Stem cells play pivotal roles in esophageal squamous cell carcinoma (ESCC) recurrence and metastasis. The self-renewal ability of stem cells was associated with specific microRNAs (miRs). Herein, we identified the effects of miR-377 on ESCC stem cell activities. First, the expression of miR-377 in ESCC and adjacent normal tissues was determined. The relationship between miR-377 and chromobox protein homolog 3 (CBX3) was assessed by a dual-luciferase reporter gene assay. miR-377 was overexpressed or inhibited in ESCC stem cells to explore its role in ESCC. To further investigate the mechanism of miR-377 in ESCC, cells were introduced with short hairpin RNA against CBX3 or pifithrin-α (inhibitor of P53 pathway). Besides, the expression of P21, P53, CD133, CD13, Nanog, sex determining region Y-Box 2 (Sox2), and octamer-binding transcription factor 4 (Oct4), cell sphere formation, colony formation, and proliferation were evaluated respectively. Finally, limiting dilution assay in vivo and tumor xenograft in nude mice were conducted to confirm the roles of miR-377 in vivo. miR-377 was poorly expressed in ESCC. Overexpression of miR-377 could suppress the stem-like trait of ESCC as well as the tumor growth in vivo. miR-377 targeted CBX3 to activate the P53/P21 pathway. Besides, the expression of stem-like markers including CD133, CD13, Oct4, Sox2, and Nanog was decreased, and the abilities of cell sphere formation, colony formation, proliferation, and tumorigenicity were significantly reduced by overexpressing miR-377 or silencing CBX3. The results were reversed after inactivating the P53/P21 pathway. In summary, upregulation of miR-377 inhibits the self-renewal of ESCC stem cells by inhibiting CBX3 expression and promoting activation of the P53/P21 pathway.
Atypical polypoid adenomyoma (APAM) is an uncommon uterine lesion composed of complex endometrioid glands with frequent squamous morular metaplasia and fibromuscular stroma. On endometrial curettage, biopsy or polypectomy specimens, the admixture of endometrioid glands and smooth muscle raises the differential diagnosis of myoinvasive endometrioid carcinoma. Reproductive-age APAM patients may opt for fertility preservation, whereas myoinvasive carcinoma is treated surgically. One previous study reported an incidental finding that the stroma of APAM, in contrast to that of other polypoid lesions, was SATB2-positive. APAM has also been reported to show increased stromal p16 staining. We aimed to assess whether SATB2 and p16 are useful stains for the distinction of APAM from myoinvasive carcinoma and benign adenomyomatous polyps.

Cases of 'atypical polypoid adenomyoma' (n=32), 'adenomyomatous polyp' (n=39) and 'myoinvasive endometrioid carcinoma' (n=30) were identified. Morphological features were assessed, l evaluation of endometrial biopsies/curettings.
With non-surgical treatment, T4b oral squamous cell carcinoma (OSCC) have an unacceptably poor prognosis. A subset of patients if selected wisely for surgery, can have significantly improved survival. The present study aims to explore the feasibility of radical resection and neoadjuvant chemotherapy (NACT) in the T4b OSCC and their impact on survival, along with the factors affecting it.

This is a retrospective analysis of 302 consecutive patients with T4b OSCC presented at our institute between July 2015 and January 2016.

Three different treatment protocols were decided depending on the extent of the disease-upfront resection, NACT (followed by surgery or chemo/radiation depending on the response), or upfront non-surgical treatment (chemotherapy and/or radiotherapy).

Upfront surgery was done in 67 (22.19%) patients and 155 (51.32%) patients received NACT. The rest of the patients received upfront non-surgical treatment. The overall response rate of NACT was 23.23% and the resectability rate was 36.13%. The median OS for the whole population was 12 months (30 months for the surgical group and 9 months for the non-surgical group). There was no survival difference between supra versus infra-notch tumors (P value=.552) or post-NACT versus upfront surgery (P value=.932). Nodal involvement was the most important poor prognostic factor affecting both DFS (P=.006) and OS (P=.002).

With proper patient selection after thorough clinico-radiological assessment, a subset of T4b OSCC can be operated with curative intention; either upfront or after downstaging with NACT, which ultimately translates into improved survival.

3 Laryngoscope, 131E2266-E2274, 2021.
3 Laryngoscope, 131E2266-E2274, 2021.Leaching of irrigation water from blueberry (Vaccinium spp.) plants intensifies when sandy soils are amended with pine (Pinus spp.) bark. In a greenhouse study, leaching fractions of water (LFW) and nutrients (LFN) were determined from two blueberry (V. corymbosum L.) cultivars, 'Emerald' and 'Jewel', grown in biochar-treated and nontreated sandy subsoil and irrigated with drip emitters using one of three pulse frequencies in a factorial design. The LFW was >50% under Emerald and 5 pulses d-1 to supply the daily water requirements in pine bark-amended sandy soil.Iron (Fe) is an essential element for plant growth, development and metabolism. Due to its lack of solubility and low bioavailability in soil, Fe levels are usually far below the optimum amount for most plants' growth and development. In apple production, excessive use of nitrogen fertilizer may cause iron chlorosis symptoms in the newly growing leaves, but the regulatory mechanisms underlying this phenomenon are unclear. In this study, low nitrate (NO3 - , LN) application alleviated the symptoms of Fe deficiency and promoted lower rhizosphere pH, which was beneficial for root Fe acquisition. At the same time, LN treatment increased citrate and abscisic acid accumulation in roots, which promoted Fe transport from root to shoot and maintained Fe homeostasis. https://www.selleckchem.com/products/hoipin-8.html Moreover, qRT-PCR analysis showed that nitrate application caused differential expression of genes related to Fe uptake and transport, as well as transcriptional regulators. In summary, our data reveal that low nitrate alleviated Fe deficiency through multiple pathways, demonstrating a new option for minimizing Fe deficiency by regulating the balance between nutrients.
Breast cancer is the most common cancer and the leading cause of cancer-related deaths for women all over the world. Recently, automated breast ultrasound (ABUS) has become a new and promising screening modality for whole breast examination. However, reviewing volumetric ABUS is time-consuming and lesions could be missed during the examination. Therefore, computer-aided cancer detection in ABUS volume is extremely expected to help clinician for the breast cancer screening.

