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Background/purpose Palbociclib is an FDA-approved cyclin-dependent kinase (CDK) 4/6 inhibitor that has been clinically proven to be effective in breast cancer. However, its use in oral cancer is not well researched. In this study, we investigated the inhibitory activity of palbociclib against oral squamous cell carcinoma (OSCC) cells and explored the mechanism of inhibition. Methods The effects of palbociclib on the cytotoxicity of OSCC cells were determined by MTT and colony formation assays. β-Galactosidase staining and cell-cycle analysis were used to determine palbociclib-induced cellular senescence and apoptosis of OSCC cells. Wound healing and transwell assays were performed to assess the effects of palbociclib treatment on migration and invasion ability of OSCC cells. Whole transcriptome sequencing was conducted to show the relationship between DNA damage repair of OSCC cells and palbociclib treatment. Palbociclib-induced DNA damage and repair capacity of OSCC cells were confirmed by comet assay and immunofluorescence confocal microscopy. Western blotting was used to verify the palbociclib-mediated changes in the CDK/pRB/c-Myc/CDC25A pathway. Finally, in vitro findings were tested in a mouse xenograft model. Results Our results showed that palbociclib can significantly inhibit the growth, migration, and invasive ability of OSCC cells and can accelerate cellular senescence and apoptosis. We found that palbociclib induced DNA damage and p21 expression through the p53-independent pathway, thereby downregulating c-Myc and CDC25A expression to inhibit cell cycle progression. In addition, palbociclib downregulated RAD51 expression to inhibit DNA damage repair ability of OSCC cell. Conclusion Palbociclib was found to have anti-oral squamous cell carcinoma activity and to simultaneously induce DNA damage and inhibit its repair, and to accelerated cellular senescence and apoptosis.

The advent of wearable and Internet of Things (IoT)‐connected technologies has enabled and brought to light the potential for a cornucopia of new health‐applied wearable devices. Given a dense implementation of RFID devices for medical and biomonitoring applications owing to the advent of the IoT, a proper way to simultaneously interrogate and gather useful information from an array of sensors is required. An attractive means to achieve this is through the employment of RADAR principles, specifically frequency‐modulated continuous wave. The use of additive manufacturing technologies–such as the commonly encountered inkjet‐printing technology or the popular forms of 3D printing approaches–enables, through their versatility, a surprising wealth of solutions to the limitations of the state‐of‐the‐art health wearables. This chapter presents new strategies enabling the powering of printed wearable systems using both legacy radio‐frequency wireless networks and upcoming 5G millimeter‐wave implementations.

Introduction: A voluntary cerebral palsy (CP) registry was established in 2017 to describe the clinical characteristics and functional outcomes of CP in Singapore. Methods: People with CP born after 1994 were recruited through KK Women’s and Children’s Hospital, National University Hospital and Cerebral Palsy Alliance Singapore. Patient-reported basic demographics, service utilisation and quality of life measures were collected with standardised questionnaires. Clinical information was obtained through hospital medical records. Results: Between 1 September 2017 and 31 March 2020, 151 participants were recruited. A majority (n=135, 89%) acquired CP in the pre/perinatal period, where prematurity (n=102, 76%) and the need for emergency caesarean section (n=68, 50%) were leading risk factors. Sixteen (11%) of the total participants had post-neonatally acquired CP. For predominant CP motor types, 109 (72%) had a spastic motor type; 32% with spastic mono/hemiplegia, 41% diplegia, 6% triplegia and 21% quadriplegia. The remaining (42, 27.8%) had dyskinetic CP. Sixty-eight (45.0%) participants suffered significant functional impairment (Gross Motor Functional Classification System levels IV–V). Most participants (n=102, 67.5%) required frequent medical follow-up (≥4 times a year). Conclusion: Optimisation of pre- and perinatal care to prevent and manage prematurity could reduce the burden of CP and their overall healthcare utilisation. Keywords: Cerebral palsy, functional outcomes, neonatal, registry

Background/purpose Honokiol and magnolol are natural components isolated from Magnolia bark that is used in traditional Chinese and Japanese herbal medicine. These two isomers are used as a component of dietary supplements and cosmetic products. In this study, we investigated the antimicrobial effect of honokiol and magnolol on pathogens causing oral diseases, their mechanism of action in biofilm formation and drug resistance of oral pathogens, and inflammatory regulation in mammalian cells. Methods We determined the minimum inhibitory concentration and minimum bactericidal concentration of honokiol and magnolol, and their stability at different temperatures and pH. We also evaluated their effect on biofilm formation, antibiotic-resistance gene expression in MRSA, and pro-inflammatory gene expression in mammalian cells. Results Honokiol showed better antimicrobial activity than magnolol. Both honokiol and magnolol showed stable bacterial inhibitory activity over a wide range of temperature and pH, reduced biofilm formation, and antibiotic resistance in oral pathogens. The biofilm formation- and antibiotic resistance-related gene expression was consistent with the respective phenotypes. Furthermore, these two isomers repressed the expression of pro-inflammatory genes in RAW264.7 cells. Conclusion Our study provides evidence of the potential application of honokiol and magnolol in dental medicine to cure or prevent oral diseases.

With the revolutionary developments in the fields of millimeter-wave (mm-wave) and Internet of Things (IoT) technologies and the billion devices promised to be implemented by the end of the decade, the realization of inexpensive, low-power, and intelligent systems is highly desirable. Additive manufacturing (AM) is a technology seeing widespread adoption due to its ability to enable rapid prototyping for iterative design; its reduced setup costs, facilitating economic small-batch production; and its ability to significantly reduce waste by-products, resulting in both environmental benefits as well as lower manufacturing costs. On the other hand, current lithography-based manufacturing technologies-a huge contributor to the growing RF and 5G wireless electronics industry-require extensive design verification, have longer turnaround times, and produce harmful byproducts. Although AM can offer time and cost benefits under the correct conditions, among the more impactful demonstrations of the manufacturing technology are the novel topologies enabled by design rules that allow feature sets, including nonorthogonal planes, conformal surfaces, multimaterial deposition, simultaneous thick- and thin-film deposition [1], complex 3D structures, integrated voids, and gradient index materials.

A broadband and miniaturized planar Yagi antenna-in-package (AiP) design for the fifth-generation (5G) wireless communication is proposed. The monopole taper radiator is adopted for the proposed Yagi antenna design to miniaturize the size, extend the bandwidth, and simplify the feeding network. The proposed AiP design is broadband enough to cover all three 5G New Radio bands simultaneously. The high-precision high-resolution multilayered glass packaging fabrication process with a new low-loss polymer material coating is adopted to realize the circuit. The operation band is from 24.25 to 40 GHz and the fractional bandwidth is 49%. The overall size for an antenna element is 3.05 mm × 5.56 mm, which is equal to 0.25 $\lambda _0$ × 0.45 $\lambda _0$ . The measured $S_{11}$ is smaller than $-$ 10 dB within the entire band and the gain is larger than 4 dBi. A two-by-one array using the proposed element is also demonstrated with a gain higher than 6.2 dBi within the entire band. Compared with previous works, the proposed AiP design can cover all 5G bands with a competitive size. Thus, it is suitable to be applied to massive arrays and easily integrated into packages to achieve compact system-in-package applications while resolving numerous current 5G challenges, including millimeter-wave (mm-wave) path loss and transmission loss.

