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Woody bamboo is environmentally friendly, abundant, and an alternative to conventional timber. Degree of lignification and lignin content and deposition affect timber properties. However, the lignification regulatory network in monocots is poorly understood. To elucidate the regulatory mechanism of lignification in moso bamboo (Phyllostachys edulis), we conducted integrated analyses using transcriptome, small RNA, and degradome sequencing followed by experimental verification. The lignification degree and lignin content increased with increased bamboo shoot height, whereas phenylalanine ammonia-lyase and Laccase activities first increased and then decreased with shoot growth. Moreover, we identified 11,504 differentially expressed genes (DEGs) in different portions of the 13th internodes of different height shoots; most DEGs associated with cell wall and lignin biosynthesis were upregulated, whereas some DEGs related to cell growth were downregulated. We identified a total of 1,502 miRNAs, of which 687 were differentially expressed. Additionally, in silico and degradome analyses indicated that 5,756 genes were targeted by 691 miRNAs. We constructed a regulatory network of lignification, including 11 miRNAs, 22 transcription factors, and 36 enzyme genes, in moso bamboo. Furthermore, PeLAC20 overexpression increased lignin content in transgenic Arabidopsis (Arabidopsis thaliana) plants. Finally, we proposed a reliable miRNA-mediated “MYB-PeLAC20” module for lignin monomer polymerization. Our findings provide definite insights into the genetic regulation of bamboo lignification. In addition to providing a platform for understanding related mechanisms in other monocots, these insights could be used to develop strategies to improve bamboo timber properties., Multi-omics and other approaches reveal the regulatory network of miRNA-mediated “Transcription Factor-enzyme genes” for lignification in moso bamboo, including 11 miRNAs, 22 TFs, and 36 enzyme genes.

PePIP2;7, a leaf-specific aquaporin gene in bamboo, is upregulated under abiotic stresses. Overexpressing PePIP2;7 confers abiotic stresses tolerance in transgenic Arabidopsis plant and yeast. Aquaporins (AQPs) participate in the regulation of water balance in plants. However, the function of AQPs in bamboo remains unclear. Here, PePIP2;7 was identified as a leaf-specific aquaporin gene in moso bamboo based on the expression analysis of transcriptome data and PCR. In situ hybridization further indicated that PePIP2;7 was mainly expressed in mesophyll cells of mature leaves, while in immature leaves it was dominant in blade edge cells followed by mesophyll cells. Interestingly, PePIP2;7 was strongly expressed in the mesophyll cells near bulliform cells of immature leaves, suggesting that PePIP2;7 might function in water transport and contribute to leaf unfolding. The transient expression assay showed that PePIP2;7 was a plasma membrane intrinsic protein. Furthermore, PePIP2;7 was upregulated under abiotic stresses such as high light, drought, and NaCl. Compared with Col-0, transgenic Arabidopsis plants overexpressing PePIP2;7 had better seed germination rate, longer taproot length, higher SOD activity, and lower MDA content under abiotic stresses. Besides, yeasts expressing PePIP2;7 also had higher tolerance to stress compared to the control. Taken together, our results show that PePIP2;7 is leaf-specific and involved in stress response, which provides new insights into aquaporin function in bamboo.

BACKGROUND Neuromyelitis optica spectrum disorder (NMOSD) is a demyelinating autoimmune disease that affects the central nervous system. It typically manifests as optic neuritis or extensive longitudinal myelitis, with or without the presence of anti-aquaporin protein 4 autoantibodies (immunoglobulin G). CASE SUMMARY We report the case of a 45-year-old woman with a history of Sjogren's syndrome who was diagnosed with NMOSD accompanied by spinal cord injury and left calf intermuscular vein thrombosis. The patient received hormone shock and gamma globulin therapy in the acute phase and standard rehabilitation treatment during convalescence. Upon discharge, the patient was able to control urination and defecation, stand independently, and walk short distances with the aid of a walker. CONCLUSION This case suggests that pharmacotherapy and standard rehabilitation treatment can improve the prognosis of NMSOD patients.

Boron (B) is an essential micronutrient for the plant normal growth. In Arabidopsis, NIP6;1 is a boric acid channel required for the proper distribution of boric acid, especially in the nodal regions of shoots. BnaA02.NIP6;1a, a homologous gene of AtNIP6;1 in Brassica napus, was reported to play a key role in B transport activity. However, little is known about the other functions of BnaA02.NIP6;1a in Brassica napus. In this study, we found that BnaA02.NIP6; 1a was localized in both plasma membrane and cytoplasm, which was different from that in Arabidopsis. The transgenic Arabidopsis plant containing a BnaA02.NIP6;1a promoter driven GUS reporter gene displayed strong GUS activity in roots, stems, leaves, especially in buds and open flowers, which are different from the expression pattern from its homologous gene in Arabidopsis. Silencing BnaA02.NIP6;1a repressed vegetative growth under B-deficient condition in Brassica napus. More importantly, knockdown of BnaA02.NIP6;1a in rapeseed resulted in the reduction of boron accumulation in the flower under boron deficiency and lead to severe sterility, which has not yet been reported before. Furthermore, nip6;1 mutant in Arabidopsis only showed the loss of apical dominance phenotype under boron deficiency at reproductive stage, whereas BnaA02.NIP6;1 RNAi lines exhibited large amounts of abnormal development of the inflorescence as compared with the wild type under boron limitation. Taken together, our results demonstrate that BnaA02.NIP6;1a encodes a boron transporter required for plant development under boron deficiency in Brassica napus, which shows its novel and diverse function in rapeseed compared with model plant Arabidopsis.

WRKY proteins compose a major transcription factor family in plants and are involved in the regulation of plant responses to a variety of stresses. Two novel WRKY genes, PheWRKY1-1 (Gene ID No. PH01000048G1770) and PheWRKY50-1 (Gene ID No. PH01000130G0430), were isolated from moso bamboo, and their coding sequence lengths were 1686 bp and 1023 bp, respectively. The PheWRKY1-1 and PheWRKY50-1 proteins contain typical WRKY domains, and the proteins are expressed in the nucleus. RT-PCR analysis revealed that PheWRKY1-1 was mainly expressed in the roots and that PheWRKY50-1 was concentrated in the leaves. Under drought and salt stress, the expression levels of these two genes in the roots, stems and leaves increased or decreased to varying degrees. The PheWRKY50-1 gene was transformed into Arabidopsis via Agrobacterium infection, and the transgenic plants showed higher resistance to stress than did the wild-type plants.

Background Autologous fat transplantation has already become a part of clinical practice for aesthetic breast augmentation even though evidence regarding its efficacy is still lacking. Objectives The authors sought to determine the current worldwide status and efficacy, techniques, and oncologic safety on this subject. Methods PubMed, EMBASE, and Cochrane Library databases were searched to identify all relevant studies. Results Eighty-four articles published between 1987 and April 2020, consisting of 6468 patients, were included, and 64 studies consisting of 5162 unique patients were included in the meta-analysis. Most studies had a low level of evidence (levels 2b-5); In this meta-analysis, there were 17 prospective cohort studies, 4 retrospective cohort studies, 6 case-control studies, and 38 case series. The publications were from 21 countries. Indications for autologous fat transplantation were aesthetic augmentation (93.2%) and congenital malformation (6.8%). Among the 5162 patients, 2 cases (0.04%) of cancer were reported. The meta-analysis revealed very high overall patient and surgeon satisfaction rates of 93% and 87%, respectively. Overall, only 1.56 sessions were needed to achieve the desired result. Long-term survival was calculated to be approximately 60% to 70% at 1-year follow-up. Only 8% of procedures resulted in clinical complications, and 5% of patients required biopsy because of abnormal clinical or radiological findings. Conclusions Autologous fat transplantation seems to be a major tool in aesthetic breast augmentation. Preoperative patient selection is essential but under-reported. Future research should focus on evaluating the technical and patient factors influencing the rate of fat survival and its oncological safety. Level of Evidence: 4

