Q11, a CYP2E1 inhibitor, exerts anti-hepatocellular carcinoma effect by inhibiting M2 macrophage polarization.

Despite significant advancements in cancer immunotherapy, many patients continue to respond poorly. Novel therapeutic strategies and drugs are urgently needed. Here, we found that CYP2E1 is upregulated in M2 macrophages.

Shedding light on imaging cancer research: Design and synthesis of 1, 8-naphthalimide-based PRMT5-targeted fluorescent ligands.

Protein Arginine Methyltransferase 5 (PRMT5) is an important player in breast cancer cell activity, and innovative fluorescent ligands targeting this enzyme offer revolutionary, real-time insights into its role in cancer progression, unlocking new avenues for diagnosis and treatment. This study introduces fluorescence-labeled PRMT5 ligands, highlighting their applications in visualizing PRMT5, monitoring enzymatic activity as well as studying toxicity. Herein, we describe the design, synthesis, and cellular imaging of a series of fluorescent ligands that target PRMT5.

Recent progress of principal techniques used in the study of Müller glia reprogramming in mice.

In zebrafish, Müller glia (MG) cells retain the ability to proliferate and de-differentiate into retinal progenitor-like cells, subsequently differentiating into retinal neurons that can replace those damaged or lost due to retinal injury. In contrast, the reprogramming potential of MG in mammals has been lost, with these cells typically responding to retinal damage through gliosis. Considerable efforts have been dedicated to achieving the reprogramming of MG cells in mammals.

De-Differentiation of Corneal Epithelial Cells Into Functional Limbal Epithelial Stem Cells After the Ablation of Innate Stem Cells.

Purpose: Regeneration after tissue injury is often associated with cell fate plasticity, which restores damaged or lost cells. Here, we examined the de-differentiation of corneal epithelial cells (CECs) into functional limbal epithelial stem cells (LESCs) after the ablation of innate stem cells.

Methods: The regeneration of LESCs after the ablation of innate LESCs was identified by a set of markers: ApoE+/Cx43low/CK12-.

Exosomes derived from IFNγ-stimulated mesenchymal stem cells protect photoreceptors in RCS rats by restoring immune homeostasis through tsRNAs.

Background: Retinitis pigmentosa is a neurodegenerative disease with major pathologies of photoreceptor apoptosis and immune imbalance. Mesenchymal stem cells (MSCs) have been approved for clinical application for treating various immune-related or neurodegenerative diseases. The objective of this research was to investigate the mechanisms underlying the safeguarding effects of MSC-derived exosomes in a retinal degenerative disease model.

Self-Reconstructed Amorphous CoO/NiCoB Heterostructure Catalysts for Enhanced HER Performance.

Amorphous electrocatalysts exhibit potentials as precursors for triggering the in situ reconstruction to generate the real catalytic active species toward electrochemical processes. In this work, a new kind of amorphous Ni-Co-B alloy pre-catalysts for hydrogen evolution reaction (HER) is reported, which is obtained via a facile electroless plating strategy on the nickel foam (NF). Interestingly, X-ray photoelectron spectroscopy, X-ray absorption spectroscopy and morphological characterizations identify the in situ reconstruction process during HER accompanied by the preferential leaching of surface B species and the formation of amorphous CoO nanosheet arrays as the real active sites.

Discovery of CYP2E1 as a novel target in rheumatoid arthritis and validation by a new specific CYP2E1 inhibitor.

Considerable evidence indicates that CYP2E1 is associated with a variety of inflammatory diseases. Here we evaluated CYP2E1 as a potential therapeutic target for rheumatoid arthritis (RA) and established the protective effect of a new CYP2E1 inhibitor. Gene-expression datasets were used to analyze the change in expression of CYP2E1 in RA patients; CYP2E1 activity in collagen-induced arthritis (CIA) rats was determined by HPLC.

Investigating Müller glia reprogramming in mice: a retrospective of the last decade, and a look to the future.

Müller glia, as prominent glial cells within the retina, plays a significant role in maintaining retinal homeostasis in both healthy and diseased states. In lower vertebrates like zebrafish, these cells assume responsibility for spontaneous retinal regeneration, wherein endogenous Müller glia undergo proliferation, transform into Müller glia-derived progenitor cells, and subsequently regenerate the entire retina with restored functionality. Conversely, Müller glia in the mouse and human retina exhibit limited neural reprogramming.

