Third harmonic generation due to free carrier in InSb using a terahertz free electron laser.

We report on the third harmonic generation (THG) in InSb semiconductor irradiated by a terahertz (THz) free electron laser (FEL). The conversion of 4 THz (wavelength 70 µm) FEL outputs into its third harmonic 12 THz was observed. We found that by tuning the sample temperature to 360 K, high conversion efficiency up to 1% can be obtained and is the highest in the THz and FIR regions below 10 THz. We also discuss the observed intensity dependence of the THG with the nonlinear order lower than 3 when the pumping intensity was high.

Breast Tumor Classification using Short-ResNet with Pixel-based Tumor Probability Map in Ultrasound Images.

Breast cancer is the most common form of cancer and is still the second leading cause of death for women in the world. Early detection and treatment of breast cancer can reduce mortality rates. Breast ultrasound is always used to detect and diagnose breast cancer. The accurate breast segmentation and diagnosis as benign or malignant is still a challenging task in the ultrasound image. In this paper, we proposed a classification model as short-ResNet with DC-UNet to solve the segmentation and diagnosis challenge to find the tumor and classify benign or malignant with breast ultrasonic images. The proposed model has a dice coefficient of 83% for segmentation and achieves an accuracy of 90% for classification with breast tumors. In the experiment, we have compared with segmentation task and classification result in different datasets to prove that the proposed model is more general and demonstrates better results. The deep learning model using short-ResNet to classify tumor whether benign or malignant, that combine DC-UNet of segmentation task to assist in improving the classification results.

Influence of temperature on sonographic images of the median nerve for the diagnosis of carpal tunnel syndrome: a case control study.

BACKGROUND: In addition to nerve conduction studies (NCSs), ultrasonography has been widely used as an alternative tool for diagnosing carpal tunnel syndrome (CTS). Although the results of NCSs are influenced by local skin temperature, few studies have explored the effects of skin temperature on ultrasonography of the median nerve. Since swelling and intraneural blood flow of the median nerve might be influenced by local temperature changes, the aim of this study was to evaluate the cross-sectional area (CSA) and intraneural blood flow of the median nerve under three skin temperatures (30 °C, 32 °C, 34 °C). METHODS: Fifty patients with CTS and 50 healthy volunteers were consecutively recruited from a community hospital. Each participant received physical examinations and NCSs and underwent ultrasonography, including power Doppler, to evaluate intraneural vascularity. RESULTS: The CSA of the median nerve in the CTS patients was significantly larger than that in the healthy controls at all three temperatures. However, significant differences in the power Doppler signals of the median nerve between the two studied groups were observed only at 30 and 32 °C, not at 34 °C. CONCLUSION: The significant difference in the intraneural vascularity of the median nerve between the patients with CTS and the healthy subjects was lost at higher temperatures (34 °C). Therefore, the results of power Doppler ultrasonography in diagnosing CTS should be cautiously interpreted in patients with a high skin temperature or those who reside in warm environments.

Effects of wrist extension on median nerve and flexor tendon excursions in patients with carpal tunnel syndrome: a case control study.