Jing Tang,1,2 Fengyong Liu,2 Hongjun Yuan,2 Xin Li,2 Xiaomei Tian,2 Kan Ji,2 Xueping Li,3 Wei Wang3 1Medical School of Chinese PLA, Beijing, People’s Republic of China; 2Department of Interventional Radiology, The First Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China; 3Department of Radiology, The First Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of ChinaCorrespondence: Fengyong LiuDepartment of Interventional Radiology, The First Medical Center, Chinese PLA General Hospital, No. 28, Fuxing Road, Haidian District, Beijing 100853, People’s Republic of ChinaTel +8613371668617Fax +86-10-66939340Email liufengyong301@163.comPurpose: To evaluate whether the pretreatment apparent diffusion coefficient (ADC) measured with diffusion weighted imaging (DWI) of tumor can be used as an imaging biomarker for predicting prognosis in solitary large hepatocellular carcinomas (HCCs) treated with transcatheter arterial chemoembolization (TACE) immediately combined with radiofrequency ablation (RFA).Patients and Methods: In this single institution retrospective study, 40 solitary large HCCs that underwent treatment with TACE immediately combined with RFA were analyzed. All patients underwent abdominal dynamic contrast-enhanced magnetic resonance imaging within one month before treatment with DWI, and ADC values in the lesions were measured by two independent radiologists. Associations among patients’ preoperative ADC values and objective response (OR), progression-free survival (PFS) and overall survival (OS) were examined. Survival curves were drawn with the Kaplan–Meier method, and differences were determined with the Log rank test. The Cox proportional-hazards model was used for univariate and multivariate analyses of PFS and OS.Results: Forty solitary large HCCs (mean 9.54 cm, range 5.04– 16.06 cm) were successfully treated with TACE in immediate combination with RFA (OR 75%). The ADC values were significantly higher in the response group than the non-response group (1.51± 0.32× 10− 3 mm2/s vs 1.09± 0.17× 10− 3 mm2/s; P< 0.001). As predicted on the basis of the ADC values, the optimal cutoff value for the efficacy of TACE combined with RFA was 1.32× 10− 3 mm2/s, with a predictive sensitivity of 0.63 and a specificity of 1.00. Patients with high ADC had longer PFS than those with low ADC (14.9 months vs 5.3 months; P< 0.001) and had significantly longer survival rates (22.6 months vs 12.1 months; P=0.004).Conclusion: Preoperative ADC values < 1.32× 10− 3 mm2/s are an independent predictor of poorer prognosis in patients with solitary large HCCs who have undergone TACE immediately combined with RFA.Keywords: solitary large hepatocellular carcinoma, apparent diffusion coefficient, TACE, radiofrequency ablation

Glioma is the most common cancer in the central nervous system and has a high mortality rate. Despite advances that have been made in the treatment of glioma, its prognosis still remains poor. Dysregulation of miRNAs has been reported in many cancers, including glioma. Here, we set out to assess the role of miR-650 in glioma, including its diagnostic and therapeutic potential. miR-650 and RAS-like estrogen-regulated growth inhibitor (RERG) expression levels were analyzed using qRT-PCR in primary glioma tissues and cell lines. Cell Counting Kit-8, 5-ethynyl-2′-deoxyuridine, colony formation, Western blotting, scratch wound healing, Transwell, adhesion, autophagy, immunofluorescence, luciferase reporter, electrophoretic mobility shift, tumor xenograft and flow cytometry assays were employed to investigate the mechanisms underlying the effect of miR-650 and RERG on glioma development. miR-650 was found to be up-regulated in glioma tissues and cell lines compared to non-cancerous brain tissues and neural progenitor cells, respectively. We also found that miR-650 promoted cell proliferation, migration and invasion in glioma cells, and enhanced glioma tumor formation and growth in vivo. We identified and validated RERG as a direct target of miR-650. RERG was shown to act as a tumor suppressor in glioma cells, and its suppressor roles were rescued by miR-650. We found that nuclear factor (NF)-κB bound to the promoter of miR-650 and enhanced its expression. PH domain and leucine rich repeat protein phosphatase 2 (PHLPP2), as a co-factor of the RERG/PHLPP2 complex, mediated miR-650-induced activation of the protein kinase B/extracellular-signal-regulated kinase/NF-κB signaling pathways. Our data revealed novel functional roles for miR-650 in glioma development and may provide new avenues for future clinical applications.

Stroke is the third leading cause of long-term disability. Effective stroke rehabilitation should be provided to patients with a moderate or severe stroke so as to achieve functional recovery. Also, stroke rehabilitation is moving towards more intense therapy models that incorporate technologies such as robotics and computer games. Evidence-based guidelines are useful for promoting the best possible clinical practices. This guideline summarises the modes of stroke rehabilitation in China—three-stage rehabilitation network, rehabilitation of stroke dysfunction, training for activities of daily living, stroke complications and rehabilitation care. The aim of this guideline was to provide a synopsis of best clinical practices in the stroke rehabilitation of adult patients in China.

Contralateral C7 nerve transfer is a new surgical treatment for stroke patients with unilateral upper extremity paralysis, but neuropathic pain in the nonparalyzed side is the common complication after surgery. We report a stroke patient with neuropathic pain after C7 nerve transfer who received combination treatment of transcutaneous electrical nerve stimulation(TENS) and pregabalin.A 53-year old, 6 months post-stroke patient with right hemiplegia after contralateral C7 nerve transfer was admitted in our department with a significant neuropathic pain in his left upper extremity. The treatment of pregabalin and TENS were used for patient. The visual analogue scale(VAS), medical outcomes study sleep scale(This report suggests that the combination of pregabalin and TENS have prominent clinical effects on neuropathic pain of nonparalyzed side in stroke patients after contralateral C7 nerve transfer.

Rationale: Developing an effective nanoplatform to realize 'multi-in-one' is essential to broaden the therapeutic potential of combination therapy. Exosomes are ideal candidates since their intrinsic abilities of integrating multiple contents and functions. However, only limited efforts have been devoted to engineering exosomes to integrate the needed properties, also considering the safety and yield, for tumor-targeted and efficient gene/chemo combination therapy. Methods: Herein, by manipulating the exosome membrane, blood exosomes with high abundance and safety are engineered as a versatile combinatorial delivery system, where the doxorubicin (Dox) and cholesterol-modified miRNA21 inhibitor (miR-21i) are co-embedded into the lipid bilayer of exosomes, and the magnetic molecules and endosomolytic peptides L17E are bind to the exosome membrane through ligand-receptor coupling and electrostatic interactions, respectively. Results: It is proved that such engineering strategy not only preserves their intrinsic features, but also readily integrates multiple properties of tumor targeting, efficient transfection and gene/chemo combination therapy into blood exosomes. The lipid bilayer structure of exosomes allows them to co-load Dox and miR-21i with high-payloads. Moreover, profiting from the integration of magnetic molecules and L17E peptides, the engineered exosomes exhibit an enhanced tumor accumulation and an improved endosome escape ability, thereby specifically and efficiently delivering encapsulated cargos to tumor cells. As a result, a remarkable inhibition of tumor growth is observed in the tumor-bearing mice, and without noticeable side effects. Conclusions: This study demonstrates the potential of engineered blood exosomes as feasible co-delivery nanosystem for tumor-targeted and efficient combination therapy. Further development by replacing the drugs combined regimens can potentially make this engineered exosome become a general platform for the design of safe and effective combination therapy modality.

High mortality of patients with cervical cancer (CC) stresses the imperative of prognostic biomarkers for CC patients. Additionally, the vital status of post‐translational modifications (PTMs) in the progression of cancers has been reported by numerous researches. Therefore, the purpose of this research was to dig a prognostic signature correlated with PTMs for CC. We built a five‐mRNA (GALNTL6, ARSE, DPAGT1, GANAB and FURIN) prognostic signature associated with PTMs to predict both disease‐free survival (DFS) (hazard ratio [HR] = 3.967, 95% CI = 1.985‐7.927; P

Effective two-way patient-provider communication is challenging and is even more difficult when patients are communication vulnerable. The results of being unheard and unacknowledged can contribute to negative feelings and may manifest as symptoms of anxiety and depression. Researchers explored symptoms of anxiety and depression when using a team-developed, patient-centered, and nurse-led intervention called Speak for Myself-Voice (formerly published as Speak for Myself) in five intensive care units at a Magnet status, university-affiliated medical center in East Tennessee. This was an equivalent control group design. The data were analyzed with a mixed-effect analysis of variance (between and within groups) with repeated measures to see if the treatment group changed differently than the control group across time (48 hours). This study report adds information about anxiety and depression in patients who are communication vulnerable and using communication technology.

