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The deployment of endovascular implants such as stents in the treatment of cardiovascular disease damages the vascular endothelium, increasing the risk of thrombosis and promoting neointimal hyperplasia. The rapid restoration of a functional endothelium is known to reduce these complications. Circulating endothelial progenitor cells (EPCs) are increasingly recognized as important contributors to device re-endothelialization. Extracellular matrix proteins prominent in the vessel wall may enhance EPC-directed re-endothelialization. We examined attachment, spreading and proliferation on recombinant human tropoelastin (rhTE) and investigated the mechanism and site of interaction. EPCs attached and spread on rhTE in a dose dependent manner, reaching a maximal level of 56±3% and 54±3%, respectively. EPC proliferation on rhTE was comparable to vitronectin, fibronectin and collagen. EDTA, but not heparan sulfate or lactose, reduced EPC attachment by 81±3%, while full attachment was recovered after add-back of manganese, inferring a classical integrin-mediated interaction. Integrin αVβ3 blocking antibodies decreased EPC adhesion and spreading on rhTE by 39±3% and 56±10% respectively, demonstrating a large contribution from this specific integrin. Attachment of EPCs on N-terminal rhTE constructs N25 and N18 accounted for most of this interaction, accompanied by comparable spreading. In contrast, attachment and spreading on N10 was negligible. αVβ3 blocking antibodies reduced EPC spreading on both N25 and N18 by 45±4% and 42±14%, respectively. In conclusion, rhTE supports EPC binding via an integrin mechanism involving αVβ3. N25 and N18, but not N10 constructs of rhTE contribute to EPC binding. The regulation of EPC activity by rhTE may have implications for modulation of the vascular biocompatibility of endovascular implants.

BACKGROUND: Endothelial progenitor cells (EPCs) are implicated in protection against vascular disease. However, studies using angiography alone have reported conflicting results when relating EPCs to epicardial coronary artery disease (CAD) severity. Moreover, the relationship between different EPC types and the coronary microcirculation is unknown. We therefore investigated the relationship between EPC populations and coronary epicardial and microvascular disease. METHODS: Thirty-three patients with a spectrum of isolated left anterior descending artery disease were studied. The coronary epicardial and microcirculation were physiologically interrogated by measurement of fractional flow reserve (FFR), index of microvascular resistance (IMR) and coronary flow reserve (CFR). Two distinct EPC populations (early EPC and late outgrowth endothelial cells [OECs]) were isolated from these patients and studied ex vivo. RESULTS: There was a significant inverse relationship between circulating OEC levels and epicardial CAD severity, as assessed by FFR and angiography (r=0.371, p=0.04; r=-0.358, p=0.04; respectively). More severe epicardial CAD was associated with impaired OEC migration and tubulogenesis (r=0.59, p=0.005; r=0.589, p=0.004; respectively). Patients with significant epicardial CAD (FFR

Abstract The power conversion efficiency of perovskite solar cells continues to increase. However, defects in perovskite materials are detrimental to their carrier dynamics and structural stability, ultimately limiting the photovoltaic characteristics and stability of perovskite solar cells. Herein, we report that 6H polytype perovskite effectively engineers defects at the interface with cubic polytype FAPbI3, which facilitates radiative recombination and improves the stability of the polycrystalline film. We particularly show the detrimental effects of shallow-level defect that originates from the formation of the most dominant iodide vacancy (VI +) in FAPbI3. Furthermore, additional surface passivation on top of the hetero-polytypic perovskite film results in an ultra-long carrier lifetime exceeding 18 μs, affords power conversion efficiencies of 24.13% for perovskite solar cells, 21.92% (certified power conversion efficiency: 21.44%) for a module, and long-term stability. The hetero-polytypic perovskite configuration may be considered as close to the ideal polycrystalline structure in terms of charge carrier dynamics and stability.

In this study, we fabricated a coplanar waveguide using a novel graphene-silver nanowire composite structure (GNCS) on a polyethylene terephthalate (PET) substrate and then investigated its radio frequency (RF) characteristics. According to the measured results, the coplanar waveguide employing GNCS exhibited a substantially lower loss of transmission line than conventional waveguides. Furthermore, compared to the conventional graphene-based coplanar waveguide, the proposed structure allowed for lower skin depth and higher conductivity, resulting from the high electric conductivity of the silver nanowire. In addition, repetitive bending tests, which were performed to investigate the electric stability of the graphene-silver nanowire, showed that the coplanar waveguide employing GNCS offered substantially better electrical stability than the conventional graphene-based coplanar waveguide. These results indicate that the graphene-silver nanowire structure is a promising candidate for application in flexible wireless communication systems. Notably, this is also the first study to investigate the RF performance and electrical stability of a graphene-silver nanowire/PET structure.

Abstract Cancer cachexia is a multifactorial condition that contributes to the death of about 20% of cancer patients. It has the potential to cause weight loss, reduction in muscle mass, and loss of fat tissue, significantly lowering the quality of life. Currently, there are no approved drugs for cancer cachexia. Here, we have explored the possible impact of brassinin (BSN) on cancer cachexia under in vitro and in vivo settings. After differentiation, C2C12 and 3T3‐L1 cells were incubated with colorectal carcinoma cells conditioned media or BSN. For preclinical studies, mice were injected with HT‐29 cells followed by intraperitoneal administration of BSN, and muscle and adipose tissues were evaluated by Western blotting and hematoxylin and eosin staining. BSN effectively suppressed muscle atrophy by down‐regulating the levels of Muscle RING‐finger protein‐1 and Atrogin‐1, while also increasing the expression of myosin heavy chain in cachexia‐induced‐C2C12 myotubes. The induction of adipogenesis by BSN prevented adipocyte atrophy in cachexia‐induced 3T3‐L1 adipocytes. We also noted that BSN disrupted the interaction between COX‐2 and signaling transducer and activator of transcription 3 (STAT3) promoter, leading to down‐regulation of STAT3 activation. Moreover, it was found that BSN inhibited weight loss in mice and demonstrated anti‐cachexic effects. Overall, our observations indicate that BSN can attenuate cancer cachexia through diverse mechanisms.

