Search

The fabrication of MCL and the mechanism of MCL-mediated antitumor effects against melanoma.

Coxsackievirus A10 (CV-A10) is recognized as one of the most important pathogens associated with hand, foot, and mouth disease (HFMD) in young children under 5 years of age worldwide, and it can lead to fatal neurological complications. However, available commercial vaccines fail to protect against CV-A10. Therefore, the study of new protein targets against CV-A10 highlight the urgent need for the development of vaccine-based strategies. Currently, advances in proteomics have enabled a comprehensive understanding of host-pathogen interactions in recent years. Here, to study CV-A10-host interaction, a global quantitative proteomic analysis could help uncover the molecular determinants of host cellular proteins and excavate key host proteins following CV-A10 infection. Through tandem mass tagging (TMT)-based mass spectrometry, it was found that a total of 6615 host proteins were quantified, with 293 proteins being differentially regulated. To ensure the validity and reliability of the proteomics data, 3 randomly selected proteins were verified by Western blot analysis, and the results were consistent with the TMT results. Further functional analysis showed that the up-regulated and down-regulated proteins were individually enriched in diverse biological activities and signaling pathways, such as metabolic process, biosynthetic process, AMPK signaling pathway, Neurotrophin signaling pathway, MAPK signaling pathway, GABAergic synapse, and so on. Moreover, subsequent bioinformatics analysis further exhibited that these differentially expressed proteins contained distinct domains, localized in different subcellular components, and generated a complex network. Finally, it was also found that HMGB1 might be a key host factor to be involved in CV-A10 replication. In summary, our findings provided comprehensive insights into the proteomic profile during CV-A10 infection and added depth to our understanding of the relationship between CV-A10 and host cell, as well as also established a proteomic signature for this viral infection. Meanwhile, based on the effect of HMGB1 on CV-A10 replication, it might be regarded as a promising therapeutic target against CV-A10 infection.

The fate of radionuclides in the environment is attracting increased attention. The effect of various environmental effects on the adsorption behavior of the strontium ion (Sr2+) by red soil colloids in Southern China was studied by a series of batch experiments, and the adsorption mechanism was briefly investigated as well. With the increase in the solid–liquid ratio and the concentration of Sr2+, the adsorption efficiency increased gradually. The effect of pH and ionic strength on adsorption was strong, while temperature had little effect. The adsorption data fitted to the Langmuir model indicates that the process is monolayered and homogeneous. The thermodynamic parameters also show that the adsorption of Sr2+ on red soil colloids is a spontaneous and exothermic process. The aim of this work is to gain insight into the role of red soil colloids on the fate of radionuclides in the field.

Gynostemma pentaphyllum (Thunb.) Makino is a perennial creeping herbaceous plant in the family Cucurbitaceae, which has great medicinal value and commercial potential, but urgent conservation efforts are needed due to the gradual decreases and fragmented distribution of its wild populations. Here, we report the high-quality diploid chromosome-level genome of G. pentaphyllum obtained using a combination of next-generation sequencing short reads, Nanopore long reads, and Hi-C sequencing technologies. The genome is anchored to 11 pseudo-chromosomes with a total size of 608.95 Mb and 26 588 predicted genes. Comparative genomic analyses indicate that G. pentaphyllum is estimated to have diverged from Momordica charantia 60.7 million years ago, with no recent whole-genome duplication event. Genomic population analyses based on genotyping-by-sequencing and ecological niche analyses indicated low genetic diversity but a strong population structure within the species, which could classify 32 G. pentaphyllum populations into three geographical groups shaped jointly by geographic and climate factors. Furthermore, comparative transcriptome analyses showed that the genes encoding enzyme involved in gypenoside biosynthesis had higher expression levels in the leaves and tendrils. Overall, the findings obtained in this study provide an effective molecular basis for further studies of demographic genetics, ecological adaption, and systematic evolution in Cucurbitaceae species, as well as contributing to molecular breeding, and the biosynthesis and biotransformation of gypenoside.

There is growing evidence supporting the implications of exosomes-shuttled microRNAs (miRs) in the phenotypes of glioblastoma stem cells (GSCs), whilst the role of exosomal miR-27b-3p remains to be established. Herein, the aim of this study was to investigate the effect of M2 tumor-associated macrophage (TAM)-derived exosomal miR-27b-3p on the function of GSCs. Clinical glioblastoma (GBM) specimens were obtained and GSCs and M2-TAMs were isolated by fluorescence-activated cell sorting (FACS), and exosomes were separated from M2-TAMs. It was observed that M2-TAM-derived exosomes promoted the stem-like properties of GSCs. Gain- and loss- of function assays were then conducted to explore the effects of exosomal miR-27b-3p and the miR-27b-3p/MLL4/PRDM1 axis on GSC phenotypes. A xenograft tumor model of GBM was further established for in vivo substantiation. Inhibition of miR-27b-3p in M2-TAMs reduced exosomal miR-27b-3p transferred into GSCs and consequently diminished GSC viability in vitro and tumor-promoting effects of GSCs in vivo. The interaction among miR-27b-3p, mixed linked leukemia 4 (MLL4), positive regulatory domain I (PRDM1) was validated by dual-luciferase and ChIP assays. MLL4 positively regulated PRDM1 expression by inducing methylation in the PRDM1 enhancer region and ultimately reduced IL-33 expression. miR-27b-3p targeted MLL4/PRDM1 to activate IL-33 and maintain the stem-like function of GSCs. In conclusion, our study elucidated that M2-TAM-derived exosomal miR-27b-3p enhanced the tumorigenicity of GSCs through the MLL4/PRDM1/IL-33 axis.

Background In this study, we determine the potential roles and uncover the regulatory mechanisms of circCCDC66 in regulating cell growth and cell metastasis of glioma. Methods qRT-PCR was used to detect the expressions of circCCDC66 in gliomas and tissues. The biological function of circCCDC66 in glioma cell lines was elucidated by functional experiments. Cell counting kit-8 and transwell were used to detect the effect of circCCDC66 on the proliferation, migration and invasion of glioma cells. Bioinformatics analysis was applied to reveal the targets of circCCDC66. Results The results showed circCCDC66 was overexpressed in glioma and acted as an oncogene. CircCCDC66 knockdown suppressed the proliferation, migration, and invasion of glioma cells. We constructed a circCCDC66 regulating miRNA network and revealed miR-320a was a potential target of circCCDC66, which was down-regulated in high-grade gliomas compared to low-grade gliomas. Bioinformatics analysis showed circCCDC66-miR-320a/b axis was involved in regulating multiple cancer-related pathways. Furthermore, we identified FOXM1 as a key target of circCCDC66, which was involved in regulating DNA damage response pathways. In mechanism study, circCCDC66 could sponge miR-320a, thereby increasing the expression of FOXM1. Conclusions CircCCDC66 could facilitate glioma cells proliferation, invasion and migration by down-regulating miR-320a and up-regulating FOXM1.

