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The commercialization process of perovskite solar cells (PSCs) is markedly restricted by the power conversion efficiency (PCE) and long-term stability. During fabrication and operation, the bottom interface of the organic-inorganic hybrid perovskite layer frequently exhibits voids and residual PbI 2 , while these defects inevitably act as recombination centers and degradation sites, affecting the efficiency and stability of the devices. Therefore, the degradation and nonradiative recombination originating from the buried interface should be thoroughly resolved. Here, we report a multifunctional passivator by introducing malonic dihydrazide as an interfacial chemical bridge between the electron transport layer and the perovskite (PVK) layer. MADH with hydrazine groups improves the surface affinity of SnO 2 and provides nucleation sites for the growth of PVK, leading to the reduced residual PbI 2 and the voids resulting from the inhomogeneous solvent volatilization at the bottom interface. Meanwhile, the hydrazine group and carbonyl group synergistically coordinate with Pb 2+ to improve the crystal growth environment, reducing the number of Pb-related defects. Eventually, the PCE of the PSCs is significantly enhanced benefiting from the reduced interfacial defects and the increased carrier transport. Moreover, the reductive nature of hydrazide further inhibits I 2 generation during long-term operation, and the device retains 90% of the initial PCE under a 1 sun continuous illumination exposure of 700 h.

Objective: As a novel drug formulation, antibody drug conjugates (ADCs) are widely used in various types of cancer. However, clinically, there is a lack of attention to the CVD produced by them, as well as a lack of research on the real-world situation. Using the Food and Drug Administration Adverse Event Reporting System (FAERS) database, to ensure its clinical safety application, we analyzed post-marketing data on antitumor ADCs to identify risk factors and drugs associated with the risk of cardiovascular events., Research Design and Methods: We used OpenVigil 2.1 to conduct a database query for adverse events (AEs) reported to the FAERS database between the time the drug was launched and the second quarter of 2023. Cardiovascular adverse events (AEs) were grouped into fourteen narrow categories using the Standardized Medical Dictionary for Regulatory Activities (MedDRA) Queries (SMQs), and the reporting odds ratio (ROR) and the proportional reporting ratio (PRR) for reporting the association between different drugs and cardiovascular disease (CVD) risk were calculated., Results: In the FAERS database, 1863 AEs associated with CVD we studied were identified in patients receiving ADC therapy. Most reports came from people aged ≥65, but a significant number of cases were found to be unknown. The number of patients with antibody-drug conjugates (ADCs)-related CVD cases aged <18 years, 18-64 years, and≥ 65 years was 52 (2.79%), 586 (31.45%), and 613 (32.90%), respectively. The proportion of female patients (834, 44.77%) was higher than that of male patients (752, 40.37%). Death (770 reports), disability (9 reports), Hospitalization initial or prolonged (407 reports), and life-threatening reactions (187 reports). Of the 770 deaths reported, 103 (31.7%) were associated with brentuximab vedotin, 10 (24.4%) with sacituzumab govitecan, 22 (19.3%) with enfortumab vedotin, and 35 (34.7%) with trastuzumab emtansine.49 (41.2%) cases were associated with polatuzumab vedotin, 62 (29%) with trastuzumab deruxtecan, 423 (54.3%) with gemtuzumab ozogamicin, and 66 (38.8%) with inotuzumab ozogamicin. In a disproportionate number of SMQS, cardiac failure ( n = 277) and embolic and thrombotic events, venous ( n = 446) were the most frequently reported CVD-related AEs in ADCs., Conclusion: By mining the FAERS database, we provided relevant information on the association between ADC use and cardiovascular-associated AEs. ADCs were associated with increased cardiovascular toxicity, deserving distinct monitoring and appropriate management. Further research is needed to confirm these findings and assess causality., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Long, Li, Pan, Wang, Chen and Wang.)

Regulating the structural and interfacial properties of transition metal phosphides (TMPs) by coupling carbon-based materials with large surface areas to enhance hydrogen evolution reaction (HER) performance presents significant progress for water splitting technology. Herein, we constructed a composite substrate of a three-dimensional porous graphene oxide matrix (3D-GO) embedded in nickel foam (NF) to grow a Co 2 P electrocatalyst. Well-defined gladiolus-like Co 2 P nanowire arrays tightly anchored on the substrate show enhanced electrochemical characteristics for the hydrogen evolution reaction (HER) based on the promoting roles of 3D porous reduced GO (3D-rGO) derived from 3D-GO, which promotes the dispersion of active components, improves the rate of electron transfer, and facilitates the transport of water molecules. As a result, the obtained Co 2 P@3D-rGO/NF electrode exhibits superior HER activity in 1.0 M KOH media, achieving overpotentials of 36.5 and 264.7 mV at current densities of 10 and 100 mA cm -2 , respectively. The electrode also has a low Tafel slope of 55.5 mV dec -1 , a large electrochemical surface area, and small charge-transfer resistance, further revealing its mechanism of high intrinsic activity. Moreover, the electrode exhibits excellent HER stability and durability without surface morphology and chemical state changes.

