Corrigendum: A rapid VEGF-gene-sequence photoluminescence detector for osteoarthritis.

[This corrects the article DOI: 10.3389/fbioe.2024.1338901.].

A rapid VEGF-gene-sequence photoluminescence detector for osteoarthritis.

Osteoarthritis (OA) has become a serious problem to the human society for years due to its high economic burden, disability, pain, and severe impact on the patient's lifestyle. The importance of current clinical imaging modalities in the assessment of the onset and progression of OA is well recognized by clinicians, but these modalities can only detect OA in the II stage with significant structural deterioration and clinical symptoms. Blood vessel formation induced by vascular endothelial growth factor (VEGF) occurs in the early stage and throughout the entire course of OA, enables VEGF relating gene sequence to act as a biomarker in the field of early diagnosis and monitoring of the disease. Here in, a facile rapid detection of VEGF relating ssDNA sequence was developed, in which manganese-based zeolitic imidazolate framework nanoparticles (Mn-ZIF-NPs) were synthesized by a simple coprecipitation strategy, followed by the introduction and surficial absorption of probe ssDNAs and the CRISPR/Cas12a system components. Furthermore, fluorescence experiments demonstrated that the biosensor displayed a low detection limit of 2.49 nM, a good linear response to the target ssDNA ranging from 10 nM to 500 nM, and the ability of distinguishing single nucleotide polymorphism. This finding opens a new window for the feasible and rapid detection of ssDNA molecules for the early diagnose of OA.

Preparation of low molecular weight polysaccharides from Tremella fuciformis by ultrasonic-assisted H2O2-Vc method: Structural characteristics, in vivo antioxidant activity and stress resistance.

Different methods were used to degrade Tremella fuciformis polysaccharides (TFP) and prepare low molecular weight polysaccharides of Tremella fuciformis (TFLP) to improve their bioavailability. It was found that the TFLP prepared by ultrasonic-assisted H2O2-Vc method showed the highest level of antioxidant activity and stress resistance in C. elegans. The structural characteristics, in vivo antioxidant and stress resistance of TFLP-1 were evaluated after isolation and purification of TFLP, it was found that TFLP-1 was an acid polysaccharide with a molecular weight of 75770 Da, which mainly composed of mannose. Meanwhile, it could regulate the antioxidant activity and stress resistance in C. elegans by upregulating the transcription of fat-5, fat-7, acs-2, glp-1, hsf-1, hsp-1, mtl-1, nhr-49, skn-1 and sod-3 mRNA. The improvement effects were closely related to the significant regulation of galactose metabolism, alpha linolenic acid metabolism, and pantothenate and CoA biosynthesis metabolic pathways. These results provided insights into the high value application of Tremella fuciformis in the food industry and the development of antioxidant related functional foods.

Safrole oxide induced 5-HT neuron-like cell differentiation of bone marrow mesenchymal stem cells by elevating G9a.

In our previous study, we found that safrole oxide (SFO) could induce bone marrow mesenchymal stem cell differentiation into neuron-like cells. However, which kind of neuron cells was induced by SFO was unknown. Here, we found that SFO could induce BMSC differentiation into 5-hydroxytryptamine (5-HT) neuron-like cells. Microarray analysis of BMSCs treated with SFO for 6 h revealed a total of 35 genes changed more than twice. We selected G9a, a histone methyltransferase for further study. The upregulation of G9a was confirmed by RT-PCR and Western blot analysis. Small interfering RNA knockdown of G9a blocked SFO-induced BMSC differentiation. These results demonstrated that G9a was the pivotal factor in SFO-medicated 5-HT neuronal differentiation of BMSCs. Our findings provide a new clue for further investigating the gene control of BMSC differentiation into 5-HT neuron-like cells and provide a putative strategy for depression diseases therapies.

PDGFD switches on stem cell endothelial commitment.

The critical factors regulating stem cell endothelial commitment and renewal remain not well understood. Here, using loss- and gain-of-function assays together with bioinformatic analysis and multiple model systems, we show that PDGFD is an essential factor that switches on endothelial commitment of embryonic stem cells (ESCs). PDGFD genetic deletion or knockdown inhibits ESC differentiation into EC lineage and increases ESC self-renewal, and PDGFD overexpression activates ESC differentiation towards ECs. RNA sequencing reveals a critical requirement of PDGFD for the expression of vascular-differentiation related genes in ESCs. Importantly, PDGFD genetic deletion or knockdown increases ESC self-renewal and decreases blood vessel densities in both embryonic and neonatal mice and in teratomas. Mechanistically, we reveal that PDGFD fulfills this function via the MAPK/ERK pathway. Our findings provide new insight of PDGFD as a novel regulator of ESC fate determination, and suggest therapeutic implications of modulating PDGFD activity in stem cell therapy.

