Compositional study of Ti-Nb oxide (TiNbO, TiNbO, TiNbO, and TiNbO) anodes for high power Li ion batteries.

Titanium niobium oxides (TNOs) are attractive anode materials for high power density Li-ion batteries. However, the details of capacity storage in TNOs are not fully understood today as it depends on the Ti and Nb composition and their changes in the oxidation state. This is further complicated by a wide variation in gravimetric capacities reported in the literature for TNO anodes.

UK Biobank data demonstrate long-term exposure to floods is a risk factor for incident dementia.

Background: Flooding has emerged as the most prevalent natural disaster, impacting billions of individuals worldwide. However, the long-term effects of flooding exposure on dementia remain unclear.

Methods: With a nested case-control design, a risk-set sampling method was used to match cases and controls.

The connection between 91 inflammatory cytokines and frailty mediated by 1400 metabolites: An exploratory two-step Mendelian randomization analysis.

Background: Frailty, a common, multifaceted, and significant geriatric condition, involves crucial roles of inflammation and metabolic factors in its onset and progression. Nevertheless, the ambiguities and complexities in earlier observational studies make current research into their interactions somewhat insufficient. Our goals were to clarify the causal link between inflammatory cytokines and frailty and to explore the potential mediating effect of metabolites using Mendelian randomization (MR) analysis.

Synergistic Microstructure-driven Polarization and Conductive Loss in 3D Chrysanthemum-like MoC@NiCo LDH Composite for Ultra-high Microwave Absorption Performance.

The development of efficient electromagnetic wave (EMW) absorbing materials relies on rational microstructures and loss mechanisms. This study innovatively proposes a design strategy based on micronano structural regulation─heterogeneous interface construction─synergistic loss optimization and fabricates a MoC@NiCo layered double hydroxide (LDH) composite material with a 3D chrysanthemum-like morphology. The petal-like microstructure enhances the multiple reflection and scattering effects of the incident EMWs, while heterogeneous interfaces further stimulate interface polarization.

Hyperferritinemia is Associated with Thrombocytopenia and Increased Mortality Risk in Adult Sepsis Patients: A Retrospective Study of Two Observational Cohorts.

Objective: Markedly elevated serum ferritin serves as a laboratory marker of macrophage activation syndrome and is associated with increased mortality in sepsis, where hyperinflammation, coagulopathy, and immune dysregulation interplay. Although laboratory studies suggest a relationship between hyperferritinemia and coagulopathy in sepsis, clinical evidence remains limited. This study aims to assess mortality risk and the interplay between hyperferritinemia (ferritin ≥ 500 ng/mL) and thrombocytopenia in two sequential cohorts of adult patients with sepsis.

Improving Cycle Life of Ni-Rich Li-Ion Battery Cathodes by Using Compartmentalized Anode and Cathode Electrolytes.

As new, ever more energy-dense battery materials are being developed, it is becoming increasingly challenging for electrolytes to cater for both requirements set by the anode and cathode. Ethylene carbonate plays a key role in forming a stable solid-electrolyte-interphase on the graphite anodes, but in combination with nickel-rich cathodes, such as LiNiMnCoO (NMC811), it leads to excessive cathode oxygen loss at high voltage. In this work, the study proposes a cell design, where different electrolytes are compartmentalized in the anode and the cathode.

An oral tricyclic STING agonist suppresses tumor growth through remodeling of the immune microenvironment.

Stimulator of interferon genes (STING) agonists could overcome immunosuppressive microenvironment to improve cancer immunotherapy. However, it is challenging to develop oral STING agonists to achieve systemic immunity. In this study, we discovered ZSA-51 as a potent oral STING agonist with distinct benzo[4,5]thieno[2,3-c]pyrrole-1,3-dione scaffold through tricyclic scaffold screening.

Characterization of an Enhancer RNA Signature Reveals Treatment Strategies for Improving Immunotherapy Efficacy in Cancer.