Circular RNAs (circRNAs) are a group of noncoding RNAs derived from back-splicing events. CircRNA is reported to be involved in various tumor progressions, including glioma. Although there are a few reports of circular RNAs participating in gliomas, it is still unclear whether circular RNAs regulate the occurrence of gliomas. In our research, we found that the expression of circITGA7 in glioma tissues and glioma cells increased significantly. Knocking down circITGA7 can significantly inhibit the proliferation of glioma cells and reduce cell metastasis. Through analysis and dual-luciferase report assay, we found that circITGA7 acts as a sponge for miR-34a-5p targeting VEGFA in glioma. Our study showed that circITGA7 regulates the proliferation and metastasis of glioma cell lines (SW1783&U373) by regulating the miR-34a-5p/VEGFA pathway. In conclusion, our study revealed a regulatory loop for the circITGA7/miR-34a-5p/VEGFA axis to regulate glioma development.

Osteoarthritis (OA) is one of the most common joint diseases and a major global public health concern. Mesenchymal stem cells (MSCs) have been widely used for the treatment of OA owing to their paracrine secretion of trophic factors, a phenomenon in which exosomes may play a major role. Here, we investigate the potential of exosomes from human umbilical cord-derived MSCs (hUC-MSCs-Exos) in alleviating OA.The hUC-MSCs-Exos were harvested from hUC-MSC-conditioned medium using ultracentrifugation. Rats with surgically-induced OA were intra-articularly injected with hUC-MSCs-Exos. The effect of hUC-MSCs-Exos in repairing osteoarticular cartilage was assessed using hematoxylin and eosin (HE) staining, safranin-O and fast green staining and immunohistochemistry. TheThe results showed that hUC-MSCs-Exos prevented severe damage to the knee articular cartilage in the rat OA model. We confirmed the high efficacy of hUC-MSCs-Exos in promoting chondrocyte proliferation and migration and inhibiting chondrocyte apoptosis. Additionally, hUC-MSCs-Exos could reverse IL-1β-induced injury of chondrocytes and regulate the polarization of macrophagesThere is potential for hUC-MSCs-Exos to be used as a treatment strategy for OA.

Background Retinitis pigmentosa is a rod-cone degenerative disease that induces irreversible vision loss. This study probed the protective capacity of mesenchymal stem cell-derived small EVs (MSC-EVs) on the retinas of rd10 mice and the underlying mechanism. Methods MSC-EVs were injected into the vitreous of rd10 mice at postnatal day 14 and P21; morphology and function were examined at P28. The mechanism of action was explored by using co-culture of photoreceptor cell line 661 W and microglia cell line BV2. Results Treatment with MSC-EVs increased the survival of photoreceptors and preserved their structure. Visual function, as reflected by optomotor and electroretinogram responses, was significantly enhanced in MSC-EVs-treated rd10 mice. Mechanistically, staining for Iba1, GFAP, F4/80, CD68 and CD206 showed that MSC-EVs suppressed the activation of microglial, Müller glial and macrophages. Furthermore, western blotting showed that the treatment inhibited the NF-κB pathway. RNA-seq and qPCR showed that MSC-EVs upregulated anti-inflammatory cytokines while downregulating pro-inflammatory cytokines. MSC-EVs application in vitro decreased the number of TUNEL-positive 661 W cells co-cultured with LPS-stimulated BV2, with similar impact on the cytokine expression as in vivo study. Genetic screening predicted miR-146a to be the downstream target of MSC-EVs, which was detected in MSC-EVs and upregulated in co-cultured 661 W cells and BV2 cells after MSC-EVs treatment. Upregulation of miR-146a by using its mimic decreased the expression of the transcription factor Nr4a3, and its downregulation inhibition promoted Nr4a3 expression in both 661 W and BV2 cells. Nr4a3 was further identified as the target gene of miR-146a by dual-luciferase assay. Furthermore, overexpressing miR-146a significantly decreased the expression of LPS-induced pro-inflammatory cytokines in BV2 cells. Conclusions MSC-EVs delays retinal degeneration in rd10 mice mainly by its anti-inflammatory effect via the miR-146a-Nr4a3axis. Hence, MSC-EVs may be used in the treatment of neurodegenerative diseases.

Background: LINC01198 has been suggested to be able to predict overall prognosis for glioma; however, it has been little described in glioma. Results: It was shown that LINC01198 was markedly enriched in neoplasmic tissues relative to normal controls; and that elevated LINC01198 significantly correlated with unfavorable overall prognosis. Moreover, activation of STAT5A, identified as transcription factor (TF), can induce the expression of LINC01198. DGCR8, a kind of RNA-binding proteins (RBPs), was identified to be able to bind with LINC01198 that can stabilize the DGCR8. Five differential miRNAs with most significant difference, including miR-21-5p, miR-34-5p, miR-1246, miR-4488 and miR-494, were obtainable after silencing of DGCR8. Conclusions: Together, the data we presented here suggested that STAT5 induced LINC01198 promotes proliferation and motility of glioma cells through stabilizing DGCR8 in glioma cells. Methods: Expression of LINC01198 was appraised by quantitative PCR (qPCR) and in situ hybridization (ISH) in glioma clinical specimens, totaling 100 cases. Post hoc statistical analysis was conducted. In vitro, LINC01198 was stably silenced or re-expressed by transfection with lentiviral-based vectors. Chromatin-immunoprecipitation (CHIP) was applied to identify the relevant TFs that can bind with LINC01198, which was corroborated with electrophoretic mobility shift (EMSA) assay. RNA-immunoprecipitation (RIP) was used to identify the RNA-binding protein that can bind with LINC01198. Moreover, miRNA microarray was used to screen out differential miRNAs after silencing of DGCR8.

Gynostemma microspermum C. Y. Wu et S. K. Chen is an endemic creeping herbaceous species mainly distributed in dense forests on limestone in northwestern China. Here, the complete chloroplast genome sequence of G. microspermum was obtained by Illumina pair-end sequencing. The circular complete chloroplast genome of G. microspermum is 158,692 bp in length and contains a large single copy region (87,452 bp), a small single copy region (19,068 bp) and two short inverted repeat regions (26,086 bp). The genome sequence encodes 133 genes including 87 protein-coding genes, 37 transfer RNA genes, 8 ribosomal RNA genes and 1 pseudogene. The maximum likelihood (ML) phylogeny estimation shows that G. microspermum is sister to all other analyzed species of the genus Gynostemma with high bootstrap support.