Abstract Perovskite solar cells (PSCs) have the potential to produce solar energy at a low cost, with flexibility, and high power conversion efficiency (PCE). However, there are still challenges to be addressed before mass production of PSCs, such as prevention from degradation under external stresses and the uniform, large-area formation of all layers. Among them, the most challenging aspect of mass production of PSCs is creating a high-quality perovskite layer using environmentally sustainable processes that are compatible with industry standards. In this review, we briefly introduce the recent progresses upon eco-friendly perovskite solutions/antisolvents and film formation processes. The eco-friendly production methods are categorized into two: (1) employing environmentally friendly solvents for perovskite precursor ink/solution, and (2) replacing harmful, volatile antisolvents or even limiting their use during the perovskite film formation process. General considerations and criteria for each category are provided, and detailed examples are presented, specifically focused on the works have done since 2021. In addition, the importance of controlling the crystallization behavior of the perovskite layer is highlighted to develop antisolvent-free perovskite formation methods. Graphical Abstract

Abstract Efficient energy consumption is crucial for achieving sustainable energy goals in the era of climate change and grid modernization. Thus, it is vital to understand how energy is consumed at finer resolutions such as household in order to plan demand-response events or analyze impacts of weather, electricity prices, electric vehicles, solar, and occupancy schedules on energy consumption. However, availability and access to detailed energy-use data, which would enable detailed studies, has been rare. In this paper, we release a unique, large-scale, digital-twin of residential energy-use dataset for the residential sector across the contiguous United States covering millions of households. The data comprise of hourly energy use profiles for synthetic households, disaggregated into Thermostatically Controlled Loads (TCL) and appliance use. The underlying framework is constructed using a bottom-up approach. Diverse open-source surveys and first principles models are used for end-use modeling. Extensive validation of the synthetic dataset has been conducted through comparisons with reported energy-use data. We present a detailed, open, high resolution, residential energy-use dataset for the United States.

The load networks of advanced Doherty power amplifiers (DPAs) have traditionally been designed according to the ABCD parameters. In this paper, design conditions as an impedance transformation condition and an effective electrical length were used to design the output matching networks (OMNs) for the carrier and peaking amplifiers of the virtual-stub DPAs (VS-DPAs). An optimization method for the effective electrical length was proposed that was specifically constructed for the load impedances of the carrier amplifier at the low power level to have broadband characteristics through the load-pull simulation. Using the optimized design conditions for broadband design, compact OMNs for the carrier and peaking amplifiers were designed using quasi-lumped components. Moreover, an asymmetric structure with an increased power capacity of the peaking amplifier for the VS-DPA was proposed to compensate for a relatively low peak fundamental current of the peaking amplifier due to its deep class-C operation as well as the extended output back-off (OBO) range of the VS-DPA. To verify the proposed load network, a broadband asymmetric VS-DPA for the 3.3 - 4.2 GHz band was designed and implemented using GaN HEMTs with power capacities of 6 and 10 W. Using a 5G new radio (5G NR) signal with a signal bandwidth of 100 MHz and a peak-to-average power ratio (PAPR) of 7.8 dB, power gain of 8.2 - 9.1 dB, DE of 46.0 - 57.0%, ACLR of better than −45 dBc after DPD linearization at an average power of 35.0 dBm were achieved at the broad frequency range of 3.3 - 4.2 GHz.

This paper presents a 2.8-3.8 GHz broadband 2-stage fully differential Doherty power amplifier using direct interstage power division based on a 2- $\mu \text{m}$ InGaP/GaAs HBT process for 5G new radio handset applications. A compact transformer-less interstage network is proposed for direct power division for carrier and peaking amplifiers. The power division ratio at the interstage is designed to dynamically vary according to the input power level to provide higher power gain and desired load impedance modulation. By utilizing the non-linear input reactance of the peaking amplifier, broadband dynamic power division circuits were designed for an operating frequency band of as broad as 1 GHz. In addition, active bias circuits for the peaking amplifier were optimized to have sufficient gain expansion, so that the overall AM-AM characteristics is as flat as possible. A broadband load modulation network using one transformer and two quarter-wave transmission lines is proposed. For the off-chip output transformer, impedance trajectory for the wide band impedance matching is presented using a T-equivalent circuit of the transformer. The self-inductance ratio of the transformer is optimized to maximize the bandwidth. Using the 5G new radio uplink signal with a signal bandwidth of 100 MHz, the implemented Doherty PA IC exhibited a power gain of 31.9 to 38.4 dB, PAE of 22.0 to 30.6%, and average output power of 26.0 to 27.8 dBm at a given ACLR of −33.0 dBc without pre-distortion.

In the field of bone tissue engineering, which is being developed for the ideal restoration of bone defects, researchers are exploring the improvement of the bone regeneration efficacy of scaffolds through various approaches involving osteoconductive, osteoinductive, and angiogenic factors. In the current trend of research, there is also a suggestion that the topological factors of recent scaffolds may influence the attachment, migration, proliferation, and differentiation of bone cells. Building upon experimental confirmation of the effect of scaffold conformity with the defect site on enhanced bone regeneration in previous studies, we conducted this research to experimentally investigate the relationship between contact area with the defect site and bone regeneration efficacy. The results demonstrated that as the contact area of the scaffold increased, not only did the resistance to bone tissue growth increase, more significant bone regeneration also occurred, as evidenced through histological analysis and micro-CT analysis. This research confirms that the contact area between the scaffold and the defect site is a critical variable affecting bone regeneration efficacy, emphasizing its importance when designing customized scaffolds. This finding holds promising implications for future studies and applications in the field.

Additive manufacturing (AM) of customized scaffolds has been actively studied in tissue engineering. Most studies have focused on the functionalization of scaffolds for osteoinduction and osteoconduction for bone regeneration. However, in our previous study, we found that shape conformity between a defect and the scaffold was also a major factor with regard to enhancing bone regeneration. Thus, in this study, we performed a quantitative analysis of the shape conformity between the defect and scaffold using several novel experimental scaffolds. Employing several scaffolds with different conformities that increased linearly, the degree of bone regeneration was analyzed through new bone volume measurements and a histological analysis in conjunction with an in vivo experiment using rat calvaria. For the quantitative analysis, we compared the new bone volume reconstructed from a three-dimensional model based on CT data. New bone maturation was analyzed with respect to shape conformity through a histological analysis. Proliferation, maturation, and new bone formation were promoted by scaffold shape conformity. Thus, for bone regeneration, the AM precision and the fabrication technique are critical as the shape conformity of the scaffold to the bone defect is highly dependent on AM fabrication errors.

