ACTN2, regulated by PRDM9, affects the growth and inflammation of vascular smooth muscle cells by interacting with PDLIM1 in intracranial aneurysms.

Background: The occurrence of aneurysms is closely related to the growth and inflammatory response of vascular smooth muscle cells (VSMCs). The regulatory mechanism of ACTN2 in intracranial aneurysms (IA) has not yet been fully elucidated. This study aims to reveal the role of the PRDM9-ACTN2-PDLIM1 axis in the progression of aneurysms and its impact on VSMCs.

Falls and loneliness among Chinese older adults: evidence from a nationally representative longitudinal study.

Background: Falls and loneliness are both common during older adulthood and detrimental to older adults' health. However, it remains unclear whether and how falls may be longitudinally related to loneliness among older adults, despite some cross-sectional evidence in both Western and Chinese contexts. This study aimed to examine the longitudinal association between falls and loneliness among Chinese older adults, its potential variation across age groups, and the role of social adaptation in mediating the association.

Disrupting tumor homeostasis with an autoamplificatory nanoinducer to augment pyroptosis for efficient immunotherapy.

Abnormal tumor homeostasis is crucial in maintaining tumor cell survival and growth. Thus, developing effective antitumor strategies that can simultaneously disrupt multiple intracellular homeostatic mechanisms may be more effective and less laborious. Herein, an autoamplificatory nanoinducer (CLRN) composed of photosensitizer Ce6, glucose metabolism inhibitor lonidamine and methyltransferase inhibitor RG108 is designed and constructed to enhance pyroptosis and upregulate immunosurveillance by disrupting intracellular redox and metabolic homeostasis.

Event-Driven Taxonomy (EDT) Screening: Leveraging Effect-Based Spectral Libraries to Accelerate Semiquantitative Nontarget Analysis of AhR Agonists in Sediment in the Era of Big Data.

Sediments contain complex chemical mixtures. While effect-directed analysis (EDA) combined with nontarget screening (NTS) is promising, its large-scale application has been limited by time-consuming workflows. Here, we developed an event-driven taxonomy (EDT)-Screening strategy to effectively identify and semiquantify nontarget bioactive contaminants in sediment, taking aryl hydrocarbon receptor (AhR) activity as an example.

A dual-targeting strategy to inhibit colorectal cancer liver metastasis via tumor cell ferroptosis and cancer-associated fibroblast reprogramming.

Colorectal cancer (CRC) remains a leading cause of cancer-related mortality, with liver metastasis posing a significant therapeutic challenge. Within the "seed and soil" paradigm, disrupting both tumor cells and their supportive microenvironment is essential to suppress disease progression. Here, we utilized single-cell transcriptomics of clinical CRC samples identified NOX4 (NADPH oxidase 4 positive) cancer-associated fibroblasts (CAFs) and CXCR4 (C-X-C motif chemokine receptor 4 positive)/GPX4 (glutathione peroxidase 4 positive) tumor cells as critical drivers of metastasis.

Amplification of cGAS-STING pathway with "single-molecule multitarget" nanoparticles for chemo-immunotherapy of ovarian cancer.

With a low autoimmune risk and dedicated induction of type Ⅰ interferon production in immunotherapy, "STING therapy" holds broad prospects in the treatment of aggressive and metastatic cancers such as ovarian cancer (OC). Inducing pyroptosis constitutes a promising approach for activating the anti-tumor immune response. Nevertheless, compared to combination therapies, "single-molecule multitarget" drugs possess the merits of a lower interaction risk, more predictable pharmacokinetics and a lower cost of clinical trials.

The effects of fixation stability, corneal density, and epithelial hyperplasia on the efficacy of astigmatism correction by transepithelial photorefractive keratectomy.

Background: Transepithelial photorefractive keratectomy (transPRK) can be safely and predictably performed to correct low-to-high astigmatism. This study explored the effects of fixation stability, corneal density (CD), ocular residual astigmatism (ORA), and the surgically-induced change in the epithelial thickness (ΔET) on the efficacy of astigmatism correction by transPRK.

Methods: Eighty-three consecutive patients who underwent transPRK to correct myopia and myopic astigmatism were divided into two groups according to refractive astigmatism [high refractive astigmatism (RA) group: ≥ 2.

Synthesis and biological evaluation of Ga-DOTA-AngII as a radiotracer for PET/MR imaging of hepatocellular carcinoma.

The precise diagnosis of HCC is confronted with severe challenges due to the tumor heterogeneity and insidious symptoms of hepatocellular carcinoma (HCC), and meanwhile the limitations of positron emission tomography (PET) with traditional 2-deoxy-2-[fluorine-18] fluoro-d-glucose (F-FDG) tracer. Given that angiotensin II type 1 receptor (AT1R) is significantly upregulated in HCC and closely related to its progression, we have developed a novel Ga-radiolabeled compound, Ga-DOTA-AngII (Ga-DOTA-GGDRVYIHPF), and evaluated its HCC detection capability. Ga-DOTA-AngII demonstrated acceptable stability in both human plasma and phosphate buffered saline.