BACKGROUND: Reduced gliding ability of the median nerve in the carpal tunnel has been observed in patients with carpal tunnel syndrome (CTS). The purpose of this study was to evaluate the gliding abilities of the median nerve and flexor tendon in patients with CTS and healthy participants in the neutral and 30° extended positions of the wrist and to compare the gliding between the finger flexion and extension phases. METHODS: Patients with CTS and healthy participants were consecutively recruited in a community hospital. All the subjects received the Boston CTS questionnaire, physical examinations, nerve conduction study (NCS), and ultrasonography of the upper extremities. Duplex Doppler ultrasonography was performed to evaluate the gliding abilities of the median nerve and flexor tendon when the subjects continuously moved their index finger in the neutral and 30° extension positions of the wrist. RESULTS: Forty-nine patients with CTS and 48 healthy volunteers were consecutively recruited. Significant differences in the Boston CTS questionnaire, physical examination and NCS results and the cross-sectional area of the median nerve were found between the patients and the healthy controls. The degree of median nerve gliding and the ratio of median nerve excursion to flexor tendon excursion in the CTS group were significantly lower than those in the healthy control group in both the neutral and 30° wrist extension positions. Significantly increased excursion of both the median nerve and flexor tendon from the neutral to the extended positions were found in the CTS group. The ratio of median nerve excursion to flexor tendon excursion was significantly higher in the finger flexion phase than in the extended phase in both groups, and this ratio had mild to moderate correlations with answers on the Boston CTS Questionnaire and with the NCS results. CONCLUSIONS: Reduced excursion of the median nerve was found in the patients with CTS. The ratio of median nerve excursion to flexor tendon excursion was significantly lower in the patients with CTS than in the healthy volunteers. The median nerve excursion was increased while the wrist joint was extended to 30° in the patients with CTS. Wrist extension may be applied as part of the gliding exercise regimen for patients with CTS to improve median nerve mobilization.

Comparative population genomics reveals genetic divergence and selection in lotus, Nelumbo nucifera.

BACKGROUND: Lotus (Nelumbo nucifera) is an aquatic plant with important agronomic, horticulture, art and religion values. It was the basal eudicot species occupying a critical phylogenetic position in flowering plants. After the domestication for thousands of years, lotus has differentiated into three cultivated types -flower lotus, seed lotus and rhizome lotus. Although the phenotypic and genetic differentiations based on molecular markers have been reported, the variation on whole-genome level among the different lotus types is still ambiguous. RESULTS: In order to reveal the evolution and domestication characteristics of lotus, a total of 69 lotus accessions were selected, including 45 cultivated accessions, 22 wild sacred lotus accessions, and 2 wild American lotus accessions. With Illumina technology, the genomes of these lotus accessions were resequenced to > 13× raw data coverage. On the basis of these genomic data, 25 million single-nucleotide polymorphisms (SNPs) were identified in lotus. Population analysis showed that the rhizome and seed lotus were monophyletic and genetically homogeneous, whereas the flower lotus was biphyletic and genetically heterogeneous. Using population SNP data, we identified 1214 selected regions in seed lotus, 95 in rhizome lotus, and 37 in flower lotus. Some of the genes in these regions contributed to the essential domestication traits of lotus. The selected genes of seed lotus mainly affected lotus seed weight, size and nutritional quality. While the selected genes were responsible for insect resistance, antibacterial immunity and freezing and heat stress resistance in flower lotus, and improved the size of rhizome in rhizome lotus, respectively. CONCLUSIONS: The genome differentiation and a set of domestication genes were identified from three types of cultivated lotus- flower lotus, seed lotus and rhizome lotus, respectively. Among cultivated lotus, flower lotus showed the greatest variation. The domestication genes may show agronomic importance via enhancing insect resistance, improving seed weight and size, or regulating lotus rhizome size. The domestication history of lotus enhances our knowledge of perennial aquatic crop evolution, and the obtained dataset provides a basis for future genomics-enabled breeding.

Research Progress on lncRNA Functions and Mechanisms in Pituitary Adenomas.

Despite being the most common human neuroendocrine tumor, the pathogenesis of pituitary adenomas (PAs) is still unclear. Long non-coding RNA (lncRNA) is involved in a variety of physiological and pathological processes, and has been shown to play a key role in the process of tumor instigation and development by affecting the proliferation, migration, invasiveness, and metastasis of tumor cells. Therefore, lncRNAs may be used as diagnostic and prognostic markers of tumors. In this paper, the effect of lncRNA on the onset and progression of PAs is reviewed so as to provide a profound understanding of its pathogenesis and clinical reference for the early diagnosis of PAs.

MiR-181a Targets PHLPP2 to Augment AKT Signaling and Regulate Proliferation and Apoptosis in Human Keloid Fibroblasts.