In bone tissue engineering, the endogenous regeneration of bone defects still represents a clinical challenge despite the development of intervention therapy to achieve bone regeneration via autologous grafts, allogeneic grafts, bone morphogenetic protein (BMP)-2, etc. To overcome the limitation of endogenous bone regeneration, we assumed that the 3D-printed collagen pattern with BMP-2 and fibroblast growth factor (FGF)-2 in the 3D-printed polycaprolactone/nano-hydroxyapatite scaffold could guide the endogenous regeneration of bone defects. Therefore, to test our hypothesis, polycaprolactone/nano-hydroxyapatite/collagen scaffolds with dual growth factors (BMP-2 and FGF-2) and various hydrogel patterns (positive, edge, and radial patterns) were fabricated at the same ratio and concentration of dual growth factors. Consequently, we revealed that the in vitro released concentrations of BMP-2 and FGF-2 were not affected by collagen patterns in the polycaprolactone/nano-hydroxyapatite scaffold. Furthermore, endogenous bone regeneration and angiogenesis in the polycaprolactone/nano-hydroxyapatite/collagen scaffold with a radial pattern were promoted compared with those in the polycaprolactone/nano-hydroxyapatite/collagen scaffolds with positive and edge patterns. Therefore, we demonstrated that a collagen design loaded with dual growth factors in the 3D-printed scaffold could affect endogenous bone regeneration and angiogenesis.

This paper presents a generalized expression of the modified load networks (MLNs) for Doherty power amplifiers (DPAs) with an extended output power back-off (OBO) range. Based on the analysis using this new expression, a new circuit structure generally applicable to any combination of the multiple MLNs is proposed. The load network has a simple structure including impedance matching circuits and offset lines for the carrier and peaking amplifiers. A design procedure for the proposed load network is presented. A DPA using any optimized combination of the multiple MLNs can be easily designed using the proposed load network. For verification, a GaN-HEMT symmetrical DPA based on a combination of the virtual open-stub (VOS) and out-phased current combining (OCC) methods was designed and implemented for the frequency band of 3.4 - 3.7 GHz. The reversed uneven power splitting method is adopted in the design for higher power gain. Using the 5G New Radio (NR) signal with a peak-to average power ratio (PAPR) of 7.9 dB and a signal bandwidth of 100 MHz, the proposed DPA exhibited DE of 55.3 - 60.9% with a power gain of 11.9 - 12.7 dB at an average output power of 33.7 dBm. An adjacent channel leakage power ratio (ACLR) of −42.6 - −44.8 dBc was achieved at the average power level by using a digital predistortion (DPD) technique across the band.

Introduction: The development of cancer generally occurs as a result of various deregulated molecular mechanisms affecting the genes that can control normal cellular growth. Signal transducer and activator of transcription 3 (STAT3) pathway, once aberrantly activated can promote carcinogenesis by regulating the transcription of a number of oncogenic genes. Objectives: Here, we evaluated the impact of fangchinoline (FCN) to attenuate tumor growth and survival through modulation of oncogenic STAT3 signaling pathway using diverse tumor cell lines and a xenograft mouse model. Methods: To evaluate the action of FCN on STAT3 cascade, protein levels were analyzed by Western blot analysis and electrophoretic mobility shift assay (EMSA). Translocation of STAT3 was detected by immunocytochemistry. Thereafter, FCN-induced ROS was measured by GSH/GSSG assay and H2DCF-DA. FCN-induced apoptosis was analyzed using Western blot analysis and flow cytometry for various assays. Finally, anti-cancer effects of FCN in vivo was evaluated in a myeloma model. Results: We noted that FCN abrogated protein expression levels of STAT3 and upstream signals (JAK1/2 and Src). In addition, FCN also attenuated DNA binding ability of STAT3 and its translocation into the nucleus. It altered the levels of upstream signaling proteins, increased SHP-1 levels, and induced substantial apoptosis in U266 cells. FCN also promoted an increased production of reactive oxygen species (ROS) and altered GSSG/GSH ratio in tumor cells. Moreover, FCN effectively abrogated tumor progression and STAT3 activation in a preclinical myeloma model. Conclusion: Overall, this study suggests that FCN may have a tremendous potential to alter abnormal STAT3 activation and induce cell death in malignant cells along with causing the suppression of pathogenesis and growth of cancer through a pro-oxidant dependent molecular mechanism.

The load network of the carrier amplifier for the conventional Doherty power amplifier (DPA) consists of an impedance matching circuit, an offset line, and a $\lambda $ /4 transmission line (TL), so that the overall electrical length of the network can easily exceed the minimum value of 90°. Then for appropriate impedance modulation, it should be 270° with an additional 180°. This excessive electrical length of the load matching network limits the bandwidth at either the low-power or peak-power level. In this paper, a compact quasi-lumped $\lambda $ /4 impedance transformer (ITF) having simultaneous multiple functions of impedance matching and load impedance modulation with a controlled electrical length of 90° is presented. The proposed load network includes the internal components of the transistor, the simplest high-pass network using a shunt inductor, and a low-pass L-C network. Using the optimized value of the shunt inductor, the electrical length of the load network can be adjusted to 90°, while other components are accordingly changed to match the optimum load impedance. To verify the proposed load network, a DPA was designed and implemented using 10 W GaN-HEMTs for both carrier and peaking amplifiers. Using a 5G New Radio (NR) signal with signal bandwidth of 100 MHz and peak-to-average power ratio (PAPR) of 7.8 dB, a drain efficiency (DE) of 47 - 54.2%, and adjacent channel leakage power ratio (ACLR) of −27.9 - −23 dBc were achieved at an average output power level of 35.8 - 36.3 dBm for the frequency band of 3.4 - 3.8 GHz.

