AaSEPALLATA1 integrates jasmonate and light-regulated glandular secretory trichome initiation in Artemisia annua.

Glandular secretory trichomes (GSTs) can secrete and store a variety of specific metabolites. By increasing GST density, valuable metabolites can be enhanced in terms of productivity. However, the comprehensive and detailed regulatory network of GST initiation still needs further investigation. By screening a complementary DNA library derived from young leaves of Artemisia annua, we identified a MADS-box transcription factor, AaSEPALLATA1 (AaSEP1), that positively regulates GST initiation. Overexpression of AaSEP1 in A. annua substantially increased GST density and artemisinin content. The HOMEODOMAIN PROTEIN 1 (AaHD1)-AaMYB16 regulatory network regulates GST initiation via the jasmonate (JA) signaling pathway. In this study, AaSEP1 enhanced the function of AaHD1 activation on downstream GST initiation gene GLANDULAR TRICHOME-SPECIFIC WRKY 2 (AaGSW2) through interaction with AaMYB16. Moreover, AaSEP1 interacted with the JA ZIM-domain 8 (AaJAZ8) and served as an important factor in JA-mediated GST initiation. We also found that AaSEP1 interacted with CONSTITUTIVE PHOTOMORPHOGENIC 1 (AaCOP1), a major repressor of light signaling. In this study, we identified a MADS-box transcription factor that is induced by JA and light signaling and that promotes the initiation of GST in A. annua.

Genome and whole-genome resequencing of Cinnamomum camphora elucidate its dominance in subtropical urban landscapes.

BACKGROUND: Lauraceae is well known for its significant phylogenetic position as well as important economic and ornamental value; however, most evergreen species in Lauraceae are restricted to tropical regions. In contrast, camphor tree (Cinnamomum camphora) is the most dominant evergreen broadleaved tree in subtropical urban landscapes. RESULTS: Here, we present a high-quality reference genome of C. camphora and conduct comparative genomics between C. camphora and C. kanehirae. Our findings demonstrated the significance of key genes in circadian rhythms and phenylpropanoid metabolism in enhancing cold response, and terpene synthases (TPSs) improved defence response with tandem duplication and gene cluster formation in C. camphora. Additionally, the first comprehensive catalogue of C. camphora based on whole-genome resequencing of 75 accessions was constructed, which confirmed the crucial roles of the above pathways and revealed candidate genes under selection in more popular C. camphora, and indicated that enhancing environmental adaptation is the primary force driving C. camphora breeding and dominance. CONCLUSIONS: These results decipher the dominance of C. camphora in subtropical urban landscapes and provide abundant genomic resources for enlarging the application scopes of evergreen broadleaved trees.

Proteogenomics in Cancer: Then and Now.

For years, the paths of sequencing technologies and mass spectrometry have occurred in isolation, with each developing its own unique culture and expertise. These two technologies are crucial for inspecting complementary aspects of the molecular phenotype across the central dogma. Integrative multiomics strives to bridge the analysis gap among different fields to complete more comprehensive mechanisms of life events and diseases. Proteogenomics is one integrated multiomics field. Here in this review, we mainly summarize and discuss three aspects: workflow of proteogenomics, proteogenomics applications in cancer research, and the SWOT (Strengths, Weaknesses, Opportunities, Threats) analysis of proteogenomics in cancer research. In conclusion, proteogenomics has a promising future as it clarifies the functional consequences of many unannotated genomic abnormalities or noncanonical variants and identifies driver genes and novel therapeutic targets across cancers, which would substantially accelerate the development of precision oncology.

Comparative transcriptome and metabolome analyses identified the mode of sucrose degradation as a metabolic marker for early vegetative propagation in bulbs of Lycoris.

