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In this study, we demonstrate the emergence of NO2 gas sensing capabilities in the typically non-active NiWO4, a strongly correlated electron system (SCES), by introducing substitutional Fe at the Ni site. NiWO4 typically exhibits strong Coulombic repulsion between Ni atoms, resulting in a large band gap of over 3.0 eV and insulating behavior. This correlated behavior is clearly reflected in the significant increase of band gap when considering the Hubbard U correction for the cations, bringing the theoretical value closer to the observed value. The single-phase Fe0.5Ni0.5WO4 displays a notable shift in the [NiO6] symmetric vibration mode and an increase in magnetization. Additionally, theoretical calculations confirm the preservation of the wide band gap, with the Fe and O levels generated within the band gap. These findings indicate that Fe located in the Ni sites modulate Coulombic repulsion in NiWO4 SCES insulators. Unlike the poor gas-sensing performance of intrinsic NiWO4, Fe0.5Ni0.5WO4 exhibits a significant NO2 response (Rg/Ra) of 11 at 200°C than other gases and a limit of detection (LOD) of 46.4 ppb. This study provides a pathway for realizing gas-sensing performance in strongly correlated electron insulators with large band gaps through the introduction of dopant levels at the cation sites.

The demand for gas-sensing operations with lower electrical power and guaranteed sensitivity has increased over the decades due to worsening indoor air pollution. In this report, we develop room-temperature operational NH3 gas-sensing materials, which are activated through electron doping and crystal structure distortion effect in Fe0.2Ni0.8WO4. The base material, synthesized through solid-state synthesis, involves Fe cations substitutionally located at the Ni sites of the NiWO4 crystal structure and shows no gas-sensing response at room temperature. However, doping Na into the interstitial sites of Fe0.2Ni0.8WO4 activates gas adsorption on the surface via electron donation to the cations. Additionally, the hydrothermal method used to achieve a more than 70-fold increase in the surface area of structure-distorted Na-doped Fe0.2Ni0.8WO4 powder significantly enhances gas sensitivity, resulting in a 4-times increase in NH3 gas response (Rg/Ra). Photoluminescence and XPS results indicate negligible oxygen vacancies, demonstrating that cation contributions are crucial for gas-sensing activities in Na-doped Fe0.2Ni0.8WO4. This suggests the potential for modulating gas sensitivity through carrier concentration and crystal structure distortion. These findings can be applied to the development of room-temperature operational gas-sensing materials based on the cations.

Origami, the art of paper folding, addresses traditionally conflicting requirements for designing both powerful and low-cost haptic interfaces. As of today, there are no comprehensive reviews that cover origami-inspired haptic actuation, sensing, design processes, and fabrication. To fill this void, this paper summarizes existing origami-inspired haptic technologies in terms of workspace, degrees of freedom (DoF), power consumption, control methods, sensing, and actuation. The paper also presents an iterative design process for pattern generation and origami-inspired haptic characterization. Using this design process, we demonstrate a case study that involves the design, development, and evaluation of a novel syringe haptic interface for dental simulation. Our main findings suggest that origami-inspired haptics need more mathematically optimized and versatile design, as well as novel materials that offer a room for embedded sensing and actuation.

Abstract Background Despite evidence linking a safety culture with patient safety, the processes by which aspect of safety culture influences patient safety are not yet well understood. Thus, this study aimed to test a theoretical model of the relationships between three enabling factors (supervisor/clinical leader support for patient safety, hospital management support for patient safety, and psychological safety), and four enacting factors of patient safety culture (handoffs and information exchange, teamwork, error reporting intention, and withholding voice) with nurse assessments of patient safety. Methods A cross-sectional, descriptive correlational study design was used. Between May and June 2020, 526 nurses who provided direct care to patients in medical surgical units in three Korean hospitals completed an online survey that included four standardized scales or subscales. Structural equation modelling was used to test the hypothesized model. Results Among the three enabling factors, psychological safety was associated with all four enacting factors, and all enacting factors were associated with overall patient safety. Hospital management support was associated with all enacting factors except teamwork, but supervisor/clinical leader support was associated with only handoffs and information exchange, and withholding voice. Thus, teamwork was influenced only by psychological safety. Findings demonstrate overall support for the theoretical model of safety culture wherein enabling factors influence enacting factors which, in turn, lead to patient safety outcomes, but emphasize the critical nature of psychological safety among nursing staff. Conclusion This study provides further insight into the importance of support from hospital management and unit supervisors/clinical leaders for patient safety to motivate and enable hospital nurses to enact behaviours necessary for patient safety. However, such support must also take the form of enhancing psychological safety for nursing staff.

