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Thus, this study provides an advanced polidocanol form by adding glycerol and Rose-Bengal to help existing sclerotherapy.We studied the migrations of young spotted seals during their annual cycle. In May 2017, we attached satellite tags (SPOT-293A) to three individuals (two underyearlings and one yearling) captured at their breeding ground in Peter the Great Bay, western Sea of Japan/East Sea. The operational time of the installed tags ranged from 207 to 333 days; a total of 27195 locations were uploaded. All three seals migrated east and further north along the coast of the mainland. The average daily migration speed of the seals ranged between 70 and 135 km/day. The yearling moved faster than the underyearlings. During early August, they arrived at their summer habitats, which were located in the northern part of the Tatar Strait (Sea of Japan/East Sea) for the underyearling seals and in Aniva Bay (Sea of Okhotsk) for the yearling seal. While moving from the place of tagging to the summer feeding grounds, the seals covered a distance of 2300 to 3100 km. From August to October, each seal permanently stayed within the same isolated area. The reverse migration of all three seals began in November. When the seals traveled south, they used the same routes by which they had moved north in the spring, but they moved at a faster speed. By December, two seals returned to their natal islands, where both stayed until their transmitters stopped sending signals (in March 2018).The application of reclaimed asphalt pavement has been widely encouraged due to its significant economic and environmental benefits. However, it is necessary to add rejuvenators to ensure its performance. Currently, bio-oil-based regenerants have attracted attention owing to their advantages of renewability and cost savings. The purpose of this paper is to study the use of recycled vegetable oil waste (R-oil) and recycled polyethylene particles for the regeneration and modification of aged asphalt. Physical, rheological, and chemical tests were used to figure out their influence on the pavement performance of aged asphalt. According to the physical test indices (penetration, softening point, and ductility), the performance of the rejuvenated asphalt was better than that of virgin asphalt. The workability and low-temperature performance of the rejuvenated asphalt were basically the same as those of virgin asphalt, and its fatigue and high-temperature performance were better. Infrared spectroscopy showed that R-oil diluted the high-polarity sulfoxide base of aged asphalt. Gel permeation chromatography showed that its molecular weight dispersion was better than that of aged asphalt. Therefore, R-oil and polyethylene can improve the pavement performance and chemical properties of aged asphalt.This study examined the effect of using a digital game-based language learning mobile application "Liulishuo" (speaking English fluently) to develop complexity, accuracy, and fluency of English monologic oral production among 30 English language learners in China. Monologic oral production was measured using the same narrative picture description task in pre- and post-tests. The learners followed the "Imitation of English Monologues" game 30 minutes each time, twice a week, for 20 weeks. The oral production was measured using six indices the mean words per T-unit and lexical density (i.e., complexity), the mean repairs and errors per 100 words (i.e., accuracy), speech rate and the mean length of pauses (i.e., fluency). The paired sample t-tests showed that the participants produced more complex monologic speech, had significantly fewer errors, and increased speech rate, but the mean repairs and mean length of pauses remained unchanged. The unchanged repairs and pauses could be possibly due to the non-proceduralized linguistic knowledge in oral production, which may require a more extended period of treatment. Our study showed positive effects of using a digital game-based language learning mobile application on the improvement of complexity, accuracy, and fluency of English language learners in China' monologic oral production with varying effects.BACKGROUND The most common primary malignant neoplasm of the kidneys in adults is renal cell carcinoma (RCC), which originates inside the renal cortex and accounts for 80-85% of all primary renal neoplasms. RCCs can spread to many organs, including the liver, lungs, bones, and brain. Disease is quiescent until the late stages of disease in the vast majority of patients. CASE REPORT We report a case of 63-year-old woman who presented to her surveillance check-up after a right radical nephrectomy 8 years ago. Computed tomography of the chest, abdomen, and pelvis (CT-CAP) revealed a hypervascular mass in the body of the pancreas measuring 1 cm, consistent with metastatic appearance. Therefore, the tumor board decision was to proceed with spleen-preserving distal pancreatectomy. The final histopathology result showed metastatic clear cell renal cell carcinoma (CCRCC) with negative resection margins. The patient currently is under regular follow-up. The latest CT-CAP was done at 1 year postoperatively, which showed no evidence of recurrence or metastasis. CONCLUSIONS Patients with RCCs can develop asymptomatic metastatic lesions years after complete oncological resection of the primary tumor. Furthermore, metastatic RCCs can be misdiagnosed as other primary tumors. Hence, a meticulous long-term follow-up is essential to ensure that recurrence or a new distant metastasis is not missed. RCCs are known for their poor response to chemotherapy and radiation therapy. However, the new targeted therapies have shown a good