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Ocean-related global changes have altered phytoplankton community structure, especially the diatom-dinoflagellate competition, which further influences ecosystem structure and functions. The pivotal ecological roles of diatoms and dinoflagellates are strongly related with their biochemical compositions, while quantitative comparisons of biochemical changes between diatoms and dinoflagellates under variable environments are still limited. We investigated responses of lipid biomarkers (sterols and fatty acids (FAs)) to different temperatures (12, 18 and 24℃), nitrogen and phosphorus concentrations and their molar ratios (N:P ratio) of 10:1, 24:1 and 63:1 in marine diatom Phaeodactylum tricornutum and dinoflagellate Prorocentrum minimum. Over these wide ranges of temperature and nutrient conditions, sterol and FA profiles were relatively stable in the two species. For C-normalized contents of major sterols and FAs, warming caused non-significant changes in the diatom but an increase (up to 153%) in the dinoflagellate; eutrophication caused an overall decrease (up to 53%) in the diatom but an overall increase (up to 77%) in the dinoflagellate; in contrast, imbalanced N:P ratios caused an overall increase (up to 64%) in the diatom but an overall decrease (up to 53%) in the dinoflagellate. Under future ocean warming, eutrophication and imbalanced N:P ratios, major sterol and polyunsaturated FA contents would increase (ca. 9% ~ 48%) in the dinoflagellate, while those in the diatom would change non-significantly. This study expands our knowledge on lipid-based indicators of phytoplankton under changing environments, which by systematically linking with several other aspects of food quality will help to understand the ecological role of diatom-dinoflagellate community changes.

Known as a common malignant tumor among children, retinoblastoma (RB) is highly malignant and has poor prognosis, damages children's vision and degrades quality of life. To identify a potential molecular mechanism of RB, we conducted this study on legumain (LGMN), which is highly expressed in multiple tumors. In this study, we found that LGMN was significantly upregulated in RB cells and was positively expressed in RB tissues. We confirmed that LGMN overexpression (LGMN-OE) can promote RB cell proliferation and inhibit cell apoptosis through CCK8 experiments and flow cytometry. In addition, real-time quantitative polymerase chain reaction (RT‒qPCR) and Western blot results showed that LGMN-OE could regulate the expression of epithelial-mesenchymal transformation-related genes and proteins, related to tumor invasion and metastasis. Moreover, after LGMN knock down, the result was the opposite., RNA sequence analysis revealed 1159 differentially expressed genes between LGMN-OE and the negative control (NC

Wheat powdery mildew (Bgt), a fungal seeding disease, is a threat to wheat agriculture worldwide. In this study, Iron shell wheat (Triticum aestivum ssp. yunnanense King) was used as the research material. Extensive targeted metabolomic analysis was conducted on the leaves of the susceptible strain Iron shell wheat 1 (DiKe 1) and the normal resistant strain Zhenkang Iron shell wheat (Yunmai 0030); further, the dynamic physiological changes in metabolite levels between the two strains were assessed. Significant differences were identified in tryptophan and pyrimidine metabolism as well as isoquinoline alkaloid biosynthesis. The main metabolites were phenolic acids, flavonoid carboglycosides, indole alkaloids, phenolic amines, amino acids, and their derivatives. The defense response to powdery mildew in the Iron shell wheat was dominated by tryptophan metabolism. The importance of L-dopa and Tyramine in powdery mildew resistance provides new insights into the relevant mechanisms and can help identify antigens for use in the breeding of powdery-mildew-resistant wheat varieties.

Lacrimal adenoid cystic carcinoma (LACC) is the most common orbital malignant epithelial neoplasm. LACC with high-grade transformation (LACC-HGT) has higher rates of recurrence, metastasis, and mortality than LACC without HGT. This study investigated the effects of microRNA-29a-3p (miR-29a-3p) in the pathogenesis of LACC-HGT.An Agilent human miRNA microarray was used to screen the differentially expressed miRNAs (DEMs) in LACC and LACC-HGT tumor tissues. Then, the primary cells obtained in previous studies were used to determine the effect of miR-29a-3p.The expression of miR-29a-3p was abnormally lower in LACC-HGT than in LACC. miR-29a-3p can specifically target the 3' UTR of Quaking mRNA and down-regulate Quaking expression, thereby inhibiting the proliferation, migration, and epithelial-mesenchymal transition of LACC cells.This study illustrated that miR-29a-3p functions as a tumor suppressor by down-regulating the expression of Quaking to inhibit the tumorigenesis of LACC cells. This study may also reveal the pathogenesis of HGT in LACC cells and provide a reference for LACC-HGT targeted diagnosis.