Vegetative propagation (VP) is an important practice for production in many horticultural plants. Sugar supply constitutes the basis of VP in bulb flowers, but the underlying molecular basis remains elusive. By performing a combined sequencing technologies coupled with ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry approach for metabolic analyses, we compared two Lycoris species with contrasting regeneration rates: high-regeneration Lycoris sprengeri and low-regeneration Lycoris aurea. A comprehensive multi-omics analyses identified both expected processes involving carbohydrate metabolism and transcription factor networks, as well as the metabolic characteristics for each developmental stage. A higher abundance of the differentially expressed genes including those encoding ethylene responsive factors was detected at bulblet initiation stage compared to the late stage of bulblet development. High hexose-to-sucrose ratio correlated to bulblet formation across all the species examined, indicating its role in the VP process in Lycoris bulb. Importantly, a clear difference between cell wall invertase (CWIN)-catalyzed sucrose unloading in high-regeneration species and the sucrose synthase-catalyzed pathway in low-regeneration species was observed at the bulblet initiation stage, which was supported by findings from carboxyfluorescein tracing and quantitative real-time PCR analyses. Collectively, the findings indicate a sugar-mediated model of the regulation of VP in which high CWIN expression or activity may promote bulblet initiation via enhancing apoplasmic unloading of sucrose or sugar signals, whereas the subsequent high ratio of hexose-to-sucrose likely supports cell division characterized in the next phase of bulblet formation.

Bavachin protects against diet-induced hepatic steatosis and obesity in mice.

Non-alcoholic fatty liver disease (NAFLD) is a major health concern worldwide, and the incidence of metabolic disorders associated with NAFLD is rapidly increasing because of the obesity epidemic. There are currently no approved drugs that prevent or treat NAFLD. Recent evidence shows that bavachin, a flavonoid isolated from the seeds and fruits of Psoralea corylifolia L., increases the transcriptional activity of PPARγ and insulin sensitivity during preadipocyte differentiation, but the effect of bavachin on glucose and lipid metabolism remains unclear. In the current study we investigated the effects of bavachin on obesity-associated NAFLD in vivo and in vitro. In mouse primary hepatocytes and Huh7 cells, treatment with bavachin (20 µM) significantly suppressed PA/OA or high glucose/high insulin-induced increases in the expression of fatty acid synthesis-related genes and the number and size of lipid droplets. Furthermore, bavachin treatment markedly elevated the phosphorylation levels of AKT and GSK-3ß, improving the insulin signaling activity in the cells. In HFD-induced obese mice, administration of bavachin (30 mg/kg, i.p. every other day for 8 weeks) efficiently attenuated the increases in body weight, liver weight, blood glucose, and liver and serum triglyceride contents. Moreover, bavachin administration significantly alleviated hepatic inflammation and ameliorated HFD-induced glucose intolerance and insulin resistance. We demonstrated that bavachin protected against HFD-induced obesity by inducing fat thermogenesis and browning subcutaneous white adipose tissue (subWAT). We revealed that bavachin repressed the expression of lipid synthesis genes in the liver of obese mice, while promoting the expression of thermogenesis, browning, and mitochondrial respiration-related genes in subWAT and brown adipose tissue (BAT) in the mice. In conclusion, bavachin attenuates hepatic steatosis and obesity by repressing de novo lipogenesis, inducing fat thermogenesis and browning subWAT, suggesting that bavachin is a potential drug for NAFLD therapy.

The Light- and Jasmonic Acid-Induced AaMYB108-like Positive Regulates the Initiation of Glandular Secretory Trichome in Artemisia annua L.

The plant Artemisia annua L. is famous for producing "artemisinin", which is an essential component in the treatment of malaria. The glandular secretory trichomes (GSTs) on the leaves of A. annua secrete and store artemisinin. Previous research has demonstrated that raising GST density can effectively raise artemisinin content. However, the molecular mechanism of GST initiation is not fully understood yet. In this study, we identified an MYB transcription factor, the AaMYB108-like, which is co-induced by light and jasmonic acid, and positively regulates glandular secretory trichome initiation in A. annua. Overexpression of the AaMYB108-like gene in A. annua increased GST density and enhanced the artemisinin content, whereas anti-sense of the AaMYB108-like gene resulted in the reduction in GST density and artemisinin content. Further experiments demonstrated that the AaMYB108-like gene could form a complex with AaHD8 to promote the expression of downstream AaHD1, resulting in the initiation of GST. Taken together, the AaMYB108-like gene is a positive regulator induced by light and jasmonic acid for GST initiation in A. annua.

Photoprotection conferring plant tolerance to freezing stress through rescuing photosystem in evergreen Rhododendron.

