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Protein phosphatase 6 is a Ser/Thr protein phosphatase and its catalytic subunit is Ppp6c. Ppp6c is thought to be indispensable for proper growth of normal cells. On the other hand, loss of Ppp6c accelerates growth of oncogenic Ras‐expressing cells. Although it has been studied in multiple contexts, the role(s) of Ppp6c in cell proliferation remains controversial. It is unclear how oncogenic K‐Ras overcomes cell proliferation failure induced by Ppp6c deficiency; therefore, in this study, we attempted to shed light on how oncogenic K‐Ras modulates tumor cell growth. Contrary to our expectations, loss of Ppp6c decreased proliferation, anchorage‐independent growth in soft agar, and tumor formation of oncogenic Ras‐expressing mouse embryonic fibroblasts (MEFs). These findings show that oncogenic K‐RasG12V cannot overcome proliferation failure caused by loss of Ppp6c in MEFs. Protein phosphatase 6 is a Ser/Thr protein phosphatase and its catalytic subunit is Ppp6c. Ppp6c is thought to be indispensable for proper growth of normal cells. On the other hand, loss of Ppp6c accelerates growth of oncogenic Ras‐expressing cells. Here we showed that oncogenic K‐RasG12V cannot overcome proliferation failure caused by loss of Ppp6c in mouse embryonic fibroblasts.

Background Placenta accreta is a major cause of massive obstetric hemorrhage during cesarean section. In recent years, pregnancy by in vitro fertilization-embryo transfer has been reported as a risk factor for placenta accreta. Case presentation A 36-year-old G1P0 woman with systemic lupus erythematosus became pregnant by frozen-thawed embryo transfer. Emergency cesarean section was performed under general anesthesia due to the diagnosis of non-reassuring fetal status. The placenta invaded the myometrium and completely covered the entire anterior uterine wall. Following birth, 3000 mL of blood loss required rapid fluid infusion and blood transfusion. Total hysterectomy was performed because the placenta could not be separated from the uterine wall. Histological examination revealed placenta accreta/increta. Conclusions When performing cesarean section on patients who have undergone frozen-thawed embryo transfer, preoperative examinations to assess for placenta accreta should be performed, and the anesthetic management should include sufficient planning for massive obstetric hemorrhage.

In Hokkaido potato fields, tubers produced from the plants with leaf curl symptoms caused by potato leaf roll virus (PLRV) were noted to be more densely covered with Rhizoctonia sclerotia. This observation led us to hypothesize that potato infected with PLRV would have an increased susceptibility to Rhizoctonia solani . To test this hypothesis, in a pot experiment, we inoculated PLRV-infected mother tubers with Rhizoctonia . As a result, PLRV-infected plants produced significantly fewer and smaller tubers than virus-free plants did, suggesting that PLRV-infected plants are more susceptible than virus-free plants to R. solani . Virus-free seed tubers should thus be used to reduce Rhizoctonia diseases.