Abstract Background In the post-GWAS era, there is an unmet need to decode the underpinning genetic etiologies of late-onset Alzheimer’s disease (LOAD) and translate the associations to causation. Methods We conducted ATAC-seq profiling using NeuN sorted-nuclei from 40 frozen brain tissues to determine LOAD-specific changes in chromatin accessibility landscape in a cell-type specific manner. Results We identified 211 LOAD-specific differential chromatin accessibility sites in neuronal-nuclei, four of which overlapped with LOAD-GWAS regions (±100 kb of SNP). While the non-neuronal nuclei did not show LOAD-specific differences, stratification by sex identified 842 LOAD-specific chromatin accessibility sites in females. Seven of these sex-dependent sites in the non-neuronal samples overlapped LOAD-GWAS regions including APOE. LOAD loci were functionally validated using single-nuclei RNA-seq datasets. Conclusions Using brain sorted-nuclei enabled the identification of sex-dependent cell type-specific LOAD alterations in chromatin structure. These findings enhance the interpretation of LOAD-GWAS discoveries, provide potential pathomechanisms, and suggest novel LOAD-loci. Graphical Abstract

Nuclear factor kappa beta (NF-κB) is a transcriptional factor that plays a crucial role in regulating cancer cell proliferation. Therefore, the inhibition of NF-κB activity by small molecules may be beneficial in cancer therapy. In this report, methyl-thiol-bridged oxadiazole and triazole heterocycles were synthesized via click chemistry and it was observed that the lead structure, 2-(((1-(3,4-dichlorophenyl)-1H-1,2,3-triazol-4-yl)methyl)thio)-5-(4-methoxybenzyl)-1,3,4-oxadiazole (4c), reduced the viability of MCF-7 cells with an IC50 value of 7.4 µM. Compound 4c also caused concentration-dependent loss of cell viability in chronic myelogenous leukemia (CML) cells. Furthermore, compound 4c inhibited the activation of NF-κB in human CML cells as observed by nuclear translocation and DNA binding assays. Functionally, compound 4c produced PARP cleavage and also suppressed expression of Bcl-2/xl, MMP-9, COX-2, survivin, as well as VEGF, resulting in apoptosis of CML cells. Moreover, ChIP assay showed that compound 4c decreased the binding of COX-2 to the p65 gene promoter. Detailed in silico analysis also indicated that compound 4c targeted NF-κB in CML cells. In conclusion, a novel structure bearing both triazole and oxadiazole moieties has been identified that can target NF-κB in CML cells and may constitute a potential novel drug candidate.

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.

Driven by recent improvement in efficiency and stability of perovskite solar cells, the next step toward commercialisation is upscaling. Here, the authors demonstrate pilot-scale fully roll-to-roll manufacturing of flexible perovskite solar cells through gravure-printing and antisolvent bathing.

Globalization and climate change facilitate the spread and establishment of invasive species throughout the world via multiple pathways. These spread mechanisms can be effectively represented as diffusion processes on multi-scale, spatial networks. Such network-based modeling and simulation approaches are being increasingly applied in this domain. However, these works tend to be largely domain-specific, lacking any graph theoretic formalisms, and do not take advantage of more recent developments in network science. This work is aimed toward filling some of these gaps. We develop a generic multi-scale spatial network framework that is applicable to a wide range of models developed in the literature on biological invasions. A key question we address is the following: how do individual pathways and their combinations influence the rate and pattern of spread? The analytical complexity arises more from the multi-scale nature and complex functional components of the networks rather than from the sizes of the networks. We present theoretical bounds on the spectral radius and the diameter of multi-scale networks. These two structural graph parameters have established connections to diffusion processes. Specifically, we study how network properties, such as spectral radius and diameter are influenced by model parameters. Further, we analyze a multi-pathway diffusion model from the literature by conducting simulations on synthetic and real-world networks and then use regression tree analysis to identify the important network and diffusion model parameters that influence the dynamics.

Perovskite solar cells (PSCs) are emerging next-generation photovoltaics, and some breakthroughs for the commercialization have been rapidly made. To develop the technologies for large-area modules, economically feasible fabrication using a roll-to-roll (R2R) solution process may be the ultimate target for the fabrication of PSCs. In order to achieve successful R2R production of PSCs, however, several issues still need to be addressed. Roll-based continuous and scalable deposition of perovskite and charge transporting layers on a flexible substrate needs to be developed to obtain high-quality R2R-processed PSCs. There are also critical factors involved in accomplishing R2R fabrication: heat treatment at low temperature and a short processing time over the whole process with industrial-compatible methods. We briefly discuss this perspective: scalable deposition of layers, considerations for the R2R process, and progress and challenges in the R2R fabrication of the PSCs.

Yuja (Citrus junos) has been cultivated and used for food and medicinal purposes in China and Korea. Its antioxidant, anti-wrinkle, moisturizing, and whitening effects were evaluated in HaCaT, HDF, and B16F10 cells. UVB has been known to cause cellular stress and the production of reactive oxygen species (ROS). Ambivalence of oxidative stress has been reported; however, excessive levels of ROS contribute to skin aging through the loss of elasticity and collagen fibers of connective tissue in the dermis. Skin aging is one of the biological processes that is affected by various factors, including UVB. Pro-Collagen I and hyaluronic acid contents were measured in UVB-irradiated HaCaT and HDF cells to evaluate the anti-wrinkle and moisturizing effects of Yuja-peel (YJP) fractions in -EA (ethyl acetate), -Hex (hexane), and -BuOH (butanol). The expression of matrix metalloproteinases (MMPs) involved in collagen degradation was confirmed to be inhibited by YJP fractions at both the protein and mRNA levels. Filaggrin and serine palmitoyltransferase (SPT), which are moisturizing factors, were induced by YJP fractions. B16F10 cells were treated with α-MSH to induce hyperpigmentation, and then the whitening efficacy of YJP fractions was verified by observing a decrease in melanin content. Overall, our results contribute to the development of various novel skin-improving cosmetics and pharmaceuticals with YJP fractions as active ingredients.

CXCR7 and CXCR4 are G protein-coupled receptors (GPCRs) that can be stimulated by CXCL12 in various human cancers. CXCR7/4–CXCL12 binding can initiate activation of multiple pathways including JAK/STAT and manganese superoxide dismutase (MnSOD) signaling, and initiate epithelial–mesenchymal transition (EMT) process. It is established that cancer cell invasion and migration are caused because of these events. In particular, the EMT process is an important process that can determine the prognosis for cancer. Since the antitumor effect of leelamine (LEE) has been reported in various previous studies, here, we have evaluated the influence of LEE on the CXCR7/4 signaling axis and EMT processes. We first found that LEE suppressed expression of CXCR7 and CXCR4 both at the protein and mRNA levels, and showed inhibitory effects on these chemokines even after stimulation by CXCL12 ligand. In addition, LEE also reduced the level of MnSOD and inhibited the EMT process to attenuate the invasion and migration of breast cancer cells. In addition, phosphorylation of the JAK/STAT pathway, which acts down-stream of these chemokines, was also abrogated by LEE. It was also confirmed that LEE can induce an imbalance of GSH/GSSG and increases ROS, thereby resulting in antitumor activity. Thus, we establish that targeting CXCR7/4 in breast cancer cells can not only inhibit the invasion and migration of cancer cells but also can affect JAK/STAT, EMT process, and production of ROS. Overall, the findings suggest that LEE can function as a novel agent affecting the breast cancer.