Light stress is one of the important stresses for winter survival in evergreens, especially for plants with broad leaves, like evergreen rhododendrons. Photoprotection has been shown to upregulate dramatically in rhododendrons during winter, but whether it directly contributes to enhancing the freezing tolerance is still unknown. In this study, we found that the expression and circadian rhythm of an early light-induced protein (ELIP)-RhELIP3-which exerts photoprotection in Rhododendron 'Elsie Lee', could be impacted by both photoperiod and low temperature, with low temperature being the predominant inducer. Arabidopsis overexpressing RhELIP3 displayed significantly stronger freezing tolerance and better photosystem II function after a 3-day recovery from freezing treatment. Moreover, RhHY5 binds with the RhELIP3 promoter to activate its expression. Arabidopsis overexpressing RhHY5 exhibited stronger freezing tolerance and better photosystem II function. AtELIP1 and AtELIP2 were significantly induced in RhHY5-overexpressed Arabidopsis at low temperatures. We also discovered that RhBBX24 binds directly to RhELIP3 promoter and suppresses its expression. RhBBX24 can also interact with RhHY5 and inhibit the interaction of RhHY5-RhELIP3. RhELIP3, RhHY5, and RhBBX24 exhibited similar circadian rhythms under low temperature with short period. Overall, our investigation highlights that photoprotection is involved in improving the freezing tolerance of evergreen rhododendrons.

Clinical Features and Prognosis of Young and Middle-Aged Adults With Skin Sebaceous Adenocarcinoma.

BACKGROUND: Sebaceous adenocarcinoma (SAC) mostly occurs in the elderly, and SAC in young and middle-aged population is inadequately investigated. OBJECTIVE: To explore the clinical features and prognosis of young and middle-aged adults with SAC. MATERIALS AND METHODS: Patients with skin SAC between ages 18 and 59 years from the Surveillance, Epidemiology, and End Results database (1975-2016) were eligible for this study. RESULTS: Seven hundred thirty-nine cases were identified. The proportion of extraocular SAC in the nonelderly increased from 1975-2005 to 2006-2016 ( p = .001), male predominance was observed in overall patients whereas female predominance in Asian population, and young patients had more head and neck SAC than middle-aged patients ( p = .014). The prognosis of young patients was better than middle-aged patients ( p = .004). Other independent prognostic factors included sex, marital status, tumor size, surgery, chemotherapy, and multiple primary cancer history. CONCLUSION: An increasing proportion of extraocular SAC was observed in young and middle-aged patients, and the young developed more head and neck SAC than the middle-aged. Female predominance was found in Asian population, and female patients had better prognosis. Younger age and married status indicated better prognosis, and around 20% of young and middle-aged patients might have poorer survival because of Muir-Torre syndrome.

Factors affecting freezing tolerance: a comparative transcriptomics study between field and artificial cold acclimations in overwintering evergreens.

Cold acclimation (CA) is a well-known strategy employed by plants to enhance freezing tolerance (FT) in winter. Global warming could disturb CA and increase the potential for winter freeze-injury. Thus, developing robust FT through complete CA is essential. To explore the molecular mechanisms of CA in woody perennials, we compared field and artificial CAs. Transcriptomic data showed that photosynthesis/photoprotection and fatty acid metabolism pathways were specifically enriched in field CA; carbohydrate metabolism, secondary metabolism and circadian rhythm pathways were commonly enriched in both field and artificial CAs. When compared with plants in vegetative growth in the chamber, we found that the light signals with warm air temperatures in the fall might induce the accumulation of leaf abscisic acid (ABA) and jasmonic acid (JA) concentrations, and activate Ca2+ , ABA and JA signaling transductions in plants. With the gradual cooling occurrence in winter, more accumulation of anthocyanin, chlorophyll degradation, closure/degradation of photosystem II reaction centers, and substantial accumulation of glucose and fructose contributed to obtaining robust FT during field CA. Moreover, we observed that in Rhododendron 'Elsie Lee', ABA and JA decreased in winter, which may be due to the strong requirement of zeaxanthin for rapid thermal dissipation and unsaturated fatty acids for membrane fluidity. Taken together, our results indicate that artificial CA has limitations to understand the field CA and field light signals (like short photoperiod, light intensity and/or light quality) before the low temperature in fall might be essential for complete CA.