Autoimmune encephalitis (AE) is clinically heterogeneous, and its early diagnosis and prognostication remain challenging. We aimed to determine whether cerebrospinal fluid (CSF) interleukin-6 (IL-6), a marker of central nervous system inflammation, can improve AE diagnosis and predict treatment outcomes. This retrospective cohort study (April 2014-August 2024) included patients who fulfilled the criteria for at least possible AE according to the 2016 Graus criteria and had their CSF IL-6 measured. The patients with infectious encephalitis were excluded. We collected clinical, laboratory, brain MRI, and tumor screening data. In a subset of AE patients with repeat CSF testing approximately 1 month after initiation of immunotherapy, we obtained post-treatment laboratory data, hospitalization length, and modified Rankin Scale (mRS) score at discharge. Diagnostic performance was assessed using receiver operating characteristic (ROC) analyses, and multivariable regression was used to identify predictors of discharge mRS score and hospitalization length. In antibody-negative AE, we also examined the association between post-treatment CSF IL-6 (CSF IL-6_1M) and the RAPID score, a prognostic tool for antibody-negative AE. The cohort comprised 55 AE cases (25 antibody-positive). ROC analysis of CSF parameters suggested that IL-6 showed the highest sensitivity, whereas the immunoglobulin G (IgG) index demonstrated the highest specificity. In an additional analysis that included CSF IL-6 as an additional inflammatory CSF parameter within the 2016 Graus criteria, the diagnostic sensitivity increased from 73% to 85% with a specificity of 88%. Among the 35 AE patients with post-treatment CSF measurements, multivariable regression showed that only CSF IL-6_1M significantly predicted both mRS score at discharge (p = 0.0444, 95% CI 0.00104-0.0702) and hospitalization length (p = 0.0143, 95% CI 0.425-3.13). Specifically, patients with CSF IL-6_1M of < 6 pg/mL had significantly shorter hospital stays than those with higher levels (generalized Wilcoxon test, p = 0.0361). CSF IL-6_1M was also significantly associated with the RAPID score (p = 0.0492). CSF IL-6 is a useful marker for early AE diagnosis and CSF IL-6_1M may serve as a practical biomarker for treatment response and prognosis, particularly for antibody-negative AE. Thus, CSF IL-6 and CSF IL-6_1M assessment may facilitate more precise, timely, and individualized therapeutic interventions.

The performance of base‐isolated buildings during collision with a retaining wall is examined via shaking table experiments, and a simplified numerical simulation method is proposed to predict structural response. Input ground motions are scaled to various amplitudes to examine the pounding effect of the superstructure under different collision velocities. The influence of wall rigidity on the superstructure response is examined by replacing rubber member attachments on the retaining wall with pads that have different rubber hardness values. Factors influencing the response of the superstructure during collision are identified from experimental results. A numerical simulation method that uses impulse forcing function to replace the collision simulation is evaluated. Time history analysis of a lumped‐mass model considering an impulse at the expected time and location of the collision are shown to efficiently predict the maximum floor acceleration and story shear force of the superstructure during collision without employing a collision analysis model. This research contributes towards developing simplified procedures for estimating the effects of collision in base isolated structures. A novel method for the time‐history analysis using the impulse was proposed, and it can reproduce the behavior of the superstructure during collision.

This study proposes a real‐time hybrid simulation method for semi‐active control using a shaking table. The method can be used for simulating a mid‐story isolated building. This simulation system uses a test specimen for the upper structure, a semi‐active damper that is installed in the base isolation layer on the shaking table, and a lumped mass system for a lower structure for the computer simulation. A rotary inertia mass damper that contains magnetorheological fluid is used in the semi‐active control. The semi‐active control cannot avoid a control time lag. This time lag is estimated by assuming a first‐order lag system. The experimental and analytical results considering a control time lag are compared in this study. The validity of the real‐time hybrid simulation is verified. This study proposes a real‐time hybrid simulation method using a shaking table for semi‐active control. The method can be applied to this simulation of a mid‐story isolated building. A rotary inertia mass damper encapsulating magnetorheological fluid is used in this semi‐active control.

Protein phosphatase 6 is a Ser/Thr protein phosphatase and its catalytic subunit is Ppp6c. Ppp6c is thought to be indispensable for proper growth of normal cells. On the other hand, loss of Ppp6c accelerates growth of oncogenic Ras‐expressing cells. Although it has been studied in multiple contexts, the role(s) of Ppp6c in cell proliferation remains controversial. It is unclear how oncogenic K‐Ras overcomes cell proliferation failure induced by Ppp6c deficiency; therefore, in this study, we attempted to shed light on how oncogenic K‐Ras modulates tumor cell growth. Contrary to our expectations, loss of Ppp6c decreased proliferation, anchorage‐independent growth in soft agar, and tumor formation of oncogenic Ras‐expressing mouse embryonic fibroblasts (MEFs). These findings show that oncogenic K‐Ras G12V cannot overcome proliferation failure caused by loss of Ppp6c in MEFs.