Parkinson’s disease (PD) and dementia with Lewy body (DLB) are the most common synucleinopathies. SNCA gene is a major genetic risk factor for these diseases group, and dysregulation of its expression has been implicated in the genetic etiologies of several synucleinopathies. DNA methylation at CpG island (CGI) within SNCA intron 1 has been suggested as a regulatory mechanism of SNCA expression, and changes in methylation levels at this region were associated with PD and DLB. However, the role of DNA methylation in the regulation of SNCA expression in a cell-type specific manner and its contribution to the pathogenesis of PD and DLB remain poorly understood, and the data are conflicting. Here, we employed a bisulfite pyrosequencing technique to profile the DNA methylation across SNCA intron 1 CGI in PD and DLB compared to age- and sex-matched normal control subjects. We analyzed homogenates of bulk post-mortem frozen frontal cortex samples and a subset of neuronal and glia nuclei sorted by the fluorescence-activated nuclei sorting (FANS) method. Bulk brain tissues showed no significant difference in the overall DNA methylation across SNCA intron 1 CGI region between the neuropathological groups. Sorted neuronal nuclei from PD frontal cortex showed significant lower levels of DNA methylation at this region compared to normal controls, but no differences between DLB and control, while sorted glia nuclei exhibited trends of decreased overall DNA methylation in DLB only. In conclusion, our data suggested disease-dependent cell-type specific differential DNA methylation within SNCA intron 1 CGI. These changes may affect SNCA dysregulation that presumably mediates disease-specific risk. Our results can be translated into the development of the SNCA intron 1 CGI region as an attractive therapeutics target for gene therapy in patients who suffer from synucleinopathies due to SNCA dysregulation.

Epithelial-mesenchymal transition (EMT) is a crucial process in which the polarized epithelial cells acquire the properties of mesenchymal cells and gain invasive properties. We have previously demonstrated that manganese superoxide dismutase (MnSOD) can regulate the EMT phenotype by modulating the intracellular reactive oxygen species. In this report, we have demonstrated the EMT-suppressive effects of 2,3,5,6-Tetramethylpyrazine (TMP, an alkaloid isolated from Chuanxiong) in colon cancer cells. TMP suppressed the expression of MnSOD, fibronectin, vimentin, MMP-9, and N-cadherin with a parallel elevation of occludin and E-cadherin in unstimulated and TGFβ-stimulated cells. Functionally, TMP treatment reduced the proliferation, migration, and invasion of colon cancer cells. TMP treatment also modulated constitutive activated as well as TGFβ-stimulated PI3K/Akt/mTOR, Wnt/GSK3/β-catenin, and MAPK signaling pathways. TMP also inhibited the EMT program in the colon cancer cells-transfected with pcDNA3-MnSOD through modulation of MnSOD, EMT-related proteins, and oncogenic pathways. Overall, these data indicated that TMP may inhibit the EMT program through MnSOD-mediated abrogation of multiple signaling events in colon cancer cells.

Background: South Korea, home of the soybean, features diverse traditional fermented soy products. Jipjang (汁醬) is made by mixing autumn vegetables in meju powder prepared by boiling and fermenting soybeans and wheat with saccharified water. Jipjang has been documented since the early Joseon period, but its traditional path has been severed, becoming a local specialty in some southern regions and altered into other forms of jang. However, some jongka (宗家, traditional Korean family) continue to pass down jipjang recipes via the jongbu (the head daughter-in-law). Method: We conducted in-depth interviews with the jongbu of six jongkas in the Kyeongsang and Chonla provinces to investigate their jipjang recipes. Results: The Kalam, Hakbong, and Dongkye Jongka made their own meju powder by hand before mixing with hard-steamed glutinous rice or glutinous rice glue and pickled vegetables. The Nosongjeong Jongka used commercial meju mixed with glutinous rice glue, wheat yeast, eggplant, chives, and gourd. The Chunwujae Jongka mixed hard-steamed glutinous rice in meju with thin jocheong made by boiling yeotkireum water and 10 other ingredients. The Cheongjaekongpa Jongka mixed commercial meju with vegetables but used a modernized recipe. Conclusion: Although kanjang, doenjang, and gochujang require months to ferment and ripen, thereby taking longer from production to sale; using an electric rice cooker can enable jipjang to be made within a week. Hence, with the development of improved pickling technology, jipjang is predicted to become more economically feasible than other jang products. We will continue to identify Korean traditional fermented foods made in jongka and systematize their recipes. Keywords: Fermentation, Jipjang, Jongka, Korean foodways, Soybeans, Traditional food

Leelamine (LEE) has recently attracted significant attention for its growth inhibitory effects against melanoma, breast cancer, and prostate cancer cells; however, its impact on hematological malignancies remains unclear. Here, we first investigate the cytotoxic effects of LEE on several human chronic myeloid leukemia (CML) cells. We noted that LEE stimulated both apoptosis and autophagy in CML cells. In addition, the constitutive activation of signal transducer and activator of transcription 5 (STAT5) was suppressed substantially upon LEE treatment. Moreover, STAT5 knockdown with small interfering RNA (siRNA) increased LEE-induced apoptosis as well as autophagy and affected the levels of various oncogenic proteins. Thus, the targeted mitigation of STAT5 activation by LEE can contribute to its diverse anticancer effects by enhancing two distinct cell death pathways.

The importance of apolipoprotein E (APOE) in late-onset Alzheimer's disease (LOAD) has been firmly established, but the mechanisms through which it exerts its pathogenic effects remain elusive. In addition, the sex-dependent effects of APOE on LOAD risk and endophenotypes have yet to be explained. In this Review, we revisit the different aspects of APOE involvement in neurodegeneration and neurological diseases, with particular attention to sex differences in the contribution of APOE to LOAD susceptibility. We discuss the role of APOE in a broader range of age-related neurodegenerative diseases, and summarize the biological factors linking APOE to sex hormones, drawing on supportive findings from rodent models to identify major mechanistic themes underlying the exacerbation of LOAD-associated neurodegeneration and pathology in the female brain. Additionally, we list sex-by-genotype interactions identified across neurodegenerative diseases, proposing APOE variants as a shared etiology for sex differences in the manifestation of these diseases. Finally, we present recent advancements in ‘omics’ technologies, which provide a new platform for more in-depth investigations of how dysregulation of this gene affects the development and progression of neurodegenerative diseases. Collectively, the evidence summarized in this Review highlights the interplay between APOE and sex as a key factor in the etiology of LOAD and other age-related neurodegenerative diseases. We emphasize the importance of careful examination of sex as a contributing factor in studying the underpinning genetics of neurodegenerative diseases in general, but particularly for LOAD.

