The extracellular signal-regulated kinase (ERK) pathway regulates cell growth, and is hyper-activated and associated with drug resistance in hepatocellular carcinoma (HCC). Metabolic pathways are profoundly dysregulated in HCC. Whether an altered metabolic state is linked to activated ERK pathway and drug response in HCC is unaddressed.

Lead (Pb) is broadly used in various industries and causes irreversible damage to human tissues, organs, and systems. Studies have revealed that lead exerts toxic effects via interfering with calcium channel.

As a common toxic metal, lead has significant neurotoxicity to brain development. Long non-coding RNAs (lncRNAs) function in multiple biological processes. However, whether lncRNAs are involved in lead-induced neurotoxicity remains unclear. Uc.173 is a lncRNA from a transcribed ultra-conservative region (T-UCR) of human, mouse and rat genomes. We established a lead-induced nerve injury mouse model. It showed the levels of Uc.173 decreased significantly in hippocampus tissue and serum of the model. We further tested the expression of Uc.173 in serum of lead-exposed children, which also showed a tendency to decrease. To explore the effects of Uc.173 on lead-induced nerve injury, we overexpressed Uc.173 in an N2a mouse nerve cell line and found Uc.173 had an inhibitory effect on lead-induced apoptosis of N2a. To investigate the molecular mechanisms of Uc.173 in apoptosis associated with lead-induced nerve injury, we predicted the target microRNAs of Uc.173 by using miRanda, TargetScan and RegRNA. After performing quantitative real-time PCR and bioinformatics analysis, we showed Uc.173 might inter-regulate with miR-291a-3p in lead-induced apoptosis and regulate apoptosis-associated genes. Our study suggests Uc.173 significantly inhibits the apoptosis of nerve cells, which may be mediated by inter-regulation with miRNAs in lead-induced nerve injury.

Oscillatory patterns in local field potentials (LFPs) have been recognized as disease-specific physiomarkers, particularly in the context of Parkinson's disease and cervical dystonia. This characteristic oscillatory feature is currently employed in adaptive deep brain stimulation (aDBS). However, for other types of dystonia, especially Meige syndrome, a distinct physiomarker of this nature is yet to be identified.

Rapid Auger recombination represents an important challenge faced by quasi-2D perovskites, which induces resulting perovskite light-emitting diodes' (PeLEDs) efficiency roll-off. In principle, Auger recombination rate is proportional to materials' exciton binding energy (Eb). Thus, Auger recombination can be suppressed by reducing the corresponding materials' Eb. Here, a polar molecule, p-fluorophenethylammonium, is employed to generate quasi-2D perovskites with reduced Eb. Recombination kinetics reveal the Auger recombination rate does decrease to one-order-of magnitude lower compared to its PEA+ analogues. After effective passivation, nonradiative recombination is greatly suppressed, which enables resulting films to exhibit outstanding photoluminescence quantum yields in a broad range of excitation density. We herein demonstrate the very efficient PeLEDs with a peak external quantum efficiency of 20.36%. More importantly, devices exhibit a record luminance of 82,480 cd m-2 due to the suppressed efficiency roll-off, which represent one of the brightest visible PeLEDs yet.

African swine fever virus (ASFV) is a large double-stranded DNA virus with an icosahedral multilayered structure. ASFV causes a lethal swine hemorrhagic disease and is currently responsible for widespread damage to the pork industry in Asia. Neither vaccines nor antivirals are available and the molecular characterization of the ASFV particle is outstanding. Here, we describe the cryogenic electron microscopy (cryo-EM) structure of the icosahedral capsid of ASFV at 4.6-Å. The ASFV particle consists of 8,280 copies of the major capsid protein p72, 60 copies of the penton protein, and at least 8,340 minor capsid proteins, of which there might be 3 different types. Like other nucleocytoplasmic large DNA viruses, the minor capsid proteins form a hexagonal network below the outer capsid shell, functioning as stabilizers by "gluing" neighboring capsomers together. Our findings provide a comprehensive molecular model of the ASFV capsid architecture that will contribute to the future development of countermeasures, including vaccines.