BACKGROUND/AIMS: Keloids are fibrous overgrowths induced by cutaneous injury. MicroRNAs (miRNAs) have recently emerged as post-transcriptional gene repressors and participants in a diverse array of pathophysiological processes leading to skin disease. The purpose of the current study was to explore the precise functions of miR-181a in human keloid development and the underlying mechanisms. METHODS: A miRNA microarray analysis was performed to compare expression profiles between keloid and normal skin tissues. Quantitative real-time PCR was conducted to estimate miR-181a expression. Cell proliferation was determined using the cell counting kit-8 (CCK-8) and 5-ethynyl-2-deoxyuridine (EdU) assays, and cell cycle and apoptosis were detected with flow cytometry. Direct targets of miR-181a were identified using the luciferase reporter assay. RESULTS: miR-181a was significantly upregulated in human keloid tissues and fibroblasts, compared with their control counterparts. Overexpression of miR-181a enhanced keloid fibroblast DNA synthesis and proliferation and inhibited apoptosis, whereas miR-181a suppression triggered the opposite effects. Moreover, miR-181a suppressed the expression of PH domain leucine-rich repeat protein phosphatase 2 (PHLPP2) through direct interactions with its 3'UTR region and subsequently enhanced AKT activation. Overexpression of PHLPP2 without its 3'UTR attenuated the effects of miR-181a on cell proliferation and apoptosis in keloid fibroblast cells. Furthermore, miR-181a mimics increased normal skin fibroblast proliferation. CONCLUSIONS: Our results highlight a novel pathway mediated by miR-181a, which may be effectively used as a therapeutic target for treatment of keloids.

miR-542-3p suppresses invasion and metastasis by targeting the proto-oncogene serine/threonine protein kinase, PIM1, in melanoma.

Aberrant microRNAs (miRNAs) contribute to metastasis of various cancer types, including melanoma. miR-542-3p has been characterized as a tumor suppressor in several cancers. However, the exact expression patterns of miR-542-3p and the precise molecular mechanisms underlying its role in melanoma require further exploration. In the current study, we demonstrated that miR-542-3p is significantly downregulated in melanoma cell lines and clinical specimens. Exogenous expression of miR-542-3p resulted in marked inhibition of melanoma cell migration, invasion and epithelial-mesenchymal transition (EMT) in vitro and lung metastasis in vivo. The proto-oncogene serine/threonine protein kinase, PIM1, was identified as a direct target of miR-542-3p using luciferase reporter assay, qRT-PCR and western blot analyses. Overexpression of PIM1 partially rescued miR-542-3p-mediated suppression of cell migration, invasion and EMT. Our results collectively indicate that miR-542-3p serves as a metastasis suppressor in melanoma, supporting its utility as a promising therapeutic candidate.

The Effect of Tumor Necrosis Factor-α at Different Concentrations on Osteogenetic Differentiation of Bone Marrow Mesenchymal Stem Cells.

Tumor necrosis factor-alpha (TNF-α) has been demonstrated to have a close relationship with inflammation in the body. Although most researchers confirmed that TNF-α can have an effect on the expression of osteoblast specific genes, they had not elucidated the regulation of inflammatory factors in osteogenic gene expression during the process of bone marrow mesenchymal stem cells (BMMSCs) differentiating to osteoblast. The aim of this study was to investigate the effect of TNF-α at different concentrations on osteogenetic differentiation of BMMSCs. In this study, BMMSCs proliferation was analyzed by using cell counting kit-8 assay, cell osteogenic differentiation was evaluated by means of alkaline phosphatase activity assay and Von Koaas staining and the messenger RNA (mRNA) expression of bone morphogenetic proteins-2 (BMP-2) and drosophila mothers against decapentaplegic protein 1 (Smad1) was measured through real-time polymerase chain reaction. The results indicated that a low concentration of TNF-α at short-term promotes the osteogenetic differentiation of BMMSCs and increases the mRNA expression of BMP-2 and Smad1, but inhibits the osteogenetic differentiation of BMMSCs and the expression of BMP-2 and Smad1 at long term. In addition, regardless of a short or long time, a high concentration of TNF-α inhibits the osteogenetic differentiation of BMMSCs and the expression of Smad1, but results in a high expression of BMP-2.