Glycosylation is a fundamental cellular process that has a dramatic impact on the functionality of glycoconjugates such as proteins or lipids and mediates many different biological interactions including cell migration, cellular signaling, and synaptic interactions in the nervous system. In spinal cord injury (SCI), all of these cellular processes are altered, but the potential contributions of glycosylation changes to these alterations has not been thoroughly investigated. We studied the glycosylation of injured spinal cord tissue from rats that received a contusion SCI. The N- and O-linked glycosylation was assessed at 3 and 14 days post-injury (DPI), and compared with uninjured control and time-matched sham spinal tissue. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) and tandem MS (MS/MS) were performed to analyze carbohydrate structures. Results revealed diverse and abundant glycosylation in all groups, with some carbohydrate structures differentially produced in SCI animals compared with uninjured controls and shams. One such change occurred in the abundance of the Sda structure, Neu5Ac-α-(2,3)-[GalNAc-β-(1,4)-]Gal-β-(1,4)-GlcNAc, which was increased in SCI samples compared with shams and non-injured controls. Immunohistochemistry (IHC) and western blot were performed on SCI and sham samples using the CT1 antibody, which recognizes the terminal trisaccharide of Sda with high specificity. Both of these metrics confirmed elevated Sda structure in SCI tissue, where IHC further showed that Sda is expressed mainly by microglia. The results of these studies suggest that SCI causes a significant alteration in N- and O-linked glycosylation.

Oncolytic vaccinia virus (OVV) has demonstrated appropriate safety profiles for clinical development. Although designed to kill cancer cells efficiently, OVV sensitivity varies in individual cancers, and predictive biomarkers of therapeutic responses have not been identified. Here we found that OVV was much more efficient in KFTX paclitaxel-resistant ovarian cancer cells compared to that in KFlow paclitaxel-sensitive cells. Microarray analysis identified long non-coding RNA urothelial carcinoma-associated 1 (UCA1) upregulation, which contributed to both enhanced paclitaxel resistance and OVV spread. In addition, UCA1 expression correlated with efficient OVV spread in other ovarian cell lines and primary cancer cell cultures. When host pathways underlying OVV spread were analyzed, differences were detected in the activation of the Rho GTPase Cdc42, suggesting that filopodia formation enhances OVV cell-to-cell spread and tumor migration. Moreover, we established a clinically relevant mouse model of peritoneal metastasis using KFTX or KFlow cells. Paclitaxel exerted anti-tumor effects on KFlow, but not KFTX, tumors. In mice bearing KFTX cells after paclitaxel failure, OVV treatment induced the regression of residual tumors and improved survival. Our findings demonstrated that UCA1 promotes OVV cell-to-cell spread in ovarian cancer, resulting in enhanced therapeutic outcome. [Display omitted]

Vaccinia virus (VV) has been utilized in oncolytic virotherapy, but it risks a host antiviral immune response. VV has an extracellular enveloped virus (EEV) form consisting of a normal virion covered with a host-derived outer membrane that enables its spread via circulation while evading host immune mechanisms. However, the immune resistance of EEV is only partial, owing to expression of the surface protein B5R, which has four short consensus repeat (SCR) domains that are targeted by host immune factors. To engineer a more effective virus for oncolytic virotherapy, we developed an enhanced immune-evading oncolytic VV by removing the SCRs from the attenuated strain LC16mO. Although deletion of only the SCRs preserved viral replication, progeny production, and oncolytic activity, deletion of whole B5R led to attenuation of the virus. Importantly, SCR-deleted EEV had higher neutralization resistance than did B5R-wild-type EEV against VV-immunized animal serum; moreover, it retained oncolytic function, thereby prolonging the survival of tumor-bearing mice treated with anti-VV antibody. These results demonstrate that partial SCR deletion increases neutralization escape without affecting the oncolytic potency of VV, making it useful for the treatment of tumors under the anti-virus antibody existence.