Spot blotch (SB) is a fungal disease that threatens wheat yield and quality. Presently, the molecular mechanism against SB is unclear. In this study, the resistant variety Zhenkang iron shell wheat (Yunmai 0030) and susceptible variety Lincang iron shell wheat (Yunmai 0608) were selected by identifying SB of Yunnan iron shell wheat. The metabolome and transcriptome of leaves of two varieties at different positions were detected using the systemic acquired resistance theory to investigate the molecular and physiological changes in Yunnan iron shell wheat under SB stress. We found that the genes and metabolites related to benzoxazinoid biosynthesis and arginine and proline metabolism were highly enriched after infection with leaf blight. The enriched differential metabolites mainly included phenolic acids, alkaloids, and flavonoids. We further observed that DIBOA- and DIMBOA-glucoside positively affected iron shell wheat resistance to leaf blight and proline and its derivatives were important for plant self-defense. Furthermore, we confirmed that the related metabolites in benzoxazinoid biosynthesis and arginine and proline metabolism positively affected Triticum aestivum ssp. resistance to SB. This study provides new insights into the dynamic physiological changes of wheat in response to SB, helps us better understand the mechanism of resistance to SB, and contributes to the breeding and utilization of resistant varieties.

Background Oral mucositis (OM) is a common adverse effect in hematological cancer patients who have received hematopoietic stem cell transplantation (HSCT). In this study, we compared mouthwash with nystatin, aloe vera or plain water in OM prevention.Design A retrospective chart review was conducted in participants. The incidence, severity and duration of OM, duration of oral pain, and the use of antalgesics were recorded.Setting/participants Hematological cancer patients who had received HSCT from January 2014 to December 2020 in West China Hospital were included in this study.Results A total of 150 patients were included in our retrospective analysis. The nystatin group had the highest incidence (100.0%) of OM, followed by the aloe vera group (44.8%), the plain water group had the lowest incidence of OM (20.0%), and the nystatin group had the highest severity and the longest duration of oral mucositis. The incidence, severity and duration of pain in the nystatin group were significantly higher than the aloe vera group and plain water group, and the use of analgesic drugs in the nystatin group was also significantly higher than the other two groups (PConclusions In our hospital setting, plain water mouthwash achieves great effect in OM prevention in hematological cancer patients who have received HSCT.

The lacrimal gland adenoid cystic carcinoma (LACC) is a major orbital malignancy. The recurrence rate and mortality rate are higher in high proliferation LACC(HP-LACC) compared with low proliferation LACC(LP-LACC). In this study, miRNA microarray was used to explore the differentially expressed miRNAs profiling between HP-LACC and LP-LACC and its potential signaling pathway. Tissues from 17 patients with LACC were collected and made into tissue microarrays. Patients were divided into a high proliferation group and a low proliferation group based on Ki-67 value. HE, immunofluorescence (IF), and Immunohistochemistry (IHC) were performed on the tissue microarrays. Eight LACC tissues(4 HP-LACC and 4 LP-LACC) were made into miRNA microarrays and analyzed for miRNA profiles. Differentially expressed miRNAs were analyzed by volcano plot and heat map. Target gene were predicted using the miRWalk and miRDB for these differentially expressed miRNAs, the intersection of the results are used as targets for further gene ontology and KEGG pathway analysis.The four differentially expressed miRNAs were validated by qRT-PCR, the miRNAs with statistically significant differences validated by dual luciferase reporter and qRT-PCR. Finally, IHC was used for their downstream signaling pathway proteins.HE staining showed the presence of tubular, cribriform, and basaloid structures in LACC. IF showed the presence of CK7,P63 fluorescence expression in all three structures.Patients were divided into HP-LACC and LP-LACC based on Ki-67 median value of 11%. IHC and survival analysis showed with the increase of KI-67 ratio, the proportion of P63 decreased, and the expression of P53 increased. The disease-free survival and overall survival of the patients decreased. IHC and survival analysis showed as Ki-67 expression increased, P63 expression decreased, P53 expression elevated, with prognosis worse. Heat map and volcano plot yielded 15 differentially expressed miRNAs between HP-LACC and LP-LACC.The 15 differential miRNAs were used to predict target genes in miRWalk and miRDB databases respectively, and there were 559 target genes after intersection.559 predicted target genes obtained. Go and KEGG analysis showed that these target genes exerted important biological functions through multiple signaling pathways. Among the 15 differentially expressed miRNAs, miR-29a-3p was verified to be significant by qRT-PCR. Dual luciferase reporter and tissue microarray immunohistochemical assays validated that AKT2 was a direct target gene of miR-29a-3p. Current studies have identified differentially expressed miRNAs associated with LACCs of variable proliferation ability, and found that AKT2 is a direct target gene of miR-29a-3p, which will contribute to target gene therapy in patients with high proliferation LACC in the future.

