A cofactor-induced repressive type of transcription factor condensation can be induced by synthetic peptides to suppress tumorigenesis.

Transcriptional factors (TFs) act as key determinants of cell death and survival by differentially modulating gene expression. Here, we identified many TFs, including TEAD4, that form condensates in stressed cells. In contrast to YAP-induced transcription-activating condensates of TEAD4, we found that co-factors such as VGLL4 and RFXANK alternatively induced repressive TEAD4 condensates to trigger cell death upon glucose starvation.

Carotid artery transplantation of brain endothelial cells enhances neuroprotection and neurorepair in ischaemic stroke rats.

Brain microvascular endothelial cells (BMECs), an important component of the neurovascular unit, can promote angiogenesis and synaptic formation in ischaemic mice after brain parenchyma transplantation. Since the therapeutic efficacy of cell-based therapies depends on the extent of transplanted cell residence in the target tissue and cell migration ability, the delivery route has become a hot research topic. In this study, we investigated the effects of carotid artery transplantation of BMECs on neuronal injury, neurorepair, and neurological dysfunction in rats after cerebral ischaemic attack.

Reactivating Hippo by drug compounds to suppress gastric cancer and enhance chemotherapy sensitivity.

The Hippo signaling pathway plays an essential role in organ size control and tumorigenesis. Loss of Hippo signal and hyper-activation of the downstream oncogenic YAP signaling are commonly observed in various types of cancers. We previously identified STRN3-containing PP2A phosphatase as a negative regulator of MST1/2 kinases (i.

Efficacy and Safety of Inclisiran in Asian Patients: Results From ORION-18.

Background: Management of low-density lipoprotein cholesterol (LDL-C) in Asia remains suboptimal, with ∼50% of patients who are treated with lipid-lowering therapies (LLTs) unable to achieve their guideline-recommended LDL-C goals. Asian-representative studies of the use of inclisiran are needed.

Objectives: The authors sought to evaluate the efficacy and safety of inclisiran in Asian patients with atherosclerotic cardiovascular disease (ASCVD) or high risk of ASCVD, as an adjunct to diet and maximally tolerated statin dose, with or without additional LLTs.

SUN1/2 controls macrophage polarization via modulating nuclear size and stiffness.

Alteration of the size and stiffness of the nucleus triggered by environmental cues are thought to be important for eukaryotic cell fate and function. However, it remains unclear how context-dependent nuclear remodeling occurs and reprograms gene expression. Here we identify the nuclear envelope proteins SUN1/2 as mechano-regulators of the nucleus during M1 polarization of the macrophage.

Aldehyde dehydrogenase 2 deficiency reinforces formaldehyde-potentiated pro-inflammatory responses and glycolysis in macrophages.

Aldehyde dehydrogenase 2 (ALDH2) deficiency caused by   genetic variant is present in more than 560 million people of East Asian descent, which can be identified by apparent facial flushing from acetaldehyde accumulation after consuming alcohol. Recent findings indicated that ALDH2 also played a critical role in detoxification of formaldehyde (FA). Our previous studies showed that FA could enhance macrophagic inflammatory responses through the induction of HIF-1α-dependent glycolysis.

A YAP/TAZ-CD54 axis is required for CXCR2-CD44- tumor-specific neutrophils to suppress gastric cancer.

As an important part of tumor microenvironment, neutrophils are poorly understood due to their spatiotemporal heterogeneity in tumorigenesis. Here we defined, at single-cell resolution, CD44-CXCR2- neutrophils as tumor-specific neutrophils (tsNeus) in both mouse and human gastric cancer (GC). We uncovered a Hippo regulon in neutrophils with unique YAP signature genes (e.

Formaldehyde aggravates allergic contact dermatitis by facilitating NLRP3 inflammasome activation in macrophages.

Formaldehyde (FA) is known to be an environmental pollutant and contact sensitizer at 1 % or 2 % concentrations, which can induce inflammatory diseases such as allergic contact dermatitis (ACD). However, the aggravative effects of FA on ACD at legitimate low concentrations in cosmetics have not been studied. The activation of NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome in ACD was recently identified, and the inflammatory responses were attenuated by NLRP3 inhibition.

Comparison of robot versus fluoroscopy-assisted pedicle screw instrumentation in adolescent idiopathic scoliosis surgery: A retrospective study.

The aim of this study was to explore whether a robot-assisted (RA) technique has advantages over the conventional fluoroscopy-assisted (FA) technique in clinical and radiological outcomes and whether it could decrease the incidence of mis-implantations of pedicle screws in adolescent idiopathic scoliosis (AIS) correction surgery. A total of 101 patients with AIS were recruited (RA group: 45 patients underwent RA screw insertion; FA group: 56 patients underwent FA screw insertion). When comparing the radiological data between the two groups, the major and secondary curves were both corrected proficiently with no difference in Cobb angle comparison at the last follow-up, suggesting that both the RA technique and the FA technique could lead to efficient radiographic correction and similar clinical outcomes (all, 0.

Incorporating multiple magnetic resonance diffusion models to differentiate low- and high-grade adult gliomas: a machine learning approach.

