Quantification of Vascular Remodeling and Sinusoidal Capillarization to Assess Liver Fibrosis with Photoacoustic Imaging.

Background Photoacoustic microscopy (PAM) can be used to detect strong absorption from endogenous and exogenous contrast material, making it promising for detailed structural and functional imaging of hepatic sinusoids, including dynamic visualization of permeability. Purpose To evaluate whether PAM-based quantitative parameters of liver function and integrity (lacunarity, blood oxygen saturation [Sao], and Evans blue [EB] permeability) are associated with histopathologic indexes of fibrosis in a mouse model. Materials and Methods Between October 2022 and July 2023, a total of 35 male C57BL/6 mice were included in this study and received intraperitoneal injection of carbon tetrachloride to establish mouse models of progressive liver fibrosis, with seven mice in each group.

HcCnAα regulates NF-κB signaling in Hyriopsis cumingii by interacting with HcIKK and facilitating IκB phosphorylation.

Calcineurin (CN), a serine/threonine protein phosphatase regulated by Ca and calmodulin, plays a crucial role in the immune response of bivalves. In this study, we examined the effects of gene silencing of the CN subunit (HcCnAα) in Hyriopsis cumingii on the expression of genes associated with the NF-κB signaling pathway, as well as the phosphorylation of the inhibitor of NF-κB (IκB), through RNA interference (RNAi), quantitative PCR (qPCR), and Western blot (WB) analyses. The IκB kinase (HcIKK) and B-cell CLL/lymphoma 10 (HcBcl10) genes of H.

pH-Responsive Persistent Luminescent Nanosystem with Sensitized NIR Imaging and Ratiometric Imaging Modes for Tumor Surgery Navigation.

Owing to autofluorescence-free feature, persistent luminescent (PersL) nanoparticles (PLNPs) become potential materials for tumor surgical navigation. However, it is still challenging to enhance PersL intensity, contrast ratio, and imaging stability so as to meet clinical demand and avoid missed detection of microlesions. Herein, integrating a tumor microenvironment (TME)-responsive strategy, sensitization enhancement, and internal-standard ratiometric method, a dual-mode PersL imaging strategy is proposed: After loading pH-responsive fluorescent molecule Rh-ADM on PLNPs ZnGaO:Cr,Mn (ZGCM-Rh8), the fluorescence resonance energy transfer (FRET) pathways between Cr and Rh-ADM, as well as Mn and Rh-ADM, could sensitize the NIR PersL emitted by Cr and quench the green PersL from Mn at acidic TME, respectively.

circNDUFA13 stimulates adipogenesis of bone marrow-derived mesenchymal stem cells via interaction with STAT3.

Circular RNAs (circRNAs) in controlling gene expression have been highlighted by increasing evidence, and their dysregulation has been linked to various diseases. However, the limited role of circRNAs in the adipogenesis of bone marrow-derived mesenchymal stem cells (BMSCs) has been explored. High-throughput sequencing of circRNA was carried out on BMSCs and AD induction 7d BMSCs.

Persistent luminescence nanoparticles with high intensity for colorectal cancer surgery navigation and precision resection.

Surgical resection remains the main treatment for malignant tumors. Image-guided surgery aims to remove tumor tissue completely while preserving normal tissue, thereby reducing tumor recurrence rates and injury. However, challenges like tissue autofluorescence, limited probe penetration and low contrast restrict its use.

Discovery of Preclinical Candidate AD1058 as a Highly Potent, Selective, and Brain-Penetrant ATR Inhibitor for the Treatment of Advanced Malignancies.

The ataxia telangiectasia-mutated and Rad3-related protein (ATR) plays a crucial role in regulating the cellular DNA-damage response (DDR), making it a promising target for antitumor drug development through synthetic lethality. In this study, we present the discovery and detailed characterization of AD1058, a highly potent and selective ATR inhibitor, with good preclinical pharmacokinetic profiles. AD1058 exhibits superior efficacy in inhibiting cell proliferation, disrupting the cell cycle, and inducing apoptosis compared to AZD6738.

Enhancing Persistent Luminescence through Synergy between Optimal Electron Traps and Dye Sensitization.