Background: Jongka (宗家, a traditional Korean family) is a traditional Korean familial system that has existed since the mid-Chosun period (1392–1910). The present study explores the etymology and historical value of a representative ancestral ritual food of jongka, “ssam (쌈).” Over many years, ssam has been gradually modified from its original form. This study seeks to identify the history of ssam's transformation and to determine its original form. Methods: Three related dishes were considered, and finally, the “mitssam (밑쌈)” of Bangchon jongka was selected for a field study in which the author visited a jongka to prepare “mitssam” and participated in bulcheonwi (不遷位, unmovable ancestral tablet) ancestral rites. Results: It was found that the name “mitssam” is a misnomer of the proper name “mwissam (뮈쌈)” with the “mwi (뮈)” in “mwissam” being a pure Korean word referring to a sea cucumber (海蔘). Haesamjeon (海蔘煎, a pancake made with sea cucumber) probably first appeared in records in the later 17th century and early 18th century. The pure Korean word “mwi” used in the 19th century fell out of use in the 20th century as the modern term “missam (미쌈)” took over. “Mwi” was eventually replaced with “mi (미);” members of the jongka pronounced “mwissam” as “mitssam” when speaking the term, and eventually “mitssam” became the name of the dish. Conclusion: Apart from “mwissam,” other lost jongka ancestral ritual foods and related recipes should be recovered. They should be maintained along with modern recipes and Korea's traditional food culture values. Keywords: Ancestral ritual food, Haesamjeon, Jongka, Korea, Ssam food

Background: In the agrarian society of historical Korea, jesa (祭祀, traditional rite from ancestors), rituals practiced for praying to the gods for a rich harvest, was one of the most important rites. Since its founding, Chosun adopted Korean Confucianism and Neo-Confucianism as its governing principles, and karye (家禮, family rites of Zhu Xi), the customary formalities of the family, was perceived as an obligatory guideline to practice with the Confucian rites. This study aims to examine periodic changes in how the ritual table was set up in Korea's traditional head families, or jongka (宗家, the traditional Korean family), from the Chosun Dynasty (1392–1910) to the present time. Methods: We compared the varieties of food and their positioning in a diagram illustrating the placement of ritual food or jinseoldo (diagram illustrating the placement of ritual foods for ancestral rites), from karye, and three guides about family rites published during the Chosun era. We also analyzed the food arrangement style for ancestral rites from the ritual standards of the Japanese colonial era and the Simplified Family Ritual Standards issued by the Korean government. In addition, we visited eight head families to observe the varieties and positioning of fruits on the ritual table. Results: During the Japanese rule (1910–1945), the Japanese Government General of Korea declared the ritual standards for the purpose of simplifying the ritual practices of Chosun, but with an ulterior motive to disintegrate Korea's traditional rites and put the nation under its control. After independence from Japanese rule, the Korean government insisted on a new set of family ritual standards. However, the standards imposed from the outside rarely affected the rites practiced by families. Conclusion: The examination of historical records revealed that kakarye (家家禮, different rituals by each family) was being practiced among families, which causes only formalities to remain and sincerity to disappear. This is unfortunate as sincerity matters more than formalities. (The “Supplementary File” provides further explanations of each term mentioned in this article.) Keywords: Ancestral rites, Ancestral ritual food, Historical changes, Jongka, Table setting

Pyrimethamine (Pyri) is being used in combination with other medications to treat serious parasitic infections of the body, brain, or eye and to also reduce toxoplasmosis infection in the patients with HIV infection. Additionally, Pyri can display significant anti-cancer potential in different tumor models, but the possible mode of its actions remains unclear. Hence, in this study, the possible anti-tumoral impact of Pyri on human chronic myeloid leukemia (CML) was deciphered. Pyri inhibited cell growth in various types of tumor cells and exhibited a marked inhibitory action on CML cells. In addition to apoptosis, Pyri also triggered sustained autophagy. Targeted inhibition of autophagy sensitized the tumor cells to Pyri-induced apoptotic cell death. Moreover, the activation of signal transducer and activator of transcription 5 (STAT5) and its downstream target gene Bcl-2 was attenuated by Pyri. Accordingly, small interfering RNA (siRNA)-mediated STAT5 knockdown augmented Pyri-induced autophagy and apoptosis and promoted the suppressive action of Pyri on cell viability. Moreover, ectopic overexpression of Bcl-2 protected the cells from Pyri-mediated autophagy and apoptosis. Overall, the data indicated that the attenuation of STAT5-Bcl-2 cascade by Pyri can regulate its growth inhibitory properties by simultaneously targeting both apoptosis and autophagy cell death mechanism(s).

The meniscus has poor intrinsic regenerative capability, and its injury inevitably leads to articular cartilage degeneration. Although there are commercialized off-the-shelf alternatives to achieve total meniscus regeneration, each has its own shortcomings such as individualized size matching issues and inappropriate mechanical properties. We manufactured a polycaprolactone-based patient-specific designed framework via a Computed Tomography scan images and 3D-printing technique. Then, we completed the hybrid-scaffold by combining the 3D-printed framework and mixture micro-size composite which consists of polycaprolactone and sodium chloride to create a cell-friendly microenvironment. Based on this hybrid-scaffold with an autograft cell source (fibrochondrocyte), we assessed mechanical and histological results using the rabbit total meniscectomy model. At postoperative 12-week, hybrid-scaffold achieved neo-meniscus tissue formation, and its shape was maintained without rupture or break away from the knee joint. Histological and immunohistochemical analysis results showed obvious ingrowth of the fibroblast-like cells and chondrocyte cells as well as mature lacunae that were embedded in the extracellular matrix. Hybrid-scaffolding resulted in superior shape matching as compared to original meniscus tissue. Histological analysis showed evidence of extensive neo-meniscus cell ingrowth. Additionally, the hybrid-scaffold did not induce osteoarthritis on the femoral condyle surface. The 3D-printed hybrid-scaffold may provide a promising approach that can be applied to those who received total meniscal resection, using patient-specific design and autogenous cell source.

