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The oxidation of copper and its surface oxides are gaining increasing attention due to the enhanced CO2reduction reaction (CO2RR) activity exhibited by partially oxidized copper among the copper-based catalysts. The “8” surface oxide on Cu(111) is seen as a promising structure for further study due to its resemblance to the highly active Cu2O(110) surface in the C–C coupling of the CO2RR, setting it apart from other O/Cu(111) surface oxides resembling Cu2O(111). However, recent X-ray photoelectron spectroscopy analysis challenges the currently accepted atomic structure of the “8” surface oxide, prompting a need for reevaluation. This study highlights the limitations of conventional methods when addressing such challenges, leading us to adopt global optimization search techniques. After a rigorous process to ensure robustness, the unbiased global minimum of the “8” surface oxide is identified. Interestingly, this configuration differs significantly from other surface oxides and also from previous “8” models while retaining similarities to the Cu2O(110) surface.

Lead-free antiferroelectric (AFE) ceramics have attracted increasing attention in recent years for application in high-power capacitors due to their environmental friendliness and high energy density. Among these ceramics, NaNbO3is noteworthy as one of the few lead-free perovskites displaying an AFE structure. However, despite the nature of AFE symmetry in NaNbO3with Nb antipolar state, in most cases, it behaves like a ferroelectric (FE) material with an external electric field and exhibits a single polarization-electric field (P-E) hysteresis loop. In order to enhance the antiferroelectricity, a composition modification strategy based on the tolerance factor (t) has been used to stabilize the AFE phase effectively. Yet, in the context of NaNbO3ceramics, the impact of doping on the evolution of antiferroelectricity has remained unexplored. Through first-principles calculations, we unveil how the chemical modification of NaNbO3enhances antiferroelectricity by investigating local distortions that favor the AFE state over the FE state in solid solutions. This adjustment in the relative stability between the FE state and AFE state results in a significant modification in the switching barrier in NaNbO3-based antiferroelectrics, ultimately leading to well-defined double polarization loops. This work offers a rationalized atomic-scale perspective on the AFE-FE phase transition in NaNbO3-based ceramics, aiming to contribute to the development of novel lead-free antiferroelectric oxides for energy storage applications.

Background The molecular chaperone heat shock protein 90 (Hsp90) participates in preserving the expression and activity of various oncoproteins, including hypoxia-inducible factor l[alpha] (HIF-1[alpha]) and Akt. Deguelin is a rotenoid with antitumor activities. We investigated whether the antitumor activities of deguelin involve the functional inhibition of Hsp90. Method Human xenograft tumors were generated in mice from H1299 (n = 6 per group) and A549 (n = 4 per group) non-small-cell lung cancer cells, UMSCC38 (n = 5 per group) head and neck cancer cells, MKN45 (n = 5 per group) stomach cancer cells, and PC-3 (n = 3 per group) prostate cancer cells. Tumor-bearing mice were treated with deguelin at 4 or 8 mg/kg or with vehicle (as a control) twice a day by oral gavage for 15-28 days. Protein expression was assessed by western blot analysis. Akt and Hsp90 were assessed by use of adenoviral vectors expressing constitutively active Akt or Hsp90. Binding of deguelin to Hsp90 was examined by docking analysis and by competition binding experiments with ATP-Sepharose beads. The proteasome inhibitor MG132 was used to investigate deguelin's effect on the induction of ubiquitin-mediated proteasomal degradation of HIF-1[alpha]. All statistical tests were two-sided. Results Deguelin bound to the ATP-binding pocket of Hsp90 and disrupted Hsp90 function, leading to ubiquitinmediated degradation of HIF-1[alpha] Administration of deguelin to xenograft-bearing mice statistically significantly decreased tumor growth by inducing apoptosis and decreasing the expression of Hsp90 client proteins, without detectable toxic effects. For example, at 15 days after the start of deguelin treatment, the volume of untreated control H1299 xenograft tumors was 798 [mm.sup.3] and that of xenograft tumors treated with deguelin at 4 mg/kg was 115.9 [mm.sup.3] (difference = 682.1 [mm.sup.3], ,5% confidence interval = 480.4 to 883.9 [mm.sup.3]; P Conclusions The antitumor activities of deguelin appear to involve its binding to the ATP-binding pocket of Hsp90, hich suppresses Hsp90 function.