Serum-free media and the immunoregulatory properties of mesenchymal stem cells in vivo and in vitro.

BACKGROUND: Mesenchymal stem cells are capable of self-renewal and multi-lineage differentiation. They are used extensively to treat several diseases. Traditionally, mesenchymal stem cells are cultured in serum-containing media, typically supplemented with fetal bovine serum (FBS). However, the variability of FBS is likely to skew experimental results. Although serum-free media used to expand mesenchymal stem cells has facilitated remarkable achievements, immunomodulation of these cells in under serum-free conditions is poorly understood. We hypothesized that mesenchymal stem cells expanded in serum-free media will retain powerful immunoregulatory functions in vitro and in vivo. DESIGN AND METHODS: Immunosuppressive activity and the immunomodulatory cytokines produced by mesenchymal stem cells in serum-free media were characterized in vitro. Immunomodulation by serum-free mesenchymal stem cell expansion in monocrotaline-induced pulmonary hypertension was explored in vivo. RESULTS: Similar to cells in serum-containing media, mesenchymal stem cells expanded in serum-free media inhibited proliferation and apoptosis of CD4(+)T cells. They also exhibited strong immunosuppressive activities and secreted high levels of immunomodulatory cytokines such as PGE2, IDO1, COX2, IL-6, and IL-1ß, but not HGF. On the other hand, growth of mesenchymal stem cells in serum-free media attenuated pulmonary vascular remodeling and inhibited mRNA expression of proinflammatory cytokines TNF-α, IFN-γ, IL-6, IL-1ß, and IL-18. CONCLUSIONS: Mesenchymal stem cells in serum-free media maintained powerful immunomodulatory function in vitro and in vivo; serum-free media may replace serum-containing media for basic research and clinical applications.

Exploring the inverse relationship between serum total bilirubin and systemic immune-inflammation index: insights from NHANES data (2009-2018).

BACKGROUND: Bilirubin is known for its multifaceted attributes, including antioxidant, anti-inflammatory, immunomodulatory, and antiapoptotic properties. The systemic immune-inflammation index (SII) is a recent marker that reflects the balance between inflammation and immune response. Despite the wealth of information available on bilirubin's diverse functionalities, the potential correlation between the total bilirubin (TB) levels and SII has not been investigated so far. METHODS: Leveraging data from the National Health and Nutrition Examination Survey spanning 2009-2018, the TB levels were categorized using tertiles. Employing the chi-squared test with Rao and Scott's second-order correction and Spearman's rank correlation analysis, the association between TB and SII was examined. The potential nonlinearities between TB and SII were evaluated using restricted cubic spline (RCS) analysis. Weighted linear regression, adjusted for covariates, was used to explore the correlation between TB and SII, with further subgroup analyses. RESULTS: A total of 16,858 participants were included, and the findings revealed significant SII variations across TB tertiles (p < 0.001). The third tertile (Q3) exhibited the lowest SII level at 495.73 (295.00) 1000 cells/µL. Spearman rank correlation disclosed the negative association between TB and SII. RCS analysis exposed the lack of statistically significant variations in the nonlinear relationship (p > 0.05), thereby providing support for a linear relationship. Weighted linear regression analysis underscored the negative correlation between TB and SII (ß 95% CI - 3.9 [- 5.0 to - 2.9], p < 0.001). The increase in the TB levels is associated with a significant linear trend toward decreasing SII. After controlling for relative covariates, this negative correlation increased (p < 0.001). Subgroup analysis confirmed the significant negative TB-SII association. CONCLUSION: A notable negative correlation between TB and SII implies the potential protective effects of bilirubin in inflammation-related diseases.

Post-translational modifications and immune responses in liver cancer.

