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"Hong Di"
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Overexpression of the Melatonin Synthesis-Related Gene SlCOMT1 Improves the Resistance of Tomato to Salt Stress
Melatonin can increase plant resistance to stress, and exogenous melatonin has been reported to promote stress resistance in plants. In this study, a melatonin biosynthesis-related SlCOMT1 gene was cloned from tomato (Solanum lycopersicum Mill. cv. Ailsa Craig), which is highly expressed in fruits compared with other organs. The protein was found to locate in the cytoplasm. Melatonin content in SlCOMT1 overexpression transgenic tomato plants was significantly higher than that in wild-type plants. Under 800 mM NaCl stress, the transcript level of SlCOMT1 in tomato leaf was positively related to the melatonin contents. Furthermore, compared with that in wild-type plants, levels of superoxide and hydrogen peroxide were lower while the content of proline was higher in SlCOMT1 transgenic tomatoes. Therefore, SlCOMT1 was closely associated with melatonin biosynthesis confers the significant salt tolerance, providing a clue to cope with the growing global problem of salination in agricultural production.
Journal Article
Hyperuricemia and gout increased the risk of long-term mortality in patients with heart failure: insights from the National Health and Nutrition Examination Survey
Background
The prevalence of hyperuricemia, gout, and heart failure (HF) is on the rise, and these conditions often share similar risk factors. The present study aimed to evaluate the relationship among hyperuricemia, gout, HF, and all-cause mortality.
Methods
The data on nonpregnant participants aged ≥ 20 years with or without hyperuricemia, gout, and HF from the National Health and Nutrition Examination Survey 2001–2018 and 2007–2018 were included in this study. The binary logistic regression, Kaplan–Meier curve, Cox proportional-hazards model, and restricted cubic spline analysis were employed to evaluate the relationship among hyperuricemia, gout, HF, and all-cause mortality.
Results
Of 204,179,060 and 223,702,171 weighted eligible participants, 40,044,228 (19.6%) and 9,158,600 (4.1%) had hyperuricemia and gout, respectively. Older age, diabetes, stroke, and coronary artery disease were the risk factors for HF among patients with hyperuricemia and gout. The median survival time was 7.00 years and 6.25 years and the 5-year survival rate was 59.9% and 55.9% for patients with HF and hyperuricemia and those with HF and gout, respectively. Patients with hyperuricemia or gout were 2.46 and 2.35 times more likely to have HF and 1.37 and 1.45 times more likely to experience all-cause mortality compared with those who did not exhibit these conditions. The restricted cubic spline showed a nonlinear correlation between uric acid levels and HF and a J-shaped correlation between uric acid levels and all-cause mortality.
Conclusions
Ambulatory patients with hyperuricemia or gout were more likely to have HF compared with those without hyperuricemia or gout. Patients with HF with hyperuricemia or gout were more likely to experience all-cause mortality in the long-term follow-up.
Journal Article
Transparent Polyurethane Nanofiber Air Filter for High-Efficiency PM2.5 Capture
Fine particulate matter (PM) has seriously affected human life, such as affecting human health, climate, and ecological environment. Recently, many researchers use electrospinning to prepare nanofiber air filters for effective removal of fine particle matter. However, electrospinning of the polymer fibers onto the window screen uniformly is only achieved in the laboratory, and the realization of industrialization is still very challenging. Here, we report an electrospinning method using a rotating bead spinneret for large-scale electrospinning of thermoplastic polyurethane (TPU) onto conductive mesh with high productivity of 1000 m
2
/day. By changing the concentration of TPU in the polymer solution, PM2.5 removal efficiency of nanofiber-based air filter can be up to 99.654% with good optical transparency of 60%, and the contact angle and the ventilation rate of the nanofiber-based air filter is 128.5° and 3480 mm/s, respectively. After 10 times of filtration, the removal efficiency is only reduced by 1.6%. This transparent air filter based on TPU nanofibers has excellent filtration efficiency and ventilation rate, which can effectively ensure indoor air quality of the residential buildings.
Journal Article
LncRNA TROJAN promotes proliferation and resistance to CDK4/6 inhibitor via CDK2 transcriptional activation in ER+ breast cancer
Background
Estrogen receptor-positive (ER+) breast cancers represent approximately two-thirds of all breast cancers and have a sustained risk of late disease recurrence. Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors have shown significant efficacy in ER+ breast cancer. However, their effects are still limited by drug resistance. In this study, we aim to explore the role of long noncoding RNA TROJAN in ER+ breast cancer.
Methods
The expression level of TROJAN in breast cancer tissue and cell lines was determined by quantitative real-time PCR. In vitro and in vivo assays as well as patient derived organoid were preformed to explore the phenotype of TROJAN in ER+ breast cancer. The TROJAN-NKRF-CDK2 axis were screened and validated by RNA pull-down, mass spectrometry, RNA immunoprecipitation, microarray, dual-luciferase reporter and chromatin immunoprecipitation assays.