Background: Pancreatic cancer (PC) is an aggressive cancer with worse survival in the world. Emerging evidence suggested that the imbalance of alternative splicing (AS) is a hallmark of cancer and indicated poor prognosis of patients. Genes-derived splicing events can produce neoepitopes for immunotherapy. However, the profound study of splicing profiling in PC is still elusive. We aimed to identification of novel prognostic signature across a comprehensive splicing landscape and reveal their relationship with tumor-infiltrating immune cells in pancreatic cancer microenvironment. Methods: Based on integrated analysis of splicing profiling and clinical data, differentially splicing events were filtered out. Then, stepwise Cox regression analysis was applied to identify survival-related splicing events and construct prognostic signature. Functional enrichment analysis was performed to explore biology function. Kaplan-Meier curves and receiver operating characteristic (ROC) curves were performed to validate the predictive effect of predictive signature. We also verified the clinical value of prognostic signature under the influence of different clinical parameters. For deeper analysis, we evaluated the correlation between prognostic signature and infiltrating immune cells by CIBERSORT. Results: According to systematic analyzing, a final six splicing events were identified and validated the good prognostic capability in entire TCGA dataset, validation set 1 and validation set 2 by Kaplan-Meier curves (P < 0.0001). The area under the curve (AUC) of ROC curves were also confirmed the high predictive efficiency of the prognostic signature in these three cohorts (AUC = 0.857, 0.895 and 0.788). In order to validate whether prognostic signature highlights a correlation between AS and immune contexture, CIBERSORT was performed to analyze the proportion of tumor-infiltrating immune cells in PC. Based on prognostic signature, we identified survival-related immune cells including CD8 T cells (P = 0.0111), activated CD4 memory T cells (P = 0.0329) and resting mast cells (P = 0.0352). Conclusion: In conclusion, our study contribute to provide a promising prognostic signature based on six splicing events and revealed prognosis-related immune cells which indeed represented novel tumor drivers and provide potential targets for personalized therapeutic.

Background: Colorectal cancer (CRC) is one of the most common malignant tumors in the world. Lymph node metastasis (LNM) is a common mode of metastasis of CRC. However, the combined mRNA biomarkers associated with LNM of CRC that can effectively predict CRC prognosis have not been reported yet. Methods: To identify biomarkers that are associated with LNM, we collected data from the The Cancer Genome Atlas (TCGA) database. The edgeR package was searched to seek LNM-related genes by comparisons between cancer samples and normal colorectal tissues and between LNM and non-LNM (NLNM) of CRC. Univariate and multivariate regression analysis of genes in the intersection to build gene signature associated with independent prognosis of CRC, and then verified by Kaplan-Meier curve and log-rank test, receiver operating characteristic (ROC) curve was used to determine the efficiency of survival prediction of our four-mRNA signature. Finally, the potential molecular mechanisms and properties of these gene signature were also explored with functional and pathway enrichment analysis. Results: 329 mRNAs were up-regulated in CRC tissues with LNM, and 8461 mRNAs were up-regulated in CRC tissues, the intersection is 100 mRNAs. After univariate and multivariate Cox regression analysis of 100 mRNAs, a novel four LNM related mRNAs (EPHA8, KRT85, GABRA3, and CLPSL1) were screened as independent prognostic indicators of CRC. Surprisingly, the four-mRNA signature can predict the prognosis of CRC patients independently of clinical factors andthe area under the curve (AUC) of the ROC is 0.730. The novel four-mRNA signature was used to identify high and low-risk groups. Stratified analysis indicated the risk score based on four-mRNA signature was an independent prognostic indicator for female, T3+T4, N1+N2 ,stage III+IV and patients with no new tumor event. Functional annotation of this risk model in high-risk patients revealed that pathways associated with neuroactive ligand-receptor interaction, estrogen signaling pathway, and steroid hormone biosynthesis. Conclusions: By conducting TCGA data mining, our study demonstrated that a four-mRNA signature associated with LNM can be used as a combined biomarker for independent prognosis of CRC.

Background Lingguizhugan decoction (LGZG), an ancient Chinese herbal formula, has been used to treat cardiovascular diseases in eastern Asia. We investigated whether LGZG has protective activity and the mechanism underlying its effect in an animal model of heart failure (HF). Methods A rat model of HF was established by administering eight intraperitoneal injections of doxorubicin (DOX) (cumulative dose of 16 mg/kg) over a 4-week period. Subsequently, LGZG at 5, 10, and 15 mL/kg/d was administered to the rats intragastrically once daily for 4 weeks. The body weight, heart weight index (HWI), heart weight/tibia length ratio (HW/TL), and serum BNP level were investigated to assess the effect of LGZG on HF. Echocardiography was performed to investigate cardiac function, and H&E staining to visualize myocardial morphology. Myocardial ultrastructure and T-tubule-sarcoplasmic reticulum (TT-SR) junctions were observed by transmission electron microscopy. The JP-2 protein level was determined by Western blotting. The mRNA level of CACNA1S and RyR2 and the microRNA-24 (miR-24) level were assayed by quantitative RT-PCR. Results Four weeks after DOX treatment, rats developed cardiac damage and exhibited a significantly increased BNP level compared with the control rats (169.6 ± 29.6 pg/mL versus 80.1 ± 9.8 pg/mL, P P P P P 2+ transients and cell contraction, which may underly the beneficial effect of LGZG on HF. Conclusions LGZG exerted beneficial effects on DOX-induced HF in rats, which were mediated in part by improved TT-SR microstructural remodeling.

As an inhibitor of ethylene receptors, 1-methylcyclopropene (1-MCP) can delay the ripening of papaya. However, improper 1-MCP treatment will cause a rubbery texture in papaya. Understanding of the underlying mechanism is still lacking. In the present work, a comparative sRNA analysis was conducted after different 1-MCP treatments and identified a total of 213 miRNAs, of which 44 were known miRNAs and 169 were novel miRNAs in papaya. Comprehensive functional enrichment analysis indicated that plant hormone signal pathways play an important role in fruit ripening. Through the comparative analysis of sRNAs and transcriptome sequencing, a total of 11 miRNAs and 12 target genes were associated with the ethylene and auxin signaling pathways. A total of 1741 target genes of miRNAs were identified by degradome sequencing, and nine miRNAs and eight miRNAs were differentially expressed under the ethylene and auxin signaling pathways, respectively. The network regulation diagram of miRNAs and target genes during fruit ripening was drawn. The expression of 11 miRNAs and 12 target genes was verified by RT-qPCR. The target gene verification showed that cpa-miR390a and cpa-miR396 target CpARF19-like and CpERF RAP2-12-like, respectively, affecting the ethylene and auxin signaling pathways and, therefore, papaya ripening.

Lung adenocarcinoma (LUAD) is one of the most malignant tumor types worldwide. Our objective was to identify a genetic signature that could predict the prognosis of patients with LUAD. We extracted gene data sets from The Cancer Genome Atlas and obtained differentially expressed genes that were highly expressed at every stage. These genes were analyzed using gene set enrichment analysis to obtain four biological processes associated with LUAD. Subsequently, Cox univariate and multivariate analyses were performed to generate four optimized models (G2M checkpoint, E2F targets, mitotic spindle, and glycolysis). We identified a mitotic spindle-related signature (KIF15, BUB1, CCNB2, CDK1, KIF4A, DLGAP5, ECT2, and ANLN), which could be an independent prognostic indicator, to predict the prognosis of patients with LUAD. This new discovery should offer opportunities to explore the pathogenesis of LUAD and prove clinically useful in predicting LUAD patient prognosis.

Nitrous oxide (N2O) was investigated for the potential use on inhibiting the postharvest decay of the grape. In this study, 50 μL L−1 N2O gas was used for fumigating the ‘Munage’ grape which was used as the test material at room temperature for 6 h. Results indicated that N2O had no direct effect on the Botrytis cinerea inhibition. But N2O can promote the accumulation of total phenolic, flavonoids and lignin, as well as increase the activities of phenylalanine ammonia-lyase (PAL), cinnamate-4-hydroxylase (C4H), and 4-coumarate CoA ligase (4CL), which were the key enzymes in the metabolism of phenylpropanol. N2O also induced PAL family genes expression in a short time at the molecular level. Thereby the N2O significantly reduced the lesion diameter and incidence of the grape fruit inoculated with Botrytis cinerea. These results suggested that N2O participated in enhancement of disease resistance by improving the phenylpropanoid pathway metabolism of the grape fruit and it could be a promising strategy to suppress postharvest disease.