The abnormally expressed long non-coding RNA (lncRNA) H19 has a crucial function in the development and progression of cardiovascular disease; however, its role in atherosclerosis is yet to be known. We aimed to examine the impacts of lncRNA H19 on atherogenesis as well as the involved mechanism. The outcomes from this research illustrated that the expression of lncRNA H19 was elevated in mouse blood and aorta with lipid-loaded macrophages and atherosclerosis. Adeno-associated virus (AAV)-mediated lncRNA H19 overexpression significantly increased the atherosclerotic plaque area in apoE−/− mice supplied with a Western diet. The upregulation of lncRNA H19 decreased the miR-146a-5p expression but increased the levels of ANGPTL4 in mouse blood and aorta and THP-1 cells. Furthermore, lncRNA H19 overexpression promoted lipid accumulation in oxidized low-density lipoprotein (ox-LDL)-induced THP-1 macrophages. However, the knockdown of lncRNA H19 served as a protection against atherosclerosis in apoE−/− mice and lowered the accumulation of lipids in ox-LDL-induced THP-1 macrophages. lncRNA H19 promoted the expression of ANGPTL4 via competitively binding to miR-146a-5p, thus promoting lipid accumulation in atherosclerosis. These findings altogether demonstrated that lncRNA H19 facilitated the accumulation of lipid in macrophages and aggravated the progression of atherosclerosis through the miR-146a-5p/ANGPTL4 pathway. Targeting lncRNA H19 might be an auspicious therapeutic approach for preventing and treating atherosclerotic disease.

Glioblastoma (GBM) cell-derived extracellular vesicles (EVs) have been demonstrated to modulate tumor microenvironment. In the present study, we attempted to discuss the role of hsa-microRNA-27a-3p (miR-27a-3p) delivered by GBM-EVs in M2 macrophage polarization. The isolated GBM-EVs were co-cultured with macrophages. After co-culture under normoxia/hypoxia, the effect of EV-derived hsa-miR-27a-3p on GBM cell biological processes was analyzed. Additionally, the target genes of hsa-miR-27a-3p were predicted. Moreover, the binding of enhancer of zeste homologue 1 (EZH1) to lysine-specific demethylase 3A (KDM3A) promoter region and the interaction between KDM3A and connective tissue growth factor (CTGF) were analyzed. GBM mouse models were established to verify the functions of EV-derived hsa-miR-27a-3p in vivo. We found increased hsa-miR-27a-3p in GBM tissues as well as GBM-EVs, which induced M2 polarization, thus promoting proliferative, migrative and invasive potentials of GBM cells. hsa-miR-27a-3p targeted EZH1 and promoted KDM3A expression to elevate the CTGF expression. GBM-EV-delivered hsa-miR-27a-3p promoted the KDM3A-upregulated CTGF by downregulating EZH1, thereby promoting M2 macrophage polarization and development of GBM in vivo. We demonstrated that EV-derived hsa-miR-27a-3p may promote M2 macrophage polarization to induce GBM.

The abnormally expressed long non-coding RNA (lncRNA) H19 has a crucial function in the development and progression of cardiovascular disease; however, its role in atherosclerosis is yet to be known. We aimed to examine the impacts of lncRNA H19 on atherogenesis as well as the involved mechanism. The outcomes from this research illustrated that the expression of lncRNA H19 was elevated in mouse blood and aorta with lipid-loaded macrophages and atherosclerosis. Adeno-associated virus (AAV)-mediated lncRNA H19 overexpression significantly increased the atherosclerotic plaque area in apoE−/− mice supplied with a Western diet. The upregulation of lncRNA H19 decreased the miR-146a-5p expression but increased the levels of ANGPTL4 in mouse blood and aorta and THP-1 cells. Furthermore, lncRNA H19 overexpression promoted lipid accumulation in oxidized low-density lipoprotein (ox-LDL)-induced THP-1 macrophages. However, the knockdown of lncRNA H19 served as a protection against atherosclerosis in apoE−/− mice and lowered the accumulation of lipids in ox-LDL-induced THP-1 macrophages. lncRNA H19 promoted the expression of ANGPTL4 via competitively binding to miR-146a-5p, thus promoting lipid accumulation in atherosclerosis. These findings altogether demonstrated that lncRNA H19 facilitated the accumulation of lipid in macrophages and aggravated the progression of atherosclerosis through the miR-146a-5p/ANGPTL4 pathway. Targeting lncRNA H19 might be an auspicious therapeutic approach for preventing and treating atherosclerotic disease.

Eutrema salsugineum has long been used as the model for examining salt and other abiotic stress in plants. In addition to the forward genetics approaches widely used in the lab, natural variations undoubtedly will provide a rich genetic resource for studying molecular mechanisms underlying the stress tolerance and local adaptation of this species. We used 90 resequencing whole genomes of natural populations of this species across its Asian and North American distributions to detect the selection signals for genes involved in salt and other stresses at the species-range level and local distribution. We detected selection signals for genes involved in salt and other abiotic tolerance at the species level. In addition, several cold-induced and defense genes showed selection signals due to local adaptation in North America-NE Russia or northern China, respectively. These variations and findings provide valuable resources for further deciphering genetic mechanisms underlying the stress tolerance and local adaptations of this model species.

Objective We focused on the effects of PTGS2/NF‐κB signaling pathway on the radiation resistance of glioma in the study. Methods We downloaded the microarray data from the Gene Expression Omnibus (GEO) database. We verified transfection successfully through QRT‐PCR analysis. Immunofluorescence was used to detect γH2AX content under 2 Gy radiation. The survival rates of cells under 2 Gy irradiation were tested by clonogenic survival assay. Flow cytometry was used to detect cell cycle. Western blot was applied to detect the expression of NF‐κB pathway‐related proteins. We also used MTT assay to detect the proliferation of cells. Results In this research, we discovered that the expression of the PTGS2 was upregulated in radiation‐resistant glioma cells. The radio‐tolerance rate of U87 cells was obviously elevated after the overexpression of PTGS2. The radioresistance of U87R cells was significantly reduced after the knockdown of PTGS2. After radiotherapy, the number of cells arrested in G2/M phase decreased after PTGS2 overexpression in U87cells but increased in PTGS2 knockdown in U87R cells. The survival rate of U87 and U87R cells under radiation decreased significantly after the addition of NF‐κB inhibitor. The proliferation of U87 cells was suppressed by radiation and the addition of Bay 11. In addition, PTGS2 activated NF‐κB signaling pathway and prevented DNA damage after radiotherapy. Lastly, PTGS2 was proved to facilitate tumor cell proliferation and improve the radio‐tolerance. Conclusion PTGS2/NF‐κB signaling pathway was involved in radio‐tolerance of glioma cells, which provided a new insight into glioma therapy.

