability to repress Wnt/β-catenin signaling in FLS. The translational potential of this article: This study provides new insight into the clinical application of LIPUS as a therapeutic option to manage synovial fibrosis in OA

Donor-Derived CD7 Chimeric Antigen Receptor T Cells for T-Cell Acute Lymphoblastic Leukemia: First-in-Human, Phase I Trial

PURPOSEPatients with relapsed or refractory T-cell acute lymphoblastic leukemia (r/r T-ALL) have few options and poor prognosis. The aim was to assess donor-derived anti-CD7 chimeric antigen receptor (CAR) T-cell safety and efficacy in patients with r/r T-ALL.METHODSIn this single-center, phase I trial, we administered anti-CD7 CAR T cells, manufactured from either previous stem-cell transplantation donors or new donors, to patients with r/r T-ALL, in single infusions at doses of 5 × 105or 1 × 106(±30%) cells per kilogram of body weight. The primary end point was safety with efficacy secondary.RESULTSTwenty participants received infusions. Adverse events including cytokine release syndrome grade 1-2 occurred in 90% (n = 18) and grade 3-4 in 10% (n = 2), cytopenia grade 3-4 in 100% (n = 20), neurotoxicity grade 1-2 in 15% (n = 3), graft-versus-host disease grade 1-2 in 60% (n = 12), and viral activation grade 1-2 in 20% (n = 4). All adverse events were reversible, except in one patient who died through pulmonary hemorrhage related to fungal pneumonia, which occurred at 5.5 months, postinfusion. Ninety percent (n = 18) achieved complete remission with seven patients proceeding to stem-cell transplantation. At a median follow-up of 6.3 months (range, 4.0-9.2), 15 remained in remission. CAR T cells were still detectable in five of five patients assessed in month 6, postinfusion. Although patients' CD7-positive normal T cells were depleted, CD7-negative T cells expanded and likely alleviated treatment-related T-cell immunodeficiency.CONCLUSIONAmong 20 patients with r/r T-ALL enrolled in this trial, donor-derived CD7 CAR T cells exhibited efficient expansion and achieved a high complete remission rate with manageable safety profile. A multicenter, phase II trial of donor-derived CD7 CAR T cells is in progress ( NCT04689659 ).</jats:sec