Objective This study aimed to evaluate the preference for antivascular endothelial growth factor (anti-VEGF) versus laser ablation therapy as primary and additional treatment in aggressive retinopathy of prematurity (ROP) and type 1 ROP.Methods This multicentre retrospective study was conducted at nine medical centres across South Korea. A total of 94 preterm infants with ROP who underwent primary treatment between January 2020 and December 2021 were enrolled. All eyes were classified as having type 1 ROP or aggressive ROP. Data on the zone, primary treatment chosen, injection dose, presence of reactivation and additional treatment were collected and analysed.Results Seventy infants (131 eyes) with type 1 ROP and 24 infants (45 eyes) with aggressive ROP were included. Anti-VEGF injection was selected as the primary treatment in 74.05% of the infants with type 1 ROP and 88.89% with aggressive ROP. Anti-VEGF injection was selected as the ROP was located in zone I or posterior zone II, and laser ablation was selected when it was located in zone II. The anti-VEGF injection doses varied and tended to be higher in the aggressive ROP group. Infants with aggressive ROP were 2.08 times more likely to require additional treatment than those with type 1 ROP. When ROP reactivation occurred, laser therapy was preferred as an additional treatment.Conclusion In Korea, the preference for anti-VEGF therapy or laser therapy differed according to ROP subtype, zone and primary or secondary treatment. These findings suggest that ROP treatment are considered according to ROP subtype, location and reactivation.

Acinar cell cystadenoma, also known as an acinar cystic transformation of the pancreas, is an exceedingly rare but benign pancreatic lesion. A 51-year-old woman was transferred to Inje University Busan Paik Hospital because of an 8 cm-sized calcified, multiseptated, and multilocular cystic mass in the pancreatic tail observed during abdominal CT performed at another hospital. The patient did not complain of abdominal pain or other symptoms, and her laboratory findings were normal. MRI showed that the cyst was not connected to the main pancreatic duct. A pancreatic serous cystadenoma was suspected, and a laparoscopic distal pancreatectomy was performed. The resected mass was composed of variable sized multilocular cysts with incomplete septa and focally lined by epithelium with acinar differentiation. The patient was diagnosed with acinar cell cystadenoma and is currently being followed up regularly. No complications or recurrences have been observed.

Abstract Many groups are working to improve the results of clinical allogeneic islet transplantation in a primate model. However, few studies have focused on the optimal islet dose for achieving normal glycemia without exogenous insulin after transplantation in primate models or on the relationship between rejection and islet amyloid polypeptide (IAPP) expression. We evaluated the dose (10,000, 20,000, and > 25,000 islet equivalents (IEQ)/kg) needed to achieve normal glycemia without exogenous insulin after transplantation using eleven cynomolgus monkeys, and we analyzed the characteristics exhibited in the islets after transplantation. 10,000 IEQ/kg (N = 2) failed to control blood glucose level, despite injection with the highest dose of exogenous insulin, and 20,000 IEQ/kg group (N = 5) achieved unstable control, with a high insulin requirement. However, 25,000 IEQ/kg (N = 4) achieved normal glycemia without exogenous insulin and maintained it for more than 60 days. Immunohistochemistry results from staining islets found in liver biopsies indicated that as the number of transplanted islets decreased, the amount of IAPP accumulation within the islets increased, which accelerated CD3+ T cell infiltration. In conclusion, the optimal transplantation dose for achieving a normal glycemia without exogenous insulin in our cynomolgus monkey model was > 25,000 IEQ/kg, and the accumulation of IAPP early after transplantation, which depends on the transplanted islet dose, can be considered one factor in rejection.

