Effect of GARP on osteogenic differentiation of bone marrow mesenchymal stem cells via the regulation of TGFβ1 in vitro

Mesenchymal stem cells (MSCs), which have multipotential differentiation and self-renewal potential, are possible cells for tissue engineering. Transforming growth factor β1 (TGFβ1) can be produced by MSCs in an inactive form, and the activation of TGFβ1 functions as an important regulator of osteogenic differentiation in MSCs. Recently, studies showed that Glycoprotein A repetitions predominant (GARP) participated in the activation of latent TGFβ1, but the interaction between GARP and TGFβ1 is still undefined. In our study, we successfully isolated the MSCs from bone marrow of rats, and showed that GARP was detected in bone mesenchymal stem cells (BMSCs). During the osteogenic differentiation of BMSCs, GARP expression was increased over time. To elucidate the interaction between GARP and TGFβ1, we downregulated GARP expression in BMSCs to examine the level of active TGFβ1. We then verified that the downregulation of GARP decreased the secretion of active TGFβ1. Furthermore, osteogenic differentiation experiments, alkaline phosphatase (ALP) activity analyses and Alizarin Red S staining experiments were performed to evaluate the osteogenic capacity. After the downregulation of GARP, ALP activity and Alizarin Red S staining significantly declined and the osteogenic indicators, ALP, Runx2, and OPN, also decreased, both at the mRNA and protein levels. These results demonstrated that downregulated GARP expression resulted in the reduction of TGFβ1 and the attenuation of osteoblast differentiation of BMSCs in vitro

Earlier Activation of Interferon and Pro-Inflammatory Response Is Beneficial to Largemouth Bass (<i>Micropterus salmoides</i>) against Rhabdovirus Infection

In order to understand the immune response of largemouth bass against Micropterus salmoides Rhabdovirus (MSRV), assisting disease resistance breeding, three largemouth bass breeding varieties Micropterus salmoides “Youlu No 3” (U3), “Youlu No 1” (U1) and “Zhelu No 1” (P1) were challenged intraperitoneally with MSRV. Serum and tissues were sampled to study the changes in non-specific immune parameters, viral loads, and transcript levels of immune-related genes, and the cumulative mortality rate was recorded daily for 14 days. The results showed that the cumulative mortality rates in the U1, P1, and U3 groups were 6.66% ± 2.89%, 3.33% ± 2.89%, and 0, respectively. The higher mortality may attribute to the increased viral loads after infection in the liver (2.79 × 105 and 2.38 × 105 vs. 1.3 × 104 copies/mg), spleen (2.14 × 105 and 9.40 × 104 vs. 4.21 × 103 copies/mg), and kidney (3.59 × 104 and 8.40 × 103 vs. 2.42 × 103 copies/mg) in the U1 and P1 groups compared to the U3 group. The serum non-specific immune parameters (lysozyme, catalase, and acid phosphatase) were found to be increased significantly in the U3 group. In addition, the transcripts of interferon-related genes (IFN-γ, IRF3, and IRF7) and pro-inflammatory-related genes (TNF-α and IL-1β) exhibited up-regulation and peaked at 6 h post infection in the U3 group, which also exhibited up-regulation but peaked at 12–24 h post infection in the U1 and P1 groups. In conclusion, these findings indicate that earlier activation of interferon and pro-inflammatory response is beneficial to largemouth bass against MSRV infection. This experiment may provide an insight into understanding the immune mechanism of largemouth bass against MSRV infection and contributes to molecular-assisted selection

Different functional alteration in attention-deficit/hyperactivity disorder across developmental age groups: A meta-analysis and an independent validation of resting-state functional connectivity studies

