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ABSTRACT Objectives Methods Results Conclusion The role of glycogen synthase kinase (GSK)‐3β in adult T‐cell leukemia (ATL) caused by human T‐cell leukemia virus type 1 (HTLV‐1) is paradoxical and enigmatic. Here, we investigated the role of GSK‐3β and its potential as a therapeutic target for ATL.Cell proliferation/survival, cell cycle, apoptosis, and reactive oxygen species (ROS) generation were examined using the WST‐8 assay, flow cytometry, and Hoechst 33342 staining, respectively. Expression of GSK‐3β and cell cycle/death‐related proteins, and survival signals was analyzed using RT‐PCR, immunofluorescence staining, and immunoblotting.HTLV‐1‐infected T‐cell lines showed nuclear accumulation of GSK‐3β. GSK‐3β knockdown and its inhibition with 9‐ING‐41 and LY2090314 suppressed cell proliferation/survival. 9‐ING‐41 induced G2/M arrest by enhancing the expression of γH2AX, p53, p21, and p27, and suppressing the expression of CDK1, cyclin A/B, and c‐Myc. It induced caspase‐mediated apoptosis by decreasing the expression of Bcl‐xL, Mcl‐1, XIAP, c‐IAP1/2, and survivin, and increasing the expression of Bak and Bax. 9‐ING‐41 also induced ferroptosis and necroptosis, promoted JNK phosphorylation, and suppressed IKKγ and JunB expression. It inhibited the phosphorylation of IκBα, Akt, and STAT3/5, induced ROS production, and reduced glycolysis‐derived lactate levels.GSK‐3β functions as an oncogene in ATL and could be a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Common cutworm, Spodoptera litura is an important pest of corn causing significant crop yield loss. Synthetic insecticides have mostly been used to combat this pest, raising human and environmental health concerns. Plant growth-promoting rhizobacteria (PGPR) could compensate for or augment the harmful effects of agrochemicals. Herein, we aimed to assess whether PGPR-induced defenses in corn plants impact the host-plant selection behavior of S. litura. Headspace volatile organic compounds were analyzed using gas chromatography–mass spectrometry. Larvae fed inoculated corn exhibited lower weights and relative growth rate than noninoculated plants. Under choice experiments, PGPR-treated plants significantly reduced percentage leaf damage area and oviposition rate compared to untreated plants. Volatile organic compound ratio emission varied significantly between control and PGPR treatments, which, in part, explains feeding and oviposition deterrence in PGPR-treated plants. The results demonstrate that PGPR inoculation can enhance corn resistance to S. litura , making it a promising candidate for crop protection strategies. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to determine the role of dihydroorotate dehydrogenase (DHODH) in pathogenesis of adult T‐cell leukemia (ATL) caused by human T‐cell leukemia virus type 1 (HTLV‐1) and the effects of its inhibition on the de novo pyrimidine biosynthesis pathway. Methods: Cell proliferation, viability, cycle, and apoptosis were analyzed using WST‐8 assays, flow cytometry, and Hoechst 33342 staining. To elucidate the molecular mechanisms involved in the anti‐ATL effects of DHODH knockdown and inhibition, RT‐PCR and immunoblotting were conducted. Results: HTLV‐1‐infected T‐cell lines aberrantly expressed DHODH. Viral infection and the oncoprotein, Tax, enhanced DHODH expression, while knockdown of DHODH decreased HTLV‐1‐infected T‐cell growth. In addition, BAY2402234, a DHODH inhibitor, exerted an anti‐proliferative effect, which was reversed by uridine supplementation. BAY2402234 induced DNA damage and S phase arrest by downregulating c‐Myc, CDK2, and cyclin A and upregulating p53 and cyclin E. It also induced caspase‐mediated apoptosis by the upregulation of pro‐apoptotic and downregulation of anti‐apoptotic proteins. Furthermore, BAY2402234 induced caspase‐independent ferroptosis and necroptosis. It decreased phosphorylation of IKK, IκBα, PTEN, Akt, and its downstream targets, suggesting that inhibition of NF‐κB and Akt signaling is involved in its anti‐ATL action. Conclusion: These findings highlight DHODH as a potential therapeutic target for treating ATL. [ABSTRACT FROM AUTHOR]

A tube-block structure is proposed to realize tunable elastic wave transmission and resonance, consisting of periodically aligned circular tubes sandwiched and joined by two blocks. Finite element simulations for a unit structure are carried out to reveal the frequency dependence of the transmission behavior for the normal incidence of longitudinal and transverse waves in the tube-block structure. As a result, the transmission ratios are found to take multiple local maxima at different peak frequencies. Eigenfrequency analysis shows that the local resonances of the tube and the block surfaces occur at the peak frequencies in the transmission ratios. The peak frequencies originating from the local resonance of the tube depend on its radius and thickness, while those from the resonance on the block surfaces are in good agreement with the theoretical relation between the interval of the periodically aligned tubes and the wavelength of the Rayleigh wave. Furthermore, when the tube-block structure is subjected to compressive loading, the deformation shifts the peak frequencies of the transmission ratio corresponding to the local resonance of the tube. This result implies that the proposed structure has the potential to serve as a tunable meta-interface between solid blocks. [ABSTRACT FROM AUTHOR]