Package-integrated and ultrathin power dividers with footprint smaller than unit $\lambda ~_{0}~^{\mathrm{ 2}}$ at the operating frequency of 28-GHz 5G new radio (NR) n257 and n258 bands are presented for the first time for small-cell applications. These power dividers are also configured as antenna arrays using endfire Yagi–Uda antenna elements. Utilizing minimal matching techniques, two-, three-, and four-element antenna arrays are designed without compromising on the bandwidth of operation or electrical performance. These thin-film power dividers exhibit a cross-sectional height of $147~\mu \text{m}$ and can be implemented in the top metal layer of front-end module packages. Panel-compatible semiadditive patterning (SAP) process is utilized to realize these structures, which yields precise line space dimensions required for millimeter-wave (mm-wave) applications. This results in power dividers with low added insertion loss, low VSWR, and minimal phase difference between output ports. The added insertion loss is 25% less than similar structures reported on integrated fan-out architectures. The antenna arrays exhibit high gain and efficiency. Excellent model-to-hardware correlation is observed with multiple coupons of the same structure. Package-integrated power dividers and antenna arrays based on ultrathin laminated glass substrate represent a major step toward realizing compact mm-wave antenna-in-package for 5G small-cell applications.

BACKGROUND Repeated endoscopic probe dilatation is the most preferred treatment for esophageal stenosis which may cause high levels of symptom distress in the patient's home rehabilitation stage. AIM To explore the changes in the symptom distress level and its correlation with the dilation effect in patients with esophageal carcinoma undergoing repeated dilations for lumen stenosis. METHODS The difference (R2-R1) between the diameter of the esophageal stenosis opening (R1) of the patients before dilation (R1) and after dilation (R2) was calculated to describe the extent and expansion of the esophageal stenosis before and after dilation. The M.D. Anderson Symptom Inventory was used to describe the symptom distress level of patients with dilation intermittence during their stay at home and to explore the correlation between the dilation effect and symptom distress level. RESULTS The diameter of the esophagus (R1) increased before each dilation in patients undergoing esophageal dilation (P < 0.05). The diameter (R2) increased after dilation (P < 0.05); the dilation effect (R2-R1) decreased with the number of dilations (P < 0.05). The total symptom distress score significantly increased with the number of dilations (P < 0.05). The symptom distress scores of the patients were negatively correlated (P < 0.05) with the previous dilation effect (R2-R1) and the esophageal diameter (R2) after the previous dilation. After the 1st to 4th dilations, the patient's symptom distress score was negatively correlated with the esophageal diameter (R12) before the next dilation, while there was no significant correlation (P > 0.05) with the other dilations. CONCLUSION In patients who have undergone repeated dilations, better effect stands for lower symptom distress level and the increase in symptom distress has a prompt effect on the severity of the next occurrence of restenosis.

Additive manufacturing (AM) technologies are emerging fabrication methods that are expanding rapidly in both industrial applications and academic research. The most popular AM technologies are inkjet printing and three‐dimensional (3D) printing. This chapter first provides a detailed introduction to different AM technologies, including inkjet printing, and discusses a variety of 3D printing technologies and their relevance to radio frequency applications. Next, the material characterization methods are given, and a hybrid fabrication process by integrating 3D printed packaging substrates and inkjet printing conductive traces are introduced. The chapter also introduces a broadband 5G antenna‐in‐package (AiP) design realized with AM and the respective measurement results. Finally, the summary and future visions of realizing complex 3D AiP and system‐on‐package design using AM are included.

Unlike conventional energy harvesters that are tuned to individual frequencies and are directional, the proposed wideband (23% fractional bandwidth), omnidirectional system harvests from all FM towers in vicinity. Hence, it does not require each sensor node to be carefully aligned to any one source and makes itself suited for mass-deployment applications such as precision agriculture and structural health monitoring. It harvests as much as 923 $\mu \text{W}$ on a rooftop at 1.54 km from an FM tower while retaining omnidirectionality partly thanks to the proposed antenna, which has a wider bandwidth and a higher measured gain (2.0 dBi) than the commercial reference wideband antenna. It achieves competitive efficiency (56%) and sensitivity (−17 dBm) while retaining wideband operation rather than being specifically optimized to individual frequencies. The system (fabricated on low-cost FR4) harvested outside ambient FM energy indoors at the same 1.54-km location to power a wireless sensor node without needing to shut down periodically.

In 2013, the Global Standards Initiatives on Internet of Things (IoT) defined the IoT as "a global infrastructure for the information society, enabling advanced services by interconnecting things based on existing and evolving interoperable information and communication technologies," with the term "thing" described as an object in the information world that is capable of being indentified and integrated into communication networks. Things in the IoT sense can, therefore, refer to a wide variety of devices for media, environmental monitoring, infrastructure management, manufacturing, energy management, medicine and health care, building and home automation, transportation, metropolitan-scale deployments, and consumer applications that demand accurate and reliable methods to sense changes, even in extremely rugged environments [1].

The purpose of this study was to evaluate the protective effect of swertiamarin on heart failure. To this end, a rat model of heart failure was established via left coronary artery ligation. Infarct size of heart tissues was determined using triphenyl tetrazolium chloride staining. Echocardiography was performed to evaluate cardiac function by the determination of ejection fraction, left ventricular internal dimension in diastole and left ventricular internal dimension in systole. The effect of swertiamarin on oxidative stress was evaluated via enzyme-linked immunosorbent assay. The mechanism was evaluated using western blot. Administration of swertiamarin reduced the infarct size of heart tissues in rat models with heart failure. Moreover, swertiamarin treatment ameliorated the cardiac function, increased ejection fraction and fractional shortening, decreased left ventricular internal dimension in diastole and left ventricular internal dimension in systole. Swertiamarin improved oxidative stress with reduced malondialdehyde, while increased superoxide dismutase, glutathione, and GSH peroxidase. Furthermore, nuclear-factor erythroid 2-related factor 2, heme oxygenase and NAD(P)H dehydrogenase (quinone 1) were elevated by swertiamarin treatment in heart tissues of rat model with heart failure. Swertiamarin alleviated heart failure through suppression of oxidative stress response via nuclear-factor erythroid 2-related factor 2/heme oxygenase-1 pathway providing a novel therapeutic strategy for heart failure.

In this article, the implementation of a machine learning (ML) strategy based on neural networks for the real-time range-adaptive automatic impedance matching of wireless power transfer (WPT) applications is discussed. This approach for the effective prediction of the optimal parameters of the tunable matching network and the selection of range-adaptive transmitter coils (Tx) is introduced in this article, aiming to achieve an effective automatic impedance matching over a wide range of relative distances. We propose a WPT system consisting of a tunable matching circuit and three Tx coils that have different radii and are simultaneously controlled by trained neural network models, returning an output set of matching capacitances as well as the optimal single transmitter among the three transmitters. In addition, a proof-of-concept prototype of the entire real-time range-adaptive automatic impedance-matching system is built and characterized. Finally, the proposed approach achieves a power transfer efficiency (PTE) of around 90% for ranges within 10–25 cm.