Cell-cycle system controls flower and fruit growth, size and mass precisely, accompanied by cumulative cell proliferation and cell expansion. Vaccinium corymbosum shows significant variation in berry size, but its underlying anatomical and molecular mechanisms are poorly known. In this study, single fruit mass and cell layers of Southern highbush blueberry cultivars 'O'Neal' and 'Bluerain' were analyzed, and 12 cell-cycle related genes were isolated and detected its expression tendency. The results showed that blueberry flower buds had a lower contribution to mature fruit mass, and fruit growth exhibited a double-sigmoid pattern. Ovary wall (or pericarp) was the vital component for final fruit size, and approximately 70% cell layers of pericarp were produced before anthesis. Cell division in the blueberry fruit was arrested at pre- and post-anthesis. The sequences of Vccyclins and VcCDKs were relatively conserved, and its expression tendency followed flower bud and fruit developmental pattern, while VcCycA2L, VcCycB2L, VcCycD3;1L, VcCycT1;4L, VcCDKB2;2, VcCDKC1L and VcCDKE1 might be directly involved in cell proliferation and cell expansion. However, the difference of expression pattern between two cultivars was not quite significant, indicated that isolated Vccyclins and VcCDKs were not the key factors for blueberry fruit size. Collectively, this study expands our understanding of the complex cell division and cell expansion mechanisms, and cell-cycle regulatory mechanisms were involved in V. corymbosum flower and fruit during ontogeny.

Brassinosteroids (BRs) are a group of plant steroid hormones that play crucial roles in a range of plant growth and development processes. BR action includes active BR formation by a complex biosynthesis process and driving BR biological function through signal transduction. Although the characterization of several BR action-related genes has been conducted in a few model plants, systematic information about these genes in bamboo is still lacking. We identified 64 genes related to BR action from the genome of moso bamboo (Phyllostachys edulis), including twenty that participated in BR biosynthesis and forty-four involved in BR signal transduction. The characteristics of all these candidate genes were identified by bioinformatics methods, including the gene structures, basic physical and chemical properties of proteins, conserved domains and evolutionary relationships. Based on the transcriptome data, the candidate genes demonstrated different expression patterns, which were further validated by qRT-PCR using templates from bamboo shoots with different heights. Thirty-four positive and three negative co-expression modules were identified by 44 candidate genes in the newly emerging bamboo shoot. The gene expression patterns and co-expression modules of BR action-related genes in bamboo shoots indicated that they might function to promote bamboo growth through BR biosynthesis and signal transduction processes. This study provides the first step towards the cloning and functional dissection of the role of BR action-related genes in moso bamboo, which also presents an excellent opportunity for genetic engineering using the candidate genes to improve bamboo quantity and quality.

Trihelix proteins, which are a plant-specific family of transcription factors (TFs), play important roles in plant growth and development, as well as in the plant response to biotic and abiotic stressors. The DNA-binding domain of trihelix proteins is a tryptophan-enriched tandem repeat, forming a helix–loop–helix–loop–helix structure. Here, we identified and characterized 24 full-length trihelix genes from Phyllostachys edulis and classified these genes into 6 previously described subfamilies. Within a given subfamily, the trihelix genes shared similar conserved motifs and structures. Most of the promoters of the trihelix genes in P. edulis contained stress-related cis-elements. Our tissue-specific and gene expression analysis using quantitative real-time PCR indicated that the trihelix genes were expressed primarily in the stems, followed by leaves and roots, and were regulated by cold, drought, and salt stresses. This study delivers novel insights into the phylogenetic relationships and functions of the trihelix TFs of P. edulis. Our results provide a framework for further functional studies investigating the diverse roles of trihelix genes in other bamboo species.

Background Low-intensity pulsed ultrasound (LIPUS) can induce mesenchymal stem cell (MSC) differentiation, although the mechanism of its potential effects on chondrogenic differentiation is unknown. Since autophagy is known to regulate the differentiation of MSCs, the aim of our study was to determine whether LIPUS induced chondrogenesis via autophagy regulation. Methods MSCs were isolated from the rat bone marrow, cultured in either standard or chondrogenic medium, and stimulated with 3 MHz of LIPUS given in 20% on–off cycles, with or without prior addition of an autophagy inhibitor or agonist. Chondrogenesis was evaluated on the basis of aggrecan (AGG) organization and the amount of type II collagen (COL2) and the mRNA expression of AGG, COL2, and SRY-related high mobility group-box gene 9 (SOX9) genes. Results LIPUS promoted the chondrogenic differentiation of MSCs, as shown by the changes in the extracellular matrix (ECM) proteins and upregulation of chondrogenic genes, and these effects were respectively augmented and inhibited by the autophagy inhibitor and agonist. Conclusions Taken together, these results indicate that LIPUS promotes MSC chondrogenesis by inhibiting autophagy.

BACKGROUND Region-growing-based phase unwrapping methods have the potential for lossless phase aliasing removal, but generally suffer from unwrapping error propagation associated with discontinuous phase and/or long calculation times. The tradeoff point between robustness and efficiency of phase unwrapping methods in the region-growing category requires improvement. PURPOSE To demonstrate an accurate, robust, and efficient region-growing phase unwrapping method for MR phase imaging applications. STUDY TYPE Prospective. SUBJECTS, PHANTOM: normal human subjects (10) / brain surgery patients (2) / water phantoms / computer simulation. FIELD STRENGTH/SEQUENCE 3 T/gradient echo sequences (2D and 3D). ASSESSMENT A seed prioritized unwrapping (SPUN) method was developed based on single-region growing, prioritizing only a portion (eg, 100 seeds or 1% seeds) of available seed voxels based on continuity quality during each region-growing iteration. Computer simulation, phantom, and in vivo brain and pelvis scans were performed. The error rates, seed percentages, and calculation times were recorded and reported. SPUN unwrapped phase images were visually evaluated and compared with Laplacian unwrapped results. STATISTICAL TESTS Monte Carlo simulation was performed on a 3D dipole phase model with a signal-to-noise ratio (SNR) of 1-9 dB, to obtain the mean and standard deviation of calculation error rates and calculation times. RESULTS Simulation revealed a very robust unwrapping performance of SPUN, reaching an error rate of

To investigate the association between proximal internal carotid artery (ICA) luminal narrowing and diffuse wall thickening (DWT) in ipsilateral petrous ICA in moyamoya disease (MMD) patients. Forty-one MMD (mean age 42.8 ± 11.0 years, 19 males) and 36 atherosclerotic patients (mean age 61.5 ± 7.1 years, 31 males) and 41 healthy controls were recruited and underwent carotid MR vessel wall imaging. The luminal narrowing of proximal ICA was evaluated by the diameter ratio of ICA to common carotid artery (DRICA/CCA). The wall thickness of petrous ICA was measured on T1-VISTA images. The enhancement degree of petrous ICA was recorded and graded into four grades (none to marked) on the CE-T1-VISTA images. The correlation between wall thickness in petrous ICA and DRICA/CCA was analyzed. In total, 81 arteries of MMD patients and 64 arteries of atherosclerotic patients were included for analysis. The DRICA/CCA was significantly correlated with the wall thickness in petrous ICA in MMD (r = − 0.434, P

Background Epilepsy is a common neurological disease that cannot be well controlled by existing antiepileptic drugs. Studies have implicated oxidative stress and inflammation in the pathophysiology of epilepsy. Rhein has a comprehensive pharmacological function in reducing inflammation and can play a neuroprotective role in many neurological diseases, however little is known about its effects on epilepsy. Methods A model of acute epilepsy in mice was established using the Pentylenetetrazol (PTZ) ignition method to evaluate the effects of Rhein on the duration and latency of convulsions, and the number and severity of seizures. Modified Neurological Severity Score (mNSS), Rotarod and open-field behavioral task tests were performed to evaluate the neuroprotective effect of Rhein. TUNEL staining was used to assess neuronal damage, and western blot, qPCR and ELISA kits were utilized to determine the expression of inflammatory signaling protein molecules and levels of inflammatory cytokines. Results In this study, we demonstrate that Rhein delayed the onset of seizures, decreased their severity, and reduced the duration and frequency of seizures in PTZ-induced epileptic mice. Furthermore, we found that Rhein blocked neurological deficits induced by PTZ. In addition, our results show that Rhein inhibited the activation of the TLR4-NFκB signaling pathway and decreased the secretion of the inflammatory cytokines TNF-α, IL-6, IL-1β, and IL-18. Conclusion Our results suggest that the anticonvulsant and neuroprotective effects of Rhein are achieved by disrupting the processes involved in PTZ acquisition of epilepsy.