Multi-Modal Interaction Graph Convolutional Network for Temporal Language Localization in Videos.

This paper focuses on tackling the problem of temporal language localization in videos, which aims to identify the start and end points of a moment described by a natural language sentence in an untrimmed video. However, it is non-trivial since it requires not only the comprehensive understanding of the video and sentence query, but also the accurate semantic correspondence capture between them. Existing efforts are mainly centered on exploring the sequential relation among video clips and query words to reason the video and sentence query, neglecting the other intra-modal relations (e.g., semantic similarity among video clips and syntactic dependency among the query words). Towards this end, in this work, we propose a Multi-modal Interaction Graph Convolutional Network (MIGCN), which jointly explores the complex intra-modal relations and inter-modal interactions residing in the video and sentence query to facilitate the understanding and semantic correspondence capture of the video and sentence query. In addition, we devise an adaptive context-aware localization method, where the context information is taken into the candidate moments and the multi-scale fully connected layers are designed to rank and adjust the boundary of the generated coarse candidate moments with different lengths. Extensive experiments on Charades-STA and ActivityNet datasets demonstrate the promising performance and superior efficiency of our model.

2D materials for bone therapy.

Due to their prominent physicochemical properties, 2D materials are broadly applied in biomedicine. Currently, 2D materials have achieved great success in treating many diseases such as cancer and tissue engineering as well as bone therapy. Based on their different characteristics, 2D materials could function in various ways in different bone diseases. Herein, the application of 2D materials in bone tissue engineering, joint lubrication, infection of orthopedic implants, bone tumors, and osteoarthritis are firstly reviewed comprehensively together. Meanwhile, different mechanisms by which 2D materials function in each disease reviewed below are also reviewed in detail, which in turn reveals the versatile functions and application of 2D materials. At last, the outlook on how to further broaden applications of 2D materials in bone therapies based on their excellent properties is also discussed.

BCL6B hypermethylation predicts metastasis and poor prognosis in early-stage hepatocellular carcinoma after thermal ablation.

AIMS: The aim of this study was to evaluate the role of BCL6B methylation in the progression of early-stage hepatocellular carcinoma (HCC) after thermal ablation. SETTINGS AND DESIGN: This is a retrospective study and written informed consent was obtained from all patients or their legal guardians. SUBJECTS AND METHODS: Between October 2008 and December 2013, 73 patients with early-stage HCC within the Milan criteria, who received thermal ablation, were recruited. STATISTICAL ANALYSIS USED: Based on methylation-specific polymerase chain reaction, the relationship between BCL6B methylation and patient characteristics and prognosis was analyzed using univariate, multivariate, and Kaplan-Meier analysis. RESULTS: The median follow-up period was 56 (8-110) months. For the BCL6B unmethylated group, the 1-, 3- and 5-year metastasis and overall survival (OS) rates after thermal ablation were 10.0%, 10.0%, and 40.0% and 100%, 100% and 90.0%, respectively. The 1-, 3-, and 5-year metastasis and OS rates of the methylated group were 23.8%, 66.7% and 88.9% and 66.2%, 71.4% and 41.3%, respectively. Levels of absolute count lymphocyte, serum cholinesterase and albumin in the BCL6B unmethylated group were higher than those in the methylated group (P = 0.020, 0.000, and 0.009, respectively). Kaplan-Meier analysis revealed that BCL6B methylation was related to metastasis and poor prognosis (P = 0.001 and 0.018, respectively). Univariate analysis revealed that BCL6B methylation was a risk factor for metastasis and poor prognosis (odds ratio [OR]: 5.663; 95% confidence interval [CI], 1.745-18.375, P = 0.004 and OR: 3.734; 95% CI, 1.151-12.110, P = 0.028, respectively). Multivariate analysis revealed that BCL6B methylation was an independent risk factor for metastasis (OR: 3.736; 95% CI, 1.000-13.963,P = 0.05) and not for prognosis (OR: 2.780; 95% CI, 0.835-9.250,P = 0.096). CONCLUSIONS: BCL6B methylation could be a valuable prognostic factor for metastasis and poor prognosis in early-stage HCC after thermal ablation, which is an independent risk factor for metastasis. Our findings provide insights for combining ablation and epigenetic therapy for patients with HCC.

