Lagrangian study of floating debris transport around the Pearl River Estuary in summer.

Transport of floating debris around the Pearl River Estuary (PRE, China) in summer is investigated by using drifter trajectories, a regional ocean model and a particle tracking model. Comparisons between simulated and drifter trajectories demonstrate that the particle tracking model accurately simulates the movement of floating debris. Ideal experiment results show that 85 % of floating debris is stranded in the PRE due to density currents, tidal currents, and wind effects.

ALKBH5 deletion ameliorates inflammation by regulating IRF3 signaling in an mA-dependent manner after myocardial infarction.

AlkB homolog 5 (ALKBH5) plays an important role in ischemia/reperfusion (I/R), cardiac hypertrophy and other cardiovascular diseases (CVDs). However, whether ALKBH5 regulates the inflammatory response by mediating M1/M2 macrophage conversion after myocardial infarction (MI) is unclear. In this study, we found that ALKBH5 protein expression was significantly downregulated in MI mice.

Tumor Microenvironment-Responsive Nanocapsule Delivery CRISPR/Cas9 to Reprogram the Immunosuppressive Microenvironment in Hepatoma Carcinoma.

Cancer immunotherapy has demonstrated significant efficacy in various tumors, but its effectiveness in treating Hepatocellular Carcinoma (HCC) remains limited. Therefore, there is an urgent need to identify a new immunotherapy target and develop corresponding intervention strategies. Bioinformatics analysis has revealed that growth differentiation factor 15 (GDF15) is highly expressed in HCC and is closely related to poor prognosis of HCC patients.

Involvement of Embryo-Derived and Monocyte-Derived Intestinal Macrophages in the Pathogenesis of Inflammatory Bowel Disease and Their Prospects as Therapeutic Targets.

Inflammatory bowel disease (IBD) is a group of intestinal inflammatory diseases characterized by chronic, recurrent, remitting, or progressive inflammation, which causes the disturbance of the homeostasis between immune cells, such as macrophages, epithelial cells, and microorganisms. Intestinal macrophages (IMs) are the largest population of macrophages in the body, and the abnormal function of IMs is an important cause of IBD. Most IMs come from the replenishment of blood monocytes, while a small part come from embryos and can self-renew.

Biomimetic Macrophage Membrane-Camouflaged Nanoparticles Induce Ferroptosis by Promoting Mitochondrial Damage in Glioblastoma.

The increasing understanding of ferroptosis has indicated its role and therapeutic potential in cancer; however, this knowledge has yet to be translated into effective therapies. Glioblastoma (GBM) patients face a bleak prognosis and encounter challenges due to the limited treatment options available. In this study, we conducted a genome-wide CRISPR-Cas9 screening in the presence of a ferroptosis inducer (RSL3) to identify the key driver genes involved in ferroptosis.

Engineered Extracellular Vesicle-Delivered CRISPR/Cas9 for Radiotherapy Sensitization of Glioblastoma.

Radiotherapy is a mainstay of glioblastoma (GBM) treatment; however, the development of therapeutic resistance has hampered the efficacy of radiotherapy, suggesting that additional treatment strategies are needed. Here, an loss-of-function genome-wide CRISPR screen was carried out in orthotopic tumors in mice subjected to radiation treatment to identify synthetic lethal genes associated with radiotherapy. Using functional screening and transcriptome analyses, glutathione synthetase (GSS) was found to be a potential regulator of radioresistance through ferroptosis.

Rac GTPase activating protein 1 promotes the glioma growth by regulating the expression of MCM3.

Glioma is the most common tumor of the nervous system. The diffuse growth and proliferation of glioma poses great challenges for its treatment. Here, Transcriptomic analysis revealed that Rac GTPase activating protein 1 (RACGAP1) is highly expressed in glioma.

Clinical Analysis of Laparoscopic Common Bile Duct Primary Suture and T-Tube Drainage in the Treatment of Common Bile Duct Stones.

At present, T-tube drainage or primary suture for common bile duct stones is common management. The clinical data of 100 patients who underwent laparoscopic common bile duct exploration and T-tube drainage or primary suture for common bile duct stones from 2019 to 2021 were analyzed retrospectively, including 50 cases of primary suture and 50 cases of T-tube drainage. The operation time and postoperative hospital stay of patients with primary suture were lower than those in T-tube drainage group ( < .