response rate. Nevertheless, complete oncological resection of the pancreatic metastasis remains the best treatment modality and is associated with a 5-year survival rate of 75%.2'3'-cGAMP is known as a nonclassical second messenger and small immune modulator that possesses potent antitumor and antiviral activities via inducing the stimulator of IFN genes-mediated (STING-mediated) signaling pathway. However, its function in regulating type 2 immune responses remains unknown. Therefore, we sought to determine a role of STING activation by 2'3'-cGAMP in type 2 inflammatory reactions in multiple mouse models of eosinophilic asthma. We discovered that 2'3'-cGAMP administration strongly attenuated type 2 lung immunopathology and airway hyperreactivity induced by IL-33 and a fungal allergen, Aspergillus flavus. Mechanistically, upon the respiratory delivery, 2'3'-cGAMP was mainly internalized by alveolar macrophages, in which it activated the STING/IFN regulatory factor 3/type I IFN signaling axis to induce the production of inhibitory factors containing IFN-α, which blocked the IL-33-mediated activation of group 2 innate lymphoid (ILC2) cells in vivo. We further demonstrated that 2'3'-cGAMP directly suppressed the proliferation and function of both human and mouse ILC2 cells in vitro. Taken together, our findings suggest that STING activation by 2'3'-cGAMP in alveolar macrophages and ILC2 cells can negatively regulate type 2 immune responses, implying that the respiratory delivery of 2'3'-cGAMP might be further developed as an alternative strategy for treating type 2 immunopathologic diseases such as eosinophilic asthma.Diarrhea is a major cause of global mortality, and outbreaks of secretory diarrhea such as cholera remain an important problem in the developing world. Current treatment of secretory diarrhea primarily involves supportive measures, such as fluid replacement. The calcium-sensing receptor (CaSR) regulates multiple biological activities in response to changes in extracellular Ca2+. The FDA-approved drug cinacalcet is an allosteric activator of CaSR used for treatment of hyperparathyroidism. Here, we found by short-circuit current measurements in human colonic T84 cells that CaSR activation by cinacalcet reduced forskolin-induced Cl- secretion by greater than 80%. Cinacalcet also reduced Cl- secretion induced by cholera toxin, heat-stable E. coli enterotoxin, and vasoactive intestinal peptide (VIP). The cinacalcet effect primarily involved indirect inhibition of cystic fibrosis transmembrane conductance regulator-mediated (CFTR-mediated) Cl- secretion following activation of CaSR and downstream phospholipase C and phosphodiesterases. In mice, cinacalcet reduced fluid accumulation by more than 60% in intestinal closed loop models of cholera and traveler's diarrhea. The cinacalcet effect involved both inhibition of CFTR-mediated secretion and stimulation of sodium-hydrogen exchanger 3-mediated absorption. These findings support the therapeutic utility of the safe and commonly used drug cinacalcet in CFTR-dependent secretory diarrheas, including cholera, traveler's diarrhea, and VIPoma.Osteosarcoma (OS) is an aggressive mesenchymal tumor for which no molecularly targeted therapies are available. We have previously identified TRAF2- and NCK-interacting protein kinase (TNIK) as an essential factor for the transactivation of Wnt signal target genes and shown that its inhibition leads to eradication of colorectal cancer stem cells. The involvement of Wnt signaling in the pathogenesis of OS has been implicated. The aim of the present study was to examine the potential of TNIK as a therapeutic target in OS. RNA interference or pharmacological inhibition of TNIK suppressed the proliferation of OS cells. Transcriptome analysis suggested that a small-molecule inhibitor of TNIK upregulated the expression of genes involved in OS cell metabolism and downregulated transcription factors essential for maintaining the stem cell phenotype. Metabolome analysis revealed that this TNIK inhibitor redirected the metabolic network from carbon flux toward lipid accumulation in OS cells. Using in vitro and in vivo OS models, we confirmed that TNIK inhibition abrogated the OS stem cell phenotype, simultaneously driving conversion of OS cells to adipocyte-like cells through induction of PPARγ. In relation to potential therapeutic targeting in clinical practice, TNIK was confirmed to be in an active state in OS cell lines and clinical specimens. From these findings, we conclude that TNIK is applicable as a potential target for treatment of OS, affecting cell fate determination.The role of insulin receptor (IR) activated by hyperinsulinemia in obesity-induced kidney injury is not well understood. We hypothesized that activation of kidney proximal tubule epithelial IR contributes to obesity-induced kidney injury. We administered normal-fat diet (NFD) or high-fat diet (HFD) to control and kidney proximal tubule IR-knockout (KPTIRKO) mice for 4 months. Renal cortical IR expression was decreased by 60% in male and female KPTIRKO mice. Baseline serum glucose, serum creatinine, and the ratio of urinary albumin to creatinine (ACR) were similar in KPTIRKO mice compared to those of controls. On HFD, weight gain and increase in serum cholesterol were similar in control and KPTIRKO mice; blood glucose did not change. HFD increased the following parameters in the male control mice renal cortical contents of phosphorylated IR and Akt, matrix proteins, urinary ACR, urinary kidney injury molecule-1-to-creatinine ratio, and systolic blood pressure. Renal cortical generation of hydrogen sulfide was reduced in HFD-fed male control mice.
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