Results
Herein, we showed that TROJAN was highly expressed in ER+ breast cancer. TROJAN promoted cell proliferation and resistance to a CDK4/6 inhibitor and was associated with poor survival in ER+ breast cancer. TROJAN can bind to NKRF and inhibit its interaction with RELA, upregulating the expression of CDK2. The inhibition of TROJAN abolished the activity of CDK2, reversing the resistance to CDK4/6 inhibitor. A TROJAN antisense oligonucleotide sensitized breast cancer cells and organoid to the CDK4/6 inhibitor palbociclib both in vitro and in vivo.
Conclusions
TROJAN promotes ER+ breast cancer proliferation and is a potential target for reversing CDK4/6 inhibitor resistance.
Journal Article
Single-Molecule Real-Time and Illumina Sequencing to Analyze Transcriptional Regulation of Flavonoid Synthesis in Blueberry
Blueberries ( Vaccinium corymbosum ) contain large amounts of flavonoids, which play important roles in the plant’s ability to resist stress and can also have beneficial effects on human health when the fruits are eaten. However, the molecular mechanisms that regulate flavonoid synthesis in blueberries are still unclear. In this study, we combined two different transcriptome sequencing platforms, single-molecule real-time (SMRT) and Illumina sequencing, to elucidate the flavonoid synthetic pathways in blueberries. We analyzed transcript quantity, length, and the number of annotated genes. We mined genes associated with flavonoid synthesis (such as anthocyanins, flavonols, and proanthocyanidins) and employed fluorescence quantitative PCR to analyze the expression of these genes and their correlation with flavonoid synthesis. We discovered one R2R3 MYB transcription factor from the sequencing library, VcMYB1 , that can positively regulate anthocyanin synthesis in blueberries. VcMYB1 is mainly expressed in colored (mature) fruits. Experiments showed that overexpression and transient expression of VcMYB1 promoted anthocyanin synthesis in Arabidopsis , tobacco ( Nicotiana benthamiana ) plants and green blueberry fruits. Yeast one-hybrid (Y1H) assay, electrophoretic mobility shift assay, and transient expression experiments showed that VcMYB1 binds to the MYB binding site on the promoter of the structural gene for anthocyanin synthesis, VcMYB1 to positively regulate the transcription of VcDFR , thereby promoting anthocyanin synthesis. We also performed an in-depth investigation of transcriptional regulation of anthocyanin synthesis. This study provides background information and data for studying the synthetic pathways of flavonoids and other secondary metabolites in blueberries.
Journal Article
Characterization of the genomic landscape and actionable mutations in Chinese breast cancers by clinical sequencing
The remarkable advances in next-generation sequencing technology have enabled the wide usage of sequencing as a clinical tool. To promote the advance of precision oncology for breast cancer in China, here we report a large-scale prospective clinical sequencing program using the Fudan-BC panel, and comprehensively analyze the clinical and genomic characteristics of Chinese breast cancer. The mutational landscape of 1,134 breast cancers reveals that the most significant differences between Chinese and Western patients occurred in the hormone receptor positive, human epidermal growth factor receptor 2 negative breast cancer subtype. Mutations in p53 and Hippo signaling pathways are more prevalent, and 2 mutually exclusive and 9 co-occurring patterns exist among 9 oncogenic pathways in our cohort. Further preclinical investigation partially suggests that
NF2
loss-of-function mutations can be sensitive to a Hippo-targeted strategy. We establish a public database (Fudan Portal) and a precision medicine knowledge base for data exchange and interpretation. Collectively, our study presents a leading approach to Chinese precision oncology treatment and reveals potentially actionable mutations in breast cancer.
Chinese breast cancer patients have not been well represented in clinical sequencing studies. Here the authors analyse the mutational landscape of 1,134 Chinese breast cancer patients, finding actionable targets and a higher prevalence of p53 and Hippo pathway mutations compared to Western cohorts.
Journal Article
Comprehensive transcriptome analysis identifies novel molecular subtypes and subtype-specific RNAs of triple-negative breast cancer
Background
Triple-negative breast cancer (TNBC) is a highly heterogeneous group of cancers, and molecular subtyping is necessary to better identify molecular-based therapies. While some classifiers have been established, no one has integrated the expression profiles of long noncoding RNAs (lncRNAs) into such subtyping criterions. Considering the emerging important role of lncRNAs in cellular processes, a novel classification integrating transcriptome profiles of both messenger RNA (mRNA) and lncRNA would help us better understand the heterogeneity of TNBC.