The Effect and Safety of Dexmedetomidine Administration on Mother and Foetus/Neonates During General Anaesthesia in Caesarean Section: A Randomised Controlled Trial.

Purpose: This study aimed to assess the safety of dexmedetomidine administration to mothers, fetuses, and neonates during general anesthesia in cesarean section (CS).

Patients And Methods: A total of 60 parturients scheduled for elective CS under general anesthesia were randomly divided into anesthesia in groups (DEX1 and DEX2) and control (C) groups. Groups DEX1 and DEX2 were induced with dexmedetomidine (induction, 0.

Effectiveness of single-target fecal DNA methylation test in regional mass screening for colorectal cancer and precancerous lesions in China.

Background: Colorectal cancer (CRC) is the third-most-common malignancy and the second-leading cause of cancer-related deaths worldwide and current screening methods such as guaiac-based fecal occult blood test (gFOBT), fecal immunochemical test (FIT), and colonoscopy have their own pros and cons. This study aimed to assess the effectiveness of a fecal DNA methylation test by using methylated (m) as the epigenetic biomarker for detecting CRC in a screening-naïve population.

Methods: Fecal m test and FIT were simultaneously performed on eligible 40- to 74-year-old adults of a regional township in China.

Visible-Light-Mediated Metal/Base-Free Stereoselective -Alkyl Glycosylation via EDA Complexes of Glycosyl Xanthates and NHC-Borane.

Owing to the toxic reagent and high temperature required, the application of xanthate-based radical chemistry has been limited. To address these challenges, we report a metal- and base-free, photoinduced strategy for stereoselective -alkyl glycosylation via electron donor-acceptor (EDA) complexes of glycosyl xanthates and N-heterocyclic carbene (NHC)-BH. This method generates glycosyl radicals under mild conditions, affording compatibility with a wide range of sugars and olefins to produce -alkyl glycosides in good to excellent yields.

Development and preclinical evaluation of a gallium-68 labeled novel diagnostic tracer for visualizing ALK expression in tumor.

Anaplastic lymphoma kinase (ALK) is prominently expressed in numerous malignant tumors, which lead to aberrant tumor proliferation, invasion and metastasis. Ceritinib (LDK378), as second-generation targeted drugs, has been used to treat advanced ALK-positive non-small cell lung cancer (NSCLC). Herein, we sought to develop a novel ALK-positron emission tomography/magnetic resonance (PET/MR) tracer Ga-DOTA-CTB (Ga labeled ceritinib) based on ceritinib scaffold to monitor the ALK expression levels during targeted therapy with ceritinib.

Visible-Light-Mediated Synthesis of Anomeric -Aryl Glycosides via Electron Donor-Acceptor Complex Using Thianthrenium Salts.

-Aryl glycosides are not only popular glycosyl donors in carbohydrate chemistry but also serve as valuable tools in various biological studies, which has brought significant attention to their preparation. However, there remains a pressing need for greener synthesis methods in this area. In response, a mild, sustainable, and metal- and photocatalyst-free electron donor-acceptor (EDA)-mediated approach for synthesizing -Aryl glycosides using 1-thiosugar and aryl thianthrenium salt was developed.

Dexmedetomidine alleviates sevoflurane-induced neurotoxicity during late pregnancy by modulating apoptotic pathways and BDNF receptor expression.

To investigate the associations between the neurotoxicity of sevoflurane and the neuroprotection provided by dexmedetomidine, we measured apoptotic gene and protein expression, brain-derived neurotrophic factor (BDNF) levels, and receptor expression, and neuronal apoptosis. Pregnant rats were treated with dexmedetomidine, 2.5% sevoflurane for 6 h, or a combination of 2.

Nutrient transporter-oriented nanoinhibitor counteracts intracellular metabolic reprogramming for RT-resistant HCC treatment.

Radiotherapy (RT) is the primary treatment modality for hepatocellular carcinoma (HCC). Inevitably, the X-ray exposure also increases the metabolic stress and energy demands in surviving tumor cells, which leads to metabolic reprogramming that reduces the sensitivity of HCC to clinical treatments including RT. Nevertheless, the current research in tumor metabolic therapy predominantly focuses on inhibiting glycolytic pathways, and the consequent metabolic compensation behavior of tumor cells exacerbates the risks of drug resistance and recurrence.

Identification of Hydroxylated Chlorinated Paraffins in Human Serum and Their Potential Metabolic Pathways.

