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Flotillin-1 (Flot-1) has been shown to regulate cancer progression, but the regulatory role of post-translational modifications of Flot-1 on cancers remains elusive. Herein, we show that up-regulated E2 conjugating enzyme UBC9 sumoylates Flot-1 at Lys-51 and Lys-195 with small ubiquitin-like modifier (SUMO)-2/3 modification in metastatic prostate cancer. Mitogen induced the sumoylation and nuclear translocation of Flot-1. The nuclear-targeted Flot-1 physically interacted with Snail, and inhibited Snail degradation through the proteasome in a sumoylation-dependent manner, thereby promoting epithelial-to-mesenchymal transition (EMT). Sumoylation of Flot-1 by up-regulated UBC9 in human metastatic prostate cancer tissues and prostate cancer cells with high metastatic potential positively correlated with the stabilization of Snail and the induction of Snail-mediated EMT genes in the metastatic prostate cancer. Our study reveals a new mechanism of sumoylated Flot-1-mediating Snail stabilization, and identifies a novel sumoylated Flot-1-Snail signaling axis in EMT of metastatic prostate cancer.

This study aimed to evaluate the instant inactivation effect of dielectric filter discharge (DFD) on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) aerosols. The filter consisted of one layer of ZrO 2 beads covered by aluminum mesh electrodes; this porous structure of DFD part generates filter-type surface discharge and reactive oxygen species. In a closed cylindrical chamber, DFD treated air flow containing SARS-CoV-2 aerosols, primarily composed of particle diameters of ≤ 1 μm. A polypropylene melt-blown filter collected the treated bioaerosols for inactivation analysis. Plaque and polymerase chain reaction assays showed that the aerosolized SARS-CoV-2 that passed through the filter were more than 99.84% inactivated with degradation of SARS-CoV-2 genes ( ORF1ab and E ). However, ozone exposure without DFD passage was not found to be effective for bioaerosol inactivation in plaque assay.

BackgroundIt is well known that hemodynamic stress may impact the recanalization of coiled aneurysms. One of the most common sites for aneurysms to develop is the posterior communicating artery (PcoA), the variants of which are defined by diameter ratios (PcoA/P1 segment).ObjectiveThis study was undertaken to investigate the impact of a fetal-type posterior cerebral artery (PCA) on recanalization of PcoA aneurysms after coil embolization based on matched-pair (fetal vs non-fetal PCA) analysis.MethodsA total of 480 consecutive PcoA aneurysms (PCA: fetal, n=156; non-fetal, n=324) subjected to coil embolization between January 2007 and June 2017 were selected for study. All lesions were followed for ≥6 months via radiologic imaging, grouped by adjacent PCAs as fetal (PcoA/P1 >1) or non-fetal (PcoA/P1 ≤1) type. Paired subjects were matched (1:1) for several relevant variables.ResultsOf the 480 coiled aneurysms, 159 (33.1%) showed recanalization (minor, 76; major, 83) in the course of follow-up (mean 33.8±21.9 months), developing significantly more often in fetal (37.8%) than in non-fetal (26.9%; p=0.020) PCA types. Once matched, however, 6-month and cumulative recanalization rates did not differ significantly by group (p=0.531 and p=0.568, respectively). Complications (hemorrhage, p=0.97; thromboembolism, p=0.94) during endovascular coil embolization also showed similar rates in these groups.ConclusionsThe chances of recanalization after coil embolization seem to be greater in PcoA aneurysms than in intracranial aneurysms overall, thus calling for careful follow-up monitoring. Surprisingly, PcoA type appeared unrelated in this regard.

