Regulatory factors of Nrf2 in age-related macular degeneration pathogenesis.

Age-related macular degeneration (AMD) is a complicated disease that causes irreversible visual impairment. Increasing evidences pointed retinal pigment epithelia (RPE) cells as the decisive cell involved in the progress of AMD, and the function of anti-oxidant capacity of PRE plays a fundamental physiological role. Nuclear factor erythroid 2 related factor 2 (Nrf2) is a significant transcription factor in the cellular anti-oxidant system as it regulates the expression of multiple anti-oxidative genes.

Noninvasive prediction of lymph node metastasis in pancreatic cancer using an ultrasound-based clinicoradiomics machine learning model.

Objectives: This study was designed to explore and validate the value of different machine learning models based on ultrasound image-omics features in the preoperative diagnosis of lymph node metastasis in pancreatic cancer (PC).

Methods: This research involved 189 individuals diagnosed with PC confirmed by surgical pathology (training cohort: n = 151; test cohort: n = 38), including 50 cases of lymph node metastasis. Image-omics features were extracted from ultrasound images.

Machine learning guided prediction of warfarin blood levels for personalized medicine based on clinical longitudinal data from cardiac surgery patients: a prospective observational study.

Background: Warfarin is a common oral anticoagulant, and its effects vary widely among individuals. Numerous dose-prediction algorithms have been reported based on cross-sectional data generated via multiple linear regression or machine learning. This study aimed to construct an information fusion perturbation theory and machine-learning prediction model of warfarin blood levels based on clinical longitudinal data from cardiac surgery patients.

PDZK1 confers sensitivity to sunitinib in clear cell renal cell carcinoma by suppressing the PDGFR-β pathway.

Background: Sunitinib has emerged as the primary treatment for advanced or metastatic clear cell renal cell carcinoma (ccRCC) due to its significant improvement in patients' average survival time. However, drug resistance and adverse effects of sunitinib pose challenges to its clinical benefits.

Methods: The differentially expressed genes (DEGs) associated with sunitinib sensitivity and resistance in ccRCC were investigated.

A Randomized Trial Comparing Standard of Care to Bayesian Warfarin Dose Individualization.

The quality of warfarin treatment may be improved if management is guided by the use of models based upon pharmacokinetic-pharmacodynamic theory. A prospective, two-armed, single-blind, randomized controlled trial compared management aided by a web-based dose calculator (NextDose) with standard clinical care. Participants were 240 adults receiving warfarin therapy following cardiac surgery, followed up until the first outpatient appointment at least 3 months after warfarin initiation.

Biomimetic exosomal vesicles loaded with siRNA improves antitumor immune responses by inhibiting the secretion of tumor-derived exosome PD-L1.

Tumor-derived exosome PD-L1 exhaustsTcells and permits tumor cells to evade immune surveillance; thus, the inhibition of ExoPD-L1 secretion can significantly enhance the clinical efficacy of PD-L1 antibody. In this study, we combined exosome membrane, apoA1 and phospholipid into biomimetic exosome vesicles (apoA1-bExo) which were then incubated with cholesterol modified siRNA to generate apoA1-bExo containing siRNA (apoA1-bExo/siRNA). Thepreparedvesicleswere uniformandsphericalin size and could be loaded effectively with siRNA to protect from nuclease degradation.

Systemic lupus erythematosus is associated with lower risk of hepatitis B virus infection: A multivariable Mendelian randomization study in East Asian population.

The relationship between systemic lupus erythematosus (SLE) and hepatitis B virus (HBV) infection is still unclear. We conducted a two-sample Mendelian randomization (MR) analysis using summary statistics from genome-wide association studies for SLE and HBV infection in individuals of East Asian ancestry. The inverse-variance weighted (IVW) method, weighted median (WM) method, and MR-Egger method were used to estimate the causal effect of SLE on HBV infection.

A highly robust, concrete-inspired superhydrophobic nanocomposite coating.

Durability is still the main issue hindering the practical applications of superhydrophobic surfaces. In the case of superhydrophobic coatings, employing nanoparticles for constructing and retaining superhydrophobic surfaces without lowering the robustness is still a conundrum. Herein, inspired by concrete, which has a high filler portion and high robustness, we fabricated a superhydrophobic coating using a synthesized hydrophobic organic/inorganic hybrid resin and categorized micro/nano fillers with varying sizes.

Exploring the complex relationship between vitamin K, gut microbiota, and warfarin variability in cardiac surgery patients.

Background And Objectives: Due to the high individual variability of anticoagulant warfarin, this study aimed to investigate the effects of vitamin K concentration and gut microbiota on individual variability of warfarin in 246 cardiac surgery patients.

Methods: The pharmacokinetics and pharmacodynamics (PKPD) model predicted international normalized ratio (INR) and warfarin concentration. Serum and fecal samples were collected to detect warfarin and vitamin K [VK1 and menaquinone-4 (MK4)] concentrations and gut microbiota diversity, respectively.

Determination of the Procoagulant Activity of Extracellular Vesicle (EV) Using EV-Activated Clotting Time (EV-ACT).

The role of extracellular vesicles (EV) in various diseases is gaining increased attention, particularly due to their potent procoagulant activity. However, there is an urgent need for a bedside test to assess the procoagulant activity of EV in clinical settings. This study proposes the use of thrombin activation time of EV-rich plasma as a measure of EV's procoagulant activity.

Causal associations between human gut microbiota and cholelithiasis: a mendelian randomization study.

Background: There was some evidence that gut microbiota was closely related to cholelithiasis, but the causal relationship between them remained unclear. In this study, we try to use Two-sample Mendelian randomization (MR) to clarify the potential causal relationship between gut microbiota and cholelithiasis.

