Hsa_circ_0043603 promotes the progression of esophageal squamous cell carcinoma by sponging miR-1178-3p and regulating AADAC expression.

This study aims to investigate the regulatory impact of hsa_circ_0043,603, a circular RNA, on the progression of esophageal squamous cell carcinoma (ESCC), which ranks as the sixth leading cause of global mortality. We evaluated the expression, origin, and localization of hsa_circ_0043,603 in ESCC tumors using qRT-PCR, bioinformatics, and FISH analysis. Functional studies were conducted by manipulating the hsa_circ_0043,603 expression in Eca109 cells through overexpression and silencing plasmids. Additionally, xenografts derived from circ_0043,603-overexpressing Eca109 cells enabled us to investigate tumor growth, proliferation, and apoptosis. Through Starbase analysis, we identified miR-1178-3p as a target of circ_0043,603, which was validated using RIP and luciferase assays. Furthermore, we predicted arylacetamide deacetylase (AADAC) as a target of miR-1178-3p and examined its expression in ESCC tissues using Western blot. Lastly, we performed AADAC silencing and overexpression in Eca109 cells to study their impact on cellular phenotypic features, apoptosis, and their interaction with miR-1178-3p mimics and inhibitors. The low expression of hsa_circ_0043,603 in ESCC tissue was associated with poor prognosis. Overexpression of hsa_circ_0043,603 inhibited ESCC growth, invasion, migration, and proliferation, while promoting apoptosis in vitro and suppressing tumor growth in vivo. hsa_circ_0043,603 achieved these effects by targeting the oncogenic miR-1178-3p. Furthermore, AADAC was identified as a target of miR-1178-3p, and its reduced expression was confirmed in ESCC tissues. Overexpression of AADAC in Eca109 cells resulted in suppressed cell growth, proliferation, migration, and invasion by regulating miR-1178-3p. hsa_circ_0043,603 acts as a sponge for miR-1178-3p, leading to the regulation of AADAC expression and inhibition of ESCC development. These results suggest the potential of hsa_circ_0043,603 as a therapeutic and diagnostic target for ESCC.

The possibility of endoscopic treatment of cN0 submucosal esophageal cancer: results from a surgical cohort.

BACKGROUND: We analyzed the pathological characteristics and recurrence pattern of cN0 submucosal esophageal cancer after esophagectomy and conducted risk stratification to determine the feasibility of performing endoscopic resection for cN0pT1b esophageal squamous cell malignancies. METHODS: We retrospectively enrolled 167 patients who underwent right-sided transthoracic esophagectomy and extended thoracic/abdominal two-field lymphadenectomy. Patients with pathologically confirmed lymph node metastasis or tumor recurrence constituted the high-risk group for endoscopic submucosal resection, and the remainder were defined as low risk. Factors affecting lymphatic metastasis and long-term recurrence were identified by univariate and multivariate analyses. RESULTS: Postoperative pathology showed that five patients (5/167; 3%) had lymph node metastases. Follow-up ranged from 12-60 months, with a median of 29 months. A total of 17 patients (10.2%) had recurrences during follow-up, including three patients with pathologic nodal metastasis (pN +) found at surgery. Invasion depth, differentiation, and tumor size differed significantly in high-risk patients. Overall 3-year survival rates were 94.2% (low-risk) and 40.9% (high-risk) (p < 0.01). Twenty-one patients with sm1 cancer, high tumor differentiation, and tumor length < 2 cm had no lymph node metastasis or lymphovascular invasion, and none of these patients experienced recurrence. CONCLUSIONS: Endoscopic submucosal resection alone may be feasible for patients with small (≤ 2 cm) clinically N0 submucosal esophageal squamous cell carcinoma with low invasion depth (sm1) and higher differentiation, but prospective studies are required for confirmation. Other patients require surgical resection with extended two-field thoracic/abdominal lymphadenectomy.

Surgical management of acquired tracheo/bronchoesophageal fistula associated with esophageal diverticulum.