MicroRNAs (miRNAs/miRs) play an important role in various types of carcinoma, including sebaceous gland carcinoma (SGC) of the eyelid. miR-3907 was found to be highly expressed in lung cancer; however, to the best of our knowledge, the biological role of miR-3907 in SGC has not previously been evaluated. The aim of the present study was to determine the role and mechanism of miR-3907 in the occurrence and development of SGC. miR-3907 was screened and identified as a novel upregulated miRNA in SGC tissues and cells, as determined using miRNA microarrays and reverse transcription-quantitative (RT-q) PCR analyses. Compared with the control group, cellular proliferation and migration were enhanced in the miR-3907 mimics group, and decreased in the miR-3907 inhibitor group. Moreover, miR-3907 negatively regulated thrombospondin 1 (THBS1) expression, as shown by bioinformatics prediction, RT-qPCR, western blotting and dual-luciferase reporter assays. In addition, compared with the control group, the small interfering (si) siRNA-THBS1 group exhibited enhanced proliferation and migration abilities, which were decreased in the THBS1 overexpression group. Furthermore, THBS1 overexpression was found to attenuate the stimulative effect of miR-3907 mimics, and THBS1-knockdown reversed the inhibitory effect of the miR-3907 inhibitor in SGC cells. Collectively, the results of the present study indicated that miR-3907 promoted the proliferation and migration of SGC by downregulating THBS1, and that this axis may be a potential target for the prognostic assessment and treatment of SGC.

Previous studies highlight the need for a more active conditioning therapy in high-risk or refractory and relapsed lymphomas. Our preclinical research shows that histone deacetylase inhibitors, such as either vorinostat or chidamide, sensitize lymphoma cells to the cytotoxic combination of cladribine, gemcitabine, and busulfan, leading to cell apoptosis. To evaluate the efficacy of this chidamide-cladribine-gemcitabine-busulfan combination as a new conditioning therapy, we conducted a phase II trial, as described here. Patients with high-risk, relapsed/refractory lymphomas received chidamide, cladribine, gemcitabine, and busulfan as conditioning therapy, following transplantation with autologous peripheral stem cells. The sample comprised 105 patients in total: 60 with B-cell non-Hodgkin lymphomas (B-NHL), and 45 with T-cell, or natural killer/T-cell lymphoma (NK/T). All patients eventually achieved full hematopoietic recovery. Neutrophils and platelets engrafted at a median of 10 days (8-14) and 13 days (8-38), respectively. There was no transplant-related mortality within 100 days of transplant. Neutropenic fever, mucositis, and atopic dermatitis were the observed non-hematologic toxicities. At a median follow-up of 35.4 months, 80.6% of the patients presented with no tumor progression, and the overall survival reached as high as 86.1%. Concerning the overall survival rate, 94.5% of patients with B-NHL and 75.4% of patients with T-cell or NK/T lymphomas survived. These findings demonstrate the safety and validity of the proposed combined therapy for high-risk and refractory/relapsed lymphomas. This study was registered on the Clinical Trial Registry (clinicaltrials.gov, NCT03151876). This article is protected by copyright. All rights reserved.