Fibroma of tendon sheath (FTS) is an uncommon mass that arises from the tendon sheath of extremities. The tumor typically affects adults between ages 20 and 50 years with a predominance in males. To date, growth hormone (GH) treatment is safe for children with Turner syndrome without risk factors and is accepted worldwide. This article reports the case of a nine-year-old female patient with Turner syndrome and FTS during GH treatment. She had been treated with daily subcutaneous GH to improve growth failure with a mean dose of 0.28 mg/kg/week and the level of insulin-like growth factor-1 was within the normal range. During the follow-up period, she complained about a mass in her hand, subsequently diagnosed as FTS. This report illustrates the clinical impact of Turner syndrome and GH treatments on the occurrence of this tumor through literature reviews. Further studies are needed to highlight the association between FTS and GH treatment, especially in Turner syndrome.

Abstract Background Posteroanterior and lateral cephalogram have been widely used for evaluating the necessity of orthognathic surgery. The purpose of this study was to develop a deep learning network to automatically predict the need for orthodontic surgery using cephalogram. Methods The cephalograms of 840 patients (Class ll: 244, Class lll: 447, Facial asymmetry: 149) complaining about dentofacial dysmorphosis and/or a malocclusion were included. Patients who did not require orthognathic surgery were classified as Group I (622 patients—Class ll: 221, Class lll: 312, Facial asymmetry: 89). Group II (218 patients—Class ll: 23, Class lll: 135, Facial asymmetry: 60) was set for cases requiring surgery. A dataset was extracted using random sampling and was composed of training, validation, and test sets. The ratio of the sets was 4:1:5. PyTorch was used as the framework for the experiment. Results Subsequently, 394 out of a total of 413 test data were properly classified. The accuracy, sensitivity, and specificity were 0.954, 0.844, and 0.993, respectively. Conclusion It was found that a convolutional neural network can determine the need for orthognathic surgery with relative accuracy when using cephalogram.

Abstract This paper proposes a convolutional neural network (CNN)-based deep learning model for predicting the difficulty of extracting a mandibular third molar using a panoramic radiographic image. The applied dataset includes a total of 1053 mandibular third molars from 600 preoperative panoramic radiographic images. The extraction difficulty was evaluated based on the consensus of three human observers using the Pederson difficulty score (PDS). The classification model used a ResNet-34 pretrained on the ImageNet dataset. The correlation between the PDS values determined by the proposed model and those measured by the experts was calculated. The prediction accuracies for C1 (depth), C2 (ramal relationship), and C3 (angulation) were 78.91%, 82.03%, and 90.23%, respectively. The results confirm that the proposed CNN-based deep learning model could be used to predict the difficulty of extracting a mandibular third molar using a panoramic radiographic image.

Introduction: Epithelial-mesenchymal transition (EMT) is a process of transdifferentiation where epithelial cells attain mesenchymal phenotype to gain invasive properties and thus, can contribute to metastasis of tumor cells. Objectives: The antimetastatic and antitumor efficacy of brusatol (BT) was investigated in a hepatocellular carcinoma (HCC) model. Methods: We evaluated the action of BT on EMT process using various biological assays in HCC cell lines and its effect on tumorigenesis in an orthotopic mouse model. Results: We found that BT treatment restored the expression of Occludin, E-cadherin (epithelial markers) while suppressing the levels of different mesenchymal markers in HCC cells and tumor tissues. Moreover, we observed a decline in the expression of transcription factors (Snail, Twist). Since the expression of these two factors can be regulated by STAT3 signaling, we deciphered the influence of BT on modulation of this pathway. BT suppressed the phosphorylation of STAT3Y705 and STAT3 depletion using siRNA resulted in the restoration of epithelial markers. Importantly, BT (1mg/kg) reduced the tumor burden in orthotopic mouse model with a concurrent decline in lung metastasis. Conclusions: Overall, our results demonstrate that BT interferes with STAT3 induced metastasis by altering the expression of EMT-related proteins in HCC model.