BACKGROUND: The reports on acquired tracheoesophageal fistulas (TEFs) or bronchoesophageal fistulas (BEFs) associated with traction esophageal diverticula (TED) are rare. Here, we present our experience of six cases. METHODS: Between Jan. 2015 and Jun. 2016, 6 patients were admitted to our department for TEF/BEFs combined with esophageal diverticula. Clinical data of the 6 patients were retrospectively reviewed. RESULTS: All orifices of TEF/BEF in the esophagus side opened at the diverticula wall. The orifices in the airway side were 2 at the carina and 4 at the right intermediate bronchus. All six patients received the same intervention: a limited diverticulectomy with the fistula resection was done in the esophagus; separate layers of repair were performed for the defect in the esophagus; the muscle flap interposition was used in all six cases. All postoperative courses were uneventful. No recurrence fistula and symptomatic diverticula occurred. The airway and esophagus were patency during a median of 9-month follow-up. CONCLUSIONS: Acquired TEF/BEFs caused by esophageal diverticula can be treated successfully by surgery. A limited diverticulectomy is sufficient to ensure enough esophagus remodeling. KEYWORDS: Tracheo/bronchoesophageal fistula (TEF/BEF); esophagus diverticulum; acquired.

Nutritional imbalance suppresses migratory phenotypes of the Mongolian locust (Oedaleus asiaticus).

For many species, migration evolves to allow organisms to access better resources. However, the proximate factors that trigger these developmental changes, and how and why these vary across species, remain poorly understood. One prominent hypothesis is that poor-quality food promotes development of migratory phenotypes and this has been clearly shown for some polyphenic insects. In other animals, particularly long-distance bird migrants, it is clear that high-quality food is required to prepare animals for a successful migration. We tested the effect of diet quality on the flight behaviour and morphology of the Mongolian locust, Oedaleus asiaticus. Locusts reared at high population density and fed low-N grass (performance-enhancing for this species) had enhanced migratory morphology relative to locusts fed high-N grass. Furthermore, locusts fed synthetic diets with an optimal 1 : 2 protein : carbohydrate ratio flew for longer times than locusts fed diets with lower or higher protein : carbohydrate ratios. In contrast to the hypothesis that performance-degrading food should enhance migration, our results support the more nuanced hypothesis that high-quality diets promote development of migratory characteristics when migration is physiologically challenging.

MicroRNA-276 promotes egg-hatching synchrony by up-regulating brm in locusts.

Developmental synchrony, the basis of uniform swarming, migration, and sexual maturation, is an important strategy for social animals to adapt to variable environments. However, the molecular mechanisms underlying developmental synchrony are largely unexplored. The migratory locust exhibits polyphenism between gregarious and solitarious individuals, with the former displaying more synchronous sexual maturation and migration than the latter. Here, we found that the egg-hatching time of gregarious locusts was more uniform compared with solitarious locusts and that microRNA-276 (miR-276) was expressed significantly higher in both ovaries and eggs of gregarious locusts than in solitarious locusts. Interestingly, inhibiting miR-276 in gregarious females and overexpressing it in solitarious females, respectively, caused more heterochronic and synchronous hatching of progeny eggs. Moreover, miR-276 directly targeted a transcription coactivator gene, brahma (brm), resulting in its up-regulation. Knockdown of brm not only resulted in asynchronous egg hatching in gregarious locusts but also impaired the miR-276-induced synchronous egg hatching in solitarious locusts. Mechanistically, miR-276 mediated brm activation in a manner that depended on the secondary structure of brm, namely, a stem-loop around the binding site of miR-276. Collectively, our results unravel a mechanism by which miR-276 enhances brm expression to promote developmental synchrony and provide insight into regulation of developmental homeostasis and population sustaining that are closely related to biological synchrony.

[Adaption of surgical procedure in the treatment of submucosal esophageal cancer].

OBJECTIVES: To evaluate the efficacy and advantage of minimally invasive esophagectomy for surgical treatment of submucosal esophageal cancer compared to conventional open procedure. METHODS: Clinical data of consecutive 168 patients with stage T1b submucosal esophageal cancer undergoing minimally invasive esophagectomy (MIE, esophagectomy by thoracoscope, stomach freeing by laparoscope or open abdomen, cervical esophagogastric anastomosis) or conventional open esophagectomy (OE) at the Shanghai Chest Hospital between January 1, 2012 and December 31, 2014 were reviewed retrospectively. Intraoperative and postoperative information was compared between the two groups. RESULTS: Both groups were equally stratified by sex, body mass index and age. No patient of MIE group was transferred to open operation. As compared to the OE group, the MIE group had significantly more harvest lymph nodes (median 12 vs. median 9, P=0.004), lower rate of postoperative pneumonia [5.8% (4/69) vs. 21.2% (21/99), P=0.011] and pleural effusion [8.7% (6/69) vs. 23.2% (23/99), P=0.027], and shorter hospital stay (median 11 d vs. median 14 d, P=0.041), but positive margin was found in 1 case. There were no significant differences of respiratory failure, pneumothorax, atrial arrhythmia, pulmonary embolism, recurrent nerve palsy, anastomotic leak, reoperations and 30-day mortality between the two groups. Multivariate logistic analysis revealed recurrent nerve palsy, anastomotic leak and surgical approach were found to be the main factors of hospital stay within postoperative 12 days, while leakage when the in-hospital time more than 12 days. Kaplan-Meier analysis showed that the surgical approach was the independent factor of hospital stay, MIE could shorten the hospital stay (P=0.013). CONCLUSION: MIE should be considered as the standard approach in the treatment of T1b submucosal esophageal cancer.