Background: Attention-deficit/hyperactivity disorder (ADHD) is a highly complex and heterogeneous disorder. Abnormal brain connectivity in ADHD might be influenced by developmental ages which might lead to the lacking of significant spatial convergence across studies. However, the developmental patterns and mechanisms of ADHD brain connectivity remain to be fully uncovered. Methods: In the present study, we searched PubMed, Scopus, Web of Science, and Embase for seed-based whole-brain resting-state functional connectivity studies of ADHD published through October 12th, 2020. The seeds meeting inclusion criteria were categorized into the cortex group and subcortex group, as previous studies suggested that the cortex and subcortex have different temporal patterns of development. Activation likelihood estimation meta-analysis was performed to investigate the abnormal connectivity in different age groups (all-age group, younger: <12 years, older: ≥12 years). Moreover, significant convergence of reported foci was used as seeds for validation with our independent dataset. Results: As with previous studies, scarce results were found in the all-age group. However, we found that the younger group consistently exhibited hyper-connectivity between different parts of the cortex and left middle frontal gyrus, and hypo-connectivity between different parts of the cortex and left putamen/pallidus/amygdala. Whereas, the older group (mainly for adults) showed hyper-connectivity between the cortex and right precuneus/sub-gyral/cingulate gyrus. Besides, the abnormal cortico-cortical and cortico-subcortical functional connectivity in children, and the abnormal cortico-cortical functional connectivity in adults were verified in our independent dataset. Conclusion: Our study emphasizes the importance of developmental age effects on the study of brain networks in ADHD. Further, we proposed that cortico-cortical and cortico-subcortical connectivity might play an important role in the pathophysiology of children with ADHD, while abnormal cortico-cortical connections were more important for adults with ADHD. This work provided a potential new insight to understand the neurodevelopmental mechanisms and possible clinical application of ADHD

Transcriptome Analysis of Immune Responses and Metabolic Regulations of Chinese Soft-Shelled Turtle (Pelodiscus sinensis) against Edwardsiella tarda Infection

The Chinese soft-shelled turtle (Pelodiscus sinensis) is an important aquatic species in southern China that is threatened by many serious diseases. Edwardsiella tarda is one of the highly pathogenic bacteria that cause the white abdominal shell disease. Yet, little is known about the immune and metabolic responses of the Chinese soft-shelled turtle against E. tarda infection. In the paper, gene expression profiles in the turtle liver were obtained to study the immune responses and metabolic regulations induced by E. tarda infection using RNA sequencing. A total of 3908 differentially expressed unigenes between the experimental group and the control group were obtained by transcriptome analysis, among them, were the significantly upregulated unigenes and downregulated unigenes 2065 and 1922, respectively. Further annotation and analysis revealed that the DEGs were mainly enriched in complement and coagulation cascades, phagosome, and steroid hormone biosynthesis pathways, indicating that they were mainly associated with defense mechanisms in the turtle liver against E. tarda four days post infection. For the first time, we reported on the gene profile of anti-E. tarda response in the soft-shelled turtle, and our research might provide valuable data to support further study on anti-E. tarda defense mechanisms in turtles

A stable luminescent covalent organic framework nanosheet for sensitive molecular recognition

Despite the rapid development of fluorescence detectors over the past decade, it still remains a considerable challenge to exploit a highly stable, sensitive, and selective fluorescence platform for molecular recognition. In this study, we report a stable carbazole-based sp2 carbon fluorescence covalent organic framework (COF) nanosheet, termed JUC-557-nanosheet. Owing to the synergistic effect of AIE- and ACQ-based chromophores in JUC-557-nanosheet, this architecture shows high absolute quantum yields (up to 23.0%) in solid state and the dispersed in various solvents and excellent sensing performance toward specific analytes, such as iodine (Ka: 2.10 105 M-1 and LOD: 302 ppb), 2,4,6-trinitrotoluene (Ka: 4.38 105 M-1 and LOD: 129 ppb), and especially nitrobenzene (Ka: 6.18 106 M-1 and LOD: 5 ppb), which is superior to those of fluorescence detection materials reported so far, including porous materials, small molecule probes and inorganics. Furthermore, its fluorescence quenching mechanism has been demonstrated to be a synergistic effect of static quenching and energy transfer quenching by a combined theoretical and experimental study, including time-resolved photoluminescence measurements, UV-vis absorption spectroscopy, and density functional theory calculations. As a chemically stable material, JUC-557-nanosheet preserves strong luminescence and sensitive recognition even under harsh conditions (such as strong acid with pH = 1 or strong base with pH = 14), and allows trace detection of various analytes via a handheld UV lamp. Therefore, these findings pave the way for developing stable ultrathin COF nanomaterials for highly sensitive and selective molecular detection

A Three-Dimensional Tetraphenylethylene-Based Fluorescence Covalent Organic Framework for Molecular Recognition