Methods
Using human transcriptome microarrays, we analyzed the transcriptome profiles of 165 TNBC samples. We used k-means clustering and empirical cumulative distribution function to determine optimal number of TNBC subtypes. Gene Ontology (GO) and pathway analyses were applied to determine the main function of the subtype-specific genes and pathways. We conducted co-expression network analyses to identify interactions between mRNAs and lncRNAs.
Results
All of the 165 TNBC tumors were classified into four distinct clusters, including an immunomodulatory subtype (IM), a luminal androgen receptor subtype (LAR), a mesenchymal-like subtype (MES) and a basal-like and immune suppressed (BLIS) subtype. The IM subtype had high expressions of immune cell signaling and cytokine signaling genes. The LAR subtype was characterized by androgen receptor signaling. The MES subtype was enriched with growth factor signaling pathways. The BLIS subtype was characterized by down-regulation of immune response genes, activation of cell cycle, and DNA repair. Patients in this subtype experienced worse recurrence-free survival than others (log rank test,
P
= 0.045). Subtype-specific lncRNAs were identified, and their possible biological functions were predicted using co-expression network analyses.
Conclusions
We developed a novel TNBC classification system integrating the expression profiles of both mRNAs and lncRNAs and determined subtype-specific lncRNAs that are potential biomarkers and targets. If further validated in a larger population, our novel classification system could facilitate patient counseling and individualize treatment of TNBC.
Journal Article
Association of the American Heart Association’s new “Life’s Essential 8” with all-cause mortality in patients with chronic kidney disease: a cohort study from the NHANES 2009–2016
Background
People with chronic kidney disease (CKD) are more likely to die prematurely, and this increased risk of death is primarily attributable to deaths from cardiovascular disease (CVD). We aim to investigate the relationship between Life’s Essential 8 (LE8), a newly proposed cardiovascular health (CVH) measurement system, and all-cause mortality of CKD patients among US adults.
Methods
A total of 3,169 CKD patients aged 20 and older from the National Health and Nutritional Examination Survey in 2009–2016 were involved in this study. Participants were divided into low (0–49), moderate (50–79) and high (80–100) CVH groups according to LE8 score (range 0-100). The mortality was ascertained from the National Death Index. Cox proportional hazards regression and restricted cubic spline were used to investigate the relationship.
Results
Among the 3,169 CKD patients, the median age was 66.0 (25.0) years and 1,671 (52.7%) were female, and the median follow-up time was 6.00 years. The median LE8 score of the study cohort was 57.5 (19.4). CKD patients with low CVH, health behavior (HB) and health factors (HF) scores presented with higher all-cause mortality (both log-rank
P
-values < 0.001). After adjusted for multiple confounders, patients in higher CVH group had a lower risk of all-cause mortality, with a HR (95%CI) of 0.32 (0.19–0.55). Similar results were observed in high HB group [HR 0.36 (0.25–0.50)]. The restricted cubic spline showed a significant inverse relationship between LE8, HB and HF scores with CKD all-cause mortality, while the protective effect seemed weaker for HF score. Above results remained robust in the sensitivity analysis. Stronger inverse associations were revealed in middle-aged patients and patients with higher education levels.
Conclusions
LE8 and its subscales scores were inversely associated with all-cause mortality in patients with CKD. Promoting CVH in CKD patients is a potential way to improve their long-term survival rate.
Journal Article
Tektin4 loss promotes triple-negative breast cancer metastasis through HDAC6-mediated tubulin deacetylation and increases sensitivity to HDAC6 inhibitor
Progression of triple-negative breast cancer (TNBC) constitutes a major unresolved clinical challenge, and effective targeted therapies are lacking. Because microtubule dynamics play pivotal roles in breast cancer metastasis, we performed RNA sequencing on 245 samples from TNBC patients to characterize the landscape of microtubule-associated proteins (MAPs). Here, our transcriptome analyses revealed that low expression of one MAP, tektin4, indicated poor patient outcomes. Tektin4 loss led to a marked increase in TNBC migration, invasion, and metastasis and a decrease in microtubule stability. Mechanistically, we identified a novel microtubule-associated complex containing tektin4 and histone deacetylase 6 (HDAC6). Tektin4 loss increased the interaction between HDAC6 and α-tubulin, thus decreasing microtubule stability through HDAC6-mediated tubulin deacetylation. Significantly, we found that tektin4 loss sensitized TNBC cells, xenograft models, and patient-derived organoid models to the HDAC6-selective inhibitor ACY1215. Furthermore, tektin4 expression levels were positively correlated with microtubule stability levels in clinical samples. Together, our findings uncover a metastasis suppressor function of tektin4 and support clinical development of HDAC6 inhibition as a new therapeutic strategy for tektin4-deficient TNBC patients.
Journal Article