Accumulating evidence suggests that the gut microbiota and its metabolites may be involved in autoimmune hypothyroidism. However, the causal association between gut microbiota, metabolites and autoimmune hypothyroidism remains to be determined.

Medical artificial intelligence (AI) has been moving from the research phase to clinical implementation. However, most AI-based models are mainly built using high-quality images preprocessed in the laboratory, which is not representative of real-world settings. This dataset bias proves a major driver of AI system dysfunction. Inspired by the design of flow cytometry, DeepFundus, a deep-learning-based fundus image classifier, is developed to provide automated and multidimensional image sorting to address this data quality gap. DeepFundus achieves areas under the receiver operating characteristic curves (AUCs) over 0.9 in image classification concerning overall quality, clinical quality factors, and structural quality analysis on both the internal test and national validation datasets. Additionally, DeepFundus can be integrated into both model development and clinical application of AI diagnostics to significantly enhance model performance for detecting multiple retinopathies. DeepFundus can be used to construct a data-driven paradigm for improving the entire life cycle of medical AI practice.

Numerous prognostic gene expression signatures for breast cancer were generated previously with few overlap and limited insight into the biology of the disease. Here we introduce a novel algorithm named SCoR (Survival analysis using Cox proportional hazard regression and Random resampling) to apply random resampling and clustering methods in identifying gene features correlated with time to event data. This is shown to reduce overfitting noises involved in microarray data analysis and discover functional gene sets linked to patient survival. SCoR independently identified a common poor prognostic signature composed of cell proliferation genes from six out of eight breast cancer datasets. Furthermore, a sequential SCoR analysis on highly proliferative breast cancers repeatedly identified T/B cell markers as favorable prognosis factors. In glioblastoma, SCoR identified a common good prognostic signature of chromosome 10 genes from two gene expression datasets (TCGA and REMBRANDT), recapitulating the fact that loss of one copy of chromosome 10 (which harbors the tumor suppressor PTEN) is linked to poor survival in glioblastoma patients. SCoR also identified prognostic genes on sex chromosomes in lung adenocarcinomas, suggesting patient gender might be used to predict outcome in this disease. These results demonstrate the power of SCoR to identify common and biologically meaningful prognostic gene expression signatures.

Cervical carcinogenesis is mediated by the HPV-E6 and E7 oncoproteins, considered as biomarkers usable in managing screen-positive women.

Auxin-like 2,4-dichlorophenoxyacetic acid (2,4-D), a high-efficiency anti-stalling agent for the post-harvest fresh fruit industry, has had its use restricted due to environmental concerns. However, no other substitutes for 2,4-D are available to the post-harvest industry. Insights into the molecular mechanism underlying the effects of 2,4-D on fruit quality preservation will provide a theoretical basis for exploring new safe and effective anti-stalling agents. This study comprehensively analysed changes in the peel of Olinda Valencia orange [Citrus sinensis (L.) Osbeck] induced by 500 ppm 2,4-D using 'omic'-driven approaches. Transcriptional profiling revealed that transcriptional factor (mainly AP2/ERF, WRKY, and NAC family members), transport, and hormone metabolism genes were over-represented and up-regulated within 24h post-treatment (HPT). Stress defence genes were up-regulated, while cell wall metabolism genes were down-regulated after 48 HPT. However, secondary metabolism genes, especially phenylpropanoid and lignin biosynthesis-related genes, were over-represented at all the time points. Comparative proteomic analysis indicated that the expression of proteins implicated in stress responses (25%), hormone metabolism, and signal transduction (12%) significantly accumulated at the post-transcriptional level. Hormone levels detected by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) showed that abscisic acid, salicylic acid, and 2,4-D significantly increased, while ethylene production (detected by gas chromatography) decreased after 2,4-D treatment. In addition, lignin and water content in the fruit peel also increased and the epicuticle wax ultrastructure was modified. In conclusion, 2,4-D retarded fruit senescence by altering the levels of many endogenous hormones and by improving stress defence capabilities by up-regulating defence-related genes and proteins.