Identifying the protective effects of miR-874-3p/ATF3 axis in intervertebral disc degeneration by single-cell RNA sequencing and validation.

Intervertebral disc degeneration (IVDD) severely affects the work and the quality of life of people. We previously demonstrated that silencing activation transcription factor 3 (ATF3) blocked the IVDD pathological process by regulating nucleus pulposus cell (NPC) ferroptosis, apoptosis, inflammation, and extracellular matrix (ECM) metabolism. Nevertheless, whether miR-874-3p mediated the IVDD pathological process by targeting ATF3 remains unclear.

A Disconnection for Rapid Access to Heterocyclic Benzylic Amines with Fully Substituted α-Carbons.

2- or 4-Pyridyl benzylic amines represent a privileged motif in drug discovery. However, the formation of heterocyclic benzylic amines with fully substituted α-carbons can require the execution of lengthy synthetic routes, which limit their application. Addition of various nucleophilic agents to Ellman's imines has been well established; however, there is no precedented literature reported for pyridyl-type nucleophiles, which are very important for medicinal chemistry.

Identifying Hmga2 preserving visual function by promoting a shift of Müller glia cell fate in mice with acute retinal injury.

Background: Unlike in lower vertebrates, Müller glia (MG) in adult mammalian retinas lack the ability to reprogram into neurons after retinal injury or degeneration and exhibit reactive gliosis instead. Whether a transition in MG cell fate from gliosis to reprogramming would help preserve photoreceptors is still under exploration.

Methods: A mouse model of retinitis pigmentosa (RP) was established using MG cell lineage tracing mice by intraperitoneal injection of sodium iodate (SI).

Extracellular vesicles from organoid-derived human retinal progenitor cells prevent lipid overload-induced retinal pigment epithelium injury by regulating fatty acid metabolism.

Retinal degeneration (RD), a group of diseases leading to irreversible vision loss, is characterised by retinal pigment epithelium (RPE) or retinal neuron damage and loss. With fewer risks of immune rejection and tumorigenesis, stem cell-secreted extracellular vesicles (EVs) offer a new cell-free therapeutic paradigm for RD, which remains to be investigated. Human retinal organoid-derived retinal progenitor cells (hERO-RPCs) are an easily accessible and advanced cell source for RD treatment.

Multisensor and Multiscale Data Integration Method of TLS and GPR for Three-Dimensional Detailed Virtual Reconstruction.

Integrated TLS and GPR data can provide multisensor and multiscale spatial data for the comprehensive identification and analysis of surficial and subsurface information, but a reliable systematic methodology associated with data integration of TLS and GPR is still scarce. The aim of this research is to develop a methodology for the data integration of TLS and GPR for detailed, three-dimensional (3D) virtual reconstruction. GPR data and high-precision geographical coordinates at the centimeter level were simultaneously gathered using the GPR system and the Global Navigation Satellite System (GNSS) signal receiver.

Predictive Factors Associated with Chronic Neck Pain in Patients with Cervical Degenerative Disease: A Retrospective Cohort Study.

Purpose: To explore the predictive factors of neck pain (NP) in patients with cervical degenerative disease by retrospectively analyzing their occupational and demographic characteristics and to provide a valuable reference for preventing and treating chronic NP.

Patients And Methods: We retrospectively reviewed the occupational and demographic data of patients with cervical degenerative disease who had undergone anterior cervical surgery between June 2021 and December 2022 at our center. The patients were divided into NP and no-NP groups based on whether they had chronic NP before surgery.

Increased Expression of Inflammatory Cytokines and Discogenic Neck Pain.

Objective: Although neck pain has become a serious economic and social problem worldwide, the etiology remains poorly understood. The aim of current study is to explore the possible pathogenesis of discogenic neck pain by analyzing the relationship between inflammatory cytokines and discogenic neck pain and provide a valuable reference for the prevention and treatment of discogenic neck pain.

Methods: A total of 111 cervical disc samples were collected between October 1, 2021, and October 1, 2022: 38 samples from the discogenic neck pain group, 41 samples from the symptomatic control group, and 32 samples from the normal control group.

20 years of polybrominated diphenyl ethers on toxicity assessments.

Polybrominated diphenyl ethers (PBDEs) serve as brominated flame retardants which continue to receive considerable attention because of their persistence, bioaccumulation, and potential toxicity. Although PBDEs have been restricted and phased out, large amounts of commercial products containing PBDEs are still in use and discarded annually. Consequently, PBDEs added to products can be released into our surrounding environments, particularly in aquatic systems, thus posing great risks to human health.