We propose and demonstrate a cascaded distributed antenna system (DAS) for efficiently extending the coverage of the mmWave-based 5G indoor network. For this, we exploit the radio-over-fiber (RoF) system based on the intermediate-frequency-over-fiber (IFoF) transmission technique that is enabled to add/drop the specific wavelength to the designated remote antenna unit (RAU) with using optical splitters and coarse wavelength division multiplexing (CWDM) filters. Moreover, the IFoF transceivers (TRx) perform the subcarrier multiplexing (SCM) in order to transmit 2 × 8 frequency allocation (FA) 5G signals per a single optical carrier, where each FA has 100 MHz bandwidth, leading each RAU to support 2 × 2 MIMO operation. Consequently, the cascaded structure allows for the adaptive and flexible configuration of the order of MIMO in accordance of the required data throughput at the specific indoor area. We introduce the cascaded IFoF link structure that can support up-to 13.5 dB optical power budget with following errorvector-magnitude (EVM) performance characterizations. And then we experimentally demonstrate the RoFbased cascaded DAS network, showing that more than 1 Gb/s total throughput can be achieved per a single antenna. Furthermore, we examine the use of avalanche photodiode (APD) to further increase the optical power budget (i.e., the coverage) based on experiment as well as simulation.

Context: Citrus unshiu Markovich (Rutaceae) peel is known to contain high concentrations of flavonoids and exerts pharmacological effects on antioxidant, anti-inflammation, allergies, diabetes and viral infections. Objective: Very little is known about potential activity of fermented dried Citrus unshiu peel extracts (FCU) using Bacillus subtilis, as well as its mechanism of action. We investigated the effects of FCU on the anti-inflammatory activities in murine macrophages and moisturizing effects in human keratinocytes. Materials and methods: We isolated the Bacillus subtilis from Cheonggukjang and FCU using these Bacillus subtilis to prepare samples. The cells were pre-treated with various extracts for 2 h and then induced with LPS for 22 h. We determined the NO assay, TNF-α, IL-6 and PGE2 in RAW 264.7 ells. The expression of SPT and Filaggrin by FCU treatment was measured in HaCaT cells. Result: We found that two types of FCU highly suppressed LPS-induced nitric oxide (NO) without exerting cytotoxic effects on RAW 264.7 cells (21.9 and 15.4% reduction). FCU inhibited the expression of LPS-induced iNOS and COX-2 proteins and their mRNAs in a concentration-dependent manner. TNF-α (59 and 30.9% reduction), IL-6 (39.1 and 65.6% reduction), and PGE2 secretion (78.6 and 82.5% reduction) were suppressed by FCU in LPS-stimulated macrophages. Furthermore, FCU can induce the production of hyaluronic acid (38 and 38.9% induction) and expression of Filaggrin and SPT in HaCaT keratinocyte cells. Discussion and conclusion: FCU potentially inhibits inflammation, improves skin moisturizing efficacy, and it may be a therapeutic candidate for the treatment of inflammation and dry skin.

Due to its high prevalence, screening for hepatic fibrosis in the low-risk population is called for action in the primary care clinic. However, current guidelines provide conflicting recommendations on populations to be screened. We aimed to identify the target populations that would most benefit from screening for hepatic fibrosis in clinical practice. This study examined 1288 subjects who underwent magnetic resonance elastography. The diagnostic performance of the Fibrosis-4 (FIB-4) index and NAFLD fibrosis score was compared in the following groups: (1) ultrasonography (USG)-diagnosed NAFLD, (2) elevated liver enzyme, (3) metabolic syndrome, (4) impaired fasting glucose, and (5) type 2 diabetes regardless of fatty liver. Decision curve analysis was performed to express the net benefit of groups over a range of probability thresholds (Pts). The diabetes group showed a better area under the receiver operating characteristic curve (AUROC: 0.69) compared with subjects in the USG-diagnosed NAFLD (AUROC: 0.57) and elevated liver enzyme (AUROC: 0.55) groups based on the FIB-4 index. In decision curve analysis, the diabetes group showed the highest net benefit for the detection of significant fibrosis across a wide range of Pts. Patients with diabetes, even in the absence of fatty liver, would be preferable for hepatic fibrosis screening in low-risk populations.

The purpose of this study was to determine whether convolutional neural networks (CNNs) can predict paresthesia of the inferior alveolar nerve using panoramic radiographic images before extraction of the mandibular third molar. The dataset consisted of a total of 300 preoperative panoramic radiographic images of patients who had planned mandibular third molar extraction. A total of 100 images taken of patients who had paresthesia after tooth extraction were classified as Group 1, and 200 images taken of patients without paresthesia were classified as Group 2. The dataset was randomly divided into a training and validation set (n = 150 [50%]), and a test set (n = 150 [50%]). CNNs of SSD300 and ResNet-18 were used for deep learning. The average accuracy, sensitivity, specificity, and area under the curve were 0.827, 0.84, 0.82, and 0.917, respectively. This study revealed that CNNs can assist in the prediction of paresthesia of the inferior alveolar nerve after third molar extraction using panoramic radiographic images.