BackgroundOsteoarthritis (OA) is one of the most common joint diseases and a major public health concern. Current therapies for OA can relieve symptoms but offer no potential for cartilage regeneration. Mesenchymal stem cells (MSCs) have been widely used for the treatment of OA owing to their paracrine secretion of trophic factors, a phenomenon in which exosomes may play a major role. Here, we investigated the potential of exosomes from human umbilical cord-derived MSCs (hUC-MSCs-Exos) at alleviating OA.MethodshUC-MSCs were isolated, cultured, and identified based on the expression of MSC markers and multipotency differentiation. hUC-MSCs-Exos were harvested from hUC-MSC conditioned medium using a sequential centrifugation method. Transmission electron microscopy, dynamic light scattering, flow cytometry, and western blotting were used to identify the exosomes. The effects of hUC-MSCs-Exos on the proliferation and migration of human chondrocytes were evaluated using the cell counting kit-8, EdU-555 cell proliferation kit, and transwell assays. Annexin V-FITC/PI staining and flow cytometry were used to evaluate the effect of exosomes on chondrocyte apoptosis. An in vitro model of human articular chondrocytes treated with interleukin 1 beta (IL-1β) was used to evaluate the effects of exosomes; analyses involved using quantitative real-time polymerase chain reaction (qRT-PCR), immunofluorescence, and western blotting. The role of exosomes in macrophage polarization was examined in the monocyte cell line, THP-1. Rats with surgically induced OA (ACLT+pMMx method) were intra-articularly injected with hUC-MSCs-Exos. The efficacy of exosome injections was assessed using hematoxylin and eosin and safranin-O and fast green staining, and immunohistochemistry.ResultsWe confirmed the superior efficacy of hUC-MSCs-Exos at promoting chondrocyte proliferation and migration and inhibiting chondrocyte apoptosis. Additionally, hUC-MSCs-Exos reversed IL-1β-induced injury in vitro. hUC-MSCs-Exos could inhibit the secretion of pro-inflammatory factors, promote the expression of anti-inflammatory factors, and regulate the polarization of macrophages. hUC-MSCs-Exos attenuated the progression of OA and prevented severe damage to the knee articular cartilage in the rat OA model. ConclusionshUC-MSCs-Exos exerted immunomodulatory and therapeutic effects in a rat model of OA. These exosomes derived from hUC-MSCs can potentially serve as treatments for OA.

Dysfunction at various levels of spermatogenesis (SD) is one of the important causes of infertility in men of reproductive age and requires advanced treatment strategies. Increasing evidence suggests that the therapeutic effects of echinacoside (ECH) mainly depend on their capacity to inhibit cell death. This study aimed to explore the therapeutic potential of ECH in SD rat models. Treatment with ECH reverted the morphological changes observed in testes with spermatogenesis dysfunction. It improved total sperm number, decreased the sperm deformity rate, and increased the sperm forward motility rate. The level of glutathione (GSH) was significantly higher in ECH-treated mice, whereas the lactate dehydrogenase (LDH) and SOD activities were improved compared with those in the spermatogenesis dysfunction model. Moreover, the increased expression of p38 and JNK was partially reversed by ECH. The number of normal TM3 cells increased gradually in an Echinacea dosage-dependent manner, suggesting that ECH promoted the proliferation of TM3 cells. In addition, treatment with ECH partially reversed the increased expression of p38 and JNK in TM3 cells. ECH protects against oxidative stress damage by activating antioxidant enzymes and MAPK signaling-related factors (p38 and JNK). It suggested that treatment with ECH alleviated spermatogenetic dysfunction of testes in male mice and it could be a promising strategy for patients suffering severe SD.

Prunus triloba Lindl. is a small shrub species, with many varieties and a long history of cultivation. It has been widely used for landscaping and is grown as a traditional flowering tree species in northern China. In this study, we sequenced the P. triloba Lindl. chloroplast genome, which forms a circular structure comprising 158,455 bp, including a pair of inverted repeat regions (52,634 bp), a large single-copy region (86,386 bp), and a small single-copy region (19,028 bp). We annotated 131 genes, including 86 coding sequences, 8 rRNA sequences, and 37 tRNA sequences. Furthermore, a phylogenetic analysis revealed P. triloba Lindl. is closely related to Prunus pedunculata.

Background Skin wounding is very common and may be slow to heal. Increasing evidence shows that exosomes derived from mesenchymal stem cells (MSCs) dramatically enhance skin wound healing in a paracrine manner. However, the mechanism underlying this phenomenon has not yet been elucidated. Thus, the objective of the present study was to identify the signaling pathways and paracrine factors by which MSC-derived exosomes promote de novo skin tissue regeneration in response to wound healing. Methods In vitro and in vivo skin wound healing models were created by treating immortalized human keratinocytes (HaCaT) with hydrogen peroxide (H2O2) and excising full-thickness mouse skin, respectively. Exosomes were extracted from human umbilical cord Wharton’s jelly MSCs (hucMSC-Ex) by ultracentrifugation of cell culture supernatant. Results The hucMSC-Ex treatment significantly increased HaCaT cell proliferation and migration in a time- and dose-dependent manner, suppressed HaCaT apoptosis induced with H2O2 by inhibiting nuclear translocation of apoptosis-inducing factor (AIF) and upregulating poly ADP ribose polymerase 1 (PARP-1) and poly (ADP-ribose) (PAR). The animal experiments showed that relative to hucMSCs, hucMSC-Ex attenuated full-thickness skin wounding by enhancing epidermal re-epithelialization and dermal angiogenesis. Conclusions These findings indicated that direct administration of hucMSC-Ex may effectively treat cutaneous wounding and could be of great value in clinical settings.

Background: M2 macrophage polarization has been found to be correlated with malignancy of glioblastoma. In this study, we investigated the potential role of microRNA (miRNA) derived from extracellular vesicles of glioblastoma (glioblastoma-EVs) in M2 macrophage polarization.Methods: After isolation of human glioblastoma-EVs, transmission electron microscopy (TEM) and Nano-particle tracking analysis (NTA) were performed to identify the EVs. Besides, the proliferation, migration and invasion of glioma cells were analyzed by CCK8 and Transwell assays, respectively. The target genes of miR-27a-3p were predicted through bioinformatics analysis and verified by dual-luciferase reporter gene assay. ChIP assay was applied to detect the binding of enhancer of zeste homologue 1 (EZH1) to lysine-specific demethylase 3A (KDM3A) promoter region and the interaction between KDM3A and connective tissue growth factor (CTGF). Glioblastoma mouse models were established followed by the implement of hematoxylin-eosin (HE) and ELISA staining on pathological changes of mouse brain tissues.Results: Human glioblastoma-EVs were successfully isolated. The high expression of miR-27a-3p was found in glioblastoma tissues as well as glioblastoma-EVs, which could induce M2 polarization, thus promoting glioblastoma cell proliferation, migration and invasion. It was also shown that miR-27a-3p targeted EZH1 and promoted KDM3A expression to elevate the expression of CTGF. Glioblastoma-EVs delivered miR-27a-3p to promote the KDM3A-upregulated CTGF by downregulating EZH1, thereby promoting M2 macrophage polarization and development of glioblastoma in vivo.Conclusion: These findings highlight that EV miR-27a-3p may promote M2 macrophage polarization, which is associated with the progression of tumors.