Autoreactive CD8 + T cells play an indispensable key role in the destruction of pancreatic islet β-cells and the initiation of type 1 diabetes (T1D). Insulin is an essential β-cell autoantigen in T1D. An HLA-A*0201-restricted epitope of insulin A chain (mInsA 2-10 ) is an immunodominant ligand for autoreactive CD8 + T cells in NOD. β2m null . HHD mice. Altered peptide ligands (APLs) carrying amino acid substitutions at T cell receptor (TCR) contact positions within an epitope are potential to modulate autoimmune responses via triggering altered TCR signaling. Here, we used a molecular simulation strategy to guide the generation of APL candidates by substitution of L-amino acids with D-amino acids at potential TCR contact residues (positions 4 and 6) of mInsA 2-10 , named mInsA 2-10 DQ4 and mInsA 2-10 DC6, respectively. We found that administration of mInsA 2-10 DQ4, but not DC6, significantly suppressed the development of T1D in NOD. β2m null . HHD mice. Mechanistically, treatment with mInsA 2-10 DQ4 not only notably eliminated mInsA 2-10 autoreactive CD8 + T cell responses but also prevented the infiltration of CD4 + T and CD8 + T cells, as well as the inflammatory responses in the pancreas of NOD. β2m null .HHD mice. This study provides a new strategy for the development of APL vaccines for T1D prevention., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhang, Wang, Li, Meng, Chen, Wang, Lin and Wang.)

Structure-activity relationship studies of a reported menthol-based transient receptor potential cation channel subfamily M member 8 channel (TRPM8) antagonist, guided by computational simulations and structure-based design, uncovers a novel series of TRPM8 antagonists with >10-fold selectivity versus related TRP subtypes. Spiro[4.5]decan-8-yl analogue 14 inhibits icilin-evoked Ca 2+ entry in HEK-293 cells stably expressing human TRPM8 (hTRPM8) with an IC 50 of 2.4 ± 1.0 nM, while in whole-cell patch-clamp recordings this analogue inhibits menthol-evoked currents with a hTRPM8 IC 50 of 64 ± 2 nM. Molecular dynamics (MD) simulations of compound 14 in our homology model of hTRPM8 suggest that this antagonist forms extensive hydrophobic contacts within the orthosteric site. In the wet dog shakes (WDS) assay, compound 14 dose-dependently blocks icilin-triggered shaking behaviors in mice. Upon local administration, compound 14 dose dependently inhibits cold allodynia evoked by the chemotherapy oxaliplatin in a murine model of peripheral neuropathy at microgram doses. Our findings suggest that 14 and other biphenyl amide analogues within our series can find utility as potent antagonist chemical probes derived from (-)-menthol as well as small molecule therapeutic scaffolds for chemotherapy-induced peripheral neuropathy (CIPN) and other sensory neuropathies.

Hydrophobic charge-induction chromatography (HCIC) has emerged as a useful addition to Protein A chromatography for antibody purification due to its remarkable merits in cost and stability. However, the instability of antibody during acidic elution, which may cause inactivation and aggregation, is still a major concern for the efficiency of this method. The aim of this study is to develop a new strategy of competitive elution with inclusion complexes in HCIC, and to apply it to antibody elution under neutral pH conditions. Interactions between 4-mercaptoethylpyridine (MEP), a typical ligand of HCIC, and four different types of cyclodextrins (CDs) were investigated by molecular docking; immunoglobulin G (IgG) elution capacities of CDs were characterized on MEP-based HCIC mediums. The results demonstrated the general effectiveness of CD-based eluents for HCIC. This type of displacement eluents could allow an efficient elution of bound antibody over a broad range of pH and ion strength. With 15 mM β-CD, elution of human IgG was achieved at physiological pH, with an average IgG recovery of 87%. When this elution strategy was used to separate antibody directly from human serum, substantial elution of bound IgG could be obtained at pH 7.4, with product purity comparable to traditional method with an acidic buffer. We expect such method can be of special interest in developing HCIC elution strategy for the proteins like antibody that are sensitive to acidic conditions., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Ataxia telangiectasia-mutated and Rad3-related (ATR) protein kinase is an attractive anticancer target. In this study, comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) were performed on a series of aminopyrazine ATR inhibitors. The models generated by CoMFA had a cross-validated coefficient (q(2)) of 0.752 and a regression coefficient (r(2)) of 0.947. The CoMSIA models had a q(2) of 0.728 and an r(2) of 0.936. The reasonable quantitative structure-activity relationship model showed robust predictive ability. The contour map provided guidelines for building novel virtual compounds based on compound NO.40. In addition, the 3D structure of ATR was modeled by homology modeling. Molecular dynamic simulations were employed to optimize the structure. The docking results offered insights into the interactions between the inhibitors and the active site for potent analysis. This study provides useful guidance for the discovery of more potent compounds.

A new model is developed to recognize eukaryotic promoter sequences from non-promoter sequences based on genetic algorithms and neural network in this paper. Experiment results demonstrate the effectiveness of the system to recognize the promoter sequences on the training set and on the test set. The mean recognition rate is as high as 99% on the training set and 97% on the test set, which shows the algorithms has great prospect application in promoter recognition.