Background: We compared the clinical outcomes of cardiac valve surgery in adult Jehovah’s Witness patients refusing blood transfusion to those in non-Jehovah’s Witness patients without any transfusion limitations. Methods: From 2005 to 2014, 25 Jehovah’s Witnesses (JW group) underwent cardiac valve surgery using a blood conservation strategy. Twenty-five matched control patients (non-JW group) were selected according to sex, age, operation date, and surgeon. Both groups were managed according to general guidelines of anticoagulation for valve surgery. Results: The operative mortality rate was 4.0% in the JW group and 0% in the non-JW group (p = 1.000). There was no difference in postoperative major complications between the groups (p = 1.000). The overall survival rate at 5 and 10 years was 85.6% ± 7.9% and 85.6% ± 7.9% in the JW group, respectively, and 100.0% ± 0.0% and 66.7% ± 27.2% in the non-JW group (p = 0.313). The valve-related morbidity-free survival rates (p = 0.625) and late morbidity-free survival rates (p = 0.885) were not significantly different between the groups. Conclusions: Using a perioperative strategy for blood conservation, cardiac valve surgery without transfusion had comparable clinical outcomes in adult patients. This blood conservation strategy could be broadly applied to major surgeries with careful perioperative care.

Precocious puberty, resulting in various physical, mental, and social changes, may have negative consequences for children and their families. In this study, we investigated whether there were differences between parental obesity, children’s and parent’s awareness of body shape, and dietary habits according to obesity levels in children with precocious puberty. A total of 193 children (93.3% girls) diagnosed with precocious puberty were classified into three groups according to their obesity levels. Negative body shape awareness and dissatisfaction were significantly higher in the obese group than in the normal-weight group, and parents were more likely to perceive their children as fat than the children themselves. In addition, the obesity rate of parents in the obese group was higher, and the body mass indexes of children and parents were significantly correlated. The nutrition quotients (NQs) were revealed to be significantly lower in the obese group with significantly lower scores. The significant factors related to obesity were the awareness of a fatty body image and dissatisfaction, obesity of the parents, and the NQ. The results show that obese children with precocious puberty were more vulnerable to negative lifestyle, family environment, and self-esteem effects than their normal-weight peers. Therefore, various interventions, such as environmental management, psychological support, and nutrition education, are needed that focus on the obesity and health conditions of children with precocious puberty.

Cancer persists as one of the leading causes of deaths worldwide, contributing to approximately 9.6 million deaths per annum in recent years. Despite the numerous advancements in cancer treatment, there is still abundant scope to mitigate recurrence, adverse side effects and toxicities caused by existing pharmaceutical drugs. To achieve this, many phytochemicals from plants and natural products have been tested against cancer cell lines in vivo and in vitro. Likewise, casticin, a flavonoid extracted from the Vitex species, has been isolated from the leaves and seeds of V. trifolia and V. agnus-castus. Casticin possesses a wide range of therapeutic properties, including analgesic, anti-inflammatory, antiangiogenic, antiasthmatic and antineoplastic activities. Several studies have been conducted on the anticancer effects of casticin against cancers, including breast, bladder, oral, lung, leukemia and hepatocellular carcinomas. The compound inhibits invasion, migration and proliferation and induces apoptosis (casticin-induced, ROS-mediated and mitochondrial-dependent) and cell cycle arrest (G0/G1, G2/M, etc.) through different signaling pathways, namely the PI3K/Akt, NF-κB, STAT3 and FOXO3a/FoxM1 pathways. This review summarizes the chemo-preventive ability of casticin as an antineoplastic agent against several malignancies.