Tobacco carcinogens induce Akt activation and lung carcinogenesis. We previously demonstrated that deguelin, a natural plant product, specifically inhibits the proliferation of premalignant and malignant human bronchial epithelial cells by blocking Akt activation. To evaluate the ability of deguelin to block tobacco carcinogen-induced lung tumorigenesis, we evaluated the in vivo effects of deguelin on Akt activation and lung tumorigenesis in transgenic mice in which Akt expression was induced by tamoxifen and in 4-(methylnitrosoamino)-1-(3pyridyl)-1-butanone (NNK)/beuzo(a) pyrene (BaP)-treated A/J mice. Deguelin suppressed Akt activation in vivo, as measured by immunohistochemistry and immunoblotting, and statistically significantly reduced NNK/BaP-induced lung tumor multiplicity, volume, and load in A/J mice, as monitored by microcomputed tomography image analysis, with no detectable toxicity. These results indicate that deguelin warrants consideration as a chemopreventive agent for early-stage lung carcinogenesis in a clinical lung cancer chemoprevention trial.

Background: The farnesyltransferase inhibitor SCH66336, in combination with other receptor tyrosine kinase inhibitors, inhibits the growth of non-small-cell lung cancer (NSCLC) cells. We examined whether SCH66336 inhibits angiogenesis of aerodigestive tract cancer cells. Methods: Antiangiogenic activities of SCH66336 against NSCLC, head and neck squamous cell carcinoma (HNSCC), and endothelial cells were examined with cell proliferation, capillary tube formation, and chick aorta (under hypoxic, normoxic, insulin-like growth factor I (IGF)--stimulated, and unstimulated conditions); reverse transcription--polymerase chain reaction; and western blot analyses. The specific roles of the ubiquitin-mediated proteasome machinery, mitogen-activated protein kinase (MAPK) and Akt pathways, and heat shock protein 90 (Hsp90) in the SCH66336-mediated degradation of hypoxia-inducible factor 1[alpha] (HIF-1[alpha]) were assessed with ubiquitin inhibitors and adenoviral vectors that express constitutively active MAP kinase kinase (MEK)1, constitutively active Akt, or Hsp90. Results: SCH66336 showed antiangiogenic activities and decreased the expression of vascular endothelial cell growth factor (VEGF) and HIF-1[alpha] in hypoxic, IGF-stimulated, and unstimulated aerodigestive tract cancer and endothelial cells. SCH66336 reduced the half-life of the HIF-1[alpha] protein, and ubiquitin inhibitors protected the hypoxia- or IGF-stimulated HIF-1[alpha] protein from SCH66336-mediated degradation. SCH66336 inhibited the interaction between HIF-1[alpha] and Hsp90. The overexpression of Hsp90, but not constitutive Akt or constitutive MEK, restored HIF-1[alpha] expression in IGF-stimulated or hypoxic cells but not in unstimulated cells. Conclusions: SCH66336 appears to inhibit angiogenic activities of NSCLC and HNSCC cells by decreasing hypoxia- or IGF-stimulated HIF-1[alpha] expression and to inhibit VEGF production by inhibiting the interaction between HIF-1[alpha] and Hsp90, resulting in the proteasomal degradation of HIF-1[alpha].

Background: The Omicron variant has become the most prevalent SARS-CoV-2 variant. Omicron is known to induce milder lesions compared to the original Wuhan strain. Fatal infection of the Wuhan strain into the brain has been well documented in COVID-19 mouse models and human COVID-19 cases, but apparent infections into the brain by Omicron have not been reported in human adult cases or animal models. In this study, we investigated whether Omicron could spread to the brain using K18-hACE2 mice susceptible to SARS-CoV-2 infection. Results: K18-hACE2 mice were intranasally infected with 1 × 105PFU of the original Wuhan strain and the Omicron variant of SARS-CoV-2. A follow-up was conducted 7 days post infection. All Wuhan-infected mice showed > 20% body weight loss, defined as the lethal condition, whereas two out of five Omicron-infected mice (40%) lost > 20% body weight. Histopathological analysis based on H&E staining revealed inflammatory responses in the brains of these two Omicron-infected mice. Immunostaining analysis of viral nucleocapsid protein revealed severe infection of neuron cells in the brains of these two Omicron-infected mice. Lymphoid depletion and apoptosis were observed in the spleen of Omicron-infected mice with brain infection. Conclusion: Lethal conditions, such as severe body weight loss and encephalopathy, can occur in Omicron-infected K18-hACE2 mice. Our study reports, for the first time, that Omicron can induce brain infection with lymphoid depletion in the mouse COVID-19 model.