Purpose Endovascular treatment of fenestration-related aneurysms (FAs) is prone to technical challenges, given the inherent complexities. Herein, we have analyzed FAs in terms of angioarchitectural characteristics and outcomes achieved through endovascular intervention. Methods Data accrued prospectively between January 2002 and July 2020 were productive of 105 FAs in 103 patients, each classifiable by the nature of incorporated vasculature as proximal portion, fenestrated limb, or distal end. Our investigation focused on clinical and morphological outcomes, with emphasis on technical aspects of treatment. Results The FAs selected for study originated primarily in anterior communicating artery (AcomA: 88/105, 83.8%), followed by basilar (7/105, 6.7%), anterior cerebral (4/105, 3.8%), and internal carotid (3/105, 2.8%) arteries. In nearly all locations, proximally situated aneurysms (43/105, 41%) were more frequent than aneurysms arising at distal ends (3/105, 2.8%), but the majority of AcomA lesions involved fenestrated segments (58/88, 65.9%); and most fenestrated channels (90/105, 85.7%) were asymmetric in size. Orifices of smaller fenestrated limbs were intentionally compromised during coil embolization in 23 aneurysms (21.9%), achieving complete (nâ¯= 19) or incomplete (nâ¯= 4) compromise, without resultant symptomatic ischemia. Saccular occlusion proved satisfactory in 77 lesions (73.3%). In follow-up monitoring of 100 patients for a mean period of 35.3⯱ 26.5 months, 17 instances of recanalization (17.0%) occurred (minor, 9; major, 8). There was no recanalization of aneurysms with compromised limbs. Conclusion Coil embolization of FAs is safe and effective, enabling tailored procedures that accommodate aberrant angioanatomic configurations. Compromise of a single limb during coiling also appears safe, conferring long-term protection from recanalization.

We have shown that insulin-like growth factor-1 (IGF-1) induces palmitoylation turnover of Flotillin-1 (Flot-1) in the plasma membrane (PM) for cell proliferation, after IGF-1 receptor (IGF-1R) signaling activation. However, the enzymes responsible for the turnover have not been identified. Herein, we show that acyl protein thioesterases-1 (APT-1) catalyzes Flot-1 depalmitoylation, and zinc finger DHHC domain-containing protein palmitoyltransferase-19 (ZDHHC-19) repalmitoylation of the depalmitoylated Flot-1 for the turnover in cervical cancer cells. The turnover prevented desensitization of IGF-1R via endocytosis and lysosomal degradation, thereby exerting excessive IGF-1R activation in cervical cancer cells. FLOT1, LYPLA1 and ZDHHC19 were highly expressed, and epithelial-to-mesenchymal transition (EMT)-inducing TIAM1 and GREM1 coordinately upregulated in malignant cervical cancer tissues. And blocking the turnover suppressed the EMT, migration, and invasion of cervical cancer cells. Our study identifies the specific enzymes regulating Flot-1 palmitoylation turnover, and reveals a novel regulatory mechanism of IGF-1-mediated cervical cancer progression.

Epithelial-mesenchymal transition (EMT) is implicated in tumor progression and EMT-inducing transcription factors play multifaceted roles; however, the molecular mechanisms underlying these processes are not well understood. Previously, we showed that ZEB2 acts cooperatively with the transcription factor SP1 to function as a transcriptional activator that promotes cancer cell invasion and survival, as well as angiogenesis. The present study reported a novel role for Zinc Finger E-Box Binding Homeobox 2 (ZEB2) in conferring immunosuppressive activity on cancer cells, as well as the underlying molecular mechanism. ZEB2 cooperated with SP1 to upregulate transcription of CD274 and CCL2 by interacting with the proximal SP1 element in their promoters. ZEB2-mediated programmed cell death 1 ligand 1 (PD-L1) upregulation on tumor cells inhibited T cell activation and cytokine secretion in a co-culture system. ZEB2 upregulated C-C motif chemokine ligand 2 (CCL2) secretion to promote migration of macrophages and drive polarization to an M2-like phenotype. ZEB2 suppressed the activity of tumor-infiltrating T cells in a syngeneic mouse tumor model. Furthermore, SUMOylation of ZEB2 by PC2 was required for efficient cooperation between ZEB2 and SP1, as well as for subsequent gene expression. Clinical data showed that ZEB2 expression is associated positively with expression of CD274 and CCL2. Expression of both ZEB2 and CD274 or CBX4 has prognostic significance for predicting survival of colon cancer patients. The present study demonstrated a previously unrecognized role for ZEB2: Direct modulation of the interaction between tumor cells and immune cells. Taken together, the data increased our understanding of the molecular mechanism underlying immunosuppression mediated by an EMT-inducing transcription factor.

With the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), disease prevention has become incredibly important. Consequently, mask and air-purifier use has increased. The filter is the core component of these items. However, most filter materials lack antimicrobial properties. Copper is a sustainable antimicrobial material. When copper is deposited onto the filter’s surface, the microorganisms that come into contact with it can be effectively inactivated. In this study, we used an oxygen ion beam with a controlled process temperature to treat filter surfaces with copper. This enabled a strong adhesion of at least 4 N/cm between the copper and the filter fibers without damaging them. Upon exposing the filter to bacteria (Staphylococcus aureus ATCC 6538, Klebsiella pneumoniae ATCC 4352, Escherichia coli ATCC 25922, and Pseudomonas aeruginosa ATCC 27853) for one hour, a >99.99% removal rate was attained; when the filter was exposed to SARS-CoV-2 virus for one hour, it inactivated more than 99%. These beneficial properties minimize the risk of secondary infections, which are significantly more likely to occur when a conventional filter is replaced or removed.