Neural Compatibility Modeling with Probabilistic Knowledge Distillation.

In modern society, clothing matching plays a pivotal role in people's daily life, as suitable outfits can beautify their appearance directly. Nevertheless, how to make a suitable outfit has become a daily headache for many people, especially those who do not have much sense of aesthetics. In the light of this, many research efforts have been dedicated to the task of complementary clothing matching and have achieved great success relying on the advanced data-driven neural networks. However, most existing methods overlook the rich valuable knowledge accumulated by our human beings in the fashion domain, especially the rules regarding clothing matching, like "coats go with dresses" and "silk tops cannot go with chiffon bottoms". Towards this end, in this work, we propose a knowledge-guided neural compatibility modeling scheme, which is able to incorporate the rich fashion domain knowledge to enhance the performance of the compatibility modeling in the context of clothing matching. To better integrate the huge and implicit fashion domain knowledge into the data-driven neural networks, we present a probabilistic knowledge distillation (PKD) method, which is able to encode vast knowledge rules in a probabilistic manner. Extensive experiments on two real-world datasets have verified the guidance of rules from different sources and demonstrated the effectiveness and portability of our model. As a byproduct, we released the codes and involved parameters to benefit the research community.

A pH probe inhibits senescence in mesenchymal stem cells.

BACKGROUND: Bone marrow-derived mesenchymal stem cells (BMSCs) are gradually getting attention because of its multi-directional differentiation potential, hematopoietic support, and promotion of stem cell implantation. However, cultured BMSCs in vitro possess a very limited proliferation potential, and the presence of stem cell aging has substantially restricted the effect together with the efficiency in clinical treatment. Recently, increasing attention has been paid to the connection between cellular aging and lysosomal acidification as new reports indicated that vacuolar H+-ATPase (v-ATPase) activity was altered and lysosomal pH was dysregulated in the process of cellular aging. Therefore, promoting lysosomal acidification might contribute to inhibition of cell senescence. Our previous studies showed that a novel small molecule, 3-butyl-1-chloro imidazo [1, 5-a] pyridine-7-carboxylic acid (SGJ), could selectively and sensitively respond to acidic pH with fast response (within 3 min), but whether SGJ can promote lysosomal acidification and inhibit senescence in BMSCs is unknown. METHODS: Rat BMSCs were cultured based on our system that had been already documented. BMSCs were treated with SGJ and/or Bafilomycin-A1 (Baf-A1). The co-localization between SGJ and lysosomes was assessed by a confocal microscope. Acridine orange (AO) staining and the Lysosensor™ Green DND-189 reagents were used for indicating changes in lysosomal concentration of H+. Changes of senescence were detected by immunoblotting of p21 and senescence-associated beta-galactosidase (SA-ß-gal) staining as well as immunofluorescence assay of senescence-associated heterochromatin foci (SAHF). Changes of autophagy were detected by immunoblotting of MAP1LC3 (LC3B) and SQSTM1 (p62). Cell proliferation was determined by flow cytometry. Cell viability was calculated by sulforhodamine B assay (SRB). The V0 proton channel of v-ATPase was knocked down by transfecting with its small interfering RNA (si-ATP6V0C). RESULTS: Our work showed that SGJ can promote lysosomal acidification and inhibit senescence in BMSCs. Firstly, SGJ and lysosomes were well co-located in senescent BMSCs with the co-localization coefficient of 0.94. Secondly, SGJ increased the concentration of H+ and the protein expression of lysosome-associated membrane protein 1 (LAMP1) and lysosome-associated membrane protein 2 (LAMP2). Thirdly, SGJ suppressed the expression of p21 in the senescent BMSCs and reduced SA-ß-gal positive cells. Fourthly, SGJ promoted senescent BMSCs' proliferation and protein level of LC3B but reduced the p62/SQSTM1 protein level. Furthermore, experimental group pretreated with 20 µM SGJ showed a stronger red fluorescent intensity, thinner cell morphology, less SA-ß-gal positive cell, and less p21 protein level as well as higher cell viability in the presence of Baf-A1. Notably, ATP6V0C knockdown decreased the activity of v-ATPase and SGJ increased the concentration of H+. CONCLUSION: Our work showed that SGJ could inhibit senescence in BMSCs and protect lysosomes by promoting expression of LAMP1 and LAMP2. Meanwhile, SGJ could promote autophagy. Furthermore, our study also suggested that SGJ was a new Baf-A1 antagonist because SGJ could target and occupy the V0 proton channel of v-ATPase.