Aprepitant, a selective neurokinin-1 receptor antagonist approved for prevention of chemotherapy-induced nausea and vomiting (CINV), is an inhibitor of the cytochrome P450 3A4 (CYP3A4) enzyme, which is involved in the clearance of several chemotherapeutic agents. Here we evaluated the efficacy and toxicity of a combination of aprepitant, palonosetron, and dexamethasone as antiemetic prophylaxis in sarcoma patients receiving ifosfamide and doxorubicin chemotherapy, and examined the potential of aprepitant to affect the pharmacokinetics of ifosfamide, which is primarily metabolized by CYP3A4. A total of 108 sarcoma patients were randomly assigned to either the aprepitant group (antiemetic regimen: aprepitant, palonosetron, and dexamethasone) or the control group (antiemetic regimen: palonosetron and dexamethasone). Data on nausea, vomiting, and use of rescue medication were collected, and the primary efficacy end point was the proportion of patients with complete response (CR), defined as no vomiting and no use of rescue therapy during 120 h after initiation of chemotherapy. Tolerability was evaluated on the basis of reported adverse events and laboratory assessments. Blood samples for ifosfamide pharmacokinetic analysis were collected in ten patients. The percentage of patients achieving CR was significantly higher in the aprepitant group compared with that in the control group in the acute, delay, and overall phase (78.4% vs. 59.3%, 74.5% vs. 48.1%, and 68.6% vs. 37.0%, p < 0.05, respectively). No significant differences of adverse events or hematological toxicity were detected between the two groups. Concomitant administration of aprepitant did not cause any statistically significant changes in ifosfamide pharmacokinetics. Values for aprepitant group vs. control group were as follows: geometric mean of Cmax was 119 vs. 120 ng/mL, AUC0–last was 648 vs. 635 ng h/mL, AUC0–inf was 681 vs. 668 ng h/mL, plasma clearance was 4.40 vs. 4.49 (L/h/m2), respectively; harmonic means of t1/2 was 2.11 vs. 2.25 h. This study showed that aprepitant in combination with palonosetron and dexamethasone was safe and effectively controlled CINV in sarcoma patients receiving ifosfamide and doxorubicin chemotherapy. Aprepitant may have a low potential to affect the pharmacokinetics of chemotherapeutic agents metabolized by CYP3A4.

Key message The structural differences of MYB14 promoter in two grapevine genotypes affect the expression of MYB14 and stilbene synthesis in response to Al3+ and UV-C radiation. Abstract Grapevines provide an important fruit crop worldwide, but production is often limited by pathogen infection. Stilbenes, a class of secondary metabolite, represent phytoalexins that contribute to defence against pathogens in many plants, including grapevine. It is known that the transcription factors MYB14 and MYB15 are required for the activation of the promoters of resveratrol synthase to regulate stilbene biosynthesis. In the current study, we observed that stilbene levels were more highly induced by Al3+ and UV-C radiation treatments in the cultivar Vitis labrusca ‘Concord’ than in the cultivar V. vinifera ‘Cabernet Sauvignon’. We investigated whether genetic/structural variations in the MYB14 and MYB15 promoters between these two representative genotypes are responsible for the differences in stilbene accumulation. Significant differences in the structure and activity of the promoter of MYB14, but not MYB15 were identified between the two genotypes, following heterologous expression in Nicotiana benthamiana system and treatments with Al3+ and UV-C. Hydrogen peroxide (H2O2) was detected in Concord soon after the stress treatments, but after diphenyleneiodonium chloride pre-treatment, the expressing level of VlMYB14, the promoter activity of VlMYB14 and the accumulation of stilbenes was significantly reduced. A model is presented where the induction of MYB14 contributes to stilbene accumulation in Concord following Al3+ and UV-C treatments involving reactive oxygen species (ROS) production as an early signal. Electronic supplementary material The online version of this article (10.1007/s00299-018-2347-9) contains supplementary material, which is available to authorized users.

Background: LINC01198 has been suggested to be able to predict overall prognosis for glioma; however, it has been little described in glioma. Results: It was shown that LINC01198 was markedly enriched in neoplasmic tissues relative to normal controls; and that elevated LINC01198 significantly correlated with unfavorable overall prognosis. Moreover, activation of STAT5A, identified as transcription factor (TF), can induce the expression of LINC01198. DGCR8, a kind of RNA-binding proteins (RBPs), was identified to be able to bind with LINC01198 that can stabilize the DGCR8. Five differential miRNAs with most significant difference, including miR-21-5p, miR-34-5p, miR-1246, miR-4488 and miR-494, were obtainable after silencing of DGCR8. Conclusions: Together, the data we presented here suggested that STAT5 induced LINC01198 promotes proliferation and motility of glioma cells through stabilizing DGCR8 in glioma cells. Methods: Expression of LINC01198 was appraised by quantitative PCR (qPCR) and in situ hybridization (ISH) in glioma clinical specimens, totaling 100 cases. Post hoc statistical analysis was conducted. In vitro, LINC01198 was stably silenced or re-expressed by transfection with lentiviral-based vectors. Chromatin-immunoprecipitation (CHIP) was applied to identify the relevant TFs that can bind with LINC01198, which was corroborated with electrophoretic mobility shift (EMSA) assay. RNA-immunoprecipitation (RIP) was used to identify the RNA-binding protein that can bind with LINC01198. Moreover, miRNA microarray was used to screen out differential miRNAs after silencing of DGCR8.

Mercury is a naturally occurring element and highly toxic to humans even at a low dosage. Curcumin is a polyphenol found in turmeric (Curcuma longa), widely used as a treatment strategy to improve antioxidant and anti-inflammatory properties. The purpose of this study was to investigate the potential protective mechanisms of curcumin in spleen damage induced by HgCl2. The mice were given curcumin by intragastric administration 2 h before HgCl2 injection for 24 h. At first, splenic transcriptome analysis showed that 3334 genes (2134 up and 1200 down) were differently expressed in HgCl2-induced spleen damage model. Notably, KEGG enrichment showed phosphatidylinositol 3-kinase (PI3K)-AKT might be a key signaling pathways in HgCl2-induced spleen damage. Furthermore, our data demonstrated that HgCl2 could induce autophagic cell death, evidenced by increases the protein expression of PI3K, AKT, LC3-II and p62 and the number of apoptotic cells. Furthermore, we found that curcumin significantly combated autophagic cell death, sodium overload and calcium leak induced by HgCl2. Simultaneously, further studies demonstrated that curcumin significantly activated nuclear factor (erythroid-derived-2)-like 2 (Nrf2) signaling pathway, and subsequent enhancing antioxidant defenses. Taken together, our data indicated that inorganic mercury could result in autophagic cell death, which may be related to the regulation of PI3K-AKT signaling cascades. Furthermore, Nrf2-mediated antioxidant defenses may be the target of curcumin to confers an adaptive survival response to resist spleen damage induced by HgCl2. The present study perfects the mechanism theory of HgCl2-induced spleen damage and provides a way for pharmacological intervention to prevent spleen injury.