Purpose Endovascular treatment of fenestration-related aneurysms (FAs) is prone to technical challenges, given the inherent complexities. Herein, we have analyzed FAs in terms of angioarchitectural characteristics and outcomes achieved through endovascular intervention. Methods Data accrued prospectively between January 2002 and July 2020 were productive of 105 FAs in 103 patients, each classifiable by the nature of incorporated vasculature as proximal portion, fenestrated limb, or distal end. Our investigation focused on clinical and morphological outcomes, with emphasis on technical aspects of treatment. Results The FAs selected for study originated primarily in anterior communicating artery (AcomA: 88/105, 83.8%), followed by basilar (7/105, 6.7%), anterior cerebral (4/105, 3.8%), and internal carotid (3/105, 2.8%) arteries. In nearly all locations, proximally situated aneurysms (43/105, 41%) were more frequent than aneurysms arising at distal ends (3/105, 2.8%), but the majority of AcomA lesions involved fenestrated segments (58/88, 65.9%); and most fenestrated channels (90/105, 85.7%) were asymmetric in size. Orifices of smaller fenestrated limbs were intentionally compromised during coil embolization in 23 aneurysms (21.9%), achieving complete ( n  = 19) or incomplete ( n  = 4) compromise, without resultant symptomatic ischemia. Saccular occlusion proved satisfactory in 77 lesions (73.3%). In follow-up monitoring of 100 patients for a mean period of 35.3 ± 26.5 months, 17 instances of recanalization (17.0%) occurred (minor, 9; major, 8). There was no recanalization of aneurysms with compromised limbs. Conclusion Coil embolization of FAs is safe and effective, enabling tailored procedures that accommodate aberrant angioanatomic configurations. Compromise of a single limb during coiling also appears safe, conferring long-term protection from recanalization.

In reducing the high operating temperatures (≥800 °C) of solid-oxide fuel cells, use of protonic ceramics as an alternative electrolyte material is attractive due to their high conductivity and low activation energy in a low-temperature regime (≤600 °C). Among many protonic ceramics, yttrium-doped barium zirconate has attracted attention due to its excellent chemical stability, which is the main issue in protonic-ceramic fuel cells. However, poor sinterability of yttrium-doped barium zirconate discourages its fabrication as a thin-film electrolyte and integration on porous anode supports, both of which are essential to achieve high performance. Here we fabricate a protonic-ceramic fuel cell using a thin-film-deposited yttrium-doped barium zirconate electrolyte with no impeding grain boundaries owing to the columnar structure tightly integrated with nanogranular cathode and nanoporous anode supports, which to the best of our knowledge exhibits a record high-power output of up to an order of magnitude higher than those of other reported barium zirconate-based fuel cells. Protonic ceramic fuel cells are promising for energy applications, but maintaining high performance with long-term stability is an issue. Here the authors use a stable yttrium-doped barium zirconate electrolyte, achieving a power output one order of magnitude higher than existing protonic ceramic fuel cells.

Sarcopenia refers to the loss of muscle strength and mass in older individuals and is a major determinant of fall risk and impaired ability to perform activities of daily living, often leading to disability, loss of independence, and death. Owing to its impact on morbidity, mortality, and healthcare expenditure, sarcopenia in the elderly has become a major focus of research and public policy debates worldwide. Despite its clinical importance, sarcopenia remains under-recognized and poorly managed in routine clinical practice, partly owing to the lack of available diagnostic testing and uniform diagnostic criteria. Since the World Health Organization and the United States assigned a disease code for sarcopenia in 2016, countries worldwide have assigned their own disease codes for sarcopenia. However, there are currently no approved pharmacological agents for the treatment of sarcopenia; therefore, interventions for sarcopenia primarily focus on physical therapy for muscle strengthening and gait training as well as adequate protein intake. In this review, we aimed to examine the latest information on the epidemiology, molecular mechanisms, interventions, and possible treatments with new drugs for sarcopenia.