Polydopamine with Tailorable Photoelectrochemical Activities for the Highly Sensitive Immunoassay of Tumor Markers.

A simple and highly sensitive photoelectrochemical (PEC) immunoassay sensor was fabricated by using the two forms of polydopamine (PDA), the thin film and nanosphere, to serve as the photoelectrode-modified material and signal reporting label, respectively. The two forms of PDA show similar light absorption behavior but totally different PEC activities. The PDA film can extend the light absorption from the ultraviolet to near infrared light range, transfer a photoelectron to TiO2 nanoparticles and the underlying photoelectrode, and largely amplify the photocurrent response. However, the PDA nanospheres have insignificant photoelectron transport ability. When they are brought close to the PDA film and TiO2 nanocomposite-modified electrode via the sandwich immunoreaction, they function like a black hole to compete with the PDA film for light absorption, resist the access of the electron donor to regenerate the photoactive material, and capture the photoelectron generated from the PDA film. Besides, the heat generated from the PDA nanospheres also contributes to the photocurrent decrease. The PDA nanospheres with multiple quenching effects on the PDA film greatly decrease the photocurrent signal and lead to a highly sensitive PEC immunosensing strategy. Under optimal conditions, a wide linear range from 0.1 to 106 pg·mL-1 is obtained toward carcinoembryonic antigen, with a low limit of detection of 40 fg·mL-1. Besides, the PDA with excellent biosafety can be readily assembled with proteins, which thus simplifies the preparation procedures and decreases the costs. All these features indicate that the whole PDA-based PEC sensing strategy may have great application prospects for the point-of-care assay of various kinds of tumor markers.

High-quality evergreen azalea genome reveals tandem duplication-facilitated low-altitude adaptability and floral scent evolution.

Azalea belongs to Rhododendron, which is one of the largest genera of flowering plants and is well known for the diversity and beauty in its more than 1000 woody species. Rhododendron contains two distinct groups: the most high-altitude and a few low-altitude species; however, the former group is difficult to be domesticated for urban landscaping, and their evolution and adaptation are little known. Rhododendron ovatum has broad adaptation in low-altitude regions but possesses evergreen characteristics like high-altitude species, and it has floral fragrance that is deficient in most cultivars. Here we report the chromosome-level genome assembly of R. ovatum, which has a total length of 549 Mb with scaffold N50 of 41 Mb and contains 41 264 predicted genes. Genomic micro-evolutionary analysis of R. ovatum in comparison with two high-altitude Rhododendron species indicated that the expansion genes in R. ovatum were significantly enriched in defence responses, which may account for its adaptability in low altitudes. The R. ovatum genome contains much more terpene synthase genes (TPSs) compared with the species that lost floral fragrance. The subfamily b members of TPS are involved in the synthesis of sesquiterpenes as well as monoterpenes and play a major role in flora scent biosynthesis and defence responses. Tandem duplication is the primary force driving expansion of defence-responsive genes for extensive adaptability to the low-altitude environments. The R. ovatum genome provides insights into low-altitude adaptation and gain or loss of floral fragrance for Rhododendron species, which are valuable for alpine plant domestication and floral scent breeding.

The Patatin-Like Phospholipase Domain Containing Protein 7 Facilitates VLDL Secretion by Modulating ApoE Stability.