Soft-robotic devices such as polymeric microgrippers offer the possibility for pick and place of fragile biological cargo in hard-to-reach conduits with potential applications in drug delivery, minimally invasive surgery, and biomedical engineering. Previously, millimeter-sized self-folding thermomagnetically responsive soft grippers have been designed, fabricated, and utilized for pick-and-place applications but there is a concern that such devices could get lost or left behind after their utilization in practical clinical applications in the human body. Consequently, strategies need to be developed to ensure that these soft-robotic devices are biodegradable so that they would disintegrate if left behind in the body. In this paper, we describe the photopatterning of bilayer gels composed of a thermally responsive high-swelling poly(oligoethylene glycol methyl ether methacrylate (Mn= 500)-bis(2-methacryloyl)oxyethyl disulfide), P(OEGMA-DSDMA), and a low-swelling poly(acrylamide-N,N′-bis(acyloyl)cystamine) hydrogel, in the shape of untethered grippers. These grippers can change shape in response to thermal cues and open and close due to the temperature-induced swelling of the P(OEGMA-DSDMA) layer. We demonstrate that the grippers can be doped with magnetic nanoparticles so that they can be moved using magnetic fields or loaded with chemicals for potential applications as drug-eluting theragrippers. Importantly, they are also biodegradable at physiological body temperature (∼37 °C) on the basis of cleavage of disulfide bonds by reduction. This approach that combines thermoresponsive shape change, magnetic guidance, and biodegradability represents a significant advance to the safe implementation of untethered shape-changing biomedical devices and soft robots for medical and surgical applications.

Bioelectronic devices that offer real-time measurements, biological signal processing, and continuous monitoring while maintaining stable performance are in high demand. The materials used in organic electrochemical transistors (OECTs) demonstrate high transconductance (GM) and excellent biocompatibility, making them suitable for bioelectronics in a biological environment. However, ion migration in OECTs induces a delayed response time and low cut-off frequency, and the adverse biological environment causes OECT durability problems. Herein, we present OECTs with a faster response time and improved durability, made possible by using a nanofiber mat channel of a conventional OECT structure. Poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS)/polyacrylamide (PAAm) nanofiber mat channel OECTs are fabricated and subjected to various durability tests for the first time based on continuous measurements and mechanical stability assessments. The results indicate that the nanofiber mat channel OECTs have a faster response time and longer life spans compared to those of film channel OECTs. The improvements can be attributed to the increased surface area and fibrous structure of the nanofiber mat channel. Furthermore, the hydrogel helps to maintain the structure of the nanofiber, facilitates material exchange, and eliminates the need for a crosslinker.

Rabbits are being increasingly used as companion animals, and in research; thus, the need for proper veterinary care for rabbits has increased. Surgical access is more challenging in rabbits under inhalation anesthesia compared to other animals, such as dogs and cats. Rabbits have a very narrow and deep oral cavity, large incisors, and a large tongue. Moreover, their temporomandibular joint has limited mobility, making it more difficult to approach the larynx. Various methods have been proposed to overcome this difficulty. The video laryngoscope was introduced in 1999 and is useful when airway intubation is unsuccessful using a conventional laryngoscope. We postulated that a video laryngoscope with a modified size 1 Macintosh blade (McGrath MAC Video Laryngoscope, Medtronic, USA) would facilitate the intubation of New Zealand White rabbits. Sixteen specific-pathogen-free male New Zealand White rabbits weighing 3.45–4.70 kg were studied. All rabbits were intubated using the video laryngoscope. Typically, a 3.0 mm endotracheal tube was used for rabbits weighing < 4 kg, while a 3.5 mm tube was used in those weighing > 4 kg. During surgery, anesthesia was well maintained, and there were no major abnormalities in the animals’ conditions. No rabbit developed breathing difficulties or anorexia after recovering from anesthesia. We established an intubation method using a video laryngoscope with a modified blade and stylet in the supine (ventrodorsal) position and successfully applied it in 16 rabbits. It is useful for training novices and for treating rabbits in veterinary hospitals with few staff members and animal research facilities where there are insufficient human resources.