Methods: Summary Genome-Wide Association Studies (GWAS) statistical data for gut microbiota was obtained from MiBioGen, and the data of cholelithiasis was obtained from UK Biobank (UKB).

Systemic lupus erythematosus is causally associated with hypothyroidism, but not hyperthyroidism: A Mendelian randomization study.

Background: The relationship between systemic lupus erythematosus (SLE) and thyroid diseases is still controversial. Due to confounders and reverse causation, previous studies were not convincing. We aimed to investigate the relationship between SLE and hyperthyroidism or hypothyroidism by Mendelian randomization (MR) analysis.

Path Planning for Unmanned Delivery Robots Based on EWB-GWO Algorithm.

With the rise of robotics within various fields, there has been a significant development in the use of mobile robots. For mobile robots performing unmanned delivery tasks, autonomous robot navigation based on complex environments is particularly important. In this paper, an improved Gray Wolf Optimization (GWO)-based algorithm is proposed to realize the autonomous path planning of mobile robots in complex scenarios.

Benign gallbladder disease is a risk factor for colorectal cancer, but cholecystectomy is not: A propensity score matching analysis.

Background: Previous studies reported controversial results on the relationship between cholecystectomy (CHE) and colorectal cancer (CRC). We hypothesized that gallbladder disease (GBD), instead of cholecystectomy, increased the risk of CRC. We aimed to investigate the incidence of benign gallbladder disease (BGBD) and CHE in CRC patients and local adults undergoing annual health examination by analyzing large data from a tertiary hospital in southwest China.

E3 ubiquitin ligase MAGI3 degrades c-Myc and acts as a predictor for chemotherapy response in colorectal cancer.

Background: Recurrence and chemoresistance constitute the leading cause of death in colorectal cancer (CRC). Thus, it is of great significance to clarify the underlying mechanisms and identify predictors for tailoring adjuvant chemotherapy to improve the outcome of CRC.

Methods: By screening differentially expressed genes (DEGs), constructing random forest classification and ranking the importance of DEGs, we identified membrane associated guanylate kinase, WW and PDZ domain containing 3 (MAGI3) as an important gene in CRC recurrence.

Efficacy and Safety of Ticagrelor in East Asian Patients with Acute Coronary Syndrome: A Meta-Analysis of Randomized Controlled Trials.

Background: Although current guidelines recommend ticagrelor to clopidogrel for patients with acute coronary syndrome, its benefit and risk are unclear for East Asians. This meta-analysis was performed to assess the efficacy and safety of ticagrelor in East Asian patients with acute coronary syndrome.

Methods: Medline, EMBASE, and Cochrane Databases were searched from inception to July, 2021, for randomized controlled trials comparing ticagrelor with clopidogrel in East Asian patients with acute coronary syndrome.

The role of brain metastases in patients with pulmonary adenocarcinoma: a retrospective study.

Background: Brain metastasis is common in patients with lung cancer and has a negative impact on overall survival (OS). The aim of this study was to investigate therapeutic effects and prognosis-related factors for survival of patients with pulmonary adenocarcinoma and brain metastasis.

Methods: This was a retrospective study involving the data of patients with pulmonary adenocarcinoma and brain metastasis who were treated at the Department of Oncology, Tianjin Medical University General Hospital.

Reduced MAGI3 level by HPV18E6 contributes to Wnt/β-catenin signaling activation and cervical cancer progression.

Human papillomavirus type 18 (HPV18) has high carcinogenic power in invasive cervical cancer (ICC) development. However, the underlying mechanism remains elusive. The carcinogenic properties of HPV18 require the PDZ-binding motif of its E6 oncoprotein (HPV18 E6) to degrade its target PSD95/Dlg/ZO-1 (PDZ) proteins.

NHERF4 hijacks Mas-mediated PLC/AKT signaling to suppress the invasive potential of clear cell renal cell carcinoma cells.

The Mas receptor has been reported to promote migration and invasion of clear cell renal cell carcinoma (ccRCC) cells via Ang-(1-7)-dependent AKT signaling. However, the mechanism underlying the regulation of Mas function remains unknown. Here, eight PDZ domain-containing proteins were identified as Mas interactors using surface plasmon resonance (SPR) coupled to mass spectrometry (MS).

Plasma mutation abundance affects clinical response to first-line EGFR-TKIs in patients with advanced non-small cell lung cancer.

Background: Activated epidermal growth factor receptor () mutation is the main pathogenic cause of non-small cell lung cancer (NSCLC) in Asia. However, the impact of plasma mutation abundance, especially of the ultra-low abundance of mutation detected by highly sensitive techniques on clinical outcomes of first-line EGFR tyrosine kinase inhibitors (TKIs) for advanced NSCLC patients remains unclear.

Methods: We qualitatively detected baseline status of NSCLC tissues using amplification-refractory mutation system and quantified the plasma abundance of mutations through next-generation sequencing (NGS).

Targeting the EMT transcription factor Snail overcomes resistance to osimertinib in EGFR-mutant non-small cell lung cancer.

Background: The resistance mechanism of the third generation of epidermal growth factor (EGFR) tyrosine kinase inhibitor (TKI) osimertinib is complex. Epithelial mesenchymal transition (EMT) is a common mechanism of EGFR-TKI acquired resistance. Snail is an important transcription factor related to EMT.

Targeting DNA-PK overcomes acquired resistance to third-generation EGFR-TKI osimertinib in non-small-cell lung cancer.

The third-generation of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), represented by osimertinib, has achieved remarkable clinical outcomes in the treatment of non-small-cell lung cancer (NSCLC) with EGFR mutation. However, resistance eventually emerges in most patients and the underlying molecular mechanisms remain to be fully understood. In this study, we generated an osimertinib-acquired resistant lung cancer model from a NSCLC cell line H1975 harboring EGFR L858R and T790M mutations.