BACKGROUND AND AIMS: The regulation of hepatic very-low-density lipoprotein (VLDL) secretion is vital for lipid metabolism whose pathogenetic status is involved in fatty liver disease and dyslipidemia seen in hepatic steatosis. Accumulated evidence suggest that apolipoprotein E (ApoE) is closely related to hepatic VLDL secretion. Here, we report that the expression of patatin-like phospholipase domain containing protein 7 (PNPLA7) is strongly induced by hepatic steatosis and positively correlates with plasma triacylglycerol (TAG) levels in the human subjects, whereas the role of PNPLA7 in hepatic VLDL secretion is unknown. APPROACH AND RESULTS: Herein, with genetic manipulation in the mice, the deficiency of hepatic PNPLA7 expression resulted in reduced VLDL secretion accompanied by enhanced hepatic lipid accumulation and decreased hepatic ApoE expression. Furthermore, knockdown of PNPLA7 in the livers of the db/db mice also resulted in significant reduction in plasma TAG level but aggravated hepatic steatosis. Importantly, we observed that PNPLA7 interacted with ApoE and presumably at the site of endoplasmic reticulum. Mechanistically, we have shown that PNPLA7 could modulate polyubiquitination and proteasomal-mediated degradation of ApoE. Overexpressed ApoE restored the impaired VLDL-TAG metabolism in PNPLA7-knockdown primary hepatocytes. CONCLUSION: PNPLA7 plays a critical role in regulating hepatic VLDL secretion by modulating ApoE stability through its interaction with ApoE.

The Impact of ZIP8 Disease-Associated Variants G38R, C113S, G204C, and S335T on Selenium and Cadmium Accumulations: The First Characterization.

The metal cation symporter ZIP8 (SLC39A8) is a transmembrane protein that imports the essential micronutrients iron, manganese, and zinc, as well as heavy toxic metal cadmium (Cd). It has been recently suggested that selenium (Se), another essential micronutrient that has long been known for its role in human health and cancer risk, may also be transported by the ZIP8 protein. Several mutations in the ZIP8 gene are associated with the aberrant ion homeostasis of cells and can lead to human diseases. However, the intricate relationships between ZIP8 mutations, cellular Se homeostasis, and human diseases (including cancers and illnesses associated with Cd exposure) have not been explored. To further verify if ZIP8 is involved in cellular Se transportation, we first knockout (KO) the endogenous expression of ZIP8 in the HeLa cells using the CRISPR/Cas9 system. The elimination of ZIP8 expression was examined by PCR, DNA sequencing, immunoblot, and immunofluorescence analyses. Inductively coupled plasma mass spectrometry indicated that reduced uptake of Se, along with other micronutrients and Cd, was observed in the ZIP8-KO cells. In contrast, when ZIP8 was overexpressed, increased Se uptake could be detected in the ZIP8-overexpressing cells. Additionally, we found that ZIP8 with disease-associated single-point mutations G38R, G204C, and S335T, but not C113S, showed reduced Se transport ability. We then evaluated the potential of Se on Cd cytotoxicity prevention and therapy of cancers. Results indicated that Se could suppress Cd-induced cytotoxicity via decreasing the intracellular Cd transported by ZIP8, and Se exhibited excellent anticancer activity against not all but only selected cancer cell lines, under restricted experimental conditions. Moreover, clinical-based bioinformatic analyses revealed that up-regulated ZIP8 gene expression was common across multiple cancer types, and selenoproteins that were significantly co-expressed with ZIP8 in these cancers had been identified. Taken together, this study concludes that ZIP8 is an important protein in modulating cellular Se levels and provides insights into the roles of ZIP8 and Se in disease prevention and therapy.

Cellular analysis of a novel mutation p. Ser287Tyr in TOR1A in late-onset isolated dystonia.

BACKGROUND: Variations in TOR1A were thought to be associated with early-onset isolated dystonia. The variant S287Y (NM_000113.2: c.860C > A, p. Ser287Tyr, rs766483672) was found in our late-onset isolated dystonia patient. This missense variant is adjacent to R288Q (c.863G > A, p. Arg288Gln), which was reported to be associated with isolated dystonia. The potentially pathogenic role of S287Y is not conclusively known. METHODS: Cytological and molecular biological analyses were performed in vitro to determine whether this variant damages the structure and function of the cell. RESULTS: Compared with the SH-SY5Y cells overexpressing wild-type TOR1A, the cells overexpressing the protein with S287Y have an enlarged peri-nuclear space. The same changes in nuclear morphology were also found in the cells overexpressing the pathogenic variants ΔE (NM_000113.2:c.904_906delGAG, p. Glu302del), F205I (NM_000113.2:c.613 T > A, p. Phe205Ile), and R288Q (NM_000113.2:c.863G > A, p. Arg288Gln). Mutated proteins with S287Y presented a higher tendency to form dimers under reducing conditions. The same tendencies were observed in other mutated proteins but not in wild-type torsinA. CONCLUSIONS: TorsinA with S287Y damages the structure of the cell nucleus and may be a novel pathogenic mutation that causes isolated dystonia.

