Design, synthesis and antitumour activity of pyrimidine derivatives as novel selective EGFR kinase inhibitors.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, often linked to overexpression or abnormal activation of the epidermal growth factor receptor (EGFR). The issue of developing resistance to third-generation EGFR kinase inhibitors, such as osimertinib, underscores the urgent need for new therapies to overcome this resistance. Our findings revealed that compound A8 exhibits 88.

Appendectomy and the risk of microscopic colitis - A systematic review and meta-analysis.

Background: Microscopic colitis (MC), a chronic intestinal inflammatory disorder characterised by persistent watery diarrhoea, is categorised into collagenous and lymphocytic subtypes. Recent studies suggest that appendectomy influences the risk of MC, although the evidence remains inconclusive. This meta-analysis of available research was conducted to clarify the relationship between appendectomy and MC risk.

Advances in multi-omics integrated analysis methods based on the gut microbiome and their applications.

The gut microbiota actually shares the host's physical space and affects the host's physiological functions and health indicators through a complex network of interactions with the host. However, its role as a determinant of host health and disease is often underestimated. With the emergence of new technologies including next-generation sequencing (NGS) and advanced techniques such as microbial community sequencing, people have begun to explore the interaction mechanisms between microorganisms and hosts at various omics levels such as genomics, transcriptomics, metabolomics, and proteomics.

Ellagic Acid Modulates Necroptosis, Autophagy, Inflammations, and Stress to Ameliorate Nonalcoholic Liver Fatty Disease in a Rat Model.

Nonalcoholic fatty liver disease (NAFLD) is considered one of the most common metabolic disorders worldwide. Although the pathoetiology of NAFLD is not fully elucidated, recent evidence suggests the involvement of stress, inflammation, and programmed death in the onset and progression of the disease. This investigation aimed to evaluate the effects of ellagic acid (EA), a known herbal antioxidant, on a high-fat diet (HFD)-induced animal model of NAFLD by evaluating the status of lipid profile, necroptosis (RIPK1, RIPK3, and MLKL), autophagy (LC3, ATG5, and BECN1), inflammation (TNF-α, IL-6, IL-4, and IL-10), and stress (SOD, CAT, GR, GPx, and MDA).

Visible-Telecom Entangled-Photon Pair Generation with Integrated Photonics: Guidelines and a Materials Comparison.

Correlated photon-pair sources are key components for quantum computing, networking, synchronization, and sensing applications. Integrated photonics has enabled chip-scale sources using nonlinear processes, producing high-rate time-energy and polarization entanglement at telecom wavelengths with sub-100 microwatt pump power. Many quantum systems operate in the visible or near-infrared ranges, necessitating visible-telecom entangled-pair sources for connecting remote systems via entanglement swapping and teleportation.

Chronic implantable flexible serpentine probe reveals impaired spatial coding of place cells in epilepsy.

The development of minimally invasive and reliable electrode probes for neural signal recording is crucial for advancing neuroscience and treating major brain disorders. Flexible neural probes offer superior long-term recording capabilities over traditional rigid probes. This study introduces a parylene-based serpentine electrode probe for stable, long-term neural monitoring.

Antithrombotic therapy for a case report of acute myocardial infarction after laparoscopic radical cystectomy.

Background: Radical cystectomy constitutes the standard therapeutic approach for high-risk urothelial carcinomas of the bladder. Contemporary guidelines advise urologists to discontinue anticoagulation therapy during the perioperative period to mitigate the risk of significant intraoperative or postoperative hemorrhage. Nevertheless, in elderly patients with a history of coronary artery disease, the cessation of anticoagulant medication elevates the risk of acute myocardial infarction, thereby posing a substantial threat to their survival.

Unsupervised Ensemble Learning for Efficient Integration of Pre-trained Polygenic Risk Scores.

The growing availability of pre-trained polygenic risk score (PRS) models has enabled their integration into real-world applications, reducing the need for extensive data labeling, training, and calibration. However, selecting the most suitable PRS model for a specific target population remains challenging, due to issues such as limited transferability, data het-erogeneity, and the scarcity of observed phenotype in real-world settings. Ensemble learning offers a promising avenue to enhance the predictive accuracy of genetic risk assessments, but most existing methods often rely on observed phenotype data or additional genome-wide association studies (GWAS) from the target population to optimize ensemble weights, limiting their utility in real-time implementation.

Butyrolactol A is a phospholipid flippase inhibitor that potentiates the bioactivity of caspofungin against resistant fungi.