Post-translational modification (PTM) refers to the covalent attachment of functional groups to protein substrates, resulting in structural and functional changes. PTMs not only regulate the development and progression of liver cancer, but also play a crucial role in the immune response against cancer. Cancer immunity encompasses the combined efforts of innate and adaptive immune surveillance against tumor antigens, tumor cells, and tumorigenic microenvironments. Increasing evidence suggests that immunotherapies, which harness the immune system's potential to combat cancer, can effectively improve cancer patient prognosis and prolong the survival. This review presents a comprehensive summary of the current understanding of key PTMs such as phosphorylation, ubiquitination, SUMOylation, and glycosylation in the context of immune cancer surveillance against liver cancer. Additionally, it highlights potential targets associated with these modifications to enhance the response to immunotherapies in the treatment of liver cancer.

Mesenchymal stem cells support proliferation and terminal differentiation of B cells.

BACKGROUND: Mesenchymal stem cells (MSC) play important roles in modulating the activities of T lymphocytes, dendritic cells and natural killer cells. These immunoregulatory properties of MSC suggest their therapeutic potential in autoimmune diseases. However, the effects of MSC on B cells are still poorly understood. The present study was designed to investigate the interaction between MSC and B cells both in vitro and in vivo, and to determine the possible mechanism of action. DESIGN AND METHOD: The effect of human umbilical cord mesenchymal stem cells (UC-MSC) on proliferation and differentiation of B-cells were characterized in vitro, and we also tested the immunoregulatory properties of mouse bone marrow MSC (BM-MSC) on T cell dependent and independent antibody production in vivo in mice. RESULTS: Treatment with human UC-MSC resulted in an increase of proliferation, differentiation of B cells into plasma cells and production of antibodies in vitro. Mouse BM-MSC significantly enhanced T cell dependent and independent antibodies production in vivo in mice. PGE2 partially mediated the immunosuppressive activity of human UC-MSC but IL-6 did not regulate this activity. CONCLUSION: MSC promote proliferation and differentiation of B cells in vitro and in vivo partially through PGE2 but not IL-6.

Genetic and Epigenetic Regulation of Brain Organoids.

Revealing the mechanisms of neural development and the pathogenesis of neural diseases are one of the most challenging missions in life science. Pluripotent stem cells derived brain organoids mimic the development, maturation, signal generation, and function of human brains, providing unique advantage for neurology. Single-cell RNA sequencing (scRNA-Seq) and multielectrode array independently revealed the similarity between brain organoids and immature human brain at early developmental stages, in the context of gene transcription and dynamic network of neuronal signals. Brain organoids provided the unique opportunity to investigate the underlying mechanism of neural differentiation, senescence, and pathogenesis. In this review, we summarized the latest knowledge and technology in the brain organoid field, the current and potential applications in disease models and pre-clinic studies, with emphasizing the importance of transcriptional and epigenetic analysis.

Coumaroyl and feruloyl flavonoid glycosides from the male flowers of Ginkgo biloba L. and their inhibitory activity against α-glucosidase.

Four flavonoid glycosides containing coumaroyl or feruloyl groups were isolated from the male flowers of Ginkgo biloba L., and compounds 3 and 4 were identified as novel compounds. The inhibitory activities against α-glucosidase were investigated by docking studies, in vitro assays and kinetic studies. The docking results showed that all compounds mainly formed hydrogen-bond and π-π-stacking interactions with α-glucosidase. Compound 4 had the lowest binding energy and maximum number of hydrogen bonds. Subsequently, the in vitro assays showed that compound 4 exhibited the strongest inhibitory potency. Finally, the kinetic studies indicated the inhibitory mode of compounds 1-4 against α-glucosidase were mixed types of competitive and non-competitive. Together, these findings suggested that the isolated flavonoid glycosides in this study, especially compound 4, have potential as α-glucosidase inhibitors.

Ultrasonographical Evaluation of the Median Nerve Mobility in Carpal Tunnel Syndrome: A Systematic Review and Meta-Analysis.