Background/Purpose: Mineral trioxide aggregate (Pro-Root MTA, PR-MTA) and bioceramics (iRoot® SP Injectable Root Canal Sealer, iR-BC) are used for making apical plugs used in apexification, repairing root perforations during root canal therapy, and treating internal root resorption. The purpose of the present in vitro study was to compare the biological effects of PR-MTA- and iR-BC-based dental sealers in the mouse macrophage cell line RAW 264.7. Methods: Cytotoxicity and cell proliferation were analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and cell hemocytometer, respectively. Protein expression of biomarkers of cell proliferation, autophagy, and osteoclast differentiation was determined by western blotting. Pro-inflammatory gene expression was examined using quantitative reverse transcription-PCR. Results: PR-MTA induced cytotoxicity in RAW 264.7 cells in a dose-dependent manner, and iR-BC was more cytotoxic than PR-MTA. Low-dose and short-term treatments of both PR-MTA and iR-BC induced RAW 264.7 cell proliferation. PR-MTA induced autophagy, whereas iR-BC did not. Neither PR-MTA nor iR-BC induced osteoclastogenesis. Pro-inflammatory genes were activated by both materials. However, the expression of inducible nitric oxide synthase (iNOS) mRNA was upregulated by iR-BC treatment, but not by PR-MTA treatment. Conclusion: Overall, dental PR-MTA and iR-BC induced pro-inflammatory genes but did not induce osteoclastogenesis in macrophages. PR-MTA and iR-BC induced M2 and M1 polarization, respectively, of RAW 264.7 cells. Keywords: Bioceramics (BC), Macrophage, Mineral trioxide aggregate (MTA), Osteoclastogenesis, Polarization

Introduction: The growing years are paramount for bone growth and mineral accrual. Children with long-term neurological condition (LTNC) have multiple risk factors for poor bone health and fragility fractures. In Singapore, this has not been studied systematically therefore we aim to evaluate the risk factors associated with fragilty fractures in children with LTNC. Methods: In this study, the search for fragility fractures was done by a retrospective review of patients with LTNC who are under follow-up in the Paediatric Neurology clinic and of patients who presented with fracture to the Paediatric Orthopaedic clinic. Information on patient’s demographics, medical history, intervention, biochemical bone markers and fracture history were collected. Results: In a tertiary clinic population of 136 patients with LTNC, 65% were dependent on mobility (GMFCS V), 60% were underweight and 60% were fed via gastrostomy or nasogastric tube, or on oral pureed diet. Furthermore, 60% were on anticonvulsants. The fracture rate was 3% in this population and was associated with low-impact activities such as transfer and dressing. Only 7.4% had a vitamin D level measured and 33% had calcium measured. Conclusion: The local prevalence of fragility fractures in children with LTNC who are under follow-up at the Neurology clinic was found to be 3%. Risk factors identified were limited ambulation and compromised nutritional status associated with feeding difficulty. Recommendations to optimize bone health in children with LTNC were made. These include promoting weight-bearing activities, looking out for underweight, avoiding vitamin D deficiency and ensuring adequate calcium intake.

Breath-holding spells are common non-epileptic events with onset between 6 months and 18 months of age that are usually triggered by minor painful events or strong emotions. Symptomatic treatments for breath-holding spells include iron supplementation, glycopyrrolate and piracetam. Hyperekplexia is a rare non-epileptic disorder characterized by generalized hypertonia and exaggerated startle. Prolonged stiffening triggered by startle can lead to desaturation, cardiac asystole and sudden infant death. It is commonly treated with Clonazepam and other anti-epileptic drugs. Piracetam has been reported to be effective in some anecdotal cases. We describe a case of an infant with frequent hyperekplexia-like breath-holding events who failed to respond adequately to glycopyrrolate, pace-maker insertion and clonazepam, who had marked improvement in his symptoms with high dose Piracetam. High dose Piracetam should be considered in infants with similar severe hyperekplexia-like/breath-holding events as it may be beneficial in ameliorating the acute and chronic course in these children.

Poly-ether-ether-ketone (PEEK) is an aesthetically pleasing natural material with good biocompatibility and shock absorption characteristics. The application of PEEK as a dental implant or abutment is expected to reduce the risk of failure and enhance aesthetics. Given that approximately one in 15 patients have allergic reactions to antibiotics, photodynamic therapy (PDT) has been gaining attention as an alternative treatment. Herein, the applicability of PEEK dental implants or abutments was investigated using material analyses, biofilm formation assay, and cell viability tests. The possible use of PDT for peri-implant mucositis was evaluated with the biofilm removal assay. The obtained data were analyzed based on the multivariate analysis of variance, paired t-tests, and the Pearson correlation coefficient (α = 0.05). The results revealed that PEEK was significantly less conducive to the formation of biofilms with S. mutans and A. actinomycetemcomitan (p &lt, 0.001) but exhibited comparable MG-63 (human osteoblast-like) osteoblast cell viability (p &gt, 0.05) to the other materials. PDT had similar antimicrobial efficacy and yielded similar biofilm removal effects to antibiotics. Altogether, these findings suggest that PEEK has attractive features and can serve as an alternative material for dental implants or abutments. In cases where peri-implant mucositis occurs, PDT can be used as an accessible therapeutic approach.

Incontinentia Pigmenti (IP) is a neurocutaneous syndrome, with malformations of cortical development and neurodevelopmental delay in some patients. Neonates with IP may develop acute encephalopathy with multifocal ischemic brain lesions with a speckled pattern on diffusion-weighted magnetic resonance imaging (MRI). We observed a similar MRI pattern in 4 female patients with IP who presented with childhood acute encephalopathy syndromes. These patients, aged 9 days to 13 years old, had acute neonatal encephalitis, Influenza A virus related acute necrotizing encephalopathy (ANE) of childhood, Influenza B virus related acute encephalopathy with biphasic seizures and late restricted diffusion (AESD) and acute disseminated encephalitis (ADEM) with transverse myelitis (TM). These lesions could possibly reflect the white matter changes in IP patients with encephalopathy.

Indoxyl sulfate (IS), a uremic toxin, causes chronic kidney disease (CKD) progression via its tubulotoxicity. After cellular uptake, IS directly induces apoptotic and necrotic cell death of tubular cells. Additionally, IS increases oxidative stress and decreases antioxidant capacity, which are associated with tubulointerstitial injury. Injured tubular cells are a major source of transforming growth factor-β1 (TGF-β1), which induces myofibroblast transition from residual renal cells in damaged kidney, recruits inflammatory cells and thereby promotes extracellular matrix deposition in renal fibrosis. Moreover, IS upregulates signal transducers and activators of transcription 3 phosphorylation, followed by increases in TGF-β1, monocyte chemotactic protein-1 and α-smooth muscle actin production, which participate in interstitial inflammation, renal fibrosis and, consequently, CKD progression. Clinically, higher serum IS levels are independently associated with renal function decline and predict all-cause mortality in CKD. The poor removal of serum IS in conventional hemodialysis is also significantly associated with all-cause mortality and heart failure incidence in end-stage renal disease patients. Scavenging the IS precursor by AST-120 can markedly reduce tubular IS staining that attenuates renal tubular injury, ameliorates IS-induced oxidative stress and rescues antioxidant glutathione activity in tubular epithelial cells, thereby providing a protective role against tubular injury and ultimately retarding renal function decline.

BackgroundThe immune checkpoint blockade (ICB) targeting programmed cell death-1 (PD-1) and its ligand (PD-L1) has been proved beneficial for numerous types of cancers, including non-small-cell lung cancer (NSCLC). However, a significant number of patients with NSCLC still fail to respond to ICB due to unfavorable tumor microenvironment. To improve the efficacy, the immune-chemotherapy combination with pemetrexed, cis/carboplatin and pembrolizumab (anti-PD-1) has been recently approved as first-line treatment in advanced NSCLCs. While chemotherapeutic agents exert beneficial effects, the underlying antitumor mechanism(s) remains unclear.MethodsPemetrexed, cisplatin and other chemotherapeutic agents were tested for the potential to induce PD-L1 expression in NSCLC cells by immunoblotting and flow cytometry. The ability to prime the tumor immune microenvironment was then determined by NSCLC/T cell coculture systems and syngeneic mouse models. Subpopulations of NSCLC cells responding differently to pemetrexed were selected and subjected to RNA-sequencing analysis. The key signaling pathways were identified and validated in vitro and in vivo.ResultsPemetrexed induced the transcriptional activation ofPD-L1(encoded byCD274) by inactivating thymidylate synthase (TS) in NSCLC cells and, in turn, activating T-lymphocytes when combined with the anti-PD-1/PD-L1 therapy. Nuclear factor κB (NF-κB) signaling was activated by intracellular reactive oxygen species (ROSs) that were elevated by pemetrexed-mediated TS inactivation. The TS−ROS−NF-κB regulatory axis actively involves in pemetrexed-induced PD-L1 upregulation, whereas when pemetrexed fails to induce PD-L1 expression in NSCLC cells, NF-κB signaling is unregulated. In syngeneic mouse models, the combinatory treatment of pemetrexed with anti-PD-L1 antibody created a more favorable tumor microenvironment for the inhibition of tumor growth.ConclusionsOur findings reveal novel mechanisms showing that pemetrexed upregulates PD-L1 expression and primes a favorable microenvironment for ICB, which provides a mechanistic basis for the combinatory chemoimmunotherapy in NSCLC treatment.

Background/Purpose Arecoline, the major alkaloid of areca nut, is known to induce reactive oxygen species (ROS) and DNA damage during oral cancer progression. This study aim to evaluate whether melatonin, an antioxidant, supported or repressed the arecoline-induced carcinogenesis phenotypes in oral squamous cell carcinoma (OSCC). Methods The cytotoxicity of arecoline or melatonin treatment alone and their co-treatment in the OSCC cell line OEC-M1 were analyzed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cell cycle, cell death, and total ROS production were analyzed using flow cytometer. The protein expression was determined using western blot analysis. The genotoxicity and mutation rate were determined using micronucleus assay and hypoxanthine phosphoribosyl transferase (HPRT) forward mutation assay, respectively, in CHO-K1 cells. The ataxia telangiectasia mutated (ATM) promoter activity and DNA repair ability were determined through reporter assay. Results The result showed that both the arecoline and melatonin induced ROS production and antioxidant enzymes expression. Melatonin treatment enhanced arecoline-induced ROS production, cytotoxicity, G2/M phase arrest, and cell apoptosis in OSCC cells. On the other hand, melatonin treatment activated DNA repair activity to reverse arecoline-induced DNA damage and mutation. Conclusion These results indicated that melatonin is a potential chemopreventive agent for betel quid chewers to prevent OSCC initiation and progression.

Stem cell transplantation has been a promising treatment for peripheral arterial diseases in the past decade. Stem cells act as living bioreactors of paracrine factors that orchestrate tissue regeneration. Prestimulated adipose-derived stem cells (ADSCs) have been proposed as potential candidates but have been met with challenges in activating their secretory activities for clinical use. Here, we propose that tethering the ADSC surface with nanoparticles releasing tumor necrosis factor α (TNFα), named nanostimulator, would stimulate cellular secretory activity in situ. We examined this hypothesis by complexing octadecylamine-grafted hyaluronic acid onto a liposomal carrier of TNFα. Hyaluronic acid increased the liposomal stability and association to CD44 on ADSC surface. ADSCs tethered with these TNFα carriers exhibited up-regulated secretion of proangiogenic vascular endothelial growth factor and immunomodulatory prosteoglandin E2 (PGE(2)) while decreasing secretion of antiangiogenic pigment epithelium-derived factors. Accordingly, ADSCs tethered with nanostimulators promoted vascularization in a 3D microvascular chip and enhanced recovery of perfusion, walking, and muscle mass in a murine ischemic hindlimb compared to untreated ADSCs. We propose that this surface tethering strategy for in situ stimulation of stem cells would replace the costly and cumbersome preconditioning process and expedite clinical use of stem cells for improved treatments of various injuries and diseases.

Epidermal growth factor receptor (EGFR) is frequently overexpressed and mutated in non-small cell lung cancer (NSCLC), which is the major type of lung cancer. The EGFR tyrosine kinase inhibitors (TKIs) are the approved treatment for patients harboring activating mutations in the EGFR kinase. However, most of the patients treated with EGFR-TKIs developed resistance. Therefore, the development of compounds exhibiting unique antitumor activities might help to improve the management of NSCLC patients. The total flavonoids from Daphne genkwa Sieb. et Zucc. have been shown to contain antitumor activity. Here, we have isolated a novel flavonoid hydroxygenkwanin (HGK) that displays selective cytotoxic effects on all of the NSCLC cells tested. In this study, we employed NSCLC cells harboring EGFR mutations and xenograft mouse model to examine the antitumor activity of HGK on TKI-resistant NSCLC cells. The results showed that HGK suppressed cancer cell viability both in vitro and in vivo. Whole-transcriptome analysis suggests that EGFR is a potential upstream regulator that is involved in the gene expression changes affected by HGK. In support of this analysis, we presented evidence that HGK reduced the level of EGFR and inhibited several EGFR-downstream signalings. These results suggest that the antitumor activity of HGK against TKI-resistant NSCLC cells acts by enhancing the degradation of EGFR.