Non-coding RNA transcribed from active enhancers, known as enhancer RNA (eRNA), is a critical element in gene regulation with a highly specific expression pattern in the regulatory networks of tumor-infiltrating cells. Therefore, eRNA signatures could potentially be applied to represent anti-tumor immune cells and to improve cancer immunotherapy. Herein, we identified thousands of eRNAs that were significantly correlated with infiltrating immune cell abundance in more than 10,000 patient samples across a variety of cancer types.

Laser Welding of Micro-Wire Stent Electrode as a Minimally Invasive Endovascular Neural Interface.

Minimally invasive endovascular stent electrodes are an emerging technology in neural engineering, designed to minimize the damage to neural tissue. However, conventional stent electrodes often rely on resistive welding and are relatively bulky, restricting their use primarily to large animals or thick blood vessels. In this study, the feasibility is explored of fabricating a laser welding stent electrode as small as 300 μm.

Identifying the healthy places to live in Australia with a new environmental quality health index.

Background: Existing environmental quality indices often fail to account for the varying health impacts of different exposures and exclude socio-economic status indicators (SES).

Objectives: To develop and validate a comprehensive Environmental Quality Health Index (EQHI) that integrates multiple environmental exposures and SES to assess mortality risks across Australia.

Methods: We combined all-cause, cardiovascular, and respiratory mortality data (2016-2019) from 2,180 Statistical Areas Level 2 with annual mean values of 12 environmental exposures, including PM, ozone, temperature, humidity, normalized difference vegetation index, night light, road and building density, and socioeconomic status.

New cytotoxic compounds from (Kom.) Nakai.

Twenty-one compounds were isolated and identified from the ethanol extract of (Kom.) Nakai, including two new compounds ( and ), a new artificial product () and eighteen known compounds (). Compounds and were isolated from for the first time.

Development and Validation of an AI-Based Multimodal Model for Pathological Staging of Gastric Cancer Using CT and Endoscopic Images.

Rationale And Objectives: Accurate preoperative pathological staging of gastric cancer is crucial for optimal treatment selection and improved patient outcomes. Traditional imaging methods such as CT and endoscopy have limitations in staging accuracy.

Methods: This retrospective study included 691 gastric cancer patients treated from March 2017 to March 2024.

Discovery of SMD-3236: A Potent, Highly Selective and Efficacious SMARCA2 Degrader for the Treatment of SMARC4-Deficient Human Cancers.

SMARCA2 is an attractive synthetic lethal target in human cancers with mutated, inactivated SMARCA4. We report herein the discovery of highly potent and selective SMARCA2 PROTAC degraders, as exemplified by SMD-3236, which was designed using a new, high-affinity SMARCA ligand and a potent VHL-1 ligand. SMD-3236 achieves DC < 1 nM and > 95% against SMARCA2 and >2000-fold degradation selectivity over SMARCA4.

The Role of Sex Hormones and Sex Hormone-binding Globulin in Functional Gatrointestinal Disorders: A Bidirectional Two-sample Mendelian Randomization Study.

Background And Aims: Sex hormones and sex hormone-binding globulin (SHBG) have been confirmed to involve in the pathophysiology of functional gastrointestinal disorders (FGIDs), including irritable bowel syndrome (IBS) and functional dyspepsia (FD). However, causal associations have not yet been investigated. Utilizing data from Genome-wide association studies, we conducted bidirectional two-sample mendelian randomization (MR) analyses to assess the causal relationships between sex hormones, SHBG and FGIDs.

Patient-Derived Xenografts of Triple-Negative Breast Cancer Enable Deconvolution and Prediction of Chemotherapy Responses.

Combination chemotherapy remains essential for clinical management of triple-negative breast cancer (TNBC). Consequently, responses to multiple single agents cannot be delineated at the single patient level, even though some patients might not require all drugs in the combination. Herein, we conduct multi-omic analyses of orthotopic TNBC patient-derived xenografts (PDXs) treated with single agent carboplatin, docetaxel, or the combination.