Esophageal cancer (ESCA) is a leading cause of cancer-related mortality, with poor prognosis worldwide. DNA damage repair is one of the hallmarks of cancer. Loss of genomic integrity owing to inactivation of DNA repair genes can increase the risk of cancer progression and lead to poor prognosis. We aimed to identify a novel gene signature related to DNA repair to predict the prognosis of ESCA patients. Based on gene expression profiles of ESCA patients from The Cancer Genome Atlas and gene set enrichment analysis, 102 genes related to DNA repair were identified as candidates. After stepwise Cox regression analysis, we established a five-gene prognostic model comprising DGCR8, POM121, TAF9, UPF3B, and BCAP31. Kaplan-Meier survival analysis confirmed a strong correlation between the prognostic model and survival. Moreover, we verified the clinical value of the prognostic signature under the influence of different clinical parameters. We found that small-molecule drugs (trametinib, selumetinib, and refametinib) could help to improve patient survival. In summary, our study provides a novel and promising prognostic signature based on DNA-repair-related genes to predict survival of patients with ESCA. Systematic data mining provides a theoretical basis for further exploring the molecular pathogenesis of ESCA and identifying therapeutic targets.

Intron retention (IR) is the least well‐understood alternative splicing type in animals, and its prevalence and function in physiological and pathological processes have long been underestimated. Cellular senescence contributes to individual aging and age‐related diseases and can also serve as an important cancer prevention mechanism. Dynamic IR events have been observed in senescence models and aged tissues; however, whether and how IR impacts senescence remain unclear. Through analyzing polyA+ RNA‐seq data from human replicative senescence models, we found IR was prevalent and dynamically regulated during senescence and IR changes negatively correlated with expression alteration of corresponding genes. We discovered that knocking down (KD) splicing factor U2AF1, which showed higher binding density to retained introns and decreased expression during senescence, led to senescence‐associated phenotypes and global IR changes. Intriguingly, U2AF1‐KD‐induced IR changes also negatively correlated with gene expression. Furthermore, we demonstrated that U2AF1‐mediated IR of specific gene (CPNE1 as an example) contributed to cellular senescence. Decreased expression of U2AF1, higher IR of CPNE1, and reduced expression of CPNE1 were also discovered in dermal fibroblasts with age. We discovered prevalent IR could fine‐tune gene expression and contribute to senescence‐associated phenotypes, largely extending the biological significance of IR., Splicing factor U2AF1 binds to the last intron of CPNE1 to promote efficient splicing in younger cells. Decreased expression of U2AF1 during senescence leads to increased intron retention of target gene such as CPNE1, which in turn generates less spliced transcripts. The intron‐retained transcripts compete with spliced ones and are rapidly degraded, resulting in the decreased normal translation template and reduced CPNE1 protein production, ultimately lead to senescence‐associated phenotypes.

Fusarium equiseti is a plant pathogen with a wide range of hosts and diverse effects, including probiotic effects. However, the molecular mechanisms underlying these effects remain unclear, hindering its effective utilization. The final assembly included 16 scaffolds of contiguous sequence without gaps. The total sequence length was 40,776,005 bp, and the GC content of 48.01%. In total, we annotated the putative function of 13,134 genes, accounting for 94.97% of the candidate genes. We identified two and 23 candidate genes that are likely involved in the production of mycotoxins zearalenone and trichothecene, respectively. A comparative genomic analysis supported the high quality of the F. equiseti assembly. Our comprehensive analysis of whole-genome sequence will serve as a valuable resource for future studies of expression, regulation, function and evolution of the genes of F. equiseti as well as studies into disease prevention and control.

The limited penetration of drug delivery vehicles in tumors reduces their therapeutic efficacy, which is a major obstacle. Thus, great efforts have already been paid to regulate both tumor tissue and the physicochemical properties of drug delivery vehicles to achieve deeper penetration. However, the principles for regulating these properties remain unclear. Herein, we investigated the performance of nanocapsules in different tumor stages, and particularly focused on the difference in the performance of nanocapsules with different surface charges. Our in vivo and in vitro results showed that when the tumor was small in the early stage, the electropositive nanocapsules could penetrate much deeper than the electronegative nanocapsules; however, when the tumor was quite large in the late stage, the electronegative nanocapsules would penetrate further into the tissue. This study proposes a potential strategy for tumor therapy by selecting drug delivery vehicles with an appropriate surface charge based on the tumor development stages.

Calcium (Ca2+) is an important second messenger involved in diverse developmental and adaptive processes in plants. Calmodulin (CaM) and calmodulin-like (CML) proteins are primary Ca2+ sensors that control diverse cellular functions. In this study, 41 genes encoding CaM and CML proteins were identified in the papaya genome, three of which were CaM and others were CML. Sequence alignment, gene structural and phylogenetic analyses revealed that all CaM/CMLs contained the EF-hand, but not other functional domains, and CaM proteins were quite conservative while CML proteins exhibited sequence diversity and structural multiformity. Promoter analysis identified different types of cis-elements related to plant growth and development, hormone response, light response, stress response and transcriptional enhancement in promoter regions of CpCaM/CML genes. Gene expression analysis showed distinctive expression profiles of the CaM/CMLs in different tissue types, different fruit developmental stages and different fruit storage conditions. Several groups of CaM/CML genes were positively or negatively regulated by high and low temperature stresses, such as CML16, CML17.1, CML24 and CML36, indicating that they may play a role in temperature stress adaption. Notably, some CaM/CML genes were rigorously regulated by ethylene (ethephon and 1-MCP treatment), either in a positive or a negative manner, such as CaM7, CML15, CML16, CML17.1, CML37 and CML46. All these results indicated that CaM and CML gene families might play important roles in fruit development, in response to temperature stresses and in fruit ripening process.

Idiopathic pulmonary fibrosis (IPF) is a fatal respiratory disease with a poor prognosis characterized by transforming growth factor (TGF)-β-induced proliferation, migration, and differentiation of fibroblasts, resulting in excessive extracellular matrix (ECM) deposition. Whether Kangfuxin oral liquid (KFXOL) has a protective function in pulmonary fibrosis is largely unknown. The goal of this study was to investigate the potential efficacy of KFXOL, as well as the underlying mechanism by which KFXOL regulates pulmonary fibrosis in vivo and in vitro. We found that KFXOL dramatically attenuated intratracheal bleomycin (BLM)-induced pulmonary fibrosis in terms of both severe alveolar architecture destruction and collagen deposition. KFXOL treatment significantly inhibited the proliferation, migration, and differentiation of pulmonary fibroblasts following activation using BLM/TGF-β1 and normalized the expression of ECM deposition-related proteins, including matrix metalloproteinase (MMP)-1, MMP-9, and tissue inhibitor of metalloproteinases 1. These effects were mediated via the inhibition of TGF-β1 and phosphorylated Smad2/3 activation in vivo. Taken together, our data suggest that KFXOL attenuates the development of pulmonary fibrosis via the TGF-β1/Smad signaling pathway and thus has potential utility in the treatment of pulmonary fibrosis.

Exosomes, a class of natural nanoparticles, have recently been used for drug delivery. To move from bench to bedside, exosomes should meet the "STOP" criteria: (1) high Safety; (2) good Targeting ability; (3) rapid Obtainment; and (4) high Purity. To the best of our knowledge, however, no studies on exosomes that can satisfy all the abovementioned criteria have been reported to date. In this study, an optimized superparamagnetic nanoparticle cluster (SMNC)-based method was used to easily achieve the abovementioned objective. Multiple superparamagnetic nanoparticles (SPMNs) labeled by holo-transferrin with PEG spacers anchor onto an exosome to form an upgraded exosome-based superparamagnetic nanoparticle cluster (denoted SMNC-EXO-PLUS). SMNC-EXO-PLUSs separated exosomes from healthy animal blood to ensure high safety, and their formation based on the specific binding of SPMNs to exosomes endowed exosomes with high purity. In addition, SMNC-EXO-PLUSs possessed strong magnetic response, realizing their rapid obtainment and good targeting ability. The results demonstrated that the cell viability was maintained as high as 88% in a 1000 μg mL-1 SMNC-EXO-PLUS solution, and the time interval from the extraction of blood to the acquisition of purified exosomes could be reduced to 3.5 h. Furthermore, the effects of in vivo tumor inhibition of drug-loaded SMNC-EXO-PLUSs (denoted as D-SMNC-EXO-PLUSs) were pronounced. Based on the "STOP" criteria, we exploited a new exosome-related drug delivery vehicle, dramatically promoting the clinical translation of exosomes.