Exosome-transmitted circCABIN1 promotes temozolomide resistance in glioblastoma via sustaining ErbB downstream signaling.

Although temozolomide (TMZ) provides significant clinical benefit for glioblastoma (GBM), responses are limited by the emergence of acquired resistance. Here, we demonstrate that exosomal circCABIN1 secreted from TMZ-resistant cells was packaged into exosomes and then disseminated TMZ resistance of receipt cells. CircCABIN1 could be cyclized by eukaryotic translation initiation factor 4A3 (EIF4A3) and is highly expressed in GBM tissues and glioma stem cells (GSCs).

Pharmacokinetics, distribution, metabolism, and excretion of body-protective compound 157, a potential drug for treating various wounds, in rats and dogs.

Body-protective compound (BPC) 157 demonstrates protective effects against damage to various organs and tissues. For future clinical applications, we had previously established a solid-phase synthesis process for BPC157, verified its biological activity in different wound models, and completed preclinical safety evaluations. This study aimed to investigate the pharmacokinetics, excretion, metabolism, and distribution profiles of BPC157.

Kill two birds with one stone: Engineered exosome-mediated delivery of cholesterol modified YY1-siRNA enhances chemoradiotherapy sensitivity of glioblastoma.

Glioblastoma (GBM) is the most malignant tumor of the central nervous system in adults. Irradiation (IR) and temozolomide (TMZ) play an extremely important role in the treatment of GBM. However, major impediments to effective treatment are postoperative tumor recurrence and acquired resistance to chemoradiotherapy.

Unsupervised learning for robust working memory.

Working memory is a core component of critical cognitive functions such as planning and decision-making. Persistent activity that lasts long after the stimulus offset has been considered a neural substrate for working memory. Attractor dynamics based on network interactions can successfully reproduce such persistent activity.

Genome-wide CRISPR screen identified Rad18 as a determinant of doxorubicin sensitivity in osteosarcoma.

Background: Osteosarcoma (OS) is a malignant bone tumor mostly occurring in children and adolescents, while chemotherapy resistance often develops and the mechanisms involved remain challenging to be fully investigated.

Methods: Genome-wide CRISPR screening combined with transcriptomic sequencing were used to identify the critical genes of doxorubicin resistance. Analysis of clinical samples and datasets, and in vitro and in vivo experiments (including CCK-8, apoptosis, western blot, qRT-PCR and mouse models) were applied to confirm the function of these genes.

Targeting radiation-tolerant persister cells as a strategy for inhibiting radioresistance and recurrence in glioblastoma.

Background: Compelling evidence suggests that glioblastoma (GBM) recurrence results from the expansion of a subset of tumor cells with robust intrinsic or therapy-induced radioresistance. However, the mechanisms underlying GBM radioresistance and recurrence remain elusive. To overcome obstacles in radioresistance research, we present a novel preclinical model ideally suited for radiobiological studies.

LuHui Derivative, A Novel Compound That Inhibits the Fat Mass and Obesity-Associated (FTO), Alleviates the Inflammatory Response and Injury in Hyperlipidemia-Induced Cardiomyopathy.

Hyperlipidemia is a major risk factor for metabolic disorders and cardiovascular injury. The excessive deposition of saturated fatty acids in the heart leads to chronic cardiac inflammation, which in turn causes myocardial damage and systolic dysfunction. However, the effective suppression of cardiac inflammation has emerged as a new strategy to reduce the impact of hyperlipidemia on cardiovascular disease.

LncRNA promotes the malignant progression of colorectal cancer by regulating the miR-214-5p-JAG1 axis.

Background: Long non-coding RNAs (lncRNAs) have recently been found to be vital regulators of various cancers, including colorectal cancer (CRC). It has been previously reported that the dysregulated expression of lncRNA Five prime to Xist () is involved in carcinogenesis. However, the role of lncRNA in the progression of CRC is still unclear.