Background/purpose: Activation of cell surface CD30 by immobilized anti-CD30 monoclonal antibodies (mAb) induces strong apoptosis in human eosinophils. This anti-CD30 mAb-induced eosinophil apoptosis is inhibited by the addition of inhibitors of p38, ERK1/2 mitogen-activated protein kinases, and phosphatidylinositol 3-kinase. However, there is little data investigating the role of Bcl-2 and caspases in eosinophil apoptosis induced by anti-CD30 mAb. We sought to determine whether anti-CD30 mAb induces human eosinophil apoptosis via Bcl-2 and caspase pathways. Methods: Peripheral blood was drawn from 37 healthy volunteers. The CD30 expression on eosinophils was measured at various time points. Eosinophils were then cultured in plates precoated with anti-CD30 mAb (clone Ber-H8), isotype control immunoglobulin G1, interleukin (IL)-5, or dexamethasone. Western blot analysis was performed to determine the expression of Bcl-2, procaspase-8, -9, and -3, and caspase-8, -9, and -3 after cross-linking of CD30. Human eosinophils were also cultured in plates precoated with anti-CD30 mAb (clone Ber-H8) in the presence or absence of caspase-9 or -3 inhibitors. Eosinophil apoptosis was assessed using flow cytometry. Results: The addition of anti-CD30 mAb significantly increased eosinophil apoptosis compared with controls. In western blot analysis, the addition of anti-CD30 mAb significantly decreased the expression of Bcl-2 and procaspase-9 and -3 and increased the expression of caspase-9 and -3. The addition of caspase-9 or -3 inhibitors decreased anti-CD30 mAb-induced human eosinophil apoptosis. Procaspase-8 or caspase-8 expression was not changed in response to various stimuli. Conclusion: Anti-CD30 mAb-induced human eosinophil apoptosis is likely to be mediated through Bcl-2 and caspase-9 and -3.

Abstract Perovskite solar cells (PSCs) with mesoporous TiO2 (mp‐TiO2) as the electron transport material attain power conversion efficiencies (PCEs) above 22%; however, their poor long‐term stability is a critical issue that must be resolved for commercialization. Herein, it is demonstrated that the long‐term operational stability of mp‐TiO2 based PSCs with PCE over 20% is achieved by isolating devices from oxygen and humidity. This achievement attributes to systematic understanding of the critical role of oxygen in the degradation of PSCs. PSCs exhibit fast degradation under controlled oxygen atmosphere and illumination, which is accompanied by iodine migration into the hole transport material (HTM). A diffusion barrier at the HTM/perovskite interface or encapsulation on top of the devices improves the stability against oxygen under light soaking. Notably, a mp‐TiO2 based PSC with a solid encapsulation retains 20% efficiency after 1000 h of 1 sun (AM1.5G including UV) illumination in ambient air.

Abstract Recent advances in perovskite solar cells (PSCs) have resulted in greater than 23% efficiency with superior advantages such as flexibility and solution‐processability, allowing PSCs to be fabricated by a high‐throughput and low‐cost roll‐to‐roll (R2R) process. The development of scalable deposition processes is crucial to realize R2R production of flexible PSCs. Gravure printing is a promising candidate with the benefit of direct printing of the desired layer with arbitrary shape and size by using the R2R process. Here, flexible PSCs are fabricated by gravure printing. Printing inks and processing parameters are optimized to obtain smooth and uniform films. SnO2 nanoparticles are uniformly printed by reducing surface tension. Perovskite layers are successfully formed by optimizing the printing parameters and subsequent antisolvent bathing. 2,2′,7,7′‐Tetrakis‐(N,N‐di‐4‐methoxyphenylamino)‐9,9′‐spirobifluorene is also successfully printed. The all‐gravure‐printed device exhibits 17.2% champion efficiency, with 15.5% maximum power point tracking efficiency for 1000 s. Gravure‐printed flexible PSCs based on a two‐step deposition of perovskite layer are also demonstrated. Furthermore, a R2R process based on the gravure printing is demonstrated. The champion efficiency of 9.7% is achieved for partly R2R‐processed PSCs based on a two‐step fabrication of the perovskite layer.

Purpose: The potential effects of bergamotiin (BGM) on the suppression of cancer cachexia was evaluated under in vitro and in vivo conditions to investigate its possible inhibitory effects on the muscle and fat loss. Method: The differentiated C2C12 and 3T3L1 cells were treated with BGM after the induction of cancer-cachexia with pancreatic cancer conditioned media (CM). The expression levels of the various molecules involved in the differentiation and loss of muscle and fat (MuRF-1, Atrogin-1, C/EBPα, and PPARγ) were analyzed by Western blot and oil red O staining. For in vivo experiment, MIA PaCa-2 cells were injected into the mice (n = 6), and then BGM (1 mg/kg) was intraperitoneally administered to analyze muscle and adipose tissue by Hematoxylin and Eosin staining and Western blot. Result: BGM displayed a significant effect on the inhibition of muscle and fat catabolism under both in vitro and in vivo conditions. The results of the in vivo experiment revealed a remarkable suppressive effect of BGM on the weight loss in mice. Conclusions: The potential effects of BGM on the inhibition of muscle and fat catabolism in vitro and in vivo were thus confirmed. Based on the results, the impact of BGM on cancer cachexia could be possibly analyzed in the future clinical studies.

Primary intracranial germ cell tumor (GCT) is a rare tumor that generally occurs due to developmental anomaly. Although intracranial GCT is sensitive to treatment, a high recurrence rate, treatment-related long-term complications and the heterogeneity of this tumor group make treatment complicated. Moreover, because of its location, hydrocephalus and visual field defect, functional disturbance of the pituitary gland can occur and require attention. Treatment primarily relies on chemotherapy and radiation therapy but the management of intracranial GCT remains unsettled, especially in the case of unusual circumstances such as multifocal tumor or nongerminomatous GCT. Here, we present two unusual cases of intracranial GCT: one case with a bifocal intracranial germinoma, and the other with an intracranial choriocarcinoma. Both cases were treated with neoadjuvant chemotherapy followed by reduced-field radiation therapy without significant treatment-related complication. Further, we performed a PubMed search to investigate the appropriate treatment strategy for this unusual subtype of intracranial GCT.