Due to their unique afterglow ability, long-wavelength-light rechargeable persistent luminescence (PersL) nanoparticles (PLNPs) have been emerging as an important category of imaging probes. Among them, ZnGaO:0.6% Cr (ZGC) PLNPs have gained widespread recognition due to the ease of synthesis and uniform morphology.

Sensitization of colon cancer cells to cisplatin by Fbxw7 via negative regulation of the Nox1-mTOR pathway.

Colorectal cancer (CRC) is a human malignancy which associates with high mortality rate and poor prognosis. Despite the initial effectiveness in clinical applications of chemotherapeutic agents, a fraction of patients develops chemoresistance. Fbxw7 is an F-box protein serving as a substrate recognition subunit of E3 ubiquitin ligase, leading to degradation of various oncoproteins.

In vivo endoscopic ultrasound imaging with a rotational-scanning, all-optical ultrasound probe.

All-optical ultrasound manipulates ultrasound waves based on laser and photonics technologies, providing an alternative approach for pulse-echo ultrasound imaging. However, its endoscopic imaging capability is limited ex vivo by the multifiber connection between the endoscopic probe and the console. Here, we report on all-optical ultrasound for in vivo endoscopic imaging using a rotational-scanning probe that relies on a small laser sensor to detect echo ultrasound waves.

Light-sheet laser speckle imaging for cilia motility assessment.

Mucociliary clearance is an important innate defense mechanism predominantly mediated by ciliated cells in the upper respiratory tract. Ciliary motility on the respiratory epithelium surface and mucus pathogen trapping assist in maintaining healthy airways. Optical imaging methods have been used to obtain several indicators for assessing ciliary movement.

MiR-328-5p inhibits the adipogenic differentiation of hMSCs by targeting fatty acid synthase.

Introduction: Adipogenesis, a highly coordinated process regulated by numerous effectors, is largely responsible for the quantity and size of adipocytes. Attenuation of adipocyte differentiation has been proposed as a viable technique for reducing obesity and its associated diseases. MicroRNAs play an important role in human bone marrow mesenchymal stem cells (hMSCs) adipogenic differentiation.

SFN: A Novel Scalable Feature Network for Vulnerability Representation of Open-Source Codes.

Vulnerability detection technology has become a hotspot in the field of software security, and most of the current methods do not have a complete consideration during code characterizing, which leads to problems such as information loss. Therefore, this paper proposes one class of Scalable Feature Network (SFN), a composite feature extraction method based on Continuous Bag of Words and Convolutional Neural Network. In addition, to characterize the source code more comprehensively, we construct multiscale code metrics in terms of semantic-, line-, and function granularity.

An Aggregation-Free Local Volume Fraction Formulation for Topological Design of Porous Structure.

Cellular structure can possess superior mechanical properties and low density simultaneously. Additive manufacturing has experienced substantial progress in the past decades, which promotes the popularity of such bone-like structure. This paper proposes a methodology on the topological design of porous structure.

[Methodological Research on Rapid Detection and Genotyping of NPM1 Gene Mutations in Leukemia].

Objective: To establish a method for rapid detection and typing of NPM1 mutations in acute myeloid leukemia (AML) by fluorescence melting curve analysis technology.

Methods: A pair of primers and a fluorescent single-stranded probe (molecule beacon) were designed for the mutant genes mutA, mutB, mutD in exon 12 of nucleopsin (NPM1) and wild type. With a real-time qPCR, the A, B, and D gene mutations of NPM1 were detected and typed by different-melting curve peak value of the probe through RT-PCR.

Changes in levels of coagulation parameters in different trimesters among Chinese pregnant women.

Background: This article is to explore changes in levels of coagulation parameters in different trimesters among healthy pregnant women in China.

Methods: A total of 760 eligible women were enrolled (first-trimester group: n = 183, second-trimester group: n = 183, third-trimester group: n = 263, non-pregnant group: n = 131). Seven parameters including prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (FIB), D-dimer (DD), fibrinogen degradation products (FDP), and antithrombin III (ATIII), of all participants were collected.

Small RNA sequencing reveals a novel tsRNA-06018 playing an important role during adipogenic differentiation of hMSCs.