Pathologic diagnosis of nasopharyngeal carcinoma (NPC) can be challenging since most cases are nonkeratinizing carcinoma with little differentiation and many admixed lymphocytes. Our aim was to evaluate the possibility to identify NPC in nasopharyngeal biopsies using deep learning. A total of 726 nasopharyngeal biopsies were included. Among them, 100 cases were randomly selected as the testing set, 20 cases as the validation set, and all other 606 cases as the training set. All three datasets had equal numbers of NPC cases and benign cases. Manual annotation was performed. Cropped square image patches of 256 &times, 256 pixels were used for patch-level training, validation, and testing. The final patch-level algorithm effectively identified NPC patches, with an area under the receiver operator characteristic curve (AUC) of 0.9900. Using gradient-weighted class activation mapping, we demonstrated that the identification of NPC patches was based on morphologic features of tumor cells. At the second stage, whole-slide images were sequentially cropped into patches, inferred with the patch-level algorithm, and reconstructed into images with a smaller size for training, validation, and testing. Finally, the AUC was 0.9848 for slide-level identification of NPC. Our result shows for the first time that deep learning algorithms can identify NPC.

Wireless sensors are pervasive today for applications spanning environmental sensing, safety, health, structural integrity, smart homes, and smart cities. Implementations of wireless sensor networks and Internet of Things (IoT) systems have typically relied on power supplied by batteries, which have a limited lifetime and pose the increased burden on users of replacing or manually recharging them to keep devices up and running.

Grading scales for the surgical difficulty of laparoscopic cholecystectomy (LC) had been mentioned but not common. In order to clarify and compare grading score for the surgical difficulty of LC, we conducted this study to present our grading scoring method by measuring the time of laparoscopic cholecystectomy.

ObjectiveTo describe characteristics and course of a large UK cohort of children with moyamoya from multiple centers and examine prognostic predictors.MethodsRetrospective review of case notes/radiology, with use of logistic regression to explore predictors of outcome.ResultsEighty-eight children (median presentation age 5.1 years) were included. Thirty-six presented with arterial ischemic stroke (AIS) and 29 with TIA. Eighty had bilateral and 8 unilateral carotid circulation disease; 29 patients had posterior circulation involvement. Acute infarction was present in 36/176 hemispheres and chronic infarction in 86/176 hemispheres at the index presentation. Sixty-two of 82 with symptomatic presentation had at least one clinical recurrence. Fifty-five patients were treated surgically, with 37 experiencing fewer recurrences after surgery. Outcome was categorized as good using the Recovery and Recurrence Questionnaire in 39/85 patients. On multivariable analysis, presentation with TIA (odds ratio [OR] 0.09, 95% confidence interval [CI] 0.02–0.35), headache (OR 0.10, 95% CI 0.02–0.58), or no symptoms (OR 0.08, 95% CI 0.01–0.68) was less likely to predict poor outcome than AIS presentation. Posterior circulation involvement predicted poor outcome (OR 4.22, 95% CI 1.23–15.53). Surgical revascularization was not a significant predictor of outcome.ConclusionsMoyamoya is associated with multiple recurrences, progressive arteriopathy, and poor outcome in half of patients, especially with AIS presentation and posterior circulation involvement. Recurrent AIS is rare after surgery. Surgery was not a determinant of overall outcome, likely reflecting surgical case selection and presentation clinical status.

A novel wearable and flexible energy autonomous on-body sensing network is proposed featuring full operability through energy harvesting from a hand-held 464.5-MHz UHF two-way talk radio. Three different functions are provided utilizing the hand-held two-way talk radio as the only energy source for our proposed system. There are two types of energy harvesters (EHs) proposed for the presented system. The first EH that is mounted on the sensing capable backscattering RFID tags harvests the 464.5-MHz signal energy to drive the tags; the second EH that can be worn on hands harvests the same 464.5-MHz signal to produce both the dc power and the carrier signal. The second EH is more efficient than conventional ambient RF energy harvesting architectures because for the first time, both the dc and the second harmonics generated by the rectifier are utilized to enable two additional functions. The generated second harmonic is used to interrogate backscattering RFID tags for on-body sensing, while the dc power is used to power an RF amplifier in order to enhance the second harmonic to effectively extend the sensing and communication range. For the proof-of-concept demonstration, the measured dc and the second harmonic, 929 MHz, output power from the proposed EH are 17.5 and 1.43 dBm, respectively, while a two-way talk radio is 9 cm away. The measured second harmonic output power is increased to 13 dBm utilizing the harvester-powered RF amplifier, and the reading range of the custom backscattering sensor tag is extended to more than 70 m. Also, the interrogation of multiple sensor tags and the wireless detection of ammonia gas utilizing an inkjet printed flexible ammonia sensor are demonstrated showing the wide range of applications of the proposed approach.

Melatonin is the primary pineal hormone that relays light/dark cycle information to the circadian system. It was recently reported to exert intrinsic antitumor activity in various cancers. However, the regulatory mechanisms underlying the antitumor activity of melatonin are poorly understood. Moreover, a limited number of studies have addressed the role of melatonin in hepatocellular carcinoma (HCC), a major life-threatening malignancy in both sexes in Taiwan. In this study, we investigated the antitumor effects of melatonin in HCC and explored the regulatory mechanisms underlying these effects. We observed that melatonin significantly inhibited the proliferation, migration, and invasion of HCC cells and significantly induced the expression of the transcription factor FOXA2 in HCC cells. This increase in FOXA2 expression resulted in upregulation of lncRNA-CPS1 intronic transcript 1 (CPS1-IT1), which reduced HIF-1α activity and consequently resulted in the suppression of epithelial-mesenchymal transition (EMT) progression and HCC metastasis. Furthermore, the results of the in vivo experiments confirmed that melatonin exerts tumor suppressive effects by reducing tumor growth. In conclusion, our findings suggested that melatonin inhibited HCC progression by reducing lncRNA-CPS1-IT1-mediated EMT suppression and indicated that melatonin could be a promising treatment for HCC.

// Po-Yu Yang 1, 2, 4, * , Pei-Ling Hsieh 3, * , Tong Hong Wang 5, 6, 7, * , Cheng-Chia Yu 1, 2, 3, 4, * , Ming-Yi Lu 1, 2, 3, 4 , Yi-Wen Liao 1 , Tzu-Hsin Lee 1, 2 , Chih-Yu Peng 1, 2, 3, 4 1 School of Dentistry, Chung Shan Medical University, Taichung, Taiwan 2 Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan 3 Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan 4 Oral Medicine Center, Chung Shan Medical University, Taichung, Taiwan 5 Tissue Bank, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan 6 Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Tao-Yuan, Taiwan 7 Graduate Institute of Health Industry Technology, Chang Gung University of Science and Technology, Tao-Yuan, Taiwan * These authors contributed equally to this work Correspondence to: Chih-Yu Peng, email: cyp@csmu.edu.tw Keywords: oral squamous cell carcinomas, andrographolide, miR-218, cancer stemness Received: October 31, 2016 Accepted: November 23, 2016 Published: December 01, 2016 ABSTRACT Current evidence suggests that oral cancer stem cells (OCSCs) possess high tumorigenic and metastatic properties as well as chemo- and radioresistance. In this study, we demonstrated that andrographolide, the main bioactive component in the medicinal plant Andrographis, significantly reduced oncogenicity and restored radio-sensitivity of ALDH1 + CD44 + OCSCs. Mechanistic studies showed that andrographolide treatment increased the expression of microRNA-218 (miR-218), leading to the downregulation of Bmi1. We showed that knockdown of miR-218 in ALDH1 − CD44 − non-OCSCs enhanced cancer stemness, while silencing of Bmi1 significantly counteracted it. Furthermore, we found tumor growth was reduced in mice bearing xenograft tumors after andrographolide treatment via activation of miR-218/Bmi1 axis. Together, these data demonstrated that the inhibition of tumor aggressiveness in OCSCs by andrographolide was mediated through the upregulation of miR-218, thereby reducing Bmi1 expression. These findings suggest that andrographolide may be a valuable natural compound for anti-CSCs treatment of OSCC.