Background Gliomas are common life-threatening cancers, mainly due to their aggressive nature and frequent invasiveness and long non-coding RNAs (lncRNAs) are emerging as promising molecular targets. Therefore, we explored the regulatory mechanisms underlying the putative involvement of the lncRNA PAX-interacting protein 1- antisense RNA1/ETS proto-oncogene 1/kinesin family member 14 (PAXIP1-AS1/ETS1/KIF14) axis in glioma cell invasion and angiogenesis. Methods Firstly, we identified differentially expressed lncRNA PAXIP1-AS1 as associated with glioma based on bioinformatic data. Then, validation experiments were conducted to confirm a high expression level of lncRNA PAXIP1-AS1 in glioma tissues and cells, accompanied by upregulated KIF14. We further examined the binding between lncRNA PAXIP1-AS1, KIF14 promoter activity, and transcription factor ETS1. Next, overexpression vectors and shRNAs were delivered to alter the expression of lncRNA PAXIP1-AS1, KIF14, and ETS1 to analyze their effects on glioma progression in vivo and in vitro. Results LncRNA PAXIP1-AS1 was mainly distributed in the nucleus of glioma cells. LncRNA PAXIP1-AS1 could upregulate the KIF14 promoter activity by recruiting transcription factor ETS1. Overexpression of lncRNA PAXIP1-AS1 enhanced migration, invasion, and angiogenesis of human umbilical vein endothelial cells in glioma by recruiting the transcription factor ETS1 to upregulate the expression of KIF14, which was further confirmed by accelerated tumor growth in nude mice. Conclusions The key findings of this study highlighted the potential of the lncRNA PAXIP1-AS1/ETS1/KIF14 axis as a therapeutic target for glioma treatment, due to its role in controlling the migration and invasion of glioma cells and its angiogenesis.

Mesenchymal stem cells (MSCs) are a kind of adult stem cells with self-replication and multidirectional differentiation, which can differentiate into tissue-specific cells under physiological conditions, maintaining tissue self-renewal and physiological functions. They play a role in the pathological condition by lateral differentiation into tissue-specific cells, replacing damaged tissue cells by playing the role of a regenerative medicine , or repairing damaged tissues through angiogenesis, thereby, regulating immune responses, inflammatory responses, and inhibiting apoptosis. It has become an important seed cell for tissue repair and organ reconstruction, and cell therapy based on MSCs has been widely used clinically. The study found that the probability of stem cells migrating to the damaged area after transplantation or differentiating into damaged cells is very low, so the researchers believe the leading role of stem cell transplantation for tissue repair is paracrine secretion, secreting growth factors, cytokines or other components. Exosomes are biologically active small vesicles secreted by MSCs. Recent studies have shown that they can transfer functional proteins, RNA, microRNAs, and lncRNAs between cells, and greatly reduce the immune response. Under the premise of promoting proliferation and inhibition of apoptosis, they play a repair role in tissue damage, which is caused by a variety of diseases. In this paper, the biological characteristics of exosomes (MSCs-exosomes) derived from mesenchymal stem cells, intercellular transport mechanisms, and their research progress in the field of stem cell therapy are reviewed.

The maintenance of highly proliferative capacity and full differentiation potential is a necessary step in the initiation of stem cell-based regenerative medicine. Our recent study showed that epidermal growth factor (EGF) significantly enhanced hair follicle-derived mesenchymal stem cell (HF-MSC) proliferation while maintaining the multilineage differentiation potentials. However, the underlying mechanism remains unclear. Herein, we investigated the role of EGF in HF-MSC proliferation. HF-MSCs were isolated and cultured with or without EGF. Immunofluorescence staining, flow cytometry, cytochemistry, and western blotting were used to assess proliferation, cell signaling pathways related to the EGF receptor (EGFR), and cell cycle progression. HF-MSCs exhibited surface markers of mesenchymal stem cells and displayed trilineage differentiation potentials toward adipocytes, chondrocytes, and osteoblasts. EGF significantly increased HF-MSC proliferation as well as EGFR, ERK1/2, and AKT phosphorylation (p-EGFR, p-ERK1/2, and p-AKT) in a time- and dose-dependent manner, but not STAT3 phosphorylation. EGFR inhibitor (AG1478), PI3K-AKT inhibitor (LY294002), ERK inhibitor (U0126), and STAT3 inhibitor (STA-21) significantly blocked EGF-induced HF-MSC proliferation. Moreover, AG1478, LY294002, and U0126 significantly decreased p-EGFR, p-AKT, and p-ERK1/2 expression. EGF shifted HF-MSCs at the G1 phase to the S and G2 phase. Concomitantly, cyclinD1, phosphorylated Rb, and E2F1expression increased, while that of p16 decreased. In conclusion, EGF induces HF-MSC proliferation through the EGFR/ERK and AKT pathways, but not through STAT-3. The G1/S transition was stimulated by upregulation of cyclinD1 and inhibition of p16 expression.

Gynostemma pentaphyllum, a member of family Cucurbitaceae, is a perennial creeping herb used as a traditional medicinal plant in China. In this study, six polymorphic nSSR and four EST‐SSR primers were used to genotype 1,020 individuals in 72 wild populations of G. pentaphyllum. The genetic diversity and population structure were investigated, and ecological niche modeling was performed to reveal the evolution and demographic history of its natural populations. The results show that G. pentaphyllum has a low level of genetic diversity and high level of variation among populations because of pervasive asexual propagation, genetic drift, and long‐term habitat isolation. Results of the Mantel test demonstrate that the genetic distance and geographic distance are significantly correlated among G. pentaphyllum natural populations. The populations can be divided into two clusters on the basis of genetic structure. Asymmetrical patterns of historical gene flow were observed among the clusters. For the contemporary, almost all the bidirectional gene flow of the related pairs was symmetrical with slight differences. Recent bottlenecks were experienced by 34.72% of the studied populations. The geographic range of G. pentaphyllum continues to expand northward and eastward from Hengduan Mountains. The present distribution of G. pentaphyllum is a consequence of its complex evolution. Polyploidy in G. pentaphyllum is inferred to be polygenetic. Finally, G. pentaphyllum is a species in need of protection, so in situ and ex situ measures should be considered in the future., In the current study, the genetic diversity and population structure were investigated combining with ecological niche modelling to reveal the evolutionary and population demographic history for natural populations of Gynostemma pentaphyllum. We assessed the genetic diversity and population structure of G. pentaphyllum, explored the migration, and speculated the formation of polyploidies, as well as provided basic information to formulate the corresponding conservation strategy.

Abies chensiensis, an endemic evergreen trees distributed in Qinling Mountains, is listed in China Species Red List as an endangered species. In this study, the complete chloroplast genome (cpDNA) sequence of Abies chensiensis was determined from Illumina pair-end sequencing data. The cpDNA is 121,329 bp in length, contains a large single copy region (LSC) of 72,843 bp and a small single copy region (SSC) of 46,126 bp, which were separated by a pair of inverted repeat (IR) regions of 1180 bp. The genome contains 120 genes, including 81 protein-coding genes, 4 ribosomal RNA genes, and 35 transfer RNA genes. The overall GC content of the whole genome is 38.3%, and the corresponding values of the LSC, SSC, and IR regions are 38.8, 37.1, and 37.5%, respectively. Phylogenetic analysis based on 20 chloroplast genomes indicates that A. chensiensis is closely related to A. sibirica.

