Discovery of the Clinical Candidate as a Highly Potent and Selective ATR Inhibitor.

ATR is one of the key DNA damage response (DDR) regulatory factors to maintain genome stability. ATR inhibition induces DNA damage accumulation and apoptosis in DDR kinase mutation or deficiency cancer cells through synthetic lethality, making it a promising target for treatment of cancers with DDR defects. Herein, we describe the discovery and preclinical evaluation of , a highly potent and selective novel ATR inhibitor, with favorable ADME, safety pharmacology, and pharmacokinetics profiles.

Utilizing a modified-Postoperative Morbidity Survey for assessing morbidity after laparoscopic or robot-assisted radical prostatectomy: a retrospective observational study.

Background: Compared with open radical prostatectomy (RP), laparoscopic or robot-assisted RP have shown a notable decrease in the incidence of organ dysfunction or potentially life-threating complications after surgery. However, despite advances, the postoperative length of hospital stay (LOS) remains longer than desired in many cases. The Postoperative Morbidity Survey (POMS) is a simple approach to detect complications capable of prolonging LOS.

METTL3 inhibitor suppresses the progression of prostate cancer via IGFBP3/AKT pathway and synergizes with PARP inhibitor.

The RNA N-methyladenosine (m6A) regulator METTL3 is an important regulatory gene in various progressive processes of prostate cancer (PCa). METTL3 inhibitors have been reported to possess potent tumor suppression capacity in some cancer types. Nevertheless, the detailed influence and mechanism of METTL3 inhibitors on PCa progression and their potential synergy with other drugs are poorly understood.

A system for fluid pumping by liquid metal multi-droplets.

The transportation and control of microfluidics have an important influence on the fields of biology, chemistry, and medicine. Pump systems based on the electrocapillary effect and room-temperature liquid metal droplets have attracted extensive attention. Flow rate is an important parameter that reflects the delivery performance of the pump systems.

Nrf2-mediated redox balance alleviates LPS-induced vascular endothelial cell inflammation by inhibiting endothelial cell ferroptosis.

Ferroptosis plays an important role in inflammation and oxidative stress. Whether ferroptosis is involved in the inflammation of vascular endothelial cells and its regulation mechanism remains unclear. We estimated the correlation between serum iron ion levels and the inflammation index of 33 patients with arteriosclerosis.

TFRC, associated with hypoxia and immune, is a prognostic factor and potential therapeutic target for bladder cancer.

Background: Bladder cancer is a common malignancy of the urinary system, and the survival rate and recurrence rate of patients with muscular aggressive (MIBC) bladder cancer are not ideal. Hypoxia is a pathological process in which cells acquire special characteristics to adapt to anoxic environment, which can directly affect the proliferation, invasion and immune response of bladder cancer cells. Understanding the exact effects of hypoxia and immune-related genes in BLCA is helpful for early assessment of the prognosis of BLCA.

Deciphering the significance of anoikis in bladder cancer and systematic analysis of S100A7 as a potential therapeutic target.

Background: Bladder cancer is an epidemic and life-threating urologic carcinoma. Anoikis is a unusual type of programmed cell death which plays a vital role in tumor survival, invasion and metastasis. Nevertheless, the relationship between anoikis and bladder cancer has not been understood thoroughly.

Coalescence-Induced Droplet Jumping on Superhydrophobic Surfaces with Annular Wedge-Shaped Micropillar Arrays.

The coalescence-induced droplet jumping on superhydrophobic surfaces has extensive application potential in water harvesting, thermal management of electronic devices, and microfluidics. The rational design of the surface structure can influence the interaction between the droplet and the surface, thereby controlling the velocity and direction of the droplet's jumping. In this study, we fabricate the superhydrophobic surface with annular wedge-shaped micropillar arrays, examine the dynamic behavior of condensate droplets on the surface, and measure the temporal and spatial variations of droplet density, average radius, and surface coverage with wedge-shaped micropillars of varying sizes.

Dendrocandin U from Dendrobium officinale Kimura et Migo Inhibits M1 Polarization in Alveolar Macrophage by Suppressing NF-κB Signaling Pathway.

Dendrobium officinale Kimura et Migo is a valuable and homologous medicine and food traditional Chinese medicine. Currently there are few studies on the anti-inflammatory activity of lipophilic components. The aim of this study was to explore the anti-inflammatory effect and mechanism of the lipophilic compounds in Dendrobium officinale.

A simplified frailty index and nomogram to predict the postoperative complications and survival in older patients with upper urinary tract urothelial carcinoma.

Purpose: This study was designed to investigate the clinical value of a simplified five-item frailty index (sFI) for predicting short- and long-term outcomes in older patients with upper urinary tract urothelial carcinoma (UTUC) patients after radical nephroureterectomy (RNU).

Method: This retrospective study included 333 patients (aged ≥65 years) with UTUC. Patients were classified into five groups: 0, 1, 2, 3, and 3+, according to sFI score.

Oxidative Stress Factors Mediate the Association Between Life's Essential 8 and Accelerated Phenotypic Aging: NHANES 2005-2018.

Cardiovascular health (CVH) is a well-known predictor of morbidity and mortality, while phenotypic age (PhenoAge) is a promising biomarker of aging. This study aimed to explore the association between Life's Essential 8 (LE8), a novel CVH measure, and PhenoAge acceleration (PhenoAgeAccel), as well as the potential mediating role of oxidative stress biomarkers in this relationship. A total of 23 896 individuals were included in the National Health and Nutrition Examination Survey database (2005-2018).