This paper reports the first demonstration of antenna-in-package and seamless antenna-to-receiver signal transitions on panel-scale processed ultra-thin glass substrates, for high-speed 5G communication standards in the 28 GHz band. To demonstrate the benefits of g 1 ass for 5 G communications, package-integrated antennas with feedlines were modeled and designed on ultra-thin glass substrates laminated with low-loss dielectric thin films for highest bandwidth and efficiency in the mm-wave bands. The measured results for a miniaturized Yagi-Uda antenna, transmission lines, and through-package vias showed superior dimensional stability and good agreement with the simulated values on 100 µm glass substrates. The results showed low interconnect signal losses with a microstrip line loss of 0.108 dB/mm, and a through-package via loss of 0.095 dB/TPV. The Yagi-Uda antenna fabricated on glass substrates showed a center frequency of 28.18 GHz with a fractional bandwidth of 21.1%. The antenna also presented a wide-angle main lobe at the target frequency range implying good coverage of signal transmitting and receiving. The performance of package-integrated antenna, feedlines, through-package vias, and transmission lines on glass substrates was benchmarked in comparison to other 5G substrate technologies such as organic laminate, ceramic-based substrates, or fan-out wafer level packaging.

The present study investigated the time-of-day effects on acute response and chronic adaptations to resistance exercise (RE) in rat skeletal muscle. Male rats were divided into Early and Late training groups and performed climbing RE during the first or last hour of the active (dark) period, respectively. The first experiment measured muscle mass and strength after a 10-week climbing training program. The second experiment examined inflammatory signaling response and satellite cell (SC) numbers following an acute bout of RE. The results showed no significant differences between rats training at early and late active periods in relative muscle weight (muscle-to-weight ratio), cross sectional area (CSA) and strength. The acute study observed increased STAT1 phosphorylation, oxidative stress (2-thiobarbituric acid reacting substances, TBARS), SCs (Pax7+), neutrophils (His48+) and macrophages (CD68+), and decreased interleukin 6 (IL-6) protein expression of skeletal muscle relative to non-exercise control after an acute bout of RE. Interestingly, higher plasma IL-6 and STAT3 phosphorylation response was observed in the late training group when compared to the early training group after an acute bout of RE. The results of this study suggest that animals can adapt to resistance training at different time-of-day, by modulating inflammatory signaling of skeletal muscle.

The overview of recent advances in additive manufacturing techniques such as different metallization methods is introduced. A fully printed 5G reconfigurable antenna is proposed. The fabrication process using 3D and inkjet printer is characterized. The flexible 3D printed material is used as the base substrate and the inkjet printed silver traces are used as the conductive traces. The operational frequency range of the proposed antenna can be changed by applying pressure on the flexible to change the shape of the structure. Thus, reconfigurability can be achieved. The center of the operational frequency can be adjusted between 26 GHz to 28.9 GHz. The adjusting rate is 11 %.

A novel multilayer flexible packaging fabrication process using only additively manufacturing techniques including inkjet and 3 dimensional (3D) printing is proposed. The 3D printed ramp structures and inkjet printed transmission lines on top of that are suitable for mm-wave inter-layer connections because lower parasitics are induced to the system. Moreover, a system-on-package (SoP) design for backscattering radio-frequency identification (RFID) is proposed. It has to be stressed, that an RF energy harvester operated at 26 GHz which is embedded inside the packaging using additively manufacturing techniques is proposed for the first time. The output voltage of the harvested energy at a distance of 20 cm away from the source is 0.9 V with transmitted equivalent isotropically radiated power (EIRP) equal to 59 dBm. The harvested energy is large enough to power the TS3001 timer for backscattering and can support all energy requirements of the entire SoP design so that the SoP design is fully autonomous and no external board or components are required. The system size can be shrunk to package level and thus paving the way for a multitude of novel miniaturized autonomous modules for wearable, IoT, and 5G applications.

This work describes the implementation of a machine learning (ML) strategy based on the neural network for real-time range-adaptive automatic impedance matching of Wireless Power Transfer (WPT) applications. This approach for the effective prediction of the optimal parameters of the tunable matching network and classification range-adaptive transmitter coils (Tx) is introduced in this paper aiming to achieve an effective automatic impedance matching over a wide range of relative distances. We propose a WPT system consisting of a tunable matching circuit and 3 Tx coils which have different radius controlled by trained neural network models. The feedforward neural network algorithm was trained using 220 data and classifier’s in pattern recognition accuracy were characterized. The proposed approach achieves a Power transfer efficiency (PTE) around 90% for ranges within 10 to 25cm, is reported.

Oral submucous fibrosis (OSF) is characterized by abnormal collagen deposition. It is a precancerous disorder and transforms into a malignant tumor in 1.5–15% of all cases. Symptoms include submucous fibrosis, ulceration, xerostomia, a burning sensation, and restricted mouth opening. All of these greatly interfere with patient quality of life. The present review introduces OSF from a molecular perspective and summarizes what is known about its underlying mechanisms, diagnostic biomarkers, and therapeutic interventions. In addition to the aggressive treatment of OSF, its prevention is also important. Future research should, therefore, focus on improving the oral health literacy of the patients susceptible to OSF.

Additive packaging has garnered an increasing amount of interest due to its promising industrial scalability, and its materials and topological patterning versatility. The effort described in this paper benchmarks the performance of such a packaging approach relative to its commercial counterpart for the integration of devices operating in the mm-wave 5G bands. The approach first demonstrates the fully-inkjet-printed integration of a tunnel diode—a component empowering a plethora of emerging applications in these frequency bands—before comparing it to its pre-packaged counterpart. In an effort to enable an accurate and quantifiable comparison, the measured properties of the two integrated diodes were de-embedded using a TRL extraction method before their lumped element models were determined and compared. The comparison demonstrates a general and often significant reduction in all the packaging parasitics, up to 53%, using the additive approach. This result adds upon the growing evidence supporting the superior electrical performance of additive packaging for the integration of mm-wave dies and strengthens the appeal for the development of ultra-compact and ultra-high-performance fully-additively-manufactured mm-wave Systems in Package (SiP).