Adenoid cystic carcinoma of the lacrimal gland (LACC) is a major orbital malignancy. The recurrence rate and mortality rate are higher in LACC high-grade transformation (LACC-HGT) compared with in LACC. The present study aimed to identify the candidate microRNAs (miRNAs/miRs) and construct a competing endogenous RNA (ceRNA) regulatory network for LACC-HGT. A miRNA microarray on paraffin-embedded tissues was performed to identify the differentially expressed miRNAs (DEMs) of LACC-HGT. The overlap with the salivary adenoid cystic carcinoma miRNA/RNA sequencing dataset in the Gene Expression Omnibus was used to identify candidate miRNAs. In order to construct a ceRNA regulatory network of LACC-HGT, a microarray of mRNA and circRNA in primary cell lines was performed. The circRNAs and genes with high expression in LACC-HGT were predicted as targeting miRNAs, and the circRNA-miRNA-mRNA regulatory network was constructed. miR-140-3p was identified as part of the ceRNA network and as a candidate miRNA, therefore this was further analyzed using reverse transcription-quantitative (RT-q)PCR. Overall, the Agilent Human microarray analysis identified a total of 16 DEMs from the LACC-HGT paraffin-embedded tissues. A total of 653 DECs and 9,566 DEGs of LACC-HGT primary cell lines were screened via the microarray of mRNA and circRNA. The ceRNA regulatory network was constructed using the cross-binding of circRNA-miRNA, miRNA-mRNA and the downregulated miRNAs in LACC-HGT to clearly demonstrate the circRNA-miRNA-mRNA interaction relationship. RT-qPCR results confirmed that miR-140-3p was downregulated in LACC-HGT tissues and primary cell lines compared with LACC. Target genes CD200 and parathyroid hormone-related protein were significantly upregulated in LACC-HGT primary cell lines. miR-140-3p and its target genes may play an important role in LACC-HGT pathogenesis. In conclusion, the current bioinformatics study constructed a ceRNA network based on a microarray, which may help identify novel miRNA therapeutic targets for LACC-HGT.

Meibomian gland carcinoma (MGC) is a malignant eyelid tumor with a high malignancy degree and poor prognosis. However, the lack of suitable cell and animal models has limited the study of MGC pathogenesis. In the present study, we established and identified one human MGC cell and one meibomian gland (MG) cell model by fresh surgical resection tissue block primary culture and differentially expressed gene assays. The outgrowth of MGC and MG cells was periodically observed after primary culture, and the first passage of MGC cells proceeded on the 14th day, whereas that for MG cells after three weeks. Cell ultrastructures were observed by transmission electron microscopy (TEM). Immunofluorescence staining showed that MGC and MG cells were both positive for cytokeratin (CK) and androgen receptor (AR). Orange granules were observed in the cytoplasm of MGC and MG cells using Oil red O staining, but they were stronger for MG cells than for MGC. CCK-8 detection demonstrated that the proliferation ability of MGC cells was stronger than that of MG cells. Moreover, during RNA sequence analyses, 3023 differential expressed genes were detected between MGC and MG cells. These genes were involved in biological processes such as cell division and positive regulation of cell migration; the signaling pathways mainly covered cell cycle and DNA replication. Further, the tumorigenic potential of MGC cells was examined by inoculating them subcutaneously into the right abdomen of three severely immunodeficient NOD -SCID mice. Transplanted tumors formed on day 11 after inoculation. The xenograft mouse tissues retained the same histological characteristics as the human MGC original tumor and MGC primary cells. Altogether, these results showed that the MGC and MG models were successfully cultured and established, and differentially expressed genes were successfully detected. We provided a useful model and molecular basis for studying the biological characteristics and pathogenesis of human MGC.

Background: Number of studies have been performed to evaluate the relationship between the cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) gene variant rs5742909 polymorphism and cervical cancer risk, but the sample size was small and the results were conflicting. This meta-analysis was conducted to comprehensively evaluate the overall association. Methods: PubMed, Web of Science, Embase, China Biology Medical Literature database, China National Knowledge Infrastructure, WanFang, and Weipu databases were searched before July 31, 2018. The strength of associations was assessed using odds ratios (ORs) and 95% confidence intervals (CIs). All of the statistical analyses were conducted using Review Manager 5.3 and Stata 14.0. Results: Eleven studies involved 3899 cases and 4608 controls. Overall, significant association was observed between the CTLA-4 gene variant rs5742909 polymorphism and cervical cancer (T vs C: OR = 1.40, 95% CI = 1.12–1.76; TT vs CC: OR = 2.22, 95% CI = 1.13–4.37; TT vs CT+CC: OR = 1.96, 95% CI = 1.03–3.74; TT+CT vs CC: OR = 1.47, 95% CI = 1.14–1.90). In subgroup analysis by ethnic group, a statistically significant association was observed in Asians (T vs C: OR = 1.56, 95% CI = 1.22–1.99), but not in Caucasians (T vs C: OR = 1.19, 95% CI = 0.87–1.62). The sensitivity analysis confirmed the reliability and stability of the meta-analysis. Conclusion: our meta-analysis supports that the CTLA-4 gene variant rs5742909 polymorphism might contribute to individual susceptibility to cervical cancer in Asians.