Pharmacological targeting of casein kinase 1δ suppresses oncogenic NRAS-driven melanoma.

Activating mutations in NRAS account for 15-20% of melanoma, yet effective anti-NRAS therapies are still lacking. In this study, we unveil the casein kinase 1δ (CK1δ) as an uncharacterized regulator of oncogenic NRAS mutations, specifically Q61R and Q61K, which are the most prevalent NRAS mutations in melanoma. The genetic ablation or pharmacological inhibition of CK1δ markedly destabilizes NRAS mutants and suppresses their oncogenic functions.

An ultrasensitive multimodal intracranial pressure biotelemetric system enabled by exceptional point and iontronics.

The accurate monitoring of vital physiological parameters, exemplified by heart rate, respiratory rate, and intracranial pressure (ICP), is of paramount importance, particularly for managing severe cranial injuries. Despite the rapid development of implantable ICP sensing systems over the past decades, they still suffer from, for example, wire connection, low sensitivity, poor resolution, and the inability to monitor multiple variables simultaneously. Here, we propose an ultrasensitive multimodal biotelemetric system that amalgamates an iontronic pressure transducer with exceptional point (EP) operation for the monitoring of ICP signals.

LDF-BNN: A Real-Time and High-Accuracy Binary Neural Network Accelerator Based on the Improved BNext.

Significant progress has been made in industrial defect detection due to the powerful feature extraction capabilities of deep neural networks (DNNs). However, the high computational cost and memory requirement of DNNs pose a great challenge to the deployment of industrial edge-side devices. Although traditional binary neural networks (BNNs) have the advantages of small storage space requirements, high parallel computing capability, and low power consumption, the problem of significant accuracy degradation cannot be ignored.

Adverse reactions of immune checkpoint inhibitors combined with Proton pump inhibitors: a pharmacovigilance analysis of drug-drug interactions.

Background: Combining immune checkpoint and proton pump inhibitors is widely used in cancer treatment. However, the drug-drug interactions of these substances are currently unknown. This study aimed to explore drug-drug interactions associated with concomitant immune checkpoint and proton pump inhibitors.

Deciphering the predictive value of senescence-related signature in lung adenocarcinoma: Implications for antitumor immunity and immunotherapy efficacy.

Objective: The senescence process is pivotal in both the onset and advancement of lung adenocarcinoma (LUAD), influencing cell growth, immune evasion, the potential for metastasis, and resistance to treatments. Senescent cells' dual nature, both harmful and advantageous, adds complexity to understanding their expression patterns and clinical relevance in LUAD. In this study, we sought to evaluate the predictive value of the senescence-related signature in survival outcomes and immunotherapy efficacy in patients with LUAD.

Energy stress-activated AMPK phosphorylates Snail1 and suppresses its stability and oncogenic function.

Triple-negative breast cancer (TNBC) is a highly lethal malignancy with limited therapy options. Aberrant metabolism, a key hallmark of human cancers, plays a crucial role in tumor progression, therapeutic responses and TNBC-related death. However, the underlying mechanisms are not fully understood.

Decision model for durable clinical benefit from front- or late-line immunotherapy alone or with chemotherapy in non-small cell lung cancer.

Background: Predictive biomarkers and models of immune checkpoint inhibitors (ICIs) have been extensively studied in non-small cell lung cancer (NSCLC). However, evidence for many biomarkers remains inconclusive, and the opaqueness of machine learning models hinders practicality. We aimed to provide compelling evidence for biomarkers and develop a transparent decision tree model.

Sediment microbial fuel cell coupled floating treatment wetland for enhancing non-reactive phosphorus removal.