Past and current climatic changes have affected the demography, patterns of genetic diversity, and genetic structure of extant species. The study of these processes provides valuable information to forecast evolutionary changes and to identify conservation priorities. Here, we sequenced two functional nuclear genes and four chloroplast DNA regions for 105 samples from 21 populations of Quercus liaotungensis across its distribution range. Coalescent-based Bayesian analysis, approximate Bayesian computation (ABC), and ecological niche modeling (ENM) were integrated to investigate the genetic patterns and demographical history of this species. Association estimates including Mantel tests and multiple linear regressions were used to infer the effects of geographical and ecological factors on temporal genetic variation and diversity of this oak species. Based on multiple loci, Q. liaotungensis populations clustered into two phylogenetic groups; this grouping pattern could be the result of adaptation to habitats with different temperature and precipitation seasonality conditions. Demographical reconstructions and ENMs suggest an expansion decline trend of this species during the Quaternary climatic oscillations. Association analyses based on nuclear data indicated that intraspecific genetic differentiation of Q. liaotungensis was clearly correlated with ecological distance; specifically, the genetic diversity of this species was significantly correlated with temperature seasonality and soil pH, but negatively correlated with precipitation. Our study highlights the impact of Pleistocene climate oscillations on the demographic history of a tree species in Northern China, and suggests that climatic and soil conditions are the major factors shaping the genetic diversity and population structure of Q. liaotungensis.

Immunosuppressive tumor microenvironments (TMEs) create tremendous obstacles for an effective cancer therapy. Herein, we developed a melittin-RADA32 hybrid peptide hydrogel loaded with doxorubicin (DOX) for a potent chemoimmunotherapy against melanoma through the active regulation of TMEs. The formed melittin-RADA32-DOX (MRD) hydrogel has an interweaving nanofiber structure and exhibits excellent biocompatibility, controlled drug release properties both in vitro and in vivo, and an enhanced killing effect to melanoma cells. A single-dose injection of MRD hydrogel retarded the growth of primary melanoma tumors by more than 95% due to loaded melittin and DOX, with concomitant recruitment of activated natural killer cells in the tumors. Furthermore, MRD hydrogel can activate dendritic cells of draining lymph nodes, specifically deplete M2-like tumor-associated macrophages (TAMs), and produce active, cytotoxic T cells to further defend the cells against remaining tumors, providing potent anticancer efficacy a...

Fagaceae is one of the largest and economically important taxa within Fagales. Considering the incongruence among inferences from plastid and nuclear genes in the previous Fagaceae phylogeny studies, we assess the performance of plastid phylogenomics in this complex family. We sequenced and assembled four complete plastid genomes (Fagus engleriana, Quercus spinosa, Quercus aquifolioides, and Quercus glauca) using reference-guided assembly approach. All of the other 12 published plastid genomes in Fagaceae were retrieved for genomic analyses (including repeats, sequence divergence and codon usage) and phylogenetic inference. The genomic analyses reveal that plastid genomes in Fagaceae are conserved. Comparing the phylogenetic relationships of the key genera in Fagaceae inferred from different codon positions and gene function datasets, we found that the first two codon sites dataset recovered nearly all relationships and received high support. Thus, the result suggested that codon composition bias had great influence on Fagaceae phylogenetic inference. Our study not only provides basic understanding of Fagaceae plastid genomes, but also illuminates the effectiveness of plastid phylogenomics in resolving relationships of this intractable family.

Tanshinol borneol ester (DBZ) is a novel experimental compound that consists of two chemical structural units from danshensu and borneol. It exhibits efficacious anti-ischemic and anti-atherosclerosis activities in rats. A fecal metabolomics based on Liquid Chromatography-Mass Spectrometry combined with clinical histopathology and blood lipid estimation was employed to assess the efficacy and the metabolic changes caused by administration of DBZ in atherosclerotic rats. There were the typical pathological features of atherosclerosis and significantly increased levels of TC, TG and LDL-C in the atherosclerotic rat group. Nevertheless, atherosclerotic rats administered both DBZ (at a dose of 40 mg kg(-1)) and simvastatin (at a dose of 20 mg kg(-1)) showed good therapeutic effects. The results of the metabolomics studies showed that 55 differential metabolites such as sebacic acid, enterodiol, nonanedioic acid, dodecanedioic acid, cholic acid, 13(S)-HPODE, deoxycholic acid, some phosphatidylglycerol and phosphatidic acids were found, indicating that abnormal metabolism occurred in the pathways of fatty acid oxidation, linoleic acid metabolism, bile acid biosynthesis and glycerophospholipid metabolism in atherosclerotic rats. Compared to those in the model group, the contents of 41 differential metabolites showed a tendency to recover to a healthy level after DBZ administration. Metabolomics studies suggested that DBZ exhibited good treatment efficacy against atherosclerosis by adjusting disturbed metabolic pathways related to atherosclerosis. This study could provide an experimental basis for DBZ's application to act as a candidate drug with anti-atherosclerosis activity.

The use of human mesenchymal stem cells (hMSCs) in cell therapies has increased the demand for strategies that allow efficient cell scale-up. Preliminary data on the three-dimensional (3D) spinner culture describing the potential use of microcarriers for hMSCs culture scale-up have been reported. We exploited a rich source of autologous stem cells (human hair follicle) and demonstrated the robust in vitro long-term expansion of human hair follicle-derived mesenchymal stem cells (hHF-MSCs) by using CultiSpher(®)-G microcarriers. We analyzed the feasibility of 3D culture by using hHF-MSCs/CultiSpher(®)-G microcarrier constructs for its potential applicability in regenerative medicine by comparatively analyzing the performance of hHF-MSCs adhered to the CultiSpher(®)-G microspheres in 3D spinner culture and those grown on the gelatin-coated plastic dishes (2D culture), using various assays. We showed that the hHF-MSCs seeded at various densities quickly adhered to and proliferated well on the microspheres, thus generating at least hundreds of millions of hHF-MSCs on 1 g of CultiSpher(®)-G within 12 days. This resulted in a cumulative cell expansion of greater than 26-fold. Notably, the maximum and average proliferation rates in 3D culture were significantly greater than that of the 2D culture. However, the hHF-MSCs from both the cultures retained surface marker and nestin expression, proliferation capacity and differentiation potentials toward adipocytes, osteoblasts and smooth muscle cells and showed no significant differences as evidenced by Edu incorporation, cell cycle, colony formation, apoptosis, biochemical quantification and qPCR assays.

Cyclosporine A (CsA) enhances hair growth through caspase-dependent pathways by retarding anagen-to-catagen phase transition in the hair follicle growth cycle. Whether apoptosis-inducing factor (AIF), a protein that induces caspase-independent apoptosis, can regulate the hair follicle cycle in response to CsA is currently unclear. Here, we show that the pro-hair growth properties of CsA are in part due to blockage of AIF nuclear translocation. We first isolate hair follicles from murine dorsal skin. We then used Western blot, immunohistochemistry and immunofluorescence to evaluate the expression and localization of AIF in hair follicles. We also determined whether modulation of AIF was responsible for the effects of CsA at the anagen-to-catagen transition. AIF was expressed in hair follicles during the anagen, catagen and telogen phases. There was significant nuclear translocation of AIF as hair follicles transitioned from anagen to late catagen phase; this was inhibited by CsA, likely due to reduced cyclophilin A expression and attenuated AIF release from mitochondria. However, we note that AIF translocation was not completely eliminated, which likely explains why the transition to catagen phase was severely retarded by CsA, rather than being completely inhibited. We speculate that blockade of the AIF signalling pathway is a critical event required for CsA-dependent promotion of hair growth in mice. The study of AIF-related signalling pathways may provide insight into hair diseases and suggest potential novel therapeutic strategies.