Fungal infections cause millions of deaths annually and are challenging to treat due to limited antifungal options and increasing drug resistance. Cryptococci are intrinsically resistant to the latest generation of antifungals, echinocandins, while , a notorious global threat, is also increasingly resistant. We performed a natural product extract screen for rescue of the activity of the echinocandin caspofungin against H99, identifying butyrolactol A, which restores echinocandin efficacy against resistant fungal pathogens, including .

Origin of Crude Oils in the Lower Yanchang Formation of Yan'an Area in Ordos Basin, China.

The clastic rocks of the Yanchang Formation in the Ordos Basin display poor physical properties but are rich in petroleum resources, exhibiting significant exploration potential. However, due to the existence of multiple sets of oil-bearing formations, hydrocarbon-generating formations, and a large longitudinal span, elucidating the correspondence between crude oil and source rocks is vital for further exploration. This study concentrates on the Lower Yanchang Formation of Triassic in the Yan'an area of the Ordos Basin, aiming to perform refined oil-source correlation.

Ginger leaf polyphenols mitigate β-amyloid toxicity JNK/FOXO pathway activation in .

β-Amyloid (Aβ) aggregation is the major pathological feature of Alzheimer's disease (AD), resulting in oxidative stress and further exacerbating Aβ aggregation. Ginger leaf polyphenols (GLP) have been found to possess antioxidant activity, evidencing their potential in addressing AD. GLP is mainly composed of 12 polyphenols, 8 organic acids, and 6 glycosides, of which polyphenols are predominantly composed of apigenin, kaempferol, and quercetin derivatives.

ZmHB53, a Maize Homeodomain-Leucine Zipper I Transcription Factor Family Gene, Contributes to Abscisic Acid Sensitivity and Confers Seedling Drought Tolerance by Promoting the Activity of ZmPYL4.

Plant-specific homeodomain-leucine zipper I (HD-Zip I) transcription factors (TFs) crucially regulate plant drought tolerance. However, their specific roles in maize (Zea mays L.) regulating drought tolerance remain largely unreported.

Built-in electric field in the Mn/C heterojunction promotes electrocatalytic nitrogen reduction to ammonia.

The electrochemical nitrogen reduction reaction (NRR) has been regarded as a green and promising alternative to the traditional Haber-Bosch process. However, the high bond energy (940.95 kJ mol) of the NN triple bond hinders the adsorption and activation of N molecules, which is a critical factor restricting the catalytic performance of catalysts and their large-scale applications.

Enzyme-Inspired Single Selenium Site for Selective Oxygen Reduction.

Learning from nature has garnered significant attention in the scientific community for its potential to inspire creative solutions in material or catalyst design. The study reports a biomimetic single selenium (Se) site-modified carbon (C) moiety that retains the unique reactivity of selenoenzyme with peroxides, aiming to selectively catalyze the oxygen reduction reaction (ORR). The as-designed Se-C demonstrates nearly 100% 4-electron selectivity, evidenced by 0.

Enhanced Resistance to Pokkah Boeng Disease in Sugarcane Through Host-Induced Gene Silencing Targeting FsCYP51 in Fusarium sacchari.

Pokkah boeng disease (PBD), a common and highly destructive disease of sugarcane, is mainly caused by Fusarium sacchari. Breeding sugarcane resistant to PBD is challenging due to the limited availability of immune or highly resistant germplasm resources. Host-induced gene silencing (HIGS) based on RNA interference (RNAi) is a promising disease-control method that offers strong disease-targeting ability with low environmental impact.

A comparative study on the efficacy of kirschner wire tension band combined with anchor cross-suture internal fixation versus partial patellectomy in the treatment of comminuted inferior pole patellar fractures.

Objective: The treatment of comminuted inferior pole patellar fractures has long posed a challenge for orthopedic surgeons. This study aims to compare the biomechanical stability and clinical efficacy of Kirschner wire tension band combined with anchor cross-suture fixation versus traditional partial patellectomy in the treatment of comminuted inferior pole patellar fractures.

Methods: A retrospective analysis was conducted on 14 patients who underwent Kirschner wire tension band combined with anchor cross-suture fixation (Group A) in our department of orthopedics from September 2020 to April 2022.

Comparative Efficacy of Different Cognitive Behavior Therapy Delivery Formats for Depression in Patients With Cancer: A Network Meta-Analysis of Randomized Controlled Trials.

Background: Cognitive behavior therapy (CBT) has been shown to be effective in improving depression in patients with cancer. However, diversity exists in the CBT delivery formats, and the optimal delivery format remains unconfirmed.

Objectives: To compare the efficacy of different delivery formats of CBT interventions on depression in patients with cancer.