18 F-prostate specific membrane antigen positron emission tomography/computerized tomography for lymph node staging in medium/high risk prostate cancer: A systematic review and meta-analysis.

Background: Lymph node staging of prostate cancer (PCa) is important for planning and monitoring of treatment. 18 F-prostate specific membrane antigen positron emission tomography/computerized tomography ( 18 F-PSMA PET/CT) has several advantages over 68 Ga-PSMA PET/CT, but its diagnostic value requires further investigation. This meta-analysis focused on establishing the diagnostic utility of 18 F-PSMA PET/CT for lymph node staging in medium/high-risk PCa.

Synergetic benefits of pollution and carbon reduction from fly ash resource utilization-Based on the life cycle perspective.

Synergetic reduction of pollution and carbon is a key strategy for the fundamental improvement of ecological and environmental quality and carbon neutrality. Solid waste resource utilization can reduce the secondary pollution caused by conventional solid waste disposal and presents evident environmental potential. Based on the comparable system boundaries, this study adopts life cycle assessment (LCA) to compare the environmental impact of three fly ash utilization paths.

FOXM1-regulated ZIC2 promotes the malignant phenotype of renal clear cell carcinoma by activating UBE2C/mTOR signaling pathway.

As a transcription factor, Zic family member 2 (ZIC2) has been involved in more and more studies of tumorigenesis, which has been proved by our research team to be an effective prognostic marker for Pan-cancer. However, the prognosis, tumor promoting effect and regulatory mechanism of ZIC2 in clear cell renal cell carcinoma (ccRCC) are still unknown. The potential clinical significance of ZIC2 was evaluated by bioinformatics analysis using data from TCGA, GEO, and ArrayExpress data sets.

Acceleration of nitrogen removal performance in a biofilm reactor augmented with Pseudomonas sp. using polycaprolactone as carbon source for treating low carbon to nitrogen wastewater.

Heterotrophic nitrification-aerobic denitrification (HN-AD) process was achieved in a moving bed biofilm reactor after 180-days acclimation using PCL as carbon source for low C/N wastewater treatment. A novel HN-AD strain, JQ-H3, with ability of PCL degradation was augmented to improve nitrogen removal. TN removal efficiencies of 82.

An Oscillation System Based on a Liquid Metal Droplet and Pillars under a Direct Current Electric Field.

Gallium-based liquid metal is a new class of material that has attracted extensive attention due to its excellent deformation characteristics and great potential in applications. Based on the deformation characteristics of liquid metal droplets, researchers have developed many oscillation systems composed of gallium indium tin alloy (GaInSn) droplet and graphite, or aluminum-doped gallium indium alloy (Al-GaIn) droplet and iron, and so on. Rather than the oxidation and deoxidation mechanisms used in previous systems, an oscillation system that can achieve gallium indium alloy (EGaIn) droplet oscillation with the frequency of 0-29 Hz is designed depending on the interactions between the electric field, pillars, sodium hydroxide, and the droplet.

High-speed directional transport of condensate droplets on superhydrophobic saw-tooth surfaces.

Hypothesis: Most droplets on high-efficiency condensing surfaces have radii of less than 100 μm, but conventional droplet transport methods (such as wettability-gradient surfaces and structural-curvature-gradient surfaces) that rely on the unbalanced force of three-phase lines can only transport millimeter-sized droplets efficiently. Regulating high-speed directional transport of condensate droplets is still challenging. Therefore, we present a method for condensate droplet transportation, based on the reaction force of the superhydrophobic saw-tooth surfaces to the liquid bridge, the condensate droplets could be transported at high speed and over long distances.

Prognostic models for upper urinary tract urothelial carcinoma patients after radical nephroureterectomy based on a novel systemic immune-inflammation score with machine learning.

Purpose: This study aimed to evaluate the clinical significance of a novel systemic immune-inflammation score (SIIS) to predict oncological outcomes in upper urinary tract urothelial carcinoma(UTUC) after radical nephroureterectomy(RNU).

Method: The clinical data of 483 patients with nonmetastatic UTUC underwent surgery in our center were analyzed. Five inflammation-related biomarkers were screened in the Lasso-Cox model and then aggregated to generate the SIIS based on the regression coefficients.

Is it necessary for all patients with suspicious lesions undergo systematic biopsy in the era of MRI-TRUS fusion targeted biopsy?

Purpose: Targeted biopsy (TB) combined with systematic biopsy (SB) is an optimized mode of prostate biopsy but can often lead to oversampling and overdiagnosis accompanied by potential biopsy-related complications and patient discomfort. Here, we attempted to reasonably stratify the patient population based on multi-parameter indicators with the aim of avoiding unnecessary SB.

Methods: In total, 340 biopsy-naïve men with suspected lesions, prostate-specific antigen (PSA) < 20 ng/mL and prostate imaging-reporting and data system (PI-RADS) ≥ 3 enrolled for study underwent both TB and SB.

Sacral neuromodulation remote programming in patients with refractory lower urinary tract dysfunction: China's experience during the COVID-19 pandemic.

Objectives: Sacral neuromodulation is an effective, minimally invasive treatment for refractory lower urinary tract dysfunction. However, regular postoperative programming is crucial for the maintenance of the curative effects of electronic sacral stimulator devices. The outbreak of coronavirus disease 2019 (COVID-19) limited the ability of practitioners to perform traditional face-to-face programming of these stimulators.