The development of highly-sensitive recognition of hazardous chemicals, such as volatile organic compounds (VOCs) and polycyclic aromatic hydrocarbons (PAHs), is of significant importance because of their widespread social concerns related to environment and human health. Here, we report a three-dimensional (3D) covalent organic framework (COF, termed JUC-555) bearing tetraphenylethylene (TPE) side chains as an aggregation-induced emission (AIE) fluorescence probe for sensitive molecular recognition. Due to the rotational restriction of TPE rotors in highly interpenetrated framework after inclusion of dimethylformamide (DMF), JUC-555 shows impressive AIE-based strong fluorescence. Meanwhile, owing to the large pore size (11.4 Å) and suitable intermolecular distance of aligned TPE (7.2 Å) in JUC-555, the obtained material demonstrates an excellent performance in the molecular recognition of hazardous chemicals, e.g., nitroaromatic explosives, PAHs, and even thiophene compounds, via a fluorescent quenching mechanism. The quenching constant (KSV) is two orders of magnitude better than those of other fluorescence-based porous materials reported to date. This research thus opens 3D functionalized COFs as a promising identification tool for environmentally hazardous substances.</p

NAD Supplement Alleviates Intestinal Barrier Injury Induced by Ethanol Via Protecting Epithelial Mitochondrial Function

Background: The epithelial tight junction is an important intestinal barrier whose disruption can lead to the release of harmful intestinal substances into the circulation and cause damage to systemic injury. The maintenance of intestinal epithelial tight junctions is closely related to energy homeostasis and mitochondrial function. Nicotinamide riboside (NR) is a NAD booster that can enhance mitochondrial biogenesis in liver. However, whether NR can prevent ethanol-induced intestinal barrier dysfunction and the underlying mechanisms remain unclear. Methods: We applied the mouse NIAAA model (chronic plus binge ethanol feeding) and Caco-2 cells to explore the effects of NR on ethanol-induced intestinal barrier dysfunction and the underlying mechanisms. NAD homeostasis and mitochondrial function were measured. In addition, knockdown of SirT1 in Caco-2 cells was further applied to explore the role of SirT1 in the protection of NR. Results: We found that ethanol increased intestinal permeability, increased the release of LPS into the circulation and destroyed the intestinal epithelial barrier structure in mice. NR supplementation attenuated intestinal barrier injury. Both in vivo and in vitro experiments showed that NR attenuated ethanol-induced decreased intestinal tight junction protein expressions and maintained NAD homeostasis. In addition, NR supplementation activated SirT1 activity and increased deacetylation of PGC-1α, and reversed ethanol-induced mitochondrial dysfunction and mitochondrial biogenesis. These effects were diminished with the knockdown of SirT1 in Caco-2 cells. Conclusion: Boosting NAD by NR alleviates ethanol-induced intestinal epithelial barrier damage via protecting mitochondrial function in a SirT1-dependent manner

Made in Water: A Stable Microporous Cu(I)-carboxylate Framework (CityU-7) for CO₂, Water, and Iodine Uptake

Using water as the sole solvent, the bifunctional molecule tetrakis­(methylthio)-1,4-benzenedicarboxylic acid (TMBD) was reacted with Cu­(CH₃CN)₄BF₄ to form a robust microporous metal–organic framework (MOF, CityU-7) featuring Cu­(I) ions being simultaneously bonded to the carboxyl and thioether donors. The MOF solid is stable in air and can be easily activated by heating, without the need for treatment with organic solvents. The subnanoscopic pores (ca. 0.6 nm) of the host net allow for uptake of CO₂ and H₂O but exhibit lesser sorption for N₂ at 77 K. The microporous net can also be penetrated by I₂ molecules

AI based colorectal disease detection using real-time screening colonoscopy

Colonoscopy is an effective tool for early screening of colorectal diseases. However, the application of colonoscopy in distinguishing different intestinal diseases still faces great challenges of efficiency and accuracy. Here we constructed and evaluated a deep convolution neural network (CNN) model based on 117 055 images from 16 004 individuals, which achieved a high accuracy of 0.933 in the validation dataset in identifying patients with polyp, colitis, colorectal cancer (CRC) from normal. The proposed approach was further validated on multi-center real-time colonoscopy videos and images, which achieved accurate diagnostic performance on detecting colorectal diseases with high accuracy and precision to generalize across external validation datasets. The diagnostic performance of the model was further compared to the skilled endoscopists and the novices. In addition, our model has potential in diagnosis of adenomatous polyp and hyperplastic polyp with an area under the receiver operating characteristic curve of 0.975. Our proposed CNN models have potential in assisting clinicians in making clinical decisions with efficiency during application