[Effect of ten-eleven translocation methylcytosine dioxygenase 2 gene mutations on the secondary myelofibrosis of JAK2 positive myeloproliferative neoplasms patients].

To investigate the effect of ten-eleven translocation methylcytosine dioxygenase 2 (TET2) gene mutations on the secondary myelofibrosis (SMF) of JAK2 myeloproliferative neoplasms (MPN) patients. A retrospective collection was conducted on MPN patients with JAK2 mutation detected by second-generation sequencing in the Department of Hematology, the Second Hospital of Tianjin Medical University. TET2JAK2 MPN patients were selected as the mutant group, and TET2JAK2 MPN patients matched for age and gender were selected as the non-mutant group.

[Study on the association between different feeding methods during the first six months after birth and physical growth of children aged 3 to 5 years based on the Taicang and Wuqiang mother-child cohort study in China].

To explore the association between different feeding methods during the first six months after birth and the physical growth of children aged 3 to 5 years. Data were from the "Taicang and Wuqiang mother-child cohort study"(TAWS) in China. Children were enrolled at birth between November 2016 and September 2020 and followed up at 1, 2, 3, 6, 8, 12, 18, and 24 months, as well as at ages 3 to 5 years.

Efficient Photocatalytic Propane Direct Dehydrogenation to Propylene Over PtO Clusters.

The direct dehydrogenation of alkanes to olefins under mild conditions is challenging due to the inert nature of alkyl C─H bonds. Herein, an efficient photocatalytic system is developed for propane direct dehydrogenation (PDH) to propylene, consisting of ≈1.30 nm sized PtO clusters immobilized on a layered double hydroxide -derived ZnO/AlO support (LD-Pt).

Quality deterioration mechanism of freeze-thawed sweet potato oat dough: In terms of ice crystals and protein changes.

Sweet potato-oat composite dough is a nutritious, functional dough with promising market potential. This study investigates its quality changes during freeze-thaw cycles from the perspectives of ice crystals and protein alterations to provide theoretical support for its processing and production. After freeze-thaw cycles, both the storage modulus and loss modulus of the dough decrease, resulting in increased hardness, reduced resilience and chewiness, lower sensory scores, decreased specific volume, and darker color.

The functional regulation between extracellular vesicles and the DNA damage responses.

The DNA damage response (DDR) is a crucial regulatory mechanism for the survival of organisms, and irregularity of DDR may contribute to the development of various diseases, including tumors, making it is a prominent topic in therapeutic research. Extracellular vesicles (EVs), as important mediators of intercellular communication, have been extensively studied in recent years. Notably, an increasing number of studies have revealed a strong connection between DDR and EVs.

G-protein coupled receptor GPR124 protects against podocyte senescence and injury in diabetic kidney disease.

Although emerging studies highlight the pivotal role of podocyte senescence in the pathogenesis of diabetic kidney disease (DKD) and aging-related kidney diseases, therapeutic strategies for preventing podocyte senescence are still lacking. Here, we identified a previously unrecognized role of GPR124, a novel adhesion G protein-coupled receptor, in maintaining podocyte structure and function by regulation of cellular senescence in DKD. Podocyte GPR124 was significantly reduced in db/db diabetic (a type 2 diabetic mouse model) and streptozocin-induced diabetic mice (a type 1 diabetic model), which was further confirmed in kidney biopsies from patients with DKD.

Rare earth element erbium induces immune toxicity through the ROS/NF-κB pathway in zebrafish.

The large-scale mining and utilization of rare earth elements have significantly increased their concentration in the environment, especially in regions surrounding mining areas. These environmentally-enriched rare earth elements accumulate in agricultural products and organisms through soil and water, potentially impacting in human health through the food chain. Erbium (Er), a rare earth element of the lanthanide series (Group IIIB), plays a crucial role in various modern technological applications.

IBI310 plus sintilimab vs. placebo plus sintilimab in recurrent/metastatic cervical cancer: A double-blind, randomized controlled trial.

Background: It remains unclear whether adding CTLA-4 blockade to PD-1/PD-L1 blockade improves clinical outcomes in cervical cancer (CC).

Methods: In this randomized, double-blind, placebo-controlled, phase 2 study (ClinicalTrials.gov: NCT04590599), patients with recurrent/metastatic CC (R/M CC) who experienced disease progression after or during platinum-based chemotherapy were enrolled from 37 centers across China and randomly assigned (1:1), stratified by PD-L1 expression and prior treatment lines, to receive either IBI310 plus sintilimab or placebo plus sintilimab intravenously every 3 weeks for 12 weeks, followed by sintilimab alone.