Because of the essential role of signal transducer and activator of transcription 3 (STAT3) in proliferation, anti-apoptosis, and chemoresistance of multiple myeloma (MM), we investigated whether icariin, a prenylated flavonol glycoside, inhibits both constitutive and inducible STAT3 activation in human myeloma cell lines. We noted that icariin could block constitutive STAT3 phosphorylation as well as its nuclear translocation and DNA binding ability in U266 cells. Icariin also suppressed IL-6-induced STAT3 activation through the inhibition of upstream kinases (Janus activated kinase-1 and -2, and c-Src). We found that icariin downregulated the protein expression of STAT3 downstream target gene products such as Bcl-2, Bcl-xl, survivin, IAP-1/2, COX-2, VEGF, and matrix metallopeptidase 9 (MMP-9) in a concentration-dependent manner. Moreover, this flavonoid also exhibited the capacity to significantly induce apoptosis and suppress proliferation of MM cells. Interestingly, this agent also significantly potentiated the apoptotic effects of bortezomib through the suppression of STAT3 activation in MM cells. Altogether, our data indicates that the potential application of icariin as a STAT3 blocker in myeloma therapy.

STAT3 is a latent transcription factor that plays a vital role in the transmission of extracellular signal from receptors to the nucleus. It has been regarded as a master transcription factor due to its role in the regulation of a broad spectrum of genes, which can contribute to oncogenesis. Persistent activation of STAT3 and deregulation of its signaling has been observed in various human cancers including head and neck squamous cell carcinoma (HNSCC). In the present work, we identified brusatol (BT) as a potential blocker of STAT3 signaling pathway in diverse HNSCC cells. The data from the cell-based experiments suggested that BT-induced cytotoxicity and abrogated the activation of STAT3 and that of upstream kinases such as JAK1, JAK2, and Src. It reduced the levels of nuclear STAT3 and its DNA binding ability. BT treatment increased annexin-V-positive cells, promoted procaspase-3 and PARP cleavage, and downregulated the mRNA and protein expression of diverse proteins (Bcl-2, Bcl-xl, survivin) in HNSCC cells. Taken together, brusatol can function as a promising inhibitor targeting STAT3 signaling pathway in HNSCC.

Here, we determined the anti-neoplastic actions of formononetin (FT) against multiple myeloma (MM) and elucidated its possible mode of action. It was observed that FT enhanced the apoptosis caused by bortezomib (Bor) and mitigated proliferation in MM cells, and these events are regulated by nuclear factor-κB (NF-κB), phosphatidylinositol 3-kinase (PI3K)/AKT, and activator protein-1 (AP-1) activation. We further noted that FT treatment reduced the levels of diverse tumorigenic proteins involved in myeloma progression and survival. Interestingly, we observed that FT also blocked persistent NF-κB, PI3K/AKT, and AP-1 activation in myeloma cells. FT suppressed the activation of these oncogenic cascades by affecting a number of signaling molecules involved in their cellular regulation. In addition, FT augmented tumor growth-inhibitory potential of Bor in MM preclinical mouse model. Thus, FT can be employed with proteasomal inhibitors for myeloma therapy by regulating the activation of diverse oncogenic transcription factors involved in myeloma growth.

Aberrant activation of signal transducer and activator of transcription 3 (STAT3) has been documented in various malignancies including triple-negative breast cancers (TNBCs). The STAT3 transcription factor can regulate the different important hallmarks of tumor cells, and thus, targeting it can be a potential strategy for treating TNBC, for which only limited therapeutic options are available. In this study, we analyzed the possible effect of (-)-galiellalactone and its novel analogues, SG-1709 and SG-1721, and determined whether these agents exerted their antineoplastic effects by suppressing the STAT3 signaling pathway in TNBC cells. The two analogues, SG-1709 and SG-1721, inhibited both constitutive as well as inducible STAT3 phosphorylation at tyrosine 705 more effectively than (-)-galiellalactone, which indicates that the analogues are more potent STAT3 blockers. Moreover, SG-1721 not only inhibited nuclear translocation and DNA binding of STAT3 but also induced apoptosis, and decreased expression of diverse oncogenic proteins. Interestingly, SG-1721 also exhibited an enhanced apoptotic effect when combined with radiotherapy. Furthermore, in vivo administration of SG-1721 significantly attenuated breast xenograft tumor growth via decreasing levels of p-STAT3. Therefore, SG-1721 may be a promising candidate for further application as a pharmacological agent that can target STAT3 protein in treating TNBC.