The WRKY family of transcription factors (TFs) is one of the ten largest families of TFs in higher plants and has been implicated in multiple biological processes. Here, we identified 121 WRKY TFs in moso bamboo, including five novel members that were not annotated in the Phyllostachys edulis genomic database. Estimation of the divergence time of paralogous gene pairs revealed an important role of the recent whole-genome duplication in the expansion of the WRKY family. Expression analysis based on quantitative reverse-transcription polymerase chain reaction (qRT-PCR) data revealed that a large number of PheWRKY genes varied significantly under cold or drought stress treatments, which could be defined as abiotic stress-responsive genes. The overexpression of PheWRKY72-2 in Arabidopsis resulted in a decreased sensitivity to drought stress during early seedling growth. PheWRKY72-2 may enhance plant tolerance to stress by functioning as a positive regulator of stoma closure. Our study provides a theoretical foundation and some experimental evidence for further functional verification of the PheWRKY family of TFs.

Objective The objective of this review was to assess the therapeutic effect of ultrasound (US) on myofascial pain syndrome (MPS). Date sources PubMed, Embase, and Cochrane Library were searched to find relevant studies from January 1966 to May 2016 using keywords. Four investigators performed the data extraction. Study selection Randomized controlled trials (RCTs) investigating the outcomes of pain and physical function between MPS patients receiving and not receiving US were selected by two researchers independently. Data extraction Data were extracted from the RCTs. Risk of bias and study quality were evaluated following the recommendations of Cochrane Collaboration. Standardized mean difference (SMD) and 95% confidence interval (CI) were calculated. Data synthesis A total of 10 studies involving 428 MPS patients were included. US therapy significantly reduced pain intensity (SMD [CI]=−1.41 [−2.15, −0.67], P=0.0002) and increased pain threshold (SMD [CI]=1.08 [0.55, 1.60], P

// Yan Dai 1 , Shiguang Jin 2, 3 , Xueping Li 4 , Daxin Wang 2, 3 1 The Second Xiangya Hospital of Central South University, Changsha, China 2 Clinical Medical College, Yangzhou University, Yangzhou, China 3 Medical Research Centre, Northern Jiangsu People’s Hospital, Yangzhou, China 4 Nanjing Hospital Affiliated to Nanjing Medical University, The First Hospital of Nanjing, Nanjing, China Correspondence to: Daxin Wang, email: daxinw2002@sina.com Xueping Li, email: lixueping6504@163.com Keywords: cisplatin, Bcl-2, AKT, epithelial ovarian cancer, drug resistance Received: August 02, 2016 Accepted: November 08, 2016 Published: December 07, 2016 ABSTRACT Many studies involving patients with cisplatin-resistant ovarian cancer have shown that AKT activation leads to inhibition of apoptosis. The aim of this study was to examine the potential involvement of the Bcl-2 family proteins in AKT-regulated cell survival in response to cisplatin treatment. Cisplatin-sensitive (PEO1) and cisplatin-resistant (PEO4) cells were taken from ascites of patients with ovarian cancer before cisplatin treatment and after development of chemoresistance. It was found that cisplatin treatment activated the AKT signaling pathway and promoted cell proliferation in cisplatin-resistant EOC cells. When AKT was transfected into nucleus of cisplatin-resistant ovarian cancer cells, DNA-PK was phosphorylated at S473. The activated AKT (pAKT-S473) in these cells inhibited the death signal induced by cisplatin thereby inhibiting cisplatin-mediated apoptosis. Results from this study showed that the combination of cisplatin, DNA-PK inhibitor NU7441, and AKT inhibitor TCN can overcome drug resistance, increase apoptosis, and re-sensitize PEO4 cells to cisplatin treatment. A decrease in apoptotic activity was seen in PEO4 cells when Bad was downregulated by siRNA, which indicated that Bad promotes apoptosis in PEO4 cells. Use of the Bcl-2 inhibitor ABT-737 showed that ABT-737 binds to Bcl-2 but not Mcl-1 and releases Bax/Bak which leads to cell apoptosis. The combination of ABT-737 and cisplatin leads to a significant increase in the death of PEO1 and PEO4 cells. All together, these results indicate that Bcl-2 family proteins are regulators of drug resistance. The combination of cisplatin and Bcl-2 family protein inhibitor could be a strategy for the treatment of cisplatin-resistant ovarian cancer.

Low-temperature storage is a common strategy for preserving and transporting vegetables and fruits. However, many fruits are hypersensitive to chilling injury, including bananas. In the present study, storage conditions of 11 &deg, C delayed the ripening of Fenjiao (Musa ABB Pisang Awak) banana, and the pulp could be softened after ethephon treatment. Storage conditions of 7 &deg, C prevented fruit from fully softening, and fruit contained a significantly higher starch content and lower soluble sugar content. MaEBF1, a critical gene component in the ethylene signaling pathway, was repressed during ripening after fruit had been stored for 12 days at 7 &deg, C. The expression of a series of starch degradation-related genes and a MaNAC67-like gene were also severely repressed. Both MaEBF1 and MaNAC67-like genes were ethylene-inducible and localized in the nucleus. MaNAC67-like protein was able to physically bind to the promoter of genes associated with starch degradation, including MaBAM6, MaSEX4, and MaMEX1. Yeast two-hybrid, GST-pull down, and BiFC assays showed that MaEBF1 interacted with the MaNAC67-like protein, and their interaction further activated the promoters of MaBAM6 and MaSEX4. The current study indicates that MaNAC67-like is a direct regulator of starch degradation and potential for involvement in regulating chilling-inhibited starch degradation by interacting with the ethylene signaling components in banana fruit. The present work paves the way for further functional analysis of MaEBF1 and MaNAC67-like in banana, which will be useful for understanding the regulation of banana starch metabolism and fruit ripening.

In rapeseed, the oil content of the seed not only supplies energy for seed germination and seedling development but also provides essential dietary nutrients for humans and livestock. Recent studies have revealed that many transcription factors (TFs) regulate the accumulation of fatty acids (FAs) during seed development. WRKY6, a WRKY6 family TF, was reported to serve a function in the plant senescence processes, pathogen defense mechanisms and abiotic stress responses. However, the precise role of WRKY6 in influencing FA accumulation in seeds is still unknown. In this study, we demonstrate that WRKY6 has a high expression level in developing seeds and plays an essential role in regulating the accumulation of FAs in developing seeds of Arabidopsis. Mutation of WRKY6 resulted in significant increase in seed size, accompanied by an increase in FA content and changes in FA composition. Ultrastructure analyses showed that the absence of WRKY6 resulted in more and higher percentage of oil body in the cell of mature seeds. Quantitative real-time PCR analysis revealed changes in the expression of several genes related to photosynthesis and FA biosynthesis in wrky6 mutants at 10 or 16 days after pollination. These results reveal a novel function of WRKY6 influencing seed oil content and FAs compositions. This gene could be used as a promising gene resource to improve FA accumulation and seed yield in Brassica napus through genetic manipulation.

Background Ethylene promotes fruit ripening whereas 1-methylcyclopropene (1-MCP), a non-toxic antagonist of ethylene, delays fruit ripening via the inhibition of ethylene receptor. However, unsuitable 1-MCP treatment can cause fruit ripening disorders. Results In this study, we show that short-term 1-MCP treatment (400 nL•L− 1, 2 h) significantly delays papaya fruit ripening with normal ripening characteristics. However, long-term 1-MCP treatment (400 nL•L− 1, 16 h) causes a “rubbery” texture of fruit. The comparative transcriptome analysis showed that a total of 5529 genes were differently expressed during fruit ripening compared to freshly harvested fruits. Comprehensive functional enrichment analysis showed that the metabolic pathways of carbon metabolism, plant hormone signal transduction, biosynthesis of amino acids, and starch and sucrose metabolism are involved in fruit ripening. 1-MCP treatment significantly affected fruit transcript levels. A total of 3595 and 5998 differently expressed genes (DEGs) were identified between short-term 1-MCP, long-term 1-MCP treatment and the control, respectively. DEGs are mostly enriched in the similar pathway involved in fruit ripening. A large number of DEGs were also identified between long-term and short-term 1-MCP treatment, with most of the DEGs being enriched in carbon metabolism, starch and sucrose metabolism, plant hormone signal transduction, and biosynthesis of amino acids. The 1-MCP treatments accelerated the lignin accumulation and delayed cellulose degradation during fruit ripening. Considering the rubbery phenotype, we inferred that the cell wall metabolism and hormone signal pathways are closely related to papaya fruit ripening disorder. The RNA-Seq output was confirmed using RT-qPCR by 28 selected genes that were involved in cell wall metabolism and hormone signal pathways. Conclusions These results showed that long-term 1-MCP treatment severely inhibited ethylene signaling and the cell wall metabolism pathways, which may result in the failure of cell wall degradation and fruit softening. Our results reveal multiple ripening-associated events during papaya fruit ripening and provide a foundation for understanding the molecular mechanisms underlying 1-MCP treatment on fruit ripening and the regulatory networks. Electronic supplementary material The online version of this article (10.1186/s12870-019-1904-x) contains supplementary material, which is available to authorized users.

