Electronic structures stand at the center to essentially understand the catalytic performance and reaction mechanism of atomically dispersed transition-metal–nitrogen–carbon catalysts (ADTCs). However, under realistic electrocatalytic conditions, the dynamic electronic disturbance at metal centers originating from complicated interactions with microenvironments is commonly neglected, which makes a true structure–property correlation highly ambiguous. Here, we employ operando time-resolved X-ray absorption spectroscopy to delve deeply into dynamic electronic behaviors of a family of transition-metal centers that are observed to adaptively vary in the metal–ligand configuration during the CO2 electroreduction reaction. We identify dynamic electronic/geometric configuration and d-orbital occupation under working conditions, demonstrating an unprecedentedly precise activity descriptor, i.e., dynamic axial dz2 electron, for the CO2-to-CO conversion. Direct results validate that the half-occupied state suggests the optimum binding behaviors with intermediates, significantly promoting CO production, which has been demonstrated by a significant kinetics enhancement of 1 to 2 orders of magnitude as compared with fully occupied and unoccupied states. This work presents the first empirical demonstration for a real correlation between the dynamic electronic/geometric configuration and catalytic kinetics in ADTCs, paving a new way for modulating catalysts and designing highly efficient reaction pathways.

Acceptor–donor–acceptor (A–D–A)-configured molecules with coplanar dithieno[2,3-d:2′,3′-d’]thieno[3,2-b:3′,2′-b’]dipyrrole (DTPT) as the core are promising organic semiconductor materials utilized in organic photovoltaic devices owing to their efficient charge transportation capabilities. In addition to optoelectronic applications, they are potential in photothermal and photodynamic applications due to their light-absorption properties. This study evaluates the utilization of DTPT-based fused-ring-conjugated small molecules with strong near-infrared (NIR) absorption as stable organic photosensitizers for phototherapy by forming nanoparticles (NPs) with D-α-tocopherol polyethylene glycol 1000 succinate (TPGS). Among them, NPs prepared from the 2-(3-cyano-4,5,5-trimethylfuran-2(5H)-ylidene)malononitrile (TCF) end-capping DTPT-centered molecule, DTPTTCF, exhibit low cytotoxicity, enhance photothermal conversion efficiency and superior photodynamic activity. In vitro and in vivo experiments demonstrate the remarkable anticancer efficacy of DTPTTCF@TPGS NPs that can effectively suppress cancer cell proliferation under 808 nm laser treatment. Additionally, soft X-ray tomography (SXT) is employed as a high-resolution tool to observe intracellular variations that reveal distinct vacuolization in the NPs + Laser treated group. These observations highlight that the DTPTTCF@TPGS NPs cause significant damage to cancer cells under NIR irradiation. Furthermore, in vivo, experiments demonstrate the apoptosis of cancer cells within tumor tissues and the effective elimination of tumors upon NIR irradiation of DTPTTCF@TPGS NPs treated mice. This work manifests the potential application of the DTPT-cored A–D–A-type molecule as an advanced agent for tumor phototherapy with enhanced efficacy and selectivity.

To evaluate the tolerability of crovalimab versus eculizumab in C5 inhibitor (C5i)-naive and -experienced patients with PNH from COMMODORE 2, 3 and 1 (NCT04434092, NCT04654468 and NCT04432584). Pooled safety data were assessed in the total crovalimab and eculizumab populations and by C5i-naive versus C5i-switched status in patients receiving crovalimab. Analyses include 6.5 months of additional follow-up from the COMMODORE 2 and 1 primary analyses. COMMODORE safety data (crovalimab, 393 patients [naive, 192 patients; switched, 201 patients]; eculizumab, 111 patients) were analysed. The total patient years (PY) were 503.9 and 51.1 in the total crovalimab and eculizumab populations, respectively, with 471 and 581 adverse events (AEs) per 100 PY. Serious infection rates were 8.9 and 13.7 AEs per 100 PY, respectively; no meningococcal infections were reported. Fatal AEs occurred in eight (2%) patients receiving crovalimab (naive, six patients; switched, two patients) and one (1%) receiving eculizumab, all treatment unrelated. In C5i-switched patients, 39 (19%) had transient immune complex reactions (risk when switching between C5i and crovalimab); the majority were Grades 1-2 arthralgia and rash, and 16 (8%) had Grade 3 events. Crovalimab's safety profile was consistent with eculizumab's and was generally comparable between C5i-naive and C5i-switched patients.

CD22 (also known as Siglec-2) is a member of the Siglec family of glycan-recognition proteins and functions as a negative regulator of the B-cell receptor-mediated calcium signaling. Although the low level of CD22 expression on the B cells in patients with chronic lymphocytic leukemia (CLL) has been documented, CD22's role and its downregulation mechanism in CLL are yet to be fully studied. In this study, we confirmed that the surface CD22 protein and its mRNA are downregulated in the B cells of CLL patients. We analyzed a public transcriptomic dataset and found that the CD22 mRNA level is negatively associated with the prognosis of patients with CLL. To investigate the mechanism of CD22 downregulation, we characterized the minimal promoter of the human CD22 gene required for its transcriptional activation in B cell lines. We employed an unbiased proteomic approach to identify several transcription factors binding to the minimal CD22 promoter, including PU.1, Spi-B, and IRF4. The chromatin immunoprecipitation-quantitative PCR revealed that PU.1 was enriched in a CD22-high cell line, while IRF4 was enriched in a CD22-low cell line. We then conducted overexpression/knockout/knockdown experiments, which validated that PU.1 and Spi-B positively, and IRF4 negatively, regulate CD22 transcription. Our study thus provides insights into the transcriptional regulation of CD22 and the mechanism by which CD22 expression is downregulated in the B cells of patients with CLL.

Pei-Lin Lee serves as Clinical Associate Professor, School of Medicine, National Taiwan University; Consultant, Center of Sleep Disorder, National Taiwan University Hospital. Her current academic positions at international sleep societies include American Academy of Sleep Medicine Fellow and Co-Chair International Assembly; Asian Society of Sleep Medicine, Sleep Medicine Education Task Force committee member. Her current research focuses on the era of new technology and big data in sleep medicine; and intervention on sleep and metabolism in sleep disordered breathing.