We develop a novel end-to-end 3D convolutional network for automated cancer detection in ABUS volume, in order to accelerate reviewing and meanwhile to provide high detection sensitivity with low false positives (FPs). Specifically, an efficient 3D Inception Unet-style architecture with fusion deep supervision mechanism is proposed to attain decent detection performance. In addition, a novel asymmetric loss is designed to help the network balancing false positive and false negative regions, thus improving detection sensitivity for small cancerous lesions.

The efficacy of our network was extensively validated on a dataset including 196 patients with 661 cancer regions. Our network obtained a detection sensitivity of 95.1% with 3.0 FPs per ABUS volume. Furthermore, the average inference time of the network was 0.1 second per volume, which largely shortens the conventional reviewing time.

The proposed network provides efficient and accurate cancer detection scheme using ABUS volume, and may assist clinicians for more efficient breast cancer screening.
The proposed network provides efficient and accurate cancer detection scheme using ABUS volume, and may assist clinicians for more efficient breast cancer screening.Indirect agonism has been invoked as part of the mechanism of antipsychotic action at dopamine D2/3 receptors, and more recently as a salient neuropharmacological aspect of the serotonin 5-HT2A drug pimavanserin (Pim). We now comment on an article in this volume showing that Pim treatment attenuates the deposition of Aβ protein in brain of transgenic Alzheimer's disease model mice. Pim treatment may interfere with Aβ deposition by shifting the balance between two 5-HT2A signaling pathways, that is, antagonism of Gq/11 signaling and agonism of Gαi1 signaling. Treatment with serotonin-selective reuptake inhibitors (SSRIs) evoked also reduced amyloid deposition in transgenic mice, but SSRI treatment does not unequivocally interfere in the progression of human Alzheimer's disease, perhaps because of complex effects of chronic SSRI treatment on multiple serotonin receptor types. Preclinical findings suggest Pim as a promising pharmacological strategy for intervening against Alzheimer's pathology, perhaps at a very early stage of the disease. However, much remains to be learned about the convergence of various receptor-mediated signaling pathways on the final common path leading to net Aβ deposition.The N6-methyladenosine (m6 A) RNA modification serves crucial functions in RNA metabolism; however, the molecular mechanisms underlying the regulation of m6 A are not well understood. Here, we establish arginine methylation of METTL14, a component of the m6 A methyltransferase complex, as a novel pathway that controls m6 A deposition in mammalian cells. Specifically, protein arginine methyltransferase 1 (PRMT1) interacts with, and methylates the intrinsically disordered C terminus of METTL14, which promotes its interaction with RNA substrates, enhances its RNA methylation activity, and is crucial for its interaction with RNA polymerase II (RNAPII). Mouse embryonic stem cells (mESCs) expressing arginine methylation-deficient METTL14 exhibit significantly reduced global m6 A levels. Transcriptome-wide m6 A analysis identified 1,701 METTL14 arginine methylation-dependent m6 A sites located in 1,290 genes involved in various cellular processes, including stem cell maintenance and DNA repair. These arginine methylation-dependent m6 A sites are associated with enhanced translation of genes essential for the repair of DNA interstrand crosslinks; thus, METTL14 arginine methylation-deficient mESCs are hypersensitive to DNA crosslinking agents. Collectively, these findings reveal important aspects of m6 A regulation and new functions of arginine methylation in RNA metabolism.Circular RNAs (circRNAs) have been associated with lung cancer (LC), one of the most common cancers, but the underlying molecular mechanisms of the specific correlation with LC carcinogenesis remain unveiled. Quantitative real-time polymerase chain reaction was applied to examine the level of circZNF609. LC cells were transfected with silenced circZNF609 by siRNAs, and cell proliferation, migration, and apoptosis were evaluated to reflect the influences of circZNF609 knockdown in LC. Biotin-coupled circRNA capture, FISH and luciferase reporter assays were performed to study the relationship between circZNF609 and miR-142-3p. In current work, it was discovered that circZNF609 functioned as an onco-circRNA, which exhibited high expression as well as facilitated the proliferation and migration in LC cells. Next, we discovered that FUS RNA-binding protein, which could bind to the ZNF609 pre-mRNA, induced circZNF609 formation, and increased circZNF609 expression in LC. Furthermore, circZNF609 was verified to sponge and sequester miR-142-3p; circZNF609 enhanced LC cell proliferative and migrative ability via targeting miR-142-3p.