Strong glue of mussels has long been considered as an ideal model to design synthetic bio-adhesives but the adhesive strength of metal-crosslinked mussel-inspired glues is not often satisfactory. Herein, inspired by the adhesive environment of mussels, we obtained metal-crosslinked e-poly-L-lysine adhesives with high adhesive performance by introducing the elements of suitable adhesive environment (SAE) into the adhesives. The elements of SAE were clarified as weak alkaline conditions (pH ∼ 7.4) and low Fe3+ contents. The adhesive strength (∼105 kPa) of the metal-crosslinked adhesives endowed with the elements of SAE (PL-Cat/Fe-SAE) was about 8 times higher than that of fibrin glues. The high adhesive strength was found to originate from distinctive interfacial adhesion and cohesion strength of PL-Cat/Fe-SAE. PL-Cat/Fe-SAE showed strong interfacial adhesion capacity and nearly comparable cohesion strength to those PL-Cat/Fe adhesives with higher Fe3+ contents. The nearly comparable cohesion strength of PL-Cat/Fe-SAE was then found to be due to more amount of stable tris-complex existed in PL-Cat/Fe-SAE. In addition, PL-Cat/Fe-SAE was able to efficiently close the full thickness skin incisions. The study highlighted the importance of introducing SAE elements into the design of tissue adhesives and provided a facile and efficient strategy for constructing tissue adhesives with high adhesive performance.

Gastric cancer (GC) is one of the most fatal common cancers in worldwide. Helicobacter pylori (H. pylori) infection is closely related to the development of GC, although the mechanism is still unclear. In our study, we aim to develop a robust messenger RNA (mRNA) signature associated with H. pylori (-) GC that can sensitively and efficiently predict the prognostic. The RNA-seq expression profile and corresponding clinical data of 598 gastric cancer samples and 63 normal samples obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus database. Using gene set enrichment analysis H. pylori (+) GC and H. pylori (-) GC patients and normal samples to select certain genes for further analysis. Using univariate and multivariate Cox regression model to establish a gene signature for predicting the overall survival (OS). Finally, we identified G2/M related seven-mRNA signature (TGFB1, EGF, MKI67, ILF3, INCENP, TNPO2, and CHAF1A) closely related to the prognosis of patients with H. pylori (-) GC. The seven-mRNA signature was identified to act as an independent prognostic biomarker by stratified analysis and multivariate Cox regression analysis. It was also validated on two test groups from TCGA and GSE15460 and shown that patients with high-risk scores based on the expression of the seven mRNAs had significantly shorter survival times compared to patients with low-risk scores (P

Blood transferrin receptor-positive (TfR+) exosomes are a kind of optimized drug delivery vector compared with other kinds of exosomes due to their easy access and high bio-safety. Their application facilitates the translation from bench to bedside of exosome-based delivery vehicles. Methods: In this study, a pH-responsive superparamagnetic nanoparticles cluster (denoted as SMNC)-based method was developed for the precise and mild separation of blood TfR+ exosomes. Briefly, multiple superparamagnetic nanoparticles (SPMNs) labeled with transferrins (Tfs) could precisely bind to blood TfR+ exosomes to form an exosome-based cluster due to the specific recognition of TfR by Tf. They could realize the precise magnetic separation of blood TfR+ exosomes. More importantly, the pH-responsive dissociation characteristic of Tf and TfR led to the mild collapse of clusters to obtain pure blood TfR+ exosomes. Results: Blood TfR+ exosomes with high purity and in their original state were successfully obtained through the pH-responsive SMNC-based method. These can load Doxorubicin (DOX) with a loading capacity of ~10% and dramatically increase the tumor accumulation of DOX in tumor-bearing mice because of their innate passive-targeting ability. In addition, blood TfR+ exosomes changed the biodistribution of DOX leading to the reduction of side effects. Compared with free DOX, DOX-loaded blood TfR+ exosomes showed much better tumor inhibition effects on tumor-bearing mice. Conclusion: Taking advantage of the pH-responsive binding and disaggregation characteristics of Tf and TfR, the SMNC-based method can precisely separate blood TfR+ exosomes with high purity and in their original state. The resulting blood TfR+ exosomes showed excellent bio-safety and enable the efficient delivery of chemotherapeutics to tumors, facilitating the clinical translation of exosome-based drug delivery systems.

Polyploidy has contributed to the divergence and domestication of plants; however, estimation of the relative roles that different types of polyploidy have played during evolution has been difficult. Unbalanced and balanced gene removal was previously related to allopolyploidies and autopolyploidies, respectively. Here, to infer the types of polyploidies and evaluate their evolutionary effects, we devised a statistic, the Polyploidy-index or P-index, to characterize the degree of divergence between subgenomes of a polyploidy, to find whether there has been a balanced or unbalanced gene removal from the homoeologous regions. Based on a P-index threshold of 0.3 that distinguishes between known or previously inferred allo- or autopolyploidies, we found that 87.5% of 24 angiosperm paleo-polyploidies were likely produced by allopolyploidizations, responsible for establishment of major tribes such as Poaceae and Fabaceae, and large groups such as monocots and eudicots. These findings suggest that >99.7% of plant genomes likely derived directly from allopolyploidies, with autopolyploidies responsible for the establishment of only a few small genera, including Glycine, Malus, and Populus, each containing tens of species. Overall, these findings show that polyploids with high divergence between subgenomes (presumably allopolyploids) established the major plant groups, possibly through secondary contact between previously isolated populations and hybrid vigor associated with their re-joining.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever disease caused by SFTSV, a newly discovered phlebovirus that is named after the disease. Currently, no effective vaccines or drugs are available for use against SFTSV infection, as our understanding of the viral pathogenesis is limited. Bortezomib (PS-341), a dipeptide-boronic acid analog, is the first clinically approved proteasome inhibitor for use in humans. In this study, the antiviral efficacy of PS-341 against SFTSV infection was tested in human embryonic kidney HEK293T (293T) cells. We employed four different assays to analyze the antiviral ability of PS-341 and determined that PS-341 inhibited the proliferation of SFTSV in 293T cells under various treatment conditions. Although PS-341 did not affect the virus absorption, PS-341 treatment within a non-toxic concentration range resulted in a significant reduction of progeny viral titers in infected cells. Dual-luciferase reporter assays and Western blot analysis revealed that PS-341 could reverse the SFTSV-encoded non-structural protein (NS) mediated degradation of retinoic acid-inducible gene-1 (RIG-I), thereby antagonizing the inhibitory effect of NSs on interferons and blocking virus replication. In addition, we observed that inhibition of apoptosis promotes virus replication. These results indicate that targeting of cellular interferon pathways and apoptosis during acute infection might serve as the bases of future therapeutics for the treatment of SFTSV infections. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12250-019-00162-9) contains supplementary material, which is available to authorized users.

Aims Cellular senescence is a well-known cancer prevention mechanism, inducing cancer cells to senescence can enhance cancer immunotherapy. However, how cellular senescence is regulated is not fully understood. Dynamic chromatin changes have been discovered during cellular senescence, while the causality remains elusive. BAZ1A, a gene coding the accessory subunit of ATP-dependent chromatin remodeling complex, showed decreased expression in multiple cellular senescence models. We aim to investigate the functional role of BAZ1A in regulating senescence in cancer and normal cells. Materials and methods Knockdown of BAZ1A was performed via lentivirus mediated short hairpin RNA (shRNA) in various cancer cell lines (A549 and U2OS) and normal cells (HUVEC, NIH3T3 and MEF). A series of senescence-associated phenotypes were quantified by CCK-8 assay, SA-β-Gal staining and EdU incorporation assay, etc. Key findings Knockdown (KD) of BAZ1A induced series of senescence-associated phenotypes in both cancer and normal cells. BAZ1A-KD caused the upregulated expression of SMAD3, which in turn activated the transcription of p21 coding gene CDKN1A and resulted in senescence-associated phenotypes in human cancer cells (A549 and U2OS). Significance Our results revealed chromatin remodeling modulator BAZ1A acting as a novel regulator of cellular senescence in both normal and cancer cells, indicating a new target for potential cancer treatment.