The presence of non-reactive phosphorus (NRP) in environmental waters presents a potential risk of eutrophication and poses challenges for the removal of all phosphorus (P) fractions. This study presents the first investigation on the removal performance and mechanism of three model NRP compounds, sodium tripolyphosphate (STPP), adenosine 5'-monophosphate (AMP) and 2-phosphonobutane-1,2,4-tricarboxylic acid (PBTC), in the sediment microbial fuel cell-floating treatment wetland (SMFC-FTW). Coupling SMFC with plants proved to be effective at removing NRP via electrochemical oxidation and plant uptake, particularly the challenging-to-degrade phosphonates that contain C-P bonds.

Evaluation of first-line and salvage therapies for unresectable malignant mesothelioma: A systematic review and network meta-analysis.

Background: Randomized controlled trials (RCTs) of systemic therapies for unresectable malignant mesothelioma have reported conflicting results. It is crucial and urgent to find optimal treatment options for this malignancy, which currently has a poor prognosis.

Methods: Databases PubMed, EMBASE, Cochrane Library, ClinicalTrials.

Discovery of a novel ROS-based signature for predicting prognosis and immunosuppressive tumor microenvironment in lung adenocarcinoma.

The role of reactive oxygen species (ROS) is critical in the emergence and progression of lung adenocarcinoma (LUAD), affecting cell survival, proliferation, angiogenesis, and metastasis. Further investigations are needed to elucidate these effects' precise pathways and devise therapeutic approaches targeting ROS. Moreover, the expression pattern and clinical significance of the ROS-related genes in LUAD remain elusive.

A single-cell characterised signature integrating heterogeneity and microenvironment of lung adenocarcinoma for prognostic stratification.

Background: The high heterogeneity of tumour and the complexity of tumour microenvironment (TME) greatly impacted the tumour development and the prognosis of cancer in the era of immunotherapy. In this study, we aimed to portray the single cell-characterised landscape of lung adenocarcinoma (LUAD), and develop an integrated signature incorporating both tumour heterogeneity and TME for prognosis stratification.

Methods: Single-cell tagged reverse transcription sequencing (STRT-seq) was performed on tumour tissues and matched normal tissues from 14 patients with LUAD for immune landscape depiction and candidate key genes selection for signature construction.

Prediction performance comparison of biomarkers for response to immune checkpoint inhibitors in advanced non-small cell lung cancer.

Background: The aim of the present study was to compare the predictive accuracy of PD-L1 immunohistochemistry (IHC), tissue or blood tumor mutation burden (tTMB, bTMB), gene expression profile (GEP), driver gene mutation, and combined biomarkers for immunotherapy response of advanced non-small cell lung cancer (NSCLC).

Methods: In part 1, clinical trials involved with predictive biomarker exploration for immunotherapy in advanced NSCLC were included. The area under the curve (AUC) of the summary receiver operating characteristic (SROC), sensitivity, specificity, likelihood ratio and predictive value of the biomarkers were evaluated.

The causal association between circulating cytokines with the risk of frailty and sarcopenia under the perspective of geroscience.

Introduction: Circulating cytokines were considered to play a critical role in the initiation and propagation of sarcopenia and frailty from observational studies. This study aimed to find the casual association between circulating cytokines and sarcopenia and frailty from a genetic perspective by two-sample Mendelian randomization (MR) analysis.

Methods: Data for 41 circulating cytokines were extracted from the genome-wide association study dataset of 8,293 European participants.

One-step hydrothermal synthesis of a NiS-FeMoO nanowire-nanosheet heterostructure array for synergistically boosted oxygen evolution reaction.

A key factor for boosting oxygen evolution reaction (OER) is the design of heterostructures with steerable defects and interfaces, which can optimize the surface electronic structures and achieve efficient water splitting to produce hydrogen fuel. Herein, we propose a novel one-step hydrothermal approach to fabricate hierarchical NiS nanowires with an S-doped FeMoO nanosheet heterostructure array on Ni-Fe foam (NFF) as a self-standing electrode for synergistically boosted OER. The metalloid NiS nanowires with good conductivity support the FeMoO nanosheets and act as high-speed paths for the charge transfer.