Long-term use of high-dose glucocorticoids can lead to severe immunosuppression and increased risk of treatment-resistant pneumonia and mortality. We investigated the aetiology and prognostic risk factors of mortality in hospitalised patients who developed pneumonia while receiving glucocorticoid therapy alone or glucocorticoid and other immunosuppressant therapies.

Losing an only child (Shidu) is a grievous traumatic event that may affect brain structure, even if it does not lead to psychiatric disorders. However, longitudinal changes in brain structure and their relationship to subclinical psychiatric symptoms (SPS) have not been well investigated in Shidu parents without any psychiatric disorders (SDNP).

Permanent polymer drug eluting stents (PP-DES) may induce inflammation of the vessel wall due to the existence of the polymer, which may delay intimal healing. Polymer-free DES (PF-DES) that eliminate the polymeric carrier may potentially lead to safer DES. However, the safety and efficacy of PF-DES remains controversial.

Protein-energy malnutrition (PEM) can lead to growth hormone (GH) resistance. Leucine supplementation diets have been shown to increase protein synthesis in muscles. Our study aimed at investigating if long-term leucine supplementation could modulate GH-insulin-like growth factor (IGF)-1 system function and mammalian target of rapamycin (mTOR)-related signal transduction in skeletal muscles in a rat model of severe malnutrition.

With the identification of new targetable drivers and the recent emergence of novel targeted drugs, using comprehensive genomic profiling in lieu of the routine testing for classic drivers in the clinical care for advanced NSCLC has been increasingly advocated. However, the key assumption justifying this practice, that comprehensive genomic profiling could lead to effective anticancer therapies and improve patient outcomes, remains unproved.

We previously found that microbial disruption in Pseudomonas aeruginosa ventilator-associated pneumonia (PA-VAP) patients are long-lasting. Long-term microbial dysbiosis may lead to changes in metabolites. Short-chain fatty acids (SCFAs) are microbial fermentation products and show beneficial effects in patients with pneumonia. In this study, we aimed to explore the association between circulating SCFA levels and clinical outcomes in patients with PA-VAP.

This is a phase Ib study of anlotinib plus a programmed death-ligand 1 (PD-L1) inhibitor TQB2450 for platinum-resistant or -refractory ovarian cancer. Thirty-four patients are enrolled and receive treatment. The objective response rate (ORR) is 47.1%, and the disease control rate is 97.1%. The median duration of response (DOR) has not been reached, and 61.3% of patients have a DOR of at least 8 months. The median progression-free survival (PFS) is 7.8 months, and the median overall survival (OS) has not been reached. The PD-L1-positive group has an ORR of 25.0%, whereas the PD-L1-negative group has an ORR of 92.9%. Treatment-related grade 3 or 4 adverse events (AEs) occur in 70.6% of patients, with the most common being hypertension (29.4%) and palmar-plantar erythrodysesthesia syndrome (29.4%). Anlotinib plus TQB2450 show promising antitumor activity and manageable toxicities in patients with platinum-resistant or -refractory ovarian cancer. A phase 3 randomized controlled trial to further validate our findings is ongoing.

Kawasaki disease (KD) is a systemic vasculitis of unknown etiology in children. Coronary artery abnormalities are the most common complications of KD. Recent evidence showed that genetic polymorphisms may lead to susceptibility to KD. Genetic variants in platelet glycoprotein have been reported to be associated with coronary artery disease. The aim of the present study is to investigate the correlation between the role of platelet glycoprotein and coronary artery aneurysms in KD patients.

Sleep disturbances are highly prevalent in patients with age-related neurodegenerative diseases, which severely affect cognition and even lead to accumulated β-amyloid. Encouraging results from recent studies on transcranial direct current stimulation (tDCS) showed moderate positive effects on sleep quality in preclinical Alzheimer's disease (AD). Compared to tDCS, transcranial alternating current stimulation (tACS) enables the entrainment of neuronal activity with optimized focality through injecting electric current with a specific frequency and has significant enhancement effects on slow wave activities.