Short- and medium-chain chlorinated paraffins (SCCPs and MCCPs) are frequently detected in humans. However, information regarding their metabolites is still very limited. Herein, target analysis and halogenation-guided nontarget and suspect screening were conducted on serum samples using UHPLC-Orbitrap-HRMS.

Novel idebenone derivatives attenuated oxidative stress injury and myocardial damage.

Oxidative stress-induced cardiomyocyte apoptosis was the primary causative factor of cardiovascular disease (CVD). However, the existing therapy drugs for oxidative stress were much less investigated, which underlined the necessity for new drug discovery and development. Herein, we aimed to synthesize several novel idebenone (IDE) derivatives and investigate the protective effect and mechanism of these derivatives against HO-induced oxidative stress injury in H9C2 cells by determining cell proliferation rate, detecting the reactive oxygen species (ROS) level, and the expression of related proteins.

Efficient dual-phase PtNiCuMnMo high-entropy alloy electrocatalyst for alkaline hydrogen evolution reaction.

The realisation of high-performance cathodic hydrogen evolution reaction (HER) is of considerable importance for the development of the nascent hydrogen economy. Herein, we develop a dual-phase PtNiCuMnMo high-entropy alloy (HEA) showing excellent alkaline HER performance with an overpotential of as low as 44 mV at a current density of 10 mA/cm. Additionally, the PtNiCuMnMo HEA catalyst maintains stability after 72 h at a current density of 200 mA/cm.

Polyhalogenated carbazoles in the environment: Analysis, origins, occurrence, and toxicity.

Polyhalogenated carbazoles are a class of emerging organic compounds characterized by the substitution of one to eight hydrogen atoms in the carbazole structure with halogen atom(s). Polyhalogenated carbazoles originate from natural and anthropogenic sources and are widely distributed in the environment. They are persistent in the environment and present a range of toxic effects, notably dioxin-like activity.

STING pathway activation with cisplatin polyprodrug nanoparticles for chemo-immunotherapy in ovarian cancer.

Cisplatin serves as the cornerstone medication in ovarian cancer (OC) chemotherapy; however, numerous resistance factors exist, resulting in unsatisfactory clinical treatment outcomes. Concurrently, OC frequently establishes an immunosuppressive microenvironment, which further exacerbates the challenges of cisplatin chemotherapy. Hence, it is particularly significant to explore a therapeutic approach capable of overcoming cisplatin resistance while reversing the immunosuppressive microenvironment of OC.

Identifying and prioritizing organic toxicants in treated flowback and produced water from shale gas exploitation sites using an integrative effect-directed analysis and nontarget screening method.

The use of hydraulic fracturing in shale gas exploitation has generated substantial amount of flowback and produced water (FPW), and ecological risk of these highly complex chemical mixtures has raised worldwide concern. Herein, an integrative effect-directed analysis (EDA) and nontarget screening (NTS) workflow was developed to identify and prioritize main toxicants in the treated FPW (T-FPW). The workflow included sample extraction and fractionation, zebrafish embryo toxicity tests, target and nontarget chemical analyses, and toxicity prioritization and confirmation using toxicological priority index (ToxPi).

Fate and transformation of psychotropic drugs in urban wastewater systems and receiving rivers via the integration of targeted and suspect screening analysis.

Psychotropic drugs rank among the most prescribed pharmaceuticals in the world. The ubiquitous occurrence of psychotropic drugs in the environment evoked rising concerns due to their various toxic effect on non-target organisms at low concentrations. However, the removal, transformation, and discharging of these drugs throughout wastewater treatment plants (WWTPs) have rarely been reported.

Synthesis and biological evaluation of novel isatin-phenol hybrids as potential antitumor agents.

Chemotherapy was one of indispensable methods for treating cancer, and the development of novel antitumor drugs was necessary due to the emergent drug resistance and undesirable side effects. In the current study, we successfully constructed a novel library of isatin-phenol hybrids by chemical coupling of isatin (1) with a series of active phenols including honokiol (2), magnolol (3), bis(4-hydroxy-3-methylphenyl) sulfide (4), bisphenol A (5), carvacrol (6), and hydroxyqunioline (7) respectively. The target molecules were screened for anticancer activity, and we further investigate the anti-cancer mechanism of the most potent compound IPH10 in vitro and in vivo.

Developing a cloud-based WebGIS tool for communicating integrated ecosystem services assessment modeling to conservation stakeholders.

Various modeling efforts have been conducted to evaluate ecosystem services (ES) of agricultural conservation practices but typically these models are too complex for conservation stakeholders to use. This research developed a cloud-based WebGIS tool for communicating integrated ES modeling to conservation stakeholders. The integrated ES modeling was developed by linking farm economic, watershed hydrologic, and soil carbon modeling within a spatial optimization framework for identifying conservation practices to minimize economic costs subject to multiple ES targets including water quality and soil carbon improvement benefits.