The ancient wave of polyploidization events in flowering plants and their facilitated adaptation to environmental stress.

Flowering plants, or angiosperms, consist of more than 300,000 species, far more than any other land plant lineages. The accumulated evidence indicates that multiple ancient polyploidy events occurred around 100 to 120 million years ago during the Cretaceous and drove the early diversification of four major clades of angiosperms: gamma whole-genome triplication in the common ancestor of core eudicots, tau whole-genome duplication during the early diversification of monocots, lambda whole-genome duplication during the early diversification of magnoliids, and pi whole-genome duplication in the Nymphaeales lineage. These four polyploidy events have played essential roles in the adaptive evolution and diversification of major clades of flowering plants. Here, we specifically review the current understanding of this wave of ancient whole-genome duplications and their evolutionary significance. Notably, although these ancient whole-genome duplications occurred independently, they have contributed to the expansion of many stress-related genes (e.g., heat shock transcription factors and Arabidopsis response regulators)，and these genes could have been selected for by global environmental changes in the Cretaceous. Therefore, this ancient wave of paleopolyploidy events could have significantly contributed to the adaptation of angiosperms to environmental changes, and potentially promoted the wide diversification of flowering plants.

Down-regulation of the insulin signaling pathway by SHC may correlate with congenital heart disease in Chinese populations.

BACKGROUND/AIMS: Congenital heart disease (CHD) is one of the most common and severe congenital defects. The incidence of fetal cardiac malformation is increased in the context of maternal gestational diabetes mellitus (GDM). Therefore, we wanted to determine whether abnormalities in the insulin signaling pathway are associated with the occurrence of nonsyndromic CHD (ns-CHD). METHODS: We used digital gene expression profiling (DGE) of right atrial myocardial tissue samples from eight ns-CHD patients and four controls. The genes potentially associated with CHD were validated by real-time fluorescence quantitative PCR analysis of right atrial myocardial tissues from 37 patients and 10 controls and the H9C2 cell line. RESULTS: The results showed that the insulin signaling pathway, which is mediated by the SHC gene family, was inhibited in the ns-CHD patients. The expression levels of five genes (PTPRF, SHC4, MAP2K2, MKNK2, and ELK1) in the pathway were significantly down-regulated in the patients' atrial tissues (P<0.05 for all). In vitro, the H9C2 cells cultured in high glucose (33 mmol/l) expressed less SHC4, MAP2K2, and Elk-1 than those cultured in low glucose (25 mmol/l). Furthermore, the high glucose concentration down-regulated the 25 genes associated with blood vessel development based on Gene Ontology (GO) term enrichment analyses of RNA-seq data. CONCLUSION: We considered that changes in the insulin signaling pathway mediated by SHC might be involved in the heart development process. This mechanism might account for the increase in the incidence of fetal cardiac malformations in the context of GDM.

A copper-based metal-organic framework/graphene nanocomposite for the sensitive and stable electrochemical detection of DNA bases.

A simple and easy-operation electrode modification strategy was proposed using Cu-MOF/GO nanohybrids for physiologists and pathologists for the feasible and reliable simultaneous electrochemical detections of DNA bases, namely guanine and adenine. The nanohybrids were prepared via a simple ultrasonic method and were employed for the fabrication of a sensing interface. SEM, TEM, XRD, FT-IR, and electrochemical characterizations were used to characterize the general morphology and structure of the nonohybrids. The proposed Cu-MOF/ERGO/GCE exhibited ultra-stable and high-sensitivity performance in the simultaneous electrochemical detection of guanine and adenine. The recorded DPV curves revealed a linear increase in the faradaic signals with increase in the concentrations of guanine and adenine in the range of 0.02-10 µM and 20-100 µM for guanine, and 0.005-20 µM and 40-200 µM for adenine. The relative standard deviation of guanine and adenine for 50 consecutive detections is 1.37% and 1.92%, respectively. It was proved that the proposed Cu-MOF/ERGO/GCE can be performed for the detection of guanine and adenine in real samples, such as Herring sperm DNA, and satisfactory results were obtained. This strategy does not require complicated modification procedures, professional modification techniques, or sophisticated instruments, but it can provide a highly sensitive and stable detection method, which is expected to expand and deepen the applications of electrochemical detection in life science research.

Cancer Cell enters reversible quiescence through Intracellular Acidification to resist Paclitaxel Cytotoxicity.

Cancer cells can enter quiescent or dormant state to resist anticancer agents while maintaining the potential of reactivation. However, the molecular mechanism underlying quiescence entry and reactivation remains largely unknown. In this paper, cancer cells eventually entered a reversible quiescent state to resist long-term paclitaxel (PTX) stress. The quiescent cells were characterized with Na+/H+ exchanger 1 (NHE1) downregulation and showed acidic intracellular pH (pHi). Accordingly, decreasing pHi by NHE1 inhibitor could induce cell enter quiescence. Further, acidic pHi could activate the ubiquitin-proteasome system and inhibiting proteasome activity by MG132 prevented cells entering quiescence. In addition, we show that after partial release, the key G1-S transcription factor E2F1 protein level was not recovered, while MCM7 protein returned to normal level in the reactivated cells. More importantly, MCM7 knockdown inhibited G1/S genes transcription and inhibited the reactivated proliferation. Taken together, this study demonstrates a regulatory function of intracellular acidification and subsequent protein ubiquitination on quiescence entry, and reveals a supportive effect of MCM7 on the quiescence-reactivated proliferation.

Appraising the Value of Serum and Serum-Derived Exosomal LncRNA-EXOC7 as a Promising Biomarker in Cervical Cancer.

BACKGROUND: The abnormally expressed long non-coding RNAs (lncRNAs) are closely related to the onset and progression of various malignant tumors. In this study, we aimed to explore the value of serum and serum-derived exosomal lncRNA-EXOC7 (long non-coding RNA exocyst complex component 7) in the diagnosis and monitoring of cervical cancer (CC). METHODS: The expression of lncRNA-EXOC7 in serum and serum-derived exosomes in CC patients was detected by quantitative real-time PCR (qRT-PCR), and the correlations between lncRNA-EXOC7 expression and clinicopathological characteristics were analyzed by Spearman's and Chi-square tests. RESULTS: Serum vesicles were successfully isolated and identified. The expression of lncRNA-EXOC7 in serum and serum-derived exosomes in CC patients was markedly elevated compared with that in healthy controls. The AUCs of serum and exosomal lncRNA-EXOC7 in distinguishing CC patients from healthy controls were 0.9388 and 0.8982, respectively. The expression of lncRNA-EXOC7 in serum and exosomes was correlated with the FIGO stage of CC (p = 0.041 or 0.010), and positively correlated with levels of CYFRA211, TPS, and SCC (all with p < 0.05). Serum and exosomal lncRNA-EXOC7 was related to the treatment and recurrence of CC; that means, it was significantly repressed after treatment and up-regulated at the time of recurrence. CONCLUSIONS: Serum and exosomal lncRNA-EXOC7 can be used as an important biomarker for the diagnosis, the evaluation of curative effect and the detection of recurrence of CC.

Efficacy of topical silicone gel in scar management: A systematic review and meta-analysis of randomised controlled trials.

To assess the efficacy of topical silicone gel in the management of scars, we conducted this meta-analysis. The systematic search was performed on PubMed, Web of Science and Embase, and six randomised controlled trials with a total of 375 patients were involved. The outcome data of Vancouver Scar Scale were extracted from the studies and their effect sizes were calculated using Review Manager 5.3. As a result, topical silicone gel significantly reduced pigmentation, height, and pliability scores postoperatively compared with placebos or no treatment (Pigmentation: standard mean difference [SMD] = -0.55 [-0.83 to -0.26], P = .0002; Height: SMD = -0.73 [-1.02 to -0.44], P < .00001; Pliability: SMD = -0.49 [-0.95 to -0.03], P = .04). Topical silicone gel and silicone gel sheet were comparably effective (P > .05). The performance of topical silicone gel and other non-silicone topical treatment was also similar (P > .05). In summary, topical silicone gel was effective in post-operative scar prevention.