Inflammatory bowel disease is a chronic inflammatory disorder occurring in the gastrointestinal track. However, the efficacy of current therapeutic strategies has been limited and accompanied by side effects. In order to eliminate the limitations, herbal medicines have recently been developed for treatment of IBD. Peuraria Lobata(Peuraria L.) is one of the traditional herbal medicines that have anti-inflammatory effects. Bioavailability of Peuraria L., which is rich in isoflavones, is lower than that of their fermented forms. In this study, we generated fermented Peuraria L.extracts (fPue) and investigated the role of fPue in inflammation and intestinal barrier function in vitroand in vivo. As the mice or intestinal epithelial cells were treated with DSS/fPue, mRNA expression of pro-inflammatory cytokines was reduced and the architecture and expression of tight junction proteins were recovered, compared to the DSS-treated group. In summary, fPue treatment resulted in amelioration of DSS-induced inflammation in the colon, and the disrupted intestinal barrier was recovered as the expression and architecture of tight junction proteins were retrieved. These results suggest that use of fPue could be a new therapeutic strategy for treatment of IBD.

The long propagation delay in underwater acoustic sensor networks renders existing media access control (MAC) protocols for terrestrial wireless networks undesirable. In this paper, we propose a new cooperative MAC protocol for underwater sensor networks that is used to detect objects and monitoring the environment. Our proposed MAC protocol tries to prevent data collisions through short term scheduling among neighbor nodes with exchange of short data message. By adapting the all sensor nodes to the transmitting schedules in which time is optimized we can minimize the collision rate between nodes. Through simulations, we show our proposed protocol can minimize data collisions and not only offers a higher throughput, but also indicates a better end-to-end delay.

Most antiangiogenic therapies currently being evaluated in clinical trials target the vascular endothelial growth factor pathway; however, the tumor vasculature can acquire resistance to vascular endothelial growth factor-targeted therapy by shifting to other angiogenesis mechanisms. Insulin-like growth factor binding protein-3 (IGFBP-3) has been reported to suppress tumor growth and angiogenesis by both IGF-dependent and IGF-independent mechanisms; however, understanding of its IGF-independent mechanisms is limited. We observed that IGFBP-3 blocked tumor angiogenesis and growth in non–small cell lung cancer and head and neck squamous cell carcinoma. Conditioned media from an IGFBP-3–treated non–small cell lung cancer cell line displayed a significantly decreased capacity to induce HUVEC proliferation and aortic sprouting. In cancer cells, IGFBP-3 directly interacted with Erk1/2, leading to inactivation of Erk1/2 and Elk-1, and suppressed transcription of early growth response protein 1 and its target genes, basic fibroblast growth factor and platelet-derived growth factor. These data suggest that IGF-independent Erk1/2 inactivation and decreased IGFBP-3–induced Egr-1 expression block the autocrine and paracrine loops of angiogenic factors in vascular endothelial and cancer cells. Together, these findings provide a molecular framework of IGFBP-3's IGF-independent antiangiogenic antitumor activities. Future studies are needed for development of IGFBP-3 as a new line of antiangiogengic cancer drug.

Background: Particulate matter (PM) is one of the principal causes of human respiratory disabilities resulting from air pollution. Animal models have been applied to discover preventive and therapeutic drugs for lung diseases caused by PM. However, the induced severity of lung injury in animal models using PM varies from study to study due to disparities in the preparation of PM, and the route and number of PM administrations. In this study, we established an in vivo model to evaluate PM-induced lung injury in mice. Results: PM dispersion was prepared using SRM2975. Reactive oxygen species were increased in MLE 12 cells exposed to this PM dispersion. In vivo studies were conducted in the PM single challenge model, PM multiple challenge model, and PM challenge with ovalbumin-induced asthma using the PM dispersion. No histopathological changes were observed in lung tissues after a single injection of PM, whereas mild to moderate lung inflammation was obtained in the lungs of mice exposed to PM three times. However, fibrotic changes were barely seen, even though transmission electron microscopy (TEM) studies revealed the presence of PM particles in the alveolar macrophages and alveolar capillaries. In the OVA-PM model, peribronchial inflammation and mucous hypersecretion were more severe in the OVA+PM group than the OVA group. Serum IgE levels tended to increase in OVA+PM group than in OVA group. Conclusions: In this study, we established a PM-induced lung injury model to examine the lung damage induced by PM. Based on our results, repeated exposures of PM are necessary to induce lung inflammation by PM alone. PM challenge, in the presence of underlying diseases such as asthma, can also be an appropriate model for studying the health effect of PM.