Diagnostic ultrasound is widely used for evaluating carpal tunnel syndrome (CTS), an entrapment neuropathy of the median nerve (MN). Decreased mobility of the MN inside the carpal tunnel has been reported in CTS, and various methods have been used to evaluate MN mobility; however, there is still no conclusive understanding of its connection with CTS. The purpose of this study is to conduct a systematic review and meta-analysis of the current published literature on ultrasonographic evaluations of transverse and longitudinal MN displacement and to identify the relationship between MN mobility and CTS. This study was conducted in accordance with the 2020 PRISMA statement and the Cochrane Collaboration Handbook. Comparative studies that investigated differences in MN displacement between CTS patients and healthy controls were retrieved by searching the Cochrane Library, Embase and PubMed. A total of 15 case-control studies were included. Nine of 12 studies evaluating transverse MN displacement and 4 of 5 studies evaluating longitudinal MN gliding showed that the MN was less mobile in CTS patients than in healthy subjects. Despite the large heterogeneity among the 15 included studies, this systematic review and meta-analysis provide evidence that the mobility of the MN is significantly reduced in both transverse and longitudinal planes in CTS patients compared to healthy controls. Five of the 15 included studies reported that a decrease in transverse or longitudinal MN displacement in CTS was correlated with clinical symptoms or with severity as measured by a nerve conduction study (NCS).

Multi-energy level fusion for nodal metastasis classification of primary lung tumor on dual energy CT using deep learning.

Lymph node metastasis also called nodal metastasis (Nmet), is a clinically primary task for physicians. The survival and recurrence of lung cancer are related to the Nmet staging from Tumor-Node-Metastasis (TNM) reports. Furthermore, preoperative Nmet prediction is still a challenge for the patient in managing the surgical plan and making treatment decisions. We proposed a multi-energy level fusion model with a principal feature enhancement (PFE) block incorporating radiologist and computer science knowledge for Nmet prediction. The proposed model is custom-designed by gemstone spectral imaging (GSI) with different energy levels on dual-energy computer tomography (CT) from a primary tumor of lung cancer. In the experiment, we take three different energy level fusion datasets: lower energy level fusion (40, 50, 60, 70 keV), higher energy level fusion (110, 120, 130, 140 keV), and average energy level fusion (40, 70, 100, 140 keV). The proposed model is trained by lower energy level fusion that is 93% accurate and the value of Kappa is 86%. When we used the lower energy level images to train the fusion model, there has been a significant difference to other energy level fusion models. Hence, we apply 5-fold cross-validation, which is used to validate the performance result of the multi-keV model with different fusion datasets of energy level images in the pathology report. The cross-validation result also demonstrates that the model with the lower energy level dataset is more robust and suitable in predicting the Nmet of the primary tumor. The lower energy level shows more information of tumor angiogenesis or heterogeneity provided the proposed fusion model with a PFE block and channel attention blocks to predict Nmet from primary tumors.

Umbilical cord mesenchymal stem cells promote neurological repair after traumatic brain injury through regulating Treg/Th17 balance.

Traumatic brain injury (TBI) is a brain injury resulting from blunt mechanical external forces, which is a crucial public health and socioeconomic problem worldwide. TBI is one of the leading causes of death or disability. The primary injury of TBI is generally irreversible. Secondary injury caused by neuroinflammation could result in exacerbation of patients, which indicated that anti-inflammation and immunomodulatory were necessary for the treatment of TBI. Accumulated evidence reveals that the transplantation of umbilical cord mesenchymal stem cells (UCMSCs) could regulate the microenvironment in vivo and keep a balance of helper T 17(Th17)/ regulatory T cell (Treg). Therefore, it is reasonable to hypothesize that the UCMSCs could repair neurological impairment by maintaining the balance of Th17/Treg after TBI. In the study, we observed the phenomenon of trans-differentiation of T lymphocytes into Th17 cells after TBI. Rats were divided into Sham, TBI, and TBI + UCMSCs groups to explore the effects of the UCMSCs. The results manifested that trans-differentiation of Th17 into Treg was facilitated by UCMSCs, which was followed by promotion of neurological recovery and improvement of learning and memory in TBI rats. Furthermore, UCMSCs decreased the phosphorylation of nuclear factor-kappa B (NF-κB) and increased the expression of mothers against decapentaplegic homolog 3 (Smad3) in vivo and vitro experiments. In conclusion, UCMSCs maintained Th17/Treg balance via the transforming growth factor-ß (TGF-ß)/ Smad3/ NF-κB signaling pathway.