Adult T-cell leukemia (ATL), caused by HTLV-1, is the most lethal hematological malignancy. NEDD8-activating enzyme (NAE) is a component of the NEDD8 conjunction pathway that regulates cullin-RING ubiquitin ligase (CRL) activity. HTLV-1-infected T cells expressed higher levels of NAE catalytic subunit UBA3 than normal peripheral blood mononuclear cells. NAE1 knockdown inhibited proliferation of HTLV-1-infected T cells. The NAE1 inhibitor MLN4924 suppressed neddylation of cullin and inhibited the CRL-mediated turnover of tumor suppressor proteins. MLN4924 inhibited proliferation of HTLV-1-infected T cells by inducing DNA damage, leading to S phase arrest and caspase-dependent apoptosis. S phase arrest was associated with CDK2 and cyclin A downregulation. MLN4924-induced apoptosis was mediated by the upregulation of pro-apoptotic and downregulation of anti-apoptotic proteins. Furthermore, MLN4924 inhibited NF-κB, AP-1, and Akt signaling pathways and activated JNK. Therefore, neddylation inhibition is an attractive strategy for ATL therapy. Our findings support the use of MLN4924 in ATL clinical trials. [ABSTRACT FROM AUTHOR]

Background: Complete resection of presacral epidermoid cysts is recommended due to the potential for infection or malignancy. Transsacral and transabdominal approaches have been used to treat presacral tumors. However, there are no standard surgical approaches to resection. We present the case of a presacral epidermoid cyst in an obese male patient who underwent laparoscopic transabdominal resection. Case presentation: A 44-year-old man was referred to our hospital for treatment of a cystic tumor on the pelvic floor. Contrast-enhanced computed tomography revealed a 45 × 40-mm tumor on the left ventral side of the rectum, right side of the ischial spine, dorsal side of the seminal vesicles, and in front of the 5th sacrum. Enhanced magnetic resonance imaging revealed a multilocular cystic tumor with high and low signal intensities on T2-weighted images. The tumor was diagnosed as an epidermoid cyst. We considered the transsacral or laparoscopic approach and decided to perform a laparoscopic-assisted transabdominal resection since the tumor was in front of away from the sacrum, and a transsacral approach would result in a larger scar due to poor visibility from the thickness of the buttocks. The entire tumor was safely resected under laparoscopic guidance, because the laparoscopic transabdominal approach can provide a good and magnified field of view even in a narrow pelvic cavity with small skin incisions, allowing safe resection of the pelvic organs, vessels, and nerves while observing the tumor contour. Conclusions: The laparoscopic transabdominal approach is an effective method for treating presacral tumors in obese patients. [ABSTRACT FROM AUTHOR]

Background: Aortoesophageal fistula (AEF) is a rare but potentially life-threatening condition. The best treatment for the AEF due to esophageal carcinoma is still unresolved. Here, we report a rare case of AEF caused by esophageal cancer, that was successfully treated with emergency thoracic endovascular aortic repair (TEVAR), followed by esophagectomy and gastric tube reconstruction. Case presentation: A 64-year-old man presented with loss of consciousness and hypotension during chemoradiotherapy for advanced esophageal cancer. Enhanced computed tomography showed extravasation from the descending aorta into the esophagus at the tumor site. We performed emergency TEVAR for the AEF, which stabilized the hemodynamics. We then performed thoracoscopic subtotal esophagectomy on day 4 after TEVAR to prevent graft infection, followed by gastric tube reconstruction on day 30 after TEVAR. At 9 months after the onset of AEF, the patient continues to receive outpatient chemotherapy and leads a normal daily life. Conclusion: TEVAR is a useful hemostatic procedure for AEF. If the patient is in good condition and can continue treatment for esophageal cancer, esophagectomy and reconstruction after TEVAR should be performed to prevent graft infection and maintain quality of life. [ABSTRACT FROM AUTHOR]

We developed an oxidative synthetic method for α‐nitroketones from α‐substituted malononitriles and nitromethane under molecular oxygen. Only base and molecular oxygen are necessary without condensation reagents; this is an environmentally benign synthesis. [ABSTRACT FROM AUTHOR]

A case of cytoplasmic anaplastic lymphoma kinase (ALK)‐positive anaplastic large cell lymphoma (ALCL) initially involving the skin in a 44‐year‐old Japanese female is reported. The patient had a hemorrhagic erythematous tumor on the right thigh without any systemic symptoms. Pathology showed diffuse infiltration of CD30‐positive anaplastic large cells positive for epithelial membrane antigen and cytoplasmic ALK. The right inguinal lymph node showed infiltration of tumor cells in the marginal sinus. Only 2 weeks after radiation therapy, the patient developed multiple subcutaneous nodules and lung involvement. Even after subsequent multichemotherapy sessions, cutaneous recurrence occurred. Literature review of cytoplasmic ALK‐positive ALCL initially involving in the skin revealed that skin lesions were mostly seen in the extremities and that half of the cases developed extracutaneous lesions. Radiation and chemotherapy were effective for most cases. Inverse RT‐PCR identified a tumor necrosis factor receptor‐associated factor (TRAF)1‐ALK fusion in our case. Most reported cases with this translocation experienced repeated changes in chemotherapy, suggesting poorer prognosis. Although ALK‐positive ALCL generally responds well to chemotherapy, the presence of a TRAF1‐ALK fusion may suggest resistance to treatment. Detection of fusion partners of ALK is important for predicting clinical courses and deciding treatment options. [ABSTRACT FROM AUTHOR]