This paper demonstrates package-integrated power dividers with footprint smaller than the free-space wavelength corresponding to the operating frequency of 28 GHz band for 5G Antenna-in-Package (AiP), by utilizing precision low-loss redistribution layers (RDL) on glass substrates for highly-integrated mixed-signal systems. Two configurations of power dividers with two-way and three-way equal power split are modeled, designed and fabricated on glass substrates with thin-film build-up layers. This approach combines the benefits of ceramic and low-loss polymers for electrical performance, and silicon-like dimensional stability of glass for precision panel-scale patterning. Multilayered RDL with sub-20 micron features are utilized to design innovative power divider topologies with benefits in terms of low added insertion loss (

The prognostic value of programmed death-ligand 1 (PD-L1) expression in nasopharyngeal carcinoma (NPC) is controversial, with previous studies showing conflicting results. Most NPCs in endemic areas are Epstein-Barr virus (EBV)-positive. Our aim was to evaluate the clinical significance of PD-L1 expression in EBV-positive NPC. We retrospectively analyzed PD-L1 expression on tumor cells (TCs) and immune cells (ICs) by immunohistochemistry in 208 EBV-positive NPC patients who underwent radiotherapy (203 with concurrent chemotherapy). The percentages of TCs and ICs expressing PD-L1 were evaluated respectively. There was a strong correlation between local recurrence and low PD-L1 expression on ICs (p = 0.0012), TCs (p = 0.013) or both (p = 0.000044), whereas all clinical parameters had no influence on local recurrence. Using multivariate analysis, low PD-L1 expression on ICs was an independent adverse prognostic factor (p = 0.0080, HR = 1.88, 95% CI = 1.18&ndash, 3.00) for disease-free survival. High PD-L1 expression on both ICs and TCs was an independent favorable prognostic factor (p = 0.022, HR = 0.46, 95% CI = 0.24&ndash, 0.89) for overall survival. We show for the first time that low PD-L1 expression on ICs and TCs strongly correlates with local recurrence in EBV-positive NPC patients after radiation-based therapy. A simple immunohistochemical study for PD-L1 can identify patients prone to local recurrence, and such patients might benefit from more aggressive treatment in future clinical trials.

Recently, increasing numbers of long noncoding RNAs (lncRNAs), with both oncogenic and tumor-suppressive potential, have been found to be aberrantly expressed in various human cancers. However, the function of lncRNAs in hepatocellular carcinoma (HCC) progression remains largely unknown. In this study, we performed a comprehensive microarray analysis of lncRNA expression using human HCC specimens. After validation in 119 human HCC tissues, we identified a novel tumor suppressor lncRNA, CPS1 intronic transcript 1 (CPS1-IT1). To elucidate the clinical significance of CPS1-IT1 in HCC, correlations between CPS1-IT1 levels, clinical parameters, and survival outcomes were analyzed. In vitro and in vivo functional assays were also performed to dissect the potential underlying mechanisms. Expression of CPS1-IT1 was significantly decreased in 73% of HCC tissues, and patients with low CPS1-IT1 expression had poor survival outcomes. Furthermore, in vitro functional assays indicated that CPS1-IT1 significantly reduced cell proliferation, migration and invasion capacities through reduced Hsp90 binding to and activation of HIF-1α, thereby suppressing the epithelial-mesenchymal transition (EMT). An in vivo animal model also demonstrated the tumor suppressor role of CPS1- IT1 via decreased tumor growth and metastasis. In conclusion, lncRNA CPS1-IT1 acts as a tumor suppressor in HCC by reducing HIF-1α activation and suppressing EMT. The findings of this study establish a function for CPS1-IT1 in HCC progression and suggest its potential as a new prognostic biomarker and target for HCC therapy.

Sepsis-associated encephalopathy (SAE) is frequently encountered in critically ill patients. Hyperglycemia is a common phenomenon among patients with sepsis, and glycemic control improves patient outcomes. Therefore, here, we aimed to explore whether glycemic control using insulin inhibits the pro-inflammatory cytokine response and glial activation in the cerebrum and is concomitantly associated with the relief of SAE. Using cecal ligation and puncture (CLP), sepsis was induced in male Sprague-Dawley rats. The CLP rats were administered intravenous glucose or subjected to subcutaneous insulin implant within the first hour after CLP. The survival rate, blood glucose (BG) values, and behavioral expression were assessed daily for 5 days after CLP. At day 5 after CLP, electroencephalography (EEG) recordings and blood–brain barrier (BBB) permeability testing were performed. Immunohistochemistry, immunoblotting, and enzyme-linked immunosorbent assays were used to evaluate glial activation and the pro-inflammatory cytokine response qualitatively and quantitatively, respectively. The glucose-treated CLP rats (BG > 390 mg/dL) exhibited a decline in survival rate; insensitivity to mechanical and thermal stimuli; slowed EEG activity; and an increase in BBB permeability, pro-inflammatory cytokine (TNF-α, IL-1β, and IL-6) levels, and glial activation (astrocytes and microglia) in the cerebral tissues compared with CLP rats (BG ~ 270 mg/dL). Double-immunofluorescence showed that activated astrocytes and microglia co-expressed phosphorylated nuclear factor kappa B and mitogen-activated protein kinases, respectively. Furthermore, glycemic control using insulin therapy maintained the BG at 120–160 mg/dL and inhibited the production of pro-inflammatory cytokines and glial activation in the cerebrum of septic rats. In addition, the survival rate, sensory threshold, EEG activity, and BBB permeability recovered to near-normal levels in septic rats after insulin therapy. Taken together, the results of this study elucidated the pathophysiological alterations in brains subjected to sepsis, especially regarding glycemic control. These findings improve our understanding of SAE and support the importance of glycemic control in sepsis.

This article presents the design and demonstration of a high-bandwidth antenna-in-package (AiP) module focusing on low-loss interconnects and Yagi–Uda antenna performance fabricated on a 100- $\mu \text{m}$ low coefficient-of-thermal-expansion (CTE) glass for the 28-GHz band. It shows the modeling, design, and characterization of key technology building blocks along with the process development of advanced 3-D glass packages. The building blocks include impedance-matched antenna-to-die signal transitions, Yagi–Uda antenna, and 3-D active–passive integration with backside die assembly on 100- $\mu \text{m}$ glass substrates. The design and stack-up optimization of antenna-integrated millimeter-wave (mm-wave) modules is discussed. Process development to achieve high-density interconnects and precise dimensional control in multilayered thin glass-based packages is also described. The characterization results of the key technology building blocks show an insertion loss of 0.021 dB per through-package via (TPV), leading to the whole-chain loss of less than 1 dB and a return loss lower than 20 dB. The fabricated Yagi–Uda antenna features high repeatability of wide bandwidth due to the process control enabled by glass substrates. The antenna measurements show a bandwidth of 28.2%, which covers the entire 28-GHz fifth-generation (5G) frequency bands (n257, n258, and n261). The flip-chip assembled low-noise amplifier with 80- $\mu \text{m}$ solder balls shows a maximum gain of 20 dB as desired. The performance of the glass-based package integrated antennas is benchmarked to other 5G substrate technologies, such as organic laminates or co-fired ceramic-based substrates.