Octopamine and tyramine respectively regulate attractive and repulsive behavior in locust phase changes.

Aggregative and solitary behaviors are universal phenomena in animals. Interestingly, locusts (Locusta migratoria) can reversibly transit their behavior between gregarious and solitary phase through conspecific attraction and repulsion. However, the regulatory mechanism of neurotransmitters underlying attraction and repulsion among locusts remains unknown. In this study, we found gregarious and solitary locusts were attracted or repulsed respectively by gregarious volatiles. Solitary locusts can transform their preference for gregarious volatiles during crowding, whereas gregarious locusts avoided their volatiles during isolation. During crowding and isolation, the activities of octopamine and tyramine signalings were respectively correlated with attraction- and repulsion-response to gregarious volatiles. RNA interference verified that octopamine receptor α (OARα) signaling in gregarious locusts controlled attraction-response, whereas in solitary ones, tyramine receptor (TAR) signaling mediated repulsion-response. Moreover, the activation of OARα signaling in solitary locusts caused the behavioral shift from repulsion to attraction. Enhancement of TAR signaling in gregarious locusts resulted in the behavioral shift from attraction to repulsion. The olfactory preference of gregarious and solitary locusts co-injected by these two monoamines displayed the same tendency as the olfactory perception in crowding and isolation, respectively. Thus, the invertebrate-specific octopamine-OARα and tyramine-TAR signalings respectively mediate attractive and repulsive behavior in behavioral plasticity in locusts.

The locust genome provides insight into swarm formation and long-distance flight.

Locusts are one of the world's most destructive agricultural pests and represent a useful model system in entomology. Here we present a draft 6.5 Gb genome sequence of Locusta migratoria, which is the largest animal genome sequenced so far. Our findings indicate that the large genome size of L. migratoria is likely to be because of transposable element proliferation combined with slow rates of loss for these elements. Methylome and transcriptome analyses reveal complex regulatory mechanisms involved in microtubule dynamic-mediated synapse plasticity during phase change. We find significant expansion of gene families associated with energy consumption and detoxification, consistent with long-distance flight capacity and phytophagy. We report hundreds of potential insecticide target genes, including cys-loop ligand-gated ion channels, G-protein-coupled receptors and lethal genes. The L. migratoria genome sequence offers new insights into the biology and sustainable management of this pest species, and will promote its wide use as a model system.

Expression of Das-1, Ki67 and sulfuric proteins in gastric cardia adenocarcinoma and intestinal metaplasia lesions.

The aim of this study was to characterize histo-chemical patterns and Das-1 and Ki67 protein expression in gastric cardia adenocarcinoma (GCA) and intestinal metaplasia (IM) lesions adjacent to GCA. Histochemical techniques, including Alcian blue/periodic acid-Schiff (AB/PAS), high iron diamine/Alcian blue (HID/AB) and avidin-biotin-peroxidase complex (ABC) immunohistochemistry were applied to GCA and IM samples from patients (n=200) in Linzhou, Henan, China, a high incidence area for GCA and esophageal squamous cell carcinoma (SCC). The detection rate of IM lesions in resected tissues adjacent to GCA was 32.5% (65/200). GCA and IM lesions presented a high frequency of Das-1 and Ki67-positive staining with statistical significance (P<0.01). The expression of sulfuric proteins did not show co-expression with Das-1 and Ki67 in GCA and surrounding IM lesions (P>0.05) from the same GCA patient. The high frequency of co-expression of Das-1 and Ki67 in GCA and adjacent IM lesions indicates that IM adjacent to GCA may undergo similar molecular changes to GCA, which may be one of the mechanisms for malignant transformation of IM in the population studied.

