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HighlightsThe nucleation overpotential was regulated by sodium L-tartrate to drive smaller critical size of Zn nucleus and accelerate the nucleation rate.The L-tartrate anions and sodium ions can increase de-solvation energy barrier suitably and hinder the agglomerative Zn deposition resepectively.Nucleation overpotential in modified electrolyte could increase from 28.3 to 45.9 mV, and high Zn utilization rate of 80% at current density of 10 mA cm−2 can be achieved.Dendrite formation severely compromises further development of zinc ion batteries. Increasing the nucleation overpotential plays a crucial role in achieving uniform deposition of metal ions. However, this strategy has not yet attracted enough attention from researchers to our knowledge. Here, we propose that thermodynamic nucleation overpotential of Zn deposition can be boosted through complexing agent and select sodium L-tartrate (Na-L) as example. Theoretical and experimental characterization reveals L-tartrate anion can partially replace H2O in the solvation sheath of Zn2+, increasing de-solvation energy. Concurrently, the Na+ could absorb on the surface of Zn anode preferentially to inhibit the deposition of Zn2+ aggregation. In consequence, the overpotential of Zn deposition could increase from 32.2 to 45.1 mV with the help of Na-L. The Zn-Zn cell could achieve a Zn utilization rate of 80% at areal capacity of 20 mAh cm−2. Zn-LiMn2O4 full cell with Na-L additive delivers improved stability than that with blank electrolyte. This study also provides insight into the regulation of nucleation overpotential to achieve homogeneous Zn deposition.

HighlightsThe amphipathic phenylalanine-adsorbed layer contributes to form a nucleophilic–hydrophobic interface that homogenizes Zn2+ flux while repelling H2O molecules from contacting Zn anode.The preferential reduction of phenylalanine (Phe) prior to H2O facilitates in situ formation of an organic–inorganic hybrid solid electrolyte interphase, enhancing the interfacial stability.Benefiting from the triple protection of Phe, the Zn||Zn and Zn||LMO cells display significantly improved electrochemical performances, even at extreme diluted electrolytes.Aqueous Zn2+-ion batteries (AZIBs), recognized for their high security, reliability, and cost efficiency, have garnered considerable attention. However, the prevalent issues of dendrite growth and parasitic reactions at the Zn electrode interface significantly impede their practical application. In this study, we introduced a ubiquitous biomolecule of phenylalanine (Phe) into the electrolyte as a multifunctional additive to improve the reversibility of the Zn anode. Leveraging its exceptional nucleophilic characteristics, Phe molecules tend to coordinate with Zn2+ ions for optimizing the solvation environment. Simultaneously, the distinctive lipophilicity of aromatic amino acids empowers Phe with a higher adsorption energy, enabling the construction of a multifunctional protective interphase. The hydrophobic benzene ring ligands act as cleaners for repelling H2O molecules, while the hydrophilic hydroxyl and carboxyl groups attract Zn2+ ions for homogenizing Zn2+ flux. Moreover, the preferential reduction of Phe molecules prior to H2O facilitates the in situ formation of an organic–inorganic hybrid solid electrolyte interphase, enhancing the interfacial stability of the Zn anode. Consequently, Zn||Zn cells display improved reversibility, achieving an extended cycle life of 5250 h. Additionally, Zn||LMO full cells exhibit enhanced cyclability of retaining 77.3% capacity after 300 cycles, demonstrating substantial potential in advancing the commercialization of AZIBs.