The epithelial–mesenchymal transition (EMT) is a phenomenon that facilitates epithelial cells to acquire invasive potential to induce the initiation the metastatic spread of tumor cells. Here, we determined if brassinin (BSN) can affect the EMT process and deciphered its anti-cancer effects. BSN attenuated the levels of EMT linked genes and suppressed transforming growth factor beta (TGF-β)-mediated regulation of diverse mesenchymal markers. Additionally, BSN did increase the expression of various epithelial marker proteins in lung cancer cells. TGF-β-induced morphological changes and induction of invasive ability of tumor cells was also found to be abrogated by BSN treatment. Finally, BSN not only suppressed constitutive, but also inducible phosphoinositide-3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) phosphorylation in tumor cells.

Uranium metal particle dispersion plates have been proposed as targets for Molybdenum-99 (Mo-99) production to improve the radioisotope production efficiency of conventional low enriched uranium targets. In this study, uranium powder was produced by centrifugal atomization, and miniature target plates containing uranium particles in an aluminum matrix with uranium densities up to 9 g-U/cm3 were fabricated. Additional heat treatment was applied to convert the uranium particles into UAlx compounds by a chemical reaction of the uranium particles and aluminum matrix. Thus, these target plates can be treated with the same alkaline dissolution process that is used for conventional UAlx dispersion targets, while increasing the uranium density in the target plates

Isorhynchophylline (Rhy) is an active pharmacological component of Uncaria rhynchophylla that has been reported previously to exert significant antihypertensive and neuroprotective effects. However, very little is known about its potential anti-cancer activities. This study was carried out to evaluate the anticancer effects of Rhy against various human carcinoma cell lines. We found that Rhy exhibited substantial cytotoxic effect against human hepatocellular carcinoma HepG2 cells when compared with other human carcinoma cell lines including those of lung, pancreas, prostate, head and neck, breast, multiple myeloma, brain and renal cell carcinoma. Rhy induced apoptosis as characterized by accumulation of cells in sub G1 phase; positive Annexin V binding; activation of caspase-8, -9, and -3; and cleavage of PARP (poly-ADP ribose polymerase). This effect of Rhy correlated with the down-regulation of various proteins that mediated cell proliferation, cell survival, metastasis, and angiogenesis. Moreover, cell proliferation, migration, and constitutive CXCR4 (C-X-C chemokine receptor type 4), MMP-9 (Matrix metallopeptidase-9), and MMP-2 expression were inhibited upon Rhy treatment. We further investigated the effect of Rhy on the oncogenic cell signaling cascades through phospho-kinase array profiling assay. Rhy was found to abrogate phospho-p38, ERK, JNK, CREB, c-Jun, Akt, and STAT3 signals, but interestingly enhanced phospho-p53 signal. Overall, our results indicate, for the first time, that Rhy could exert anticancer and anti-metastatic effects through regulation of multiple signaling cascades in hepatocellular carcinoma cells.

Ginkgolic acid C 17:1 (GAC 17:1) extracted from Ginkgo biloba leaves, has been previously reported to exhibit diverse antitumor effect(s) through modulation of several molecular targets in tumor cells, however the detailed mechanism(s) of its actions still remains to be elucidated. Signal transducer and activator of transcription 3 (STAT3) is an oncogenic transcription factor that regulates various critical functions involved in progression of diverse hematological malignancies, including multiple myeloma, therefore attenuating STAT3 activation may have a potential in cancer therapy. We determined the anti-tumor mechanism of GAC 17:1 with respect to its effect on STAT3 signaling pathway in multiple myeloma cell lines. We found that GAC 17:1 can inhibit constitutive activation of STAT3 through the abrogation of upstream JAK2, Src but not of JAK1 kinases in U266 cells and also found that GAC can suppress IL-6-induced STAT3 phosphorylation in MM.1S cells. Treatment of protein tyrosine phosphatase (PTP) inhibitor blocked suppression of STAT3 phosphorylation by GAC 17:1, thereby indicating a critical role for a PTP. We also demonstrate that GAC 17:1 can induce the substantial expression of PTEN and SHP-1 at both protein and mRNA level. Further, deletion of PTEN and SHP-1 genes by siRNA can repress the induction of PTEN and SHP-1, as well as abolished the inhibitory effect of drug on STAT3 phosphorylation. GAC 17:1 down-regulated the expression of STAT3 regulated gene products and induced apoptosis of tumor cells. Overall, GAC 17:1 was found to abrogate STAT3 signaling pathway and thus exert its anticancer effects against multiple myeloma cells.