β-Catenin regulates important biological processes, including embryonic development and tumorigenesis. We have investigated the role ofβ-catenin in the regulation of the chondrocyte phenotype. Expression ofβ-catenin was high in prechondrogenic mesenchymal cells, but significantly decreased in differentiated chondrocytes both in vivo and in vitro. Accumulation of β-catenin by the inhibition of glycogen synthase kinase-3β with LiCl inhibited chondrogenesis by stabilizing cell-cell adhesion. Conversely, the low level of β-catenin in differentiated articular chondrocytes was increased by post-translational stabilization during phenotypic loss caused by a serial monolayer culture or exposure to retinoic acid or interleukin-1β. Ectopic expression of β-catenin or inhibition of β-catenin degradation with LiCl or proteasome inhibitor caused de-differentiation of chondrocytes. Transcriptional activation ofβ-catenin by its nuclear translocation was sufficient to cause phenotypic loss of differentiated chondrocytes. Expression pattern of Jun, a known target gene of β-catenin, is essentially the same as that of β-catenin both in vivo and in vitro suggesting that Jun and possibly activator protein 1 is involved in the β-catenin regulation of the chondrocyte phenotype.

When cells are first exposed to low levels of oxidative stress, they develop a resistance to a subsequent challenge of the same stress, even at higher levels. Although some protein(s) induced by oxidative stress likely mediated this adaptive response, the nature of these proteins is unknown. In this study, the total proteins extracted from human U937 leukemia cells exposed to 50 µM H2O2 for 24 h to induce an optimal protective response were analyzed by two-dimensional polyacrylamide gel electrophoresis. H2O2 treatment induced elevation of level of 34 protein spots. An analysis of these spots by a matrix associated laser desorption/ionization time-of-flight mass spectrometry identified 28 of the H2O2-induced proteins. These include proteins involved in energy metabolism, translation and RNA processing, chaperoning or mediating protein folding, cellular signaling, and redox regulation, as well as a mitochondrial channel component, and an actin-bundling protein. Therefore, it appears that the cellular adaptation to oxidative stress is a complex process, and is accompanied by a modulation of diverse cellular functions.

Signal transducer and activator of transcription 3 (STAT3) modulates a variety of genes involved in the regulation of critical functions, including cell proliferation, differentiation, apoptosis, angiogenesis, metastasis, and immunity. For many cancers, elevated levels of STAT3 signaling have been associated with a poor prognosis and the development of chemotherapy resistance. In this study, we investigated the inhibitory effects of a novel small-molecule inhibitor of STAT3, STX-0119, on the cell viability and survival of human lung cancer cells. STX-0119 inhibited activated STAT3 and the expression of STAT3-regulated oncoproteins such as c-Myc, cyclin D1, and survivin in lung cancer cells. STX-0119 also decreased the amount of STAT3 in the nuclear fraction as well as induced apoptosis of these lung cancer cell lines as evidenced by increases in apoptotic cells (Annexin V positive) and poly (ADP-ribose) polymerase (PARP) cleavage. The efficacy of STX-0119 in a mouse xenograft model was confirmed. However, a hematological side effect, which had not been previously reported, was observed. The level of white blood cells was significantly lowered when treated at the dose at which STX-0119 alone showed a significant tumor-suppressive effect. In conclusion, we suggest that STX-0119 may be a potent therapeutic agent against lung cancer. Consideration of the side effect suggests, it is necessary to study whether low-dose STX-0119 is effective for lung treatment with a combination of classic lung cancer therapeutics.

Bioabsorbable plate-screw systems are commonly used for the internal fixation of facial bone fractures. The anterior maxilla has a unique curved shape, and fractured bony fragments tend to be small and fragile; therefore, more effective rigid fixation can be achieved using a molded bioabsorbable mesh rather than a bioabsorbable plate. Herein, we describe 2 patients with cheek drooping after a rigid fixation of comminuted maxillary fracture using bioabsorbable meshes and screws.

Obesity is caused by an imbalance between energy intake and energy expenditure. Exercise is attracting attention as one of the ways to treat obesity. Exercise induces 'beige adipogenesis' in white adipose tissue, increasing total energy expenditure via energy dissipation in the form of heat. Also, beige adipogenesis can be induced by treatment with a beta-adrenergic receptor agonist. We developed a Cidea-dual reporter mouse (Cidea-P2ALuc2-T2A-tdTomato, Luciferase/tdTomato) model to trace and measure beige adipogenesis in vivo. As a result, both exercise and injection of beta-adrenergic receptor agonist induced beige adipogenesis and was detected through fluorescence and luminescence. We confirmed that exercise and beta-adrenergic receptor agonist induce beige adipogenesis in Cidea-dual reporter mouse, which will be widely used for detecting beige adipogenesis in vivo. [BMB Reports 2022; 55(4): 187-191].