The practical application of AZIBs is hindered by problems such as dendrites and hydrogen evolution reactions caused by the thermodynamic instability of Zinc (Zn) metal. Modification of the Zn surface through interface engineering can effectively solve the above problems. Here, sulfonate‐derivatized graphene–boronene nanosheets (G&B‐S) composite interfacial layer is prepared to modulate the Zn plating/stripping and mitigates the side reactions with electrolyte through a simple and green electroplating method. Thanks to the electronegativity of the sulfonate groups, the G&B‐S interface promotes a dendrite‐free deposition behavior through a fast desolvation process and a uniform interfacial electric field mitigating the tip effect. Theoretical calculations and QCM‐D experiments confirmed the fast dynamic mechanism and excellent mechanical properties of the G&B‐S interfacial layer. By coupling the dynamics‐mechanics action, the G&B‐S@Zn symmetric battery is cycled for a long‐term of 1900 h at a high current density of 5 mA cm−2, with a low overpotential of ≈30 mV. Furthermore, when coupled with the LMO cathode, the LMO//G&B‐S@Zn cell also exhibits excellent performance, indicating the durability of the G&B‐S@Zn anode. Accordingly, this novel multifunctional interfacial layer offers a promising approach to significantly enhance the electrochemical performance of AZIBs. A simple and green electroplating method is employed to prepare the G&B‐S composite interfacial layer, regulating the Zn plating/stripping and mitigating the side reactions. Based on the dynamics‐mechanics coupling action, the G&B‐S@Zn symmetric battery can achieve long‐term cycling stability of 1900 h at 5 mA cm−2 with a small overpotential of ≈30 mV.

CD38 is highly expressed on various immune cells, including long-lived plasma cells, making it a potential therapeutic target in autoimmune diseases. This phase Ib/IIa study aimed to explore the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of CM313, an anti-CD38 antibody, in patients with systemic lupus erythematosus (SLE). Eligible patients were sequentially enrolled in four ascending dose groups (2, 4, 8, and 16 mg/kg) and randomized 4:1 to receive CM313 or placebo intravenously at days 1, 29, 36, 43, and 50. The primary endpoint was safety, and efficacy was exploratorily investigated. Between October 14, 2022, and March 7, 2024, 40 patients were enrolled, including 8 patients in each CM313 dose group and the pooled placebo group. Adverse events occurred in 90.6% and 62.5% of participants receiving CM313 and placebo, all of which were mild or moderate. Upper respiratory tract infection (87.5%/62.5% vs. 12.5%), urinary tract infection (12.5%/25.0% vs. 0), and herpes zoster (25.0%/0 vs. 0) were more frequent in CM313 8 and 16 mg/kg groups than the placebo group. The CM313 groups had greater reductions in anti-ds-DNA antibodies, immunoglobulin G (IgG), IgA, IgM, IgE, and greater increases in complement C3 and C4 compared with placebo. Systemic Lupus Erythematosus Responder Index-4 response rates were 33.3%, 40.0%, 62.5%, 71.4%, and 37.5% in CM313 2, 4, 8, 16 mg/kg, and placebo groups at day 57, respectively. CM313 showed a manageable safety profile in SLE patients at 2–16 mg/kg and encouraging clinical efficacy at 8 and 16 mg/kg. The results support further investigation of CM313 for treating SLE patients (ClinicalTrials.gov ID: NCT05465707).

Proteolipid protein 2 (PLP2) is an integral ion channel membrane protein of the endoplasmic reticulum. The protein has been shown to be highly expressed in many cancer types, but its importance in glioma progression is poorly understood. Using publicly available datasets (Rembrandt, TCGA and CGGA), we found that the expression of PLP2 was significantly higher in high‐grade gliomas than in low‐grade gliomas. We confirmed these results at the protein level through IHC staining of high‐grade (n = 56) and low‐grade glioma biopsies (n = 16). Kaplan‐Meier analysis demonstrated that increased PLP2 expression was associated with poorer patient survival. In functional experiments, siRNA and shRNA PLP2 knockdown induced ER stress and increased apoptosis and autophagy in U87 and U251 glioma cell lines. Inhibition of autophagy with chloroquine augmented apoptotic cell death in U87‐ and U251‐siPLP2 cells. Finally, intracranial xenografts derived from U87‐ and U251‐shPLP2 cells revealed that loss of PLP2 reduced glioma growth in vivo. Our results therefore indicate that increased PLP2 expression promotes GBM growth and that PLP2 represents a potential future therapeutic target.