Assessment of human leukocyte antigen-based neoantigen presentation to determine pan-cancer response to immunotherapy.

Despite the central role of human leukocyte antigen class I (HLA-I) in tumor neoantigen presentation, quantitative determination of presentation capacity remains elusive. Based on a pooled pan-cancer genomic dataset of 885 patients treated with immune checkpoint inhibitors (ICIs), we developed a score integrating the binding affinity of neoantigens to HLA-I, as well as HLA-I allele divergence, termed the HLA tumor-Antigen Presentation Score (HAPS). Patients with a high HAPS were more likely to experience survival benefit following ICI treatment.

Real-world outcomes of chemoimmunotherapy and selective RET inhibitors in Chinese patients with RET fusion-positive non-small cell lung cancer.

Background: Rearranged during transfection () gene fusion is a target for non-small cell lung cancer (NSCLC) treatment, and RET inhibitors are approved for advanced NSCLC. The role of immune checkpoint inhibitors (ICIs) in fusion-positive NSCLC remains controversial. This retrospective study analyzed the efficacy of ICIs and RET inhibitors in Chinese patients with fusion-positive NSCLC.

Autophagy-related biomarkers in preeclampsia: the underlying mechanism, correlation to the immune microenvironment and drug screening.

Background: Preeclampsia is a life-threatening disease of pregnancy that lacks effective pharmaceuticals which can target its pathogenesis. Since preeclampsia involves complex pathological processes, including autophagy, this study aims to explore autophagy-related mechanisms of preeclampsia and to screen potential drugs.

Methods: Firstly, the datasets GSE75010, GSE24129, GSE66273, and autophagic genes lists were downloaded from public databases.

Deubiquitinating enzyme OTUD4 regulates metastasis in triple-negative breast cancer by stabilizing Snail1.

Metastasis is the primary cause of cancer-related deaths and remains poorly understood. Deubiquitinase OTU domain containing 4 (OTUD4) has been reported to regulate antiviral immune responses and resistance to radio- or chemo-therapies in certain cancers. However, the role of OTUD4 in cancer metastasis remain unknown.

Separate and combined effects of famine exposure and menarche age on metabolic syndrome among the elderly: a cross-sectional study in China.

Background: Epidemiological studies have revealed multiple risk factors for metabolic syndrome. However, there are no consistent findings on the association between famine exposure, age at menarche, and the prevalence of metabolic syndrome. This cross-sectional study aimed to reveal the individual and combined effects of famine exposure and age at menarche on the prevalence of metabolic syndrome among elderly women.

Ablation of ERO1A induces lethal endoplasmic reticulum stress responses and immunogenic cell death to activate anti-tumor immunity.

Immunophenotyping of the tumor microenvironment (TME) is essential for enhancing immunotherapy efficacy. However, strategies for characterizing the TME exhibit significant heterogeneity. Here, we show that endoplasmic reticular oxidoreductase-1α (ERO1A) mediates an immune-suppressive TME and attenuates the response to PD-1 blockade.

Multi-omics indicators of long-term survival benefits after immune checkpoint inhibitor therapy.

Molecular indicators of long-term survival (LTS) in response to immune-checkpoint inhibitor (ICI) treatment have the potential to provide both mechanistic and therapeutic insights. In this study, we construct predictive models of LTS following ICI therapy based on data from 158 clinical trials involving 21,023 patients of 25 cancer types with available 1-year overall survival (OS) rates. We present evidence for the use of 1-year OS rate as a surrogate for LTS.

Heat transfer and pressure drop characteristic research of sine wavy flying-wing fins.

In recent years, heat transfer enhancement of heat exchange equipment has attracted more and more attention. In this paper, the heat transfer and pressure drop characteristics of sine wavy flying-wing fins are studied by numerical method. The objective is to improve the integrated heat transfer and pressure drop performance of sine wavy flying-wing fins.