Gynostemma BL., belonging to the family Cucurbitaceae, is a genus containing 17 creeping herbaceous species mainly distributed in East Asia. It can be divided into two subgenera based on different fruit morphology. Herein, we report eight complete chloroplast genome sequences of the genus Gynostemma, which were obtained by Illumina paired-end sequencing, assembly, and annotation. The length of the eight complete cp genomes ranged from 157,576 bp (G. pentaphyllum) to 158,273 bp (G. laxiflorum). Each encoded 133 genes, including 87 protein-coding genes, 37 tRNA genes, eight rRNA genes, and one pseudogene. The four types of repeated sequences had been discovered and indicated that the repeated structure for species in the Subgen. Triostellum was greater than that for species in the Subgen. Gynostemma. The percentage of variation of the eight cp genomes in different regions were calculated, which demonstrated that the coding and inverted repeats regions were highly conserved. Phylogenetic analysis based on Bayesian inference and maximum likelihood methods strongly supported the phylogenetic position of the genus Gynostemma as a member of family Cucurbitaceae. The phylogenetic relationships among the eight species were clearly resolved using the complete cp genome sequences in this study. It will also provide potential molecular markers and candidate DNA barcodes for future studies and enrich the valuable complete cp genome resources of Cucurbitaceae.

The design of biocompatible and efficacious anticancer biomaterials to achieve relatively low tumor recurrence rates is the main pursuit of cancer photothermal therapy (PTT). RADA16-I is a synthetic amphiphilic peptide with the sequence RADARADARADARADA that can self-assemble into a peptide nanofiber hydrogel. In this study, we synthesized a novel melittin–RADA32–indocyanine green (ICG) hydrogel (“MRI hydrogel”), which contains melittin in the peptide hydrogel backbone and ICG in the hydrogel matrix, for enhanced PTT of glioblastomas. The MRI hydrogel exhibited physiologic characteristics similar to those of the RADA16 hydrogel, while displaying concentration-dependent cytotoxicity to C6 glioma cells and photothermal effects. The in vivo biodistribution of the MRI hydrogel was visualized by near-infrared fluorescence and photoacoustic imaging. More importantly, in vivo PTT provided by the MRI hydrogel significantly reduced the tumor size and the tumor recurrence rate compared with the RADR16-ICG hydrogel ...

Gynostemma BL., belonging to the family Cucurbitaceae, is a genus containing 17 creeping herbaceous species mainly distributed in East Asia. It can be divided into two subgenera based on different fruit morphology. Herein, we report eight complete chloroplast genome sequences of the genus Gynostemma, which were obtained by Illumina paired-end sequencing, assembly, and annotation. The length of the eight complete cp genomes ranged from 157,576 bp (G. pentaphyllum) to 158,273 bp (G. laxiflorum). Each encoded 133 genes, including 87 protein-coding genes, 37 tRNA genes, eight rRNA genes, and one pseudogene. The four types of repeated sequences had been discovered and indicated that the repeated structure for species in the Subgen. Triostellum was greater than that for species in the Subgen. Gynostemma. The percentage of variation of the eight cp genomes in different regions were calculated, which demonstrated that the coding and inverted repeats regions were highly conserved. Phylogenetic analysis based on Bayesian inference and maximum likelihood methods strongly supported the phylogenetic position of the genus Gynostemma as a member of family Cucurbitaceae. The phylogenetic relationships among the eight species were clearly resolved using the complete cp genome sequences in this study. It will also provide potential molecular markers and candidate DNA barcodes for future studies and enrich the valuable complete cp genome resources of Cucurbitaceae.

v/v) at a flow rate of 0.3 mL/min. A tandem mass spectrometric detection with an electrospray ionization (ESI) interface was conducted via collision induced dissociation (CID) under negative ionization mode. The MS/MS transitions monitored were m/z 343.0448 → m/z 313.2017 for usnic acid and m/z 153.1024 → m/z 136.2136 for protocatechuic acid (internal standard). The linear range was calculated to be 2.0-160.0 ng/mL with a detection limit of 3.0 pg/mL. The inter- and intra-day accuracy and precision were within ± 7.0%. Pharmacokinetic study showed that the apartment of usnic acid in vivo confirmed to be a two compartment open model. The method was fully valid and will probably be an alternative for pharmacokinetic study of usnic acid.

Chloroplast DNA (cpDNA) is frequently used for species demography, evolution, and species discrimination of plants. However, the lack of efficient and universal markers often brings particular challenges for genetic studies across different plant groups. In this study, chloroplast genomes from two closely related species (Quercus rubra and Castanea mollissima) in Fagaceae were compared to explore universal cpDNA markers for the Chinese oak species in Quercus subgenus Quercus, a diverse species group without sufficient molecular differentiation. With the comparison, nine and 14 plastid markers were selected as barcoding and phylogeographic candidates for the Chinese oaks. Five (psbA-trnH, matK-trnK, ycf3-trnS, matK, and ycf1) of the nine plastid candidate barcodes, with the addition of newly designed ITS and a single-copy nuclear gene (SAP), were then tested on 35 Chinese oak species employing four different barcoding approaches (genetic distance-, BLAST-, character-, and tree-based methods). The four methods showed different species identification powers with character-based method performing the best. Of the seven barcodes tested, a barcoding gap was absent in all of them across the Chinese oaks, while ITS and psbA-trnH provided the highest species resolution (30.30%) with the character- and BLAST-based methods, respectively. The six-marker combination (psbA-trnH + matK-trnK + matK + ycf1 + ITS + SAP) showed the best species resolution (84.85%) using the character-based method for barcoding the Chinese oaks. The barcoding results provided additional implications for taxonomy of the Chinese oaks in subg. Quercus, basically identifying three major infrageneric clades of the Chinese oaks (corresponding to Groups Quercus, Cerris, and Ilex) referenced to previous phylogenetic classification of Quercus. While the morphology-based allocations proposed for the Chinese oaks in subg. Quercus were challenged. A low variation rate of the chloroplast genome, and complex speciation patterns involving incomplete lineage sorting, interspecific hybridization and introgression, possibly have negative impacts on the species assignment and phylogeny of oak species.

A novel rhodamine based probe has been synthesized as an “off–on” chemosensor for Fe3+. Upon coordination with Fe3+, the probe displayed good brightness and fluorescent enhancement. A linear relationship was observed to exist between the relative fluorescence intensity of this probe and the concentration of Fe3+ in the range of 5 μM–20 μM with a detection limit of 5 μM. It offered highly sensitive toward Fe3+ over other ions. The recognizing behaviors toward Fe3+ have been investigated both experimentally and computationally. It can be expected that Fe3+ coordinated with the N atom of thiazole moiety in the probe accompanied by the transferring of electrons of the phenylthiazole resulted in the opening of the spiro-ring.