DNA repair systems are abnormally active in most hepatocellular carcinoma (HCC) cells due to accumulated mutations, resulting in elevated DNA repair capacity and resistance to chemotherapy and radiotherapy. Thus, targeting DNA repair mechanisms is a common treatment approach in HCC to sensitize cancer cells to DNA damage. In this study, we examined the anti-HCC effects of melatonin and elucidated the regulatory mechanisms. The results of functional assays showed that in addition to inhibiting the proliferation, migration, and invasion abilities of HCC cells, melatonin suppressed their DNA repair capacity, thereby promoting the cytotoxicity of chemotherapy and radiotherapy. Whole-transcriptome and gain- and loss-of-function analyses revealed that melatonin induces expression of the long noncoding RNA RAD51-AS1, which binds to RAD51 mRNA to inhibit its translation, effectively decreasing the DNA repair capacity of HCC cells and increasing their sensitivity to chemotherapy and radiotherapy. Animal models further demonstrated that a combination of melatonin and the chemotherapeutic agent etoposide (VP16) can significantly enhance tumor growth inhibition compared with monotherapy. Our results show that melatonin is a potential adjuvant treatment for chemotherapy and radiotherapy in HCC.

This paper presents a new compact ultra-lightweight radio frequency (RF) energy harvester fabricated on a flexible substrate. The proposed rectenna is designed to operate over the 2.4GHz ISM band. The rectifier includes a dual transmission lines tapered matching network that provides a combination of compactness, flexibility and an efficiency of up to 40%. The rectifier is then integrated with a miniaturized monopole antenna to form an ultra-compact, efficient and flexible rectenna. The system is characterized in multiple bent configurations featuring high and stable performance. It is demonstrated that for different bent states, the proposed flexible harvester displays a variation in harvested power that is less than 57 %.

This paper demonstrates seamless antenna-to-transceiver signal transitions on panel-scale processed ultra-thin glass-based 5G modules with impedance-matched transmission lines and microvias with high-precision low-loss re-distribution layer design and fabrication, for high-speed 5G communication standards at the 28 GHz band. In order to demonstrate the benefits of glass for 5G communications, various types of transmission lines and high-gain and high-bandwidth package-integrated antennas were modeled and designed on ultra-thin glass substrates with low-loss dielectric thin-films, for highest bandwidth and efficiency in the mm-wave bands. The simulated results for insertion losses of transmission lines (i.e., microstrip lines and striplines) and microvia transitions are correlated with the measured values on the thin glass substrates. In addition to the low-loss signal transitions from chip to antenna, package-integrated Yagi-Uda antennas are modeled and designed, resulting in a realized gain of higher than 4 dBi/element with a bandwidth higher than 20%. The mm-wave electrical performance of glass substrates was benchmarked with existing 5G candidates such as organic laminate substrates and fanout wafer level packaging. Along with the reduction in the overall package foot-print, reduction in link-budget losses is shown to be feasible with the proposed 3D glass packages.

Additively manufacturing techniques including 3D and inkjet printing is used to fabricate antenna and packaging structure at mm-wave range for 5G applications. The 3D printed flexible material, FLGR02, is applied to the flexible mm-wave packaging application. The fabrication process and material characterizations including solutions to surface treatment for ink adhesion, smooth of surface roughness, and CTE mismatch between the flexible material and the silver ink are proposed. Then the proposed process is used to fabricated a broadband 5G on-package antenna. The measured S11 of the proposed on-package antenna is smaller than -10 dB from 22.4 GHz to 30.1 GHz. Besides, the measured realized gain is larger than 5 dB from 22 GHz to 30.5 GHz. The differences of realized gain within the operational bandwidth is smaller than 3 dB. The fractional bandwidth is 29.3 %. The proposed antenna is broadband enough to cover the whole 5G band from 24.5 GHz to 29.5 GHz. The size of the antenna is 5mm×9mm which is 0.44?0 × 0.79?0. The radiation patterns within the operational band is also measured. Finally, a proof-of-concept demonstration of SoP design is fabricated.

This paper demonstrates six-metal-layer antenna-to-receiver signal transitions on panel-scale processed ultra-thin glass-based 5G module substrates with 50-Ω transmission lines and micro-via transitions in re-distribution layers. The glass modules consist of low-loss dielectric thin-films laminated on 100-μm glass cores. Modeling, design, fabrication, and characterization of the multilayered signal interconnects were performed at 28-GHz band. The surface planarity and dimensional stability of glass substrates enabled the fabrication of highly-controlled signal traces with tolerances of 2% inside the re-distribution layers on low-loss dielectric build-up thin-films. The fabricated transmission lines showed 0.435 dB loss with 4.19 mm length, while microvias in low-loss dielectric thin-films showed 0.034 dB/microvia. The superiority of glass substrates enable low-loss link budget with high precision from chip to antenna for 5G communications.

Increasing evidence indicates that long non-coding RNAs (lncRNAs) regulate diverse cellular processes, including cell growth, differentiation, apoptosis, and cancer progression. However, the function of lncRNAs in the progression of hepatocellular carcinoma (HCC) remains largely unknown. We performed a comprehensive microarray analysis of lncRNA expression in human HCC samples. After validation in 108 HCC specimens, we identified a differentially expressed novel tumor suppressive lncRNA termed amine oxidase, copper containing 4, pseudogene (AOC4P). The level of AOC4P expression was significantly downregulated in 68% of HCC samples and negatively correlated with advanced clinical stage, capsule invasion and vessel invasion. Low AOC4P expression correlated with poor prognostic outcomes, serving as an independent prognostic factor for HCC. In vitro functional assays indicated that AOC4P overexpression significantly reduced cell proliferation, migration and invasion by inhibiting the epithelial-mesenchymal transition (EMT). RNA immunoprecipitation assays demonstrated that AOC4P binds to vimentin and promotes its degradation. Animal model experiments confirmed the ability of AOC4P to suppress tumor growth and metastasis. Taken together, our findings suggest that AOC4P lncRNA acts as an HCC tumor suppressor by enhancing vimentin degradation and suppressing the EMT. By clarifying the mechanisms underlying HCC progression, these findings promote the development of novel therapeutic strategies for HCC.

Background Isoliquiritigenin (ISL), a natural compound extracted from licorice, has chemopreventive and antitumor activities. The purpose of this study was to investigate the anticancer effect of ISL on human oral squamous cell carcinoma (OSCC). Methods The anti-OSCC effects of ISL were evaluated using the 3-(4,5-dimethylthiazol-2-yl)−2,5-diphenyltetrazolium bromide test, flow cytometry, reverse transcription-polymerase chain reaction, Western blotting, promoter activity, terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, malignant phenotype analysis, microRNA, and xenografting. Results ISL induced OSCC cell cycle G2/M phase arrest, apoptosis, and DNA damage. However, the DNA repair-associated ataxia telangiectasia mutated (ATM) and phospho-ATM were downregulated, ATM mRNA remained unchanged, and the downstream signals were inhibited. ATM recovered when the caspase activity was blocked by Z-DVED-FMK. A low dose of ISL inhibited OSCC malignancy in vitro and reduced the tumor size in vivo. Conclusion ATM was cleaved by ISL-activated caspase, thus inhibiting DNA repair in OSCC cells. Therefore, ISL is a promising chemopreventive agent against oral cancer. © 2015 Wiley Periodicals, Inc. Head Neck, 2015