Introduction Takotsubo syndrome (TS) is an acute cardiac syndrome that mimics acute coronary syndrome (ACS) but lacks coronary obstruction and is associated with sudden physical or psychiatric episodes. Several hypotheses have been proposed for the TS mechanism, but the precise cause of this syndrome remains poorly known. Recent studies noted TS patients with acute endogenous catecholamine discharge, which could trigger an oxidative stress response and inflammatory action. Methods A single dose of the selective β-adrenergic agonist isoprenaline (ISO) was used to induce a takotsubo-like (TS-like) model. Different icariin or metoprolol doses were supplied as cardioprotective agents by intragastric administration (IG), and lipopolysaccharides (LPS) were assessed to investigate the possible mechanism of action of icariin. Transthoracic echocardiography was used to study cardiac function and morphology. The amounts of intracellular lipids and myocardial fibrosis, which represent the degree of cardiac impairment, were assessed by histological analysis. Real-time polymerase chain reaction (RT-PCR) was performed to analyze a variety of anti-oxidant elements and inflammatory factors, and Western blotting was conducted to analyze the expression of signaling pathway proteins involved in the development of TS. Results The TS-like incidence in rats was lowest with icariin precondition at 2-h post-ISO administration, and both the left ventricular ejection fraction (LVEF) and ejection volume per minute were higher than those of the other groups. However, LPS administration increased the incidence of TS and aggravated cardiac impairment. Moreover, ISO significantly increased the levels of both reactive oxygen species (ROS) and TLR4/NF-κB signaling pathway proteins compared to those of the Sha-group, whereas icariin remarkably decreased the ROS levels and increased anti-oxidant element expression while reducing pro-inflammatory factor secretion and suppressing TLR4/NF-κB signaling pathway protein expression. However, the cardioprotective effect of icariin was significantly weakened by combining treatment with LPS. Conclusion Icariin prevented ISO-induced TS-like cardiac dysfunction in rats. The effects were induced mainly through maintenance of the dynamic balance of the ROS system, promotion of anti-oxidant element activity, and suppression of TLR4/NF-κB signaling pathway protein expression. Furthermore, the ability of icariin to increase anti-inflammatory and reduce pro-inflammatory factor secretion may be involved in the protective process.

Nasopharyngeal carcinoma (NPC) is an aggressive malignancy with a high mortality on account of its frequent metastasis and poor prognosis. An extensive body of investigations has proven that long noncoding RNAs are implicated in a variety of biological processes. Although SOX2-OT has been reported to play an oncogenic role in osteosarcoma, the mechanism of SOX2-OT-driven NPC progression is still obscure. The aim of this study was to elucidate the biological function of SOX2-OT and the related possible mechanism in NPC. In our study, SOX2-OT was notably elevated in NPC samples and cells. Further, a high expression level of SOX2-OT was correlated with poor clinical outcomes of NPC. Results from loss-of-function experiments suggested that knockdown of SOX2-OT repressed cell proliferation, arrested cell cycle, facilitated cell apoptosis, and inhibited cell metastasis of NPC. To further investigate the molecular mechanism of SOX2-OT, miR-146b-5p was found to directly bind to SOX2-OT, which mediated the role of SOX2-OT in NPC tumorigenesis. In addition, HNRNPA2B1 was a target of miR-146b-5p and SOX2-OT modulated the expression of HNRNPA2B1 through competitively binding to miR-146b-5p. At last, we discovered that SOX2-OT regulated NPC progression by targeting miR-146b-5p/HNRNPA2B1 pathway, which may provide more innovative targets for the treatment of patients with NPC.

Ethylene plays a pivotal role in climacteric fruit ripening; whereas 1-MCP, a non-toxic antagonist of ethylene, prevents ethylene-dependent responses and fruit ripening. In this study, a short-term treatment (1 h) with 400 nL L−1 1-MCP delayed the ripening of harvested papaya. However, long-term application of 1-MCP (400 nL L−1, 16 h) resulted in abnormal fruit ripening, with the fruits exhibiting normal yellowing without softening, significantly higher cellulose and lignin contents, and intact cell walls (CW). Furthermore, we found that long-term treatment with 1-MCP significantly inhibited the expression of CpEBF1, an EIN3-binding F-box-1 gene. A protein interaction analysis using yeast two-hybrid, BiFC and GST pull-down assays showed that CpEBF1 interacts with the CpMADS1/3 and CpEIL1 proteins. The interaction of CpEBF1 with CpMADS1/3 further activated the activities of CW-degradation gene promoters. Subcellular localization showed that these proteins were localized in the nucleus. Additionally, the expression levels of CpMADS1/3, CpEIL1, and several CW-degradation-related genes were significantly downregulated by long-term 1-MCP treatment. Therefore, we propose that the inhibited expression of CpEBF1 and CpMADS1/3 resulted in the repressed activation of CW-degradation-related genes via their interaction, thereby resulting in fruit softening disorders., Papaya: Anti-ripening treatment prevents degradation of cell wall Long-term treatment with an anti-ripening agent inhibits the expression of regulatory genes that normally break down the cell wall of the papaya fruit. A team from Guangzhou’s South China Agricultural University led by Xueping Li and Weixin Chen applied a hormone inhibitor to papayas at the breaker stage of fruit ripening. 1 h of treatment delayed ripening, whereas 16 h of treatment caused the fruit to become rubbery, with significantly higher levels of cellulose and lignin, both structural components of the cell wall. The researchers identified two genes with reduced expression following extended hormone-blocking treatment. Both normally encode proteins that aid in degrading the cell wall to promote fruit ripening. The findings thus offer a molecular explanation for why misuse of anti-ripening agents on papaya fruits can lead to undesirable characteristics.

Eighteen sediments and four biota species were collected from mangrove wetlands of the Jiulong River Estuary (JRE) in South China to investigate the distribution of dichlorodiphenyltrichloroethane (DDT), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), decabromodiphenyl ethane (DBDPE), dechlorane plus (DP) and 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE). Concentrations of ΣDDTs, ΣPCBs, ΣPBDEs, DBDPE, DP, and BTBPE in mangrove sediments ranged from 21 to 84, 0.52–2.5, 9.0–66, 5.1–32, 0.05–0.14, and 0.03–0.25 ng/g dry weight, respectively. Levels of ΣDDTs, ΣPCBs, ΣPBDEs, DBDPE and DP in mangrove biota ranged from 950 to 30000, 56–400, 8.0–35, nd-20 and 0.44–3.1 ng/g lipid weight, respectively. DDTs were the predominant halogenated organic pollutants (HOPs) in mangrove sediments from the JRE, while PBDEs were the major HOPs in mangrove sediments from the Pearl River Estuary (PRE), suggesting that sediments in JRE and PRE had different sources of HOPs. The dominance of DDTs was found in both mangrove sediments and biota from the JRE, indicating that HOPs in JRE environment mainly come from agricultural sources. The biota-sediment accumulation factors for DDTs and PCBs were significantly higher than those of PBDEs, DBDPE and DP, suggesting high bioavailability of DDTs and PCBs in mangrove biota. Trophic magnification factors for DDTs, PCBs, PBDEs, and DP were 10.5, 3.00, 2.66 and 1.23, respectively, indicating their potential of biomagnification in mangrove food webs.

Water supply is essential for maintaining normal physiological function during the rapid growth of bamboo. Aquaporins (AQPs) play crucial roles in water transport for plant growth and development. Although 26 PeAQPs in bamboo have been reported, the aquaporin-led mechanism of maintaining diurnal water balance in bamboo shoots remains unclear. In this study, a total of 63 PeAQPs were identified, based on the updated genome of moso bamboo (Phyllostachys edulis), including 22 PePIPs, 20 PeTIPs, 17 PeNIPs, and 4 PeSIPs. All of the PeAQPs were differently expressed in 26 different tissues of moso bamboo, based on RNA sequencing (RNA-seq) data. The root pressure in shoots showed circadian rhythm changes, with positive values at night and negative values in the daytime. The quantitative real-time PCR (qRT-PCR) result showed that 25 PeAQPs were detected in the base part of the shoots, and most of them demonstrated diurnal rhythm changes. The expression levels of some PeAQPs were significantly correlated with the root pressure. Of the 86 sugar transport genes, 33 had positive co-expression relationships with 27 PeAQPs. Two root pressure-correlated PeAQPs, PeTIP4, 1 and PeTIP4, 2, were confirmed to be highly expressed in the parenchyma and epidermal cells of bamboo culm, and in the epidermis, pith, and primary xylem of bamboo roots by in situ hybridization. The authors&rsquo, findings provide new insights and a possible aquaporin-led mechanism for bamboo fast growth.