Radiomics can improve the accuracy of traditional image diagnosis to evaluate extrahepatic cholangiocarcinoma (ECC); however, this is limited by variations across radiologists, subjective evaluation, and restricted data. A radiomics-based particle swarm optimization and support vector machine (PSO-SVM) model may provide a more accurate auxiliary diagnosis for assessing differentiation degree (DD) and lymph node metastasis (LNM) of ECC. The objective of our study is to develop a PSO-SVM radiomics model for predicting DD and LNM of ECC. For this retrospective study, the magnetic resonance imaging (MRI) data of 110 patients with ECC who were diagnosed from January 2011 to October 2019 were used to construct a radiomics prediction model. Radiomics features were extracted from T1-precontrast weighted imaging (T1WI), T2-weighted imaging (T2WI), and diffusion-weighted imaging (DWI) using MaZda software (version 4.6; Institute of Electronics, Technical University of Lodz). We performed dimension reduction to obtain 30 optimal features of each sequence, respectively. A PSO-SVM radiomics model was developed to predict DD and LNM of ECC by incorporating radiomics features and apparent diffusion coefficient (ADC) values. We randomly divided the 110 cases into a training group (88/110, 80%) and a testing group (22/110, 20%). The performance of the model was evaluated by analyzing the area under the receiver operating characteristic curve (AUC). A radiomics model based on PSO-SVM was developed by using 110 patients with ECC. This model produced average AUCs of 0.8905 and 0.8461, respectively, for DD in the training and testing groups of patients with ECC. The average AUCs of the LNM in the training and testing groups of patients with ECC were 0.9036 and 0.8889, respectively. For the 110 patients, this model has high predictive performance. The average accuracy values of the training group and testing group for DD of ECC were 82.6% and 80.9%, respectively; the average accuracy values of the training group and testing group for LNM of ECC were 83.6% and 81.2%, respectively. The MRI-based PSO-SVM radiomics model might be useful for auxiliary clinical diagnosis and decision-making, which has a good potential for clinical application for DD and LNM of ECC.

To investigate the relationship between the methylation of death-associated protein kinase (DAPK) promoter and gene inactivation in papillary thyroid carcinoma, the technique of methylation-specific polymerase chain reaction (PCR (MSP)) was applied to detect the methylation status of DAPK gene promoter in 70 cases of papillary thyroid carcinoma (study group) and in 50 cases of corresponding adjacent tissues (control group). Immunohistochemical method was used to detect the protein expression; besides, the relationship of DAPK methylation and gene inactivation with pathological factors of papillary thyroid cancer was analyzed. The methylation rate of DAPK was 16% (8/50) in the control group and 71.4% (50/70) in the study group with the difference being statistically significant (χ2 = 19.724, P < 0.01). The methylation of DAPK gene promoter was not associated with age, sex, tumor size, TNM stage, and thyroid capsular infiltration in the study group with papillary thyroid carcinoma (P > 0.05), but was associated with lymph node metastasis (P < 0.05). Spearman’s rank correlation analysis showed that the methylation of DAPK promoter was negatively correlated with the expression of DAPK (r = −0.793, P < 0.01). The methylation of CpG island in the promoter region of DAPK gene can lead to gene inactivation and may be involved in the occurrence of papillary thyroid carcinoma.

[This corrects the article DOI: 10.2196/23578.].

Embedding-based retrieval models have made significant strides in retrieval-augmented generation (RAG) techniques for text and multimodal large language models (LLMs) applications. However, when it comes to speech larage language models (SLLMs), these methods are limited to a two-stage process, where automatic speech recognition (ASR) is combined with text-based retrieval. This sequential architecture suffers from high latency and error propagation. To address these limitations, we propose a unified embedding framework that eliminates the need for intermediate text representations. Specifically, the framework includes separate speech and text encoders, followed by a shared scaling layer that maps both modalities into a common embedding space. Our model reduces pipeline latency by 50\\% while achieving higher retrieval accuracy compared to traditional two-stage methods. We also provide a theoretical analysis of the challenges inherent in end-to-end speech retrieval and introduce architectural principles for effective speech-to-document matching. Extensive experiments demonstrate the robustness of our approach across diverse acoustic conditions and speaker variations, paving the way for a new paradigm in multimodal SLLMs retrieval systems.