GDF15 induces immunosuppression via CD48 on regulatory T cells in hepatocellular carcinoma.

Background: A better understanding of the molecular mechanisms that manifest in the immunosuppressive tumor microenvironment (TME) is crucial for developing more efficacious immunotherapies for hepatocellular carcinoma (HCC), which has a poor response to current immunotherapies. Regulatory T (Treg) cells are key mediators of HCC-associated immunosuppression. We investigated the selective mechanism exploited by HCC that lead to Treg cells expansion and to find more efficacious immunotherapies.

Mkx mediates tenogenic differentiation but incompletely inhibits the proliferation of hypoxic MSCs.

Background: Hypoxia has been shown to be able to induce tenogenic differentiation and proliferation of mesenchymal stem cells (MSCs) which lead hypoxia-induced MSCs to be a potential treatment for tendon injury. However, little is known about the mechanism underlying the tenogenic differentiation and proliferation process of hypoxic MSCs, which limited the application of differentiation-inducing therapies in tendon repair. This study was designed to investigate the role of Mohawk homeobox (Mkx) in tenogenic differentiation and proliferation of hypoxic MSCs.

Urinary metabolomics analysis of the protective effects of Daming capsule on hyperlipidemia rats using ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry.

Hyperlipidemia is recognized as one of the most important risk factors for morbidity and mortality due to cardiovascular diseases. Daming capsule, a Chinese patent medicine, has shown definitive efficacy in patients with hyperlipidemia. In this study, serum biochemistry and histopathology assessment were used to investigate the lipid-lowering effect of Daming capsule.

MicroRNA-98 ameliorates doxorubicin-induced cardiotoxicity via regulating caspase-8 dependent Fas/RIP3 pathway.

Cardiotoxicity is one of the primary limitations in the clinical use of the anticancer drug doxorubicin (DOX). However, the role of microRNAs (miRNAs) in DOX-induced cardiomyocyte death has not yet been covered. To investigate this, we observed a significant increase in miR-98 expression in neonatal rat ventricular myocytes after DOX treatment, and MTT, LIVE/Dead and Viability/Cytotoxicity staining showed that miR-98 mimic inhibited DOX-induced cell death.

Coflex interspinous process dynamic stabilization for lumbar spinal stenosis: Long-term follow-up.

Objective: To evaluate the long-term efficacy of Coflex dynamic stabilization device in the treatment of lumbar spinal stenosis.

Methods: The clinical and imaging data of 73 patients undergoing Coflex dynamic stabilization surgery from July 2008 to June 2012 were retrospectively analyzed. All patients had a minimum of 8 years of follow-up.

Hypoxia-Induced Mesenchymal Stem Cells Exhibit Stronger Tenogenic Differentiation Capacities and Promote Patellar Tendon Repair in Rabbits.

Tendon injury is a common but tough medical problem. Unsatisfactory clinical results have been reported in tendon repair using mesenchymal stem cell (MSC) therapy, creating a need for a better strategy to induce MSCs to tenogenic differentiation. This study was designed to examine the effect of hypoxia on the tenogenic differentiation of different MSCs and their tenogenic differentiation capacities under hypoxia condition in vitro and to investigate the in vivo inductility of hypoxia in tenogenesis.

Blockade of Discoidin Domain Receptor 2 as a Strategy for Reducing Inflammation and Joint Destruction in Rheumatoid Arthritis Via Altered Interleukin-15 and Dkk-1 Signaling in Fibroblast-Like Synoviocytes.

Objective: This study was undertaken to uncover the pathophysiologic role of discoidin domain receptor 2 (DDR-2), a putative fibrillar collagen receptor, in inflammation promotion and joint destruction in rheumatoid arthritis (RA).

Methods: In synovial tissue from patients with RA and from mice with collagen antibody-induced arthritis (CAIA) (using Ddr2 and DBA/1 mice), gene and protein expression levels of DDR-2, interleukin-15 (IL-15), and Dkk-1 were measured by quantitative reverse transcription-polymerase chain reaction, Western blotting, and immunohistochemistry. Gene knockdown of DDR2 in human RA fibroblast-like synoviocytes (FLS) was conducted via small interfering RNA.