A Novel Cytochrome P450 2E1 Inhibitor Q11 Is Effective on Lung Cancer via Regulation of the Inflammatory Microenvironment.

Lung cancer is the leading cause of death among all cancers. A persistent chronic inflammatory microenvironment is highly correlated with lung cancer. However, there are no anti-inflammatory agents effective against lung cancer.

Application of self-anchored lateral lumbar interbody fusion in lumbar degenerative diseases.

Study Design: This is a retrospective study.

Objective: The aim of the study was to evaluate the efficacy of self-anchored lateral lumbar interbody fusion (SA-LLIF) in lumbar degenerative diseases.

Methods: Forty-eight patients with lumbar degenerative disease between January 2019 and June 2020 were enrolled in this study.

Fullerol rescues the light-induced retinal damage by modulating Müller glia cell fate.

Excessive light exposure can damage photoreceptors and lead to blindness. Oxidative stress serves a key role in photo-induced retinal damage. Free radical scavengers have been proven to protect against photo-damaged retinal degeneration.

Ethanol Causes Cell Death and Neuronal Differentiation Defect During Initial Neurogenesis of the Neural Retina by Disrupting Calcium Signaling in Human Retinal Organoids.

Fetal Alcohol Syndrome (FAS) affects a significant proportion, exceeding 90%, of afflicted children, leading to severe ocular aberrations such as microphthalmia and optic nerve hypoplasia. During the early stages of pregnancy, the commencement of neural retina neurogenesis represents a critical period for human eye development, concurrently exposing the developing retinal structures to the highest risk of prenatal ethanol exposure due to a lack of awareness. Despite the paramount importance of this period, the precise influence and underlying mechanisms of short-term ethanol exposure on the developmental process of the human neural retina have remained largely elusive.

A controllable perfusion microfluidic chip for facilitating the development of retinal ganglion cells in human retinal organoids.

Retinal organoids (ROs) derived from human pluripotent stem cells (hPSCs) have become a promising model to recapitulate human retinal development, which can be further employed to explore the mechanisms of retinal diseases. However, the current culture systems for ROs lack physiologically relevant microenvironments, such as controllable mechano-physiological cues and dynamic feedback between cells and the extracellular matrix (ECM), which limits the accurate control of RO development. Therefore, we designed a controllable perfusion microfluidic chip (CPMC) with the advantages of precisely controlling fluidic shear stress (FSS) and oxygen concentration distribution in a human embryonic stem cell (hESC)-derived RO culture system.

MAP4Ks inhibition promotes retinal neuron regeneration from Müller glia in adult mice.

Mammalian Müller glia (MG) possess limited regenerative capacities. However, the intrinsic capacity of mammalian MG to transdifferentiate to generate mature neurons without transgenic manipulations remains speculative. Here we show that MAP4K4, MAP4K6 and MAP4K7, which are conserved Misshapen subfamily of ste20 kinases homologs, repress YAP activity in mammalian MG and therefore restrict their ability to be reprogrammed.

Alleviation of Photoreceptor Degeneration Based on Fullerenols in rd1 Mice by Reversing Mitochondrial Dysfunction via Modulation of Mitochondrial DNA Transcription and Leakage.

Poor therapeutic outcomes of antioxidants in ophthalmologic clinical applications, including glutathione during photoreceptor degeneration in retinitis pigmentosa (RP), are caused by limited anti-oxidative capacity. In this study, fullerenols are synthesized and proven to be highly efficient in vitro radical scavengers. Fullerenol-based intravitreal injections significantly improve the flash electroretinogram and light/dark transition tests performed for 28 days on rd1 mice, reduce the thinning of retinal outer nuclear layers, and preserve the Rhodopsin, Gnat-1, and Arrestin expressions of photoreceptors.

The CYP2E1 inhibitor Q11 ameliorates LPS-induced sepsis in mice by suppressing oxidative stress and NLRP3 activation.

Sepsis is an infection-induced, multi-organ system failure with a pathophysiology related to inflammation and oxidative stress. Increasing evidence indicates that cytochrome P450 2E1 (CYP2E1) is involved in the incidence and development of inflammatory diseases. However, a role for CYP2E1 in lipopolysaccharide (LPS)-induced sepsis has not been completely explored.