Specificity responses of grasshoppers in temperate grasslands to diel asymmetric warming.

BACKGROUND: Global warming is characterized by not only an increase in the daily mean temperature, but also a diel asymmetric pattern. However, most of the current studies on climate change have only concerned with the mean values of the warming trend. Although many studies have been conducted concerning the responses of insects to climate change, studies that address the issue of diel asymmetric warming under field conditions are not found in the literature. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a field climate manipulative experiment and investigated developmental and demographic responses to diel asymmetric warming in three grasshopper species (an early-season species Dasyhippus barbipes, a mid-season species Oedaleus asiaticus, and a late-season species Chorthippus fallax). It was found that warming generally advanced the development of eggs and nymphs, but had no apparent impacts on the hatching rate of eggs, the emergence rate of nymphs and the survival and fecundity of adults in all the three species. Nighttime warming was more effective in advancing egg development than the daytime warming. The emergence time of adults was differentially advanced by warming in the three species; it was advanced by 5.64 days in C. fallax, 3.55 days in O. asiaticus, and 1.96 days in D. barbipes. This phenological advancement was associated with increases in the effective GDDs accumulation. CONCLUSIONS/SIGNIFICANCE: Results in this study indicate that the responses of the three grasshopper species to warming are influenced by several factors, including species traits, developmental stage, and the thermal sensitivity of the species. Moreover, species with diapausing eggs are less responsive to changes in temperature regimes, suggesting that development of diapausing eggs is a protective mechanism in early-season grasshopper for avoiding the risk of pre-winter hatching. Our results highlight the need to consider the complex relationships between climate change and specificity responses of invertebrates.

Heavy livestock grazing promotes locust outbreaks by lowering plant nitrogen content.

Current paradigms generally assume that increased plant nitrogen (N) should enhance herbivore performance by relieving protein limitation, increasing herbivorous insect populations. We show, in contrast to this scenario, that host plant N enrichment and high-protein artificial diets decreased the size and viability of Oedaleus asiaticus, a dominant locust of north Asian grasslands. This locust preferred plants with low N content and artificial diets with low protein and high carbohydrate content. Plant N content was lowest and locust abundance highest in heavily livestock-grazed fields where soils were N-depleted, likely due to enhanced erosion. These results suggest that heavy livestock grazing and consequent steppe degradation in the Eurasian grassland promote outbreaks of this locust by reducing plant protein content.

Are color or high rearing density related to migratory polyphenism in the band-winged grasshopper, Oedaleus asiaticus?

Locusts represent an impressive example of migratory polyphenism, with high densities triggering a switch from a solitarious, shorter dispersal range, and sometimes greenish phenotype to a gregarious and sometimes darker form exhibiting behavioral, morphological and physiological traits associated with long-distance migratory swarms. While such polyphenism has been well documented in Locusta migratoria and Schistocerca gregaria, the extent to which other grasshoppers exhibit this type of migratory polyphenism is unclear. Anecdotally, the Chinese grasshopper, Oedaleus asiaticus, forms migratory swarms comprised mostly of a darker, brown-colored morph, but also exhibits a non-migratory green-colored morph that predominates at low densities. In a population in Inner Mongolia not currently exhibiting migratory swarms, we found that while green and brown O. asiaticus are found concurrently across our sampled range, only brown grasshoppers were found in high densities. Differences between field-collected brown and green forms matched some but not key predictions associated with the hypothesis that the brown form is morphologically and physiologically specialized for gregarious migration. Controlling for body mass, brown forms had more massive thoraxes, abdomens and legs, and higher metabolic rates, but not more flight muscle or lipid stores. Further, the brown and green grasshoppers did not differ in gregarious behavior, and neither would fly in multiple lab and field trials. Lab or field-rearing at high densities for one-to-multiple juvenile instars caused grasshoppers to exhibit some morphological traits predicted to benefit migration (larger wings and a shift in relative mass from abdomen to thorax), but did not change color or induce flight behavior. One hypothesis to explain these data is that a migratory form of O. asiaticus is partially triggered by high field densities, but that existing ecological conditions blocked full expression of such traits (and outbreak swarms). Alternatively, color variation in this species may more tightly linked to other functions in this species such as crypsis or disease resistance, and mechanisms other than late-juvenile rearing density (e.g. genetic variation, maternal effects) may be more critical for promoting variation in color and/or migratory polyphenism.