Genetic prediction of serum micronutrient levels and the risk of frailty: Evidence from a Mendelian randomization study.

Although observational studies have revealed a link between frailty and serum micronutrient levels, it remains unclear whether these 2 states are directly connected. Thus, Mendelian randomization (MR) was used to investigate the causal relationship between frailty and blood micronutrient levels. Summary-level data for 15 blood micronutrients (copper, selenium, zinc, calcium, iron, magnesium, potassium, folate, carotene, vitamin A, vitamin B6, vitamin B12, vitamin C, vitamin D, and vitamin E) were obtained from people of European ancestry from the Integrative Epidemiology Unit.

Structure-Based Development of Novel Spiro-Piperidine ASH1L Inhibitors.

The absent, small, or homeotic-like 1 (ASH1L) protein is a histone lysine methyltransferase that plays a crucial role in various cancers, including leukemia. Despite representing an attractive therapeutic target, only one class of ASH1L inhibitors was identified to date. Herein, we report development of advanced ASH1L inhibitors targeting the catalytic SET domain, which were designed to access previously unexplored binding pocket on ASH1L.

Relaxin-2 improves type I diabetes mellitus-induced erectile dysfunction in rats by protecting cavernous endothelial and smooth muscle function, and inhibiting penile fibrosis and apoptosis.

Background: Diabetes mellitus-induced erectile dysfunction (DMED) responds poorly to first-line treatments, necessitating the development of new therapeutic strategies. Relaxin-2 (RLX-2) plays a crucial role in protecting vascular endothelium, vasodilatation, and antifibrosis in various diseases. However, its effects and mechanisms on DMED remain unclear.

Global, regional, and national mortality burden attributable to air pollution from landscape fires: a health impact assessment study.

Background: Landscape fire-sourced (LFS) air pollution is an increasing public health concern in the context of climate change. However, little is known about the attributable global, regional, and national mortality burden related to LFS air pollution.

Methods: We calculated country-specific population-weighted average daily and annual LFS fine particulate matter (PM) and surface ozone (O) during 2000-19 from a validated dataset.

Deep Learning Methods for De Novo Peptide Sequencing.

Protein tandem mass spectrometry data are most often interpreted by matching observed mass spectra to a protein database derived from the reference genome of the sample being analyzed. In many application domains, however, a relevant protein database is unavailable or incomplete, and in such settings de novo sequencing is required. Since the introduction of the DeepNovo algorithm in 2017, the field of de novo sequencing has been dominated by deep learning methods, which use large amounts of labeled mass spectrometry data to train multi-layer neural networks to translate from observed mass spectra to corresponding peptide sequences.

Discovery of ERD-12310A as an Exceptionally Potent and Orally Efficacious PROTAC Degrader of Estrogen Receptor α (ERα).

Inhibition of estrogen receptor alpha (ERα) signaling is an established therapeutic approach for the treatment of ER-positive (ER+) breast cancers, but new therapeutic strategies are urgently needed to overcome clinical resistance. In the present study, we describe the discovery and extensive evaluation of ERD-12310A as an exceptionally potent and orally efficacious PROTAC degrader of ERα. ERD-12310A achieved a DC value of 47 pM and is 10 times more potent than ARV-471.

Proteolysis-targeting vaccines (PROTAVs) for robust combination immunotherapy of melanoma.

Protein/peptide subunit vaccines are promising to promote the tumor therapeutic efficacy of immune checkpoint blockade (ICB). However, current protein/peptide vaccines elicit limited antitumor T cell responses, leading to suboptimal therapeutic efficacy. Here, we present proteolysis-targeting vaccines (PROTAVs) that facilitate antigen proteolytic processing and cross-presentation to potentiate T cell responses for robust ICB combination immunotherapy of melanoma.