Background: Accurate grading of gliomas is a challenge in imaging diagnosis. This study aimed to evaluate the performance of a machine learning (ML) approach based on multiparametric diffusion-weighted imaging (DWI) in differentiating low- and high-grade adult gliomas.

Methods: A model was developed from an initial cohort containing 74 patients with pathology-confirmed gliomas, who underwent 3 tesla (3T) diffusion magnetic resonance imaging (MRI) with 21 b values.

Myricetin alleviates the formaldehyde-enhanced Warburg effect in tumor cells through inhibition of HIF-1α.

Myricetin is a flavonoid widely-distributed in foods with many beneficial health effects, which has been marketed in health products. Formaldehyde is an environmental carcinogen which can enhance the Warburg effect through the induction of human hypoxia-inducible factor 1 subunit alpha (HIF-1α), the primary regulator of cellular glycolysis. HIF-1α was verified as an important target in lung and ovarian tumors, which was also identified as a receptor for myricetin via molecular docking.

The function of FUS in neurodevelopment revealed by the brain and spinal cord organoids.

The precise control of proliferation and differentiation of neural progenitors is crucial for the development of the central nervous system. Fused in sarcoma (FUS) is an RNA-binding protein pathogenetically linked to Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Lobar Degeneration (FTLD) disease, yet the function of FUS on neurodevelopment is remained to be defined. Here we report a pivotal role of FUS in regulating the human cortical brain and spinal cord development via the human iPSCs-derived organoids.

Management of Primary Brainstem Hemorrhage: A Review of Outcome Prediction, Surgical Treatment, and Animal Model.

Primary brainstem hemorrhage (PBH) has the worst prognosis of all types of intracerebral hemorrhage. Currently, the management of PBH is controversial. Hematoma classification, scoring systems, and electrophysiological monitoring are critical for predicting the outcome of PBH.

Accumulation of Intracellular Ferrous Iron in Inflammatory-Activated Macrophages.

Macrophages are important innate immune cells which can be polarized into heterogeneous populations. The inflammatory-activated M1 cells are known to be involved in all kinds of inflammatory diseases, which were also found to be associated with dysregulation of iron metabolism. While iron overload is known to induce M1 polarization, the valence states of iron and its intracellular dynamics during macrophage inflammatory activation have not been identified.

Genomic Profiling of Chinese Cervical Cancer Patients Reveals Prevalence of DNA Damage Repair Gene Alterations and Related Hypoxia Feature.

Background: Cervical cancer is responsible for 10-15% of cancer-related deaths in women worldwide. In China, it is the most common cancer in the female genital tract. However, the genomic profiles of Chinese cervical cancer patients remain unclear.

Formaldehyde reinforces pro-inflammatory responses of macrophages through induction of glycolysis.

Formaldehyde (FA) is widely used in chemical industry, which is also known as a common indoor air pollutant. Exposure of FA has been associated with multiple detrimental health effects. Our previous study showed that FA could inhibit the development of T lymphocytes in mice, leading to impaired immune functions.

Prospective assessment of diagnostic efficacy and safety of Sonazoid and SonoVue ultrasound contrast agents in patients with focal liver lesions.

Objectives: To assess the respective diagnostic value of Sonazoid™ and SonoVue® for characterizing FLLs as benign or malignant and the corresponding safety.

Methods: This prospective Phase 3 study was conducted at 17 centres in China and Korea (May 2014 to April 2015); 424 patients (20 to 80 years) with at least 1 untreated focal liver lesion (FLL) (< 10 cm in diameter) underwent a contrast-enhanced ultrasound (CEUS) examination (218 received Sonazoid of 0.12 μL microbubbles/kg; 206 received SonoVue of 2.

The loss of SHMT2 mediates 5-fluorouracil chemoresistance in colorectal cancer by upregulating autophagy.

5-Fluorouracil (5-FU)-based chemotherapy is the first-line treatment for colorectal cancer (CRC) but is hampered by chemoresistance. Despite its impact on patient survival, the mechanism underlying chemoresistance against 5-FU remains poorly understood. Here, we identified serine hydroxymethyltransferase-2 (SHMT2) as a critical regulator of 5-FU chemoresistance in CRC.

Myricetin protects natural killer cells from arsenite induced DNA damage by attenuating oxidative stress and retaining poly(ADP-Ribose) polymerase 1 activity.

Environmental exposure to arsenite (As) is known to induce immunotoxicity. Natural killer (NK) cells are innate lymphoid cells act as professional killers of tumor cells. Our previous report indicated that 500 ppb As drinking water exposure induced significant DNA damage in the NK cells of C57BL/6 mice.

Fluorophore-Promoted Facile Deprotonation and Exocyclic Five-Membered Ring Cyclization for Selective and Dynamic Tracking of Labile Glyoxals.

The lack of effective chemical tools capable of dynamic tracking of labile glyoxal species (GOS) [e.g., methylglyoxal (MGO) and glyoxal (GO)] levels with high selectivity over other relevant electrophilic species, particularly, formaldehyde (FA) and nitric oxide (NO), has significantly hampered the understanding of their roles in a complex metabolic network and disease progressions.