Infarct-preconditioning exosomes of umbilical cord mesenchymal stem cells promoted vascular remodeling and neurological recovery after stroke in rats.

BACKGROUND: Stroke is the leading cause of disability worldwide, resulting in severe damage to the central nervous system and disrupting neurological functions. There is no effective therapy for promoting neurological recovery. Growing evidence suggests that the composition of exosomes from different microenvironments may benefit stroke. Therefore, it is reasonable to assume that exosomes secreted in response to infarction microenvironment could have further therapeutic effects. METHODS: In our study, cerebral infarct tissue extracts were used to pretreat umbilical cord mesenchymal stem cells (UCMSC). Infarct-preconditioned exosomes were injected into rats via tail vein after middle cerebral artery occlusion (MCAO). The effect of infarct-preconditioned exosomes on the neurological recovery of rats was examined using Tunel assay, 2,3,5-triphenyltetrazolium chloride (TTC) assay, magnetic resonance imaging (MRI) analyses, modified Neurological Severity Score (mNSS), Morris water maze (MWM), and vascular remodeling analysis. Mi-RNA sequencing and functional enrichment analysis were used to validate the signal pathway involved in the effect of infarct-preconditioned exosomes. Human umbilical vein endothelial cells (HUVECs) were co-cultured with the isolated exosomes. Cell Counting Kit-8 (CCK-8) assay, scratch healing, and Western blot analysis were used to detect the biological behavior of HUVECs. RESULTS: The results showed that compared with normal exosomes, infarct-preconditioned exosomes further promoted vascular remodeling and recovery of neurological function after stroke. The function of upregulated miRNAs and their target genes which is beneficial to vascular smooth muscle cells verified the importance of vascular remodeling in improving stroke. Better resistance to oxygen-glucose deprivation/reoxygenation (OGD/R), reduced apoptosis, and enhanced migration were observed in infarct-preconditioned exosomes-treated umbilical vein endothelial cells. CONCLUSIONS: Our results demonstrated that infarct-preconditioned exosomes promoted neurological recovery after stroke by enhancing vascular endothelial remodeling, suggested that infarct-preconditioned exosomes could be a novel way to alleviate brain damage following a stroke.

3D printed collagen/silk fibroin scaffolds carrying the secretome of human umbilical mesenchymal stem cells ameliorated neurological dysfunction after spinal cord injury in rats.

Although implantation of biomaterials carrying mesenchymal stem cells (MSCs) is considered as a promising strategy for ameliorating neural function after spinal cord injury (SCI), there are still some challenges including poor cell survival rate, tumorigenicity and ethics concerns. The performance of the secretome derived from MSCs was more stable, and its clinical transformation was more operable. Cytokine antibody array demonstrated that the secretome of MSCs contained 79 proteins among the 174 proteins analyzed. Three-dimensional (3D) printed collagen/silk fibroin scaffolds carrying MSCs secretome improved hindlimb locomotor function according to the Basso-Beattie-Bresnahan scores, the inclined-grid climbing test and electrophysiological analysis. Parallel with locomotor function recovery, 3D printed collagen/silk fibroin scaffolds carrying MSCs secretome could further facilitate nerve fiber regeneration, enhance remyelination and accelerate the establishment of synaptic connections at the injury site compared to 3D printed collagen/silk fibroin scaffolds alone group according to magnetic resonance imaging, diffusion tensor imaging, hematoxylin and eosin staining, Bielschowsky's silver staining, immunofluorescence staining and transmission electron microscopy. These results indicated the implantation of 3D printed collagen/silk fibroin scaffolds carrying MSCs secretome might be a potential treatment for SCI.