Transfer RNA-derived small RNAs (tsRNAs), a novel type of non-coding RNA derivative, are able to regulate a wide range of biological processes. What role these tsRNAs play in the regulation of human bone marrow mesenchymal stem cell (hMSCs) adipogenic differentiation remains uncertain. We induced the adipogenic differentiation of human bone marrow mesenchymal cells (hMSCs) and then performed small RNA transcriptomic sequencing, leading us to identify tsRNA-06018 as a target of interest based upon resultant the tsRNA expression profiles.

Investigation of a low-stress and low-contamination clamping method for large-aperture optics.

Motivated by the need to decrease initial contact seal stress on Nd:glass coated with SiO sol-gel film and effectively control the surface contaminants from film debris induced by stress in the assembly process, a novel vacuum clamping method is studied to achieve the purpose of low stress and low contamination. In this article, theoretical analyses, numerical simulations, and field experiments are used to verify the feasibility of this method. Mechanical simulation results indicate that under the same radial compression conditions, the higher the hollowness of the O-ring rubber, the less the contact stress on Nd:glass.

5-Substituted-N-pyridazinylbenzamides as potent and selective LRRK2 inhibitors: Improved brain unbound fraction enables efficacy.

We describe the discovery and optimization of 5-substituted-N-pyridazinylbenzamide derivatives as potent and selective LRRK2 inhibitors. Extensive SAR studies led to the identification of compounds 18 and 23, which demonstrated good in vitro pharmacokinetic profile and excellent selectivity over 140 other kinases. Both compounds demonstrated high unbound fractions in both blood and brain.

Author Correction: Extraordinarily potent proinflammatory properties of lactoferrin-containing immunocomplexes against human monocytes and macrophages.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Preclinical evaluation of novel PI3K/mTOR dual inhibitor SN202 as potential anti-renal cancer agent.

The PI3K/mTOR pathway is one of the most frequently aberrantly activated pathways in human malignancies, such as renal cell carcinoma (RCC), and contributes to resistance to antitumor therapies. Thus, PI3K/mTOR is an attractive target for the development of antitumor agents. In this study, we evaluated the preclinical effects of a novel inhibitor SN202.

Discovery of 4-ethoxy-7H-pyrrolo[2,3-d]pyrimidin-2-amines as potent, selective and orally bioavailable LRRK2 inhibitors.

Inhibition of LRRK2 kinase activity with small molecules has emerged as a potential novel therapeutic treatment for Parkinson's disease. Herein we disclose the discovery of a 4-ethoxy-7H-pyrrolo[2,3-d]pyrimidin-2-amine series as potent LRRK2 inhibitors identified through a kinase-focused set screening. Optimization of the physicochemical properties and kinase selectivity led to the discovery of compound 7, which exhibited potent in vitro inhibition of LRRK2 kinase activity, good physicochemical properties and kinase selectivity across the kinome.

Discovery of 5-substituent-N-arylbenzamide derivatives as potent, selective and orally bioavailable LRRK2 inhibitors.

Leucine-rich repeat kinase 2 (LRRK2) has been suggested as a potential therapeutic target for Parkinson's disease. Herein we report the discovery of 5-substituent-N-arylbenzamide derivatives as novel LRRK2 inhibitors. Extensive SAR study led to the discovery of compounds 8e, which demonstrated potent LRRK2 inhibition activity, high selectivity across the kinome, good brain exposure, and high oral bioavailability.

Extraordinarily potent proinflammatory properties of lactoferrin-containing immunocomplexes against human monocytes and macrophages.

Lactoferrin (LTF), an important first line defense molecule against infection, is a common target for humoral autoimmune reactions in humans. Since LTF is a multifunctional protein capable of activating innate immune cells via various surface receptors, we hypothesized that LTF-containing immune complexes (ICs) (LTF-ICs), likely formed in patients with high titer anti-LTF autoantibodies, could possess unique monocyte/macrophage-activating properties compared with other ICs. ELISA analysis on serum samples from rheumatoid arthritis (RA) patients (n = 80) and healthy controls (n = 35) for anti-LTF autoantibodies confirmed a positive correlation between circulating LTF-specific IgG and RA.

Collagen based film with well epithelial and stromal regeneration as corneal repair materials: Improving mechanical property by crosslinking with citric acid.

Corneal disease can lead to vision loss. It has become the second greatest cause of blindness in the world, and keratoplasty is considered as an effective treatment method. This paper presents the crosslinked collagen (Col)-citric acid (CA) films developed by making use of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS).