LINC00460 mediates HMGA2 expression through binding to miRNA-143-5p competitively in gastric carcinoma.

Background: Compelling evidence has manifested a strong association between aberrant expression of long noncoding RNAs (lncRNAs) and gastric carcinoma (GC) development. Nonetheless, biological impacts of differentially expressed lncRNAs (DElncRNAs) on GC are not scrutinized. Methods: Bioinformatics methods were employed for differential expression analysis and target gene prediction. MTT, colony formation, and Transwell methods were implemented for GC cell proliferation, migration, and invasion assessment. Western blot was implemented to test the protein level. The binding of genes was tested with dual-luciferase and RNA binding protein immunoprecipitation (RIP) approaches. Results: Noticeably high level of LINC00460 was observed in GC tissues and cells. LINC00460 silencing constrained proliferation, migration, and invasion of GC cells. FISH and nuclear-cytoplasmic separation assays confirmed the main presentation of LINC00460 in the cytoplasm. Bioinformatics predicted that LINC00460 had binding sites to miRNA-143-5p, which was upregulated in GC. Dual luciferase and RIP experiments also confirmed the binding relationship. Concurrent silencing of LINC00460s and miRNA-133-5p rescued the repressive influence of sh-LINC004600 on GC cell proliferation, migration, and invasion. HMGA2 was predicted to be a target gene downstream of miRNA-143-5p, their binding relationship was validated via dual luciferase assays. Silencing HMGA2 constrained GC cell proliferation, invasion, and migration. LINC00460 modulated HMGA2 expression via binding miRNA-143-5p, thereby affecting proliferation, invasion, and migration of GC cells. Conclusion: These findings validated that LINC00460 could regulate HMGA2 via sponging miRNA-143-5p to facilitate GC proliferation, invasion, and migration, which provides a deeper understanding of lncRNAs in the development of GC.

The role of transposon inverted repeats in balancing drought tolerance and yield-related traits in maize.

The genomic basis underlying the selection for environmental adaptation and yield-related traits in maize remains poorly understood. Here we carried out genome-wide profiling of the small RNA (sRNA) transcriptome (sRNAome) and transcriptome landscapes of a global maize diversity panel under dry and wet conditions and uncover dozens of environment-specific regulatory hotspots. Transgenic and molecular studies of Drought-Related Environment-specific Super eQTL Hotspot on chromosome 8 (DRESH8) and ZmMYBR38, a target of DRESH8-derived small interfering RNAs, revealed a transposable element-mediated inverted repeats (TE-IR)-derived sRNA- and gene-regulatory network that balances plant drought tolerance with yield-related traits. A genome-wide scan revealed that TE-IRs associate with drought response and yield-related traits that were positively selected and expanded during maize domestication. These results indicate that TE-IR-mediated posttranscriptional regulation is a key molecular mechanism underlying the tradeoff between crop environmental adaptation and yield-related traits, providing potential genomic targets for the breeding of crops with greater stress tolerance but uncompromised yield.

The wound-activated ERF15 transcription factor drives Marchantia polymorpha regeneration by activating an oxylipin biosynthesis feedback loop.

The regenerative potential in response to wounding varies widely among species. Within the plant lineage, the liverwort Marchantia polymorpha displays an extraordinary regeneration capacity. However, its molecular pathways controlling the initial regeneration response are unknown. Here, we demonstrate that the MpERF15 transcription factor gene is instantly activated after wounding and is essential for gemmaling regeneration following tissue incision. MpERF15 operates both upstream and downstream of the MpCOI1 oxylipin receptor by controlling the expression of oxylipin biosynthesis genes. The resulting rise in the oxylipin dinor-12-oxo-phytodienoic acid (dn-OPDA) levels results in an increase in gemma cell number and apical notch organogenesis, generating highly disorganized and compact thalli. Our data pinpoint MpERF15 as a key factor activating an oxylipin biosynthesis amplification loop after wounding, which eventually results in reactivation of cell division and regeneration. We suggest that the genetic networks controlling oxylipin biosynthesis in response to wounding might have been reshuffled over evolution.

Interaction between photoperiod and variation in circadian rhythms in tomato.

BACKGROUND: Many biological processes follow circadian rhythmicity and are controlled by the circadian clock. Predictable environmental changes such as seasonal variation in photoperiod can modulate circadian rhythms, allowing organisms to adjust the timing of their biological processes to the time of the year. In some crops such as rice, barley or soybean, mutations in circadian clock genes have altered photoperiod sensitivity, enhancing their cultivability in specific seasons and latitudes. However, how changes in circadian rhythms interact with the perception of photoperiod in crops remain poorly studied. In tomato, the appearance during domestication of mutations in EMPFINDLICHER IM DUNKELROTEN LICHT 1 (EID1, Solyc09g075080) and NIGHT LIGHT-INDUCIBLE AND CLOCK-REGULATED GENE 2 (LNK2, Solyc01g068560) delayed both the phase and period of its circadian rhythms. The fact that variation in period and phase are separated in tomato provides an optimal tool to study how these factors affect the perception of photoperiod. RESULTS: Here we develop tomato near isogenic lines carrying combinations of wild alleles of EID1 and LNK2 and show that they recreate the changes in phase and period that occurred during its domestication. We perform transcriptomic profiling of these near isogenic lines under two different photoperiods, and observe that EID1, but not LNK2, has a large effect on how the tomato transcriptome responds to photoperiod. This large effect of EID1 is likely a consequence of the global phase shift elicited by this gene in tomato's circadian rhythms. CONCLUSIONS: Our study shows that changes in phase that occurred during tomato domestication determine photoperiod perception in this species, while changes in period have little effect.

The application of endoscopic loop ligation in defect repair following endoscopic full-thickness resection of gastric submucosal tumors originating from the muscularis propria layer.

OBJECTIVE: We sought to investigate the clinical efficacy and safety of a novel endoscopic closure technique in repairing gastric wall defects after endoscopic full-thickness resection (EFTR) of gastric submucosal tumors (SMTs) originating from the muscularis propria layer. METHODS: From December 2016 to December 2019, patients with gastric submucosal tumors were enrolled and clinicopathological data were collected. All SMTs were resected by EFTR and gastric wall defects were closed using a novel endoscopic closure technique. The feasibility, efficacy, and safety were evaluated. RESULTS: A total of 21 patients with gastric SMTs were included in this study. Among the included SMTs, 15 tumors were located in the fundus of the stomach, and 6 were located in the upper body of the stomach. The average size of the lesions was 2.3 cm (range: 1.9-2.5 cm). All patients underwent EFTR and the gastric wall defect was closed by endoscopic closure. The average endoscopic closure time was 9 min (range: 7-15 min) and the average hospitalization stay length was five days (range: 4-6 days). One patient developed abdominal pain on the first day after the procedure and their body temperature increased; he received treatments such as anti-infection, antacid, and gastrointestinal decompression and was cured and discharged after 4 days. No instance of delayed bleeding, postoperative gastrointestinal fistula, or abdominal infection occurred. No case was transferred to surgery. The postoperative pathology profile included 18 stromal tumors and 3 leiomyomas. During the follow-up period (6-24 months), no case of residual or recurrence was recorded. CONCLUSION: The described endoscopic loop ligation technique is feasible, effective, and safe for repairing gastric wall defects after EFTR for gastric submucosal tumors originating from the muscularis propria layer.

Cell cycle checkpoint control in response to DNA damage by environmental stresses.

Being sessile organisms, plants are ubiquitously exposed to stresses that can affect the DNA replication process or cause DNA damage. To cope with these problems, plants utilize DNA damage response (DDR) pathways, consisting of both highly conserved and plant-specific elements. As a part of this DDR, cell cycle checkpoint control mechanisms either pause the cell cycle, to allow DNA repair, or lead cells into differentiation or programmed cell death, to prevent the transmission of DNA errors in the organism through mitosis or to its offspring via meiosis. The two major DDR cell cycle checkpoints control either the replication process or the G2/M transition. The latter is largely overseen by the plant-specific SOG1 transcription factor, which drives the activity of cyclin-dependent kinase inhibitors and MYB3R proteins, which are rate limiting for the G2/M transition. By contrast, the replication checkpoint is controlled by different players, including the conserved kinase WEE1 and likely the transcriptional repressor RBR1. These checkpoint mechanisms are called upon during developmental processes, in retrograde signaling pathways, and in response to biotic and abiotic stresses, including metal toxicity, cold, salinity, and phosphate deficiency. Additionally, the recent expansion of research from Arabidopsis to other model plants has revealed species-specific aspects of the DDR. Overall, it is becoming evidently clear that the DNA damage checkpoint mechanisms represent an important aspect of the adaptation of plants to a changing environment, hence gaining more knowledge about this topic might be helpful to increase the resilience of plants to climate change.

An Indole Alkaloid Extracted from Evodia rutaecarpa Inhibits Colonic Motility of Rats In Vitro.

Evodiamine (Evo) is an indole alkaloid extracted from the traditional Chinese medicinal herb Evodia rutaecarpa. Evo may regulate gastrointestinal motility, but the evidence is insufficient, and the mechanisms remain unknown. The aim of this study was to investigate the effect of Evo on colonic motility of rats and the underlying mechanisms in vitro. Rat colonic muscle was exposed to Evo (10 and 100 µM) followed by immunohistochemistry of cholecystokinin receptor 1 (CCK1R). Muscle contractions were studied in an organ bath system to determine whether CCK1R, nitric oxide (NO), and enteric neurons are involved in the relaxant effect of Evo. Whole-cell patch-clamp was used to detect L-type calcium currents (I Ca,L) in isolated colonic smooth muscle cells (SMCs). CCK1R was observed in SMCs, intermuscular neurons, and mucosa of rat colon. Evo could inhibit spontaneous muscle contractions; NO synthase, inhibitor L-NAME CCK1R antagonist, could partly block this effect, while the enteric neurons may not play a major role. Evo inhibited the peak I Ca,L in colonic SMCs at a membrane potential of 0 mV. The current-voltage (I-V) relationship of L-type calcium channels was modified by Evo, while the peak of the I-V curve remained at 0 mV. Furthermore, Evo inhibited the activation of L-type calcium channels and decreased the peak I Ca,L. The relaxant effect of Evo on colonic muscle is associated with the inhibition of L-type calcium channels. The enteric neurons, NO, and CCK1R may be partly related to the inhibitory effect of Evo on colonic motility. This study provides the first evidence that evodiamine can regulate colonic motility in rats by mediating calcium homeostasis in smooth muscle cells. These data form a theoretical basis for the clinical application of evodiamine for treatment of gastrointestinal motility diseases.

SlHAK20: a new player in plant salt tolerance.

The majority of crops remain sensitive to salt stress despite the steady increase in salt concentration in agricultural soil. In this issue of The EMBO Journal, Wang et al (2020) screen hundreds of tomato accessions to identify SlHAK20 as a gene accounting for quantitative differences in salt tolerance between accessions. SlHAK20 is a potassium transporter belonging to a poorly studied clade in a large family of transporters, and its mutation induces salt susceptibility both in tomato and rice.

Enhanced Vitamin C Production Mediated by an ABA-Induced PTP-like Nucleotidase Improves Plant Drought Tolerance in Arabidopsis and Maize.

Abscisic acid (ABA) is a key phytohormone that mediates environmental stress responses. Vitamin C, or L-ascorbic acid (AsA), is the most abundant antioxidant protecting against stress damage in plants. How the ABA and AsA signaling pathways interact in stress responses remains elusive. In this study, we characterized the role of a previously unidentified gene, PTPN (PTP-like Nucleotidase) in plant drought tolerance. In Arabidopsis, (AtPTPN was expressed in multiple tissues and upregulated by ABA and drought treatments. Loss-of-function mutants of AtPTPN were hyposensitive to ABA but hypersensitive to drought stresses, whereas plants with enhanced expression of AtPTPN showed opposite phenotypes to . Overexpression of maize PTPN (ZmPTPN) promoted, while knockdown of ZmPTPN inhibited plant drought tolerance, indicating conserved and positive roles of PTPN in plant drought tolerance. We found that both AtPTPN and ZmPTPN release Pi by hydrolyzing GDP/GMP/dGMP/IMP/dIMP, and that AtPTPN positively regulated AsA production via endogenous Pi content control. Consistently, overexpression of VTC2, the rate-limiting synthetic enzyme in AsA biosynthesis, promoted AsA production and plant drought tolerance, and these effects were largely dependent on AtPTPN activity. Furthermore, we demonstrated that the heat shock transcription factor HSFA6a directly binds the AtPTPN promoter and activates AtPTPN expression. Genetic analyses showed that AtPTPN is required for HSFA6a to regulate ABA and drought responses. Taken together, our data indicate that PTPN-mediated crosstalk between the ABA signaling and AsA biosynthesis pathways positively controls plant drought tolerance.

Submucosal tunneling endoscopic resection for large symptomatic submucosal tumors of the esophagus: A clinical analysis of 24 cases.

BACKGROUND/AIMS: Studies evaluating submucosal tunneling endoscopic resection (STER) for the treatment of upper gastrointestinal submucosal tumors (SMTs) have recently increased. However, the efficacy and safety of STER for the treatment of large symptomatic SMTs in the esophagus have not been well investigated. The aim of the present study was to evaluate the efficacy and safety of STER for the treatment of large symptomatic SMTs in the esophagus. METHODS: A total of 24 patients with large symptomatic SMTs in the esophagus who underwent STER in our hospitals between January 2015 and May 2018 were included in the study. The tumors were confirmed to be of muscularis propria layer origin. Treatment outcomes, complications, and follow-up results were retrospectively analyzed. RESULTS: All 24 lesions were resected en bloc with STER. The mean maximum transverse diameter of the lesions was 4.7 (3.5-6.5) cm. The mean maximum longitudinal diameter of the lesions was 2.1 (1.5-3.0) cm. The mean duration from mucosal incision to complete mucosal closure was 65 (50-115) min. Postoperative pathological diagnosis confirmed 18 cases with leiomyomas, 4 cases with stromal tumors, and 2 cases with schwannomas. There were no major complications. There were no residual lesions or disease recurrence during follow-up. CONCLUSION: STER is safe and effective for the treatment of large symptomatic SMTs of muscularis propria layer origin in the esophagus.

Deletion of an Endoplasmic Reticulum Stress Response Element in a ZmPP2C-A Gene Facilitates Drought Tolerance of Maize Seedlings.

Drought is a major abiotic stress that causes the yearly yield loss of maize, a crop cultured worldwide. Breeding drought-tolerant maize cultivars is a priority requirement of world agriculture. Clade A PP2C phosphatases (PP2C-A), which are conserved in most plant species, play important roles in abscisic acid (ABA) signaling and plant drought response. However, natural variations of PP2C-A genes that are directly associated with drought tolerance remain to be elucidated. Here, we conducted a candidate gene association analysis of the ZmPP2C-A gene family in a maize panel consisting of 368 varieties collected worldwide, and identified a drought responsive gene ZmPP2C-A10 that is tightly associated with drought tolerance. We found that the degree of drought tolerance of maize cultivars negatively correlates with the expression levels of ZmPP2C-A10. ZmPP2C-A10, like its Arabidopsis orthologs, interacts with ZmPYL ABA receptors and ZmSnRK2 kinases, suggesting that ZmPP2C-A10 is involved in mediating ABA signaling in maize. Transgenic studies in maize and Arabidopsis confirmed that ZmPP2C-A10 functions as a negative regulator of drought tolerance. Further, a causal natural variation, deletion allele-338, which bears a deletion of ERSE (endoplasmic reticulum stress response element) in the 5'-UTR region of ZmPP2C-A10, was detected. This deletion causes the loss of endoplasmic reticulum (ER) stress-induced expression of ZmPP2C-A10, leading to increased plant drought tolerance. Our study provides direct evidence linking ER stress signaling with drought tolerance and genetic resources that can be used directly in breeding drought-tolerant maize cultivars.