Among 3D-printed composite scaffolds for bone tissue engineering, researchers have been attracted to the use of zinc ions to improve the scaffold’s anti-bacterial activity and prevent surgical site infection. In this study, we assumed that the concentration of zinc ions released from the scaffold will be correlated with the thickness of the zinc oxide coating on 3D-printed scaffolds. We investigated the adequate thickness of zinc oxide coating by comparing different scaffolds’ characteristics, antibacterial activity, and in vitro cell response. The scaffolds’ compressive modulus decreased as the zinc oxide coating thickness increased (10, 100 and 200 nm). However, the compressive modulus of scaffolds in this study were superior to those of other reported scaffolds because our scaffolds had a kagome structure and were made of composite material. In regard to the antibacterial activity and in vitro cell response, the in vitro cell proliferation on scaffolds with a zinc oxide coating was higher than that of the control scaffold. Moreover, the antibacterial activity of scaffolds with 100 or 200 nm-thick zinc oxide coating on Escherichia coli was superior to that of other scaffolds. Therefore, we concluded that the scaffold with a 100 nm-thick zinc oxide coating was the most appropriate scaffold to use as a bone-regenerating scaffold, given its mechanical property, its antibacterial activity, and its in vitro cell proliferation.

Matrine, a quinolizidine alkaloid, is commonly employed for treating various viral and inflammatory disorders. Here, we have evaluated matrine for its activity on C-X-C chemokine receptor type 4 (CXCR4) and matrix metalloproteinases (MMP-9/2) expression, and its potential to affect tumor metastasis and invasion. The effects of matrine on CXCR4, MMP-9/2, and nuclear factor κB (NF-κB) activation in lung (A549), prostate (DU145), and pancreas (MIA PaCa-2) cells were investigated by diverse techniques. The expression level of CXCR4 and MMP-9/2 was analyzed by western blot analysis and reverse transcription polymerase chain reaction. NF-κB activation was also evaluated by western blot analysis, electrophoretic mobility shift assay as well as immunocytochemical experiments. Furthermore, we monitored cell invasion and metastasis activities by wound healing and Boyden chamber assays. We noted that matrine induced a down-regulation of CXCR4 and MMP-9/2 at both protein and mRNA levels. In addition, matrine negatively regulated human epidermal growth factor receptor 2 (HER2) and C-X-C Motif Chemokine Ligand 12 (CXCL12)-induced CXCR4 expression. Moreover, NF-κB suppression by matrine led to inhibition of metastatic potential of tumor cells. Our results suggest that matrine can block the cancer metastasis through the negative regulation of CXCR4 and MMP-9/2 and consequently it can be considered as a potential candidate for cancer therapy.

A diffusion bonding system to fabricate long tubular parts by joining of two- or more-unit tubes made of tungsten heavy alloys (THAs) is proposed and characterized in this study. The difficulty of powder processing of THA originates from the weak strength of the green compact and the high weight of the THA powders. The long tubular green compact is difficult to handle due to its weak structural integrity. Furthermore, gravity-induced slumping during liquid phase sintering induces dimensional distortion and degrades the mechanical performances. As a clue for solving these problems, the unit tubes are fabricated. However, the mass of green compacts for unit tubes is not sufficiently great as to cause problematic slumping; tubular unit tubes can be obtained without significant difficulty. Fabricated unit tubes are stacked in a furnace chamber and diffusion-bonded to produce a long tubular part having bond strength substantially equal to that of a monolithic tube. The proposed diffusion bonding system was well characterized and successfully applied to the industrial production line. The feasibility was also confirmed by investigating the bond quality, which can be assessed by metallographic microstructure and mechanical property.

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.

Brain parenchymal metastasis from a solid tumor is a serious clinical condition associated with a poor outcome because systemic chemotherapy is usually ineffective for treating brain metastases (BM) due to the blood-brain barrier. Therefore, radiotherapy such as whole brain radiotherapy (WBRT) and stereotactic radiosurgery have taken on a central role in the management of BM. However, WBRT can delay subsequent systemic treatment or cause neurologic complications such as a decline in cognitive function. Therefore, suspending WBRT is worth considering if there is an effective alternative. Although there have been no large prospective studies, many reports are available about the favorable effect of tyrosine kinase inhibitors (TKIs) for treating BM in patients with non-small cell lung cancer (NSCLC). Here, we report 3 NSCLC cases that showed a complete response in BM after TKI treatment without WBRT. Based on these remarkable response rates of BM to a TKI, the potential toxicity of WBRT can be avoided, particularly in patients with small metastatic nodules and an epidermal growth factor receptor activating mutation.

As nitrogen is nonreactive and non-flammable, it can provide a quick and simple medium of cooling and environment protection. One disadvantage of nitrogen cooling is its lower heat transfer coefficient than water. Despite its lower cooling capacity, nitrogen cooling can produce cleaner products, thereby eliminating the need to wash the parts and dispose of the contaminated water. In this study, an innovative nitrogen cooling system was developed for an accelerated and eco-friendly cooling of metallic parts. The dry nitrogen gas, transported via the nozzle of a cryogenic liquid nitrogen tank, is passed into the cooling chamber and exchanges heat with the workpiece. The heated nitrogen gas is forcibly transported to the chiller, where the heat is reduced, and the cooled gas is circulated again. The performance of this nitrogen cooling system has been evaluated with cooling experiments of sintered tungsten heavy alloys. The nitrogen-cooled product shows a clean surface with improved mechanical properties. Furthermore, nitrogen induces less distortion compared to water cooling, thus reducing the post-machining costs.

Fangchinoline (FCN) derived from Stephaniae tetrandrine S. Moore can be employed to treat fever, inflammation, rheumatism arthralgia, edema, dysuria, athlete’s foot, and swollen wet sores. FCN can exhibit a plethora of anti-neoplastic effects although its precise mode of action still remains to be deciphered. Nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) can closely regulate carcinogenesis and thus we analyzed the possible action of FCN may have on these two signaling cascades in tumor cells. The effect of FCN on NF-κB and AP-1 signaling cascades and its downstream functions was deciphered using diverse assays in both human chronic myeloid leukemia (KBM5) and multiple myeloma (U266). FCN attenuated growth of both leukemic and multiple myeloma cells and repressed NF-κB, and AP-1 activation through diverse mechanisms, including attenuation of phosphorylation of IκB kinase (IKK) and p65. Furthermore, FCN could also cause significant enhancement in TNFα-driven apoptosis as studied by various molecular techniques. Thus, FCN may exhibit potent anti-neoplastic effects by affecting diverse oncogenic pathways and may be employed as pro-apoptotic agent against various malignancies.

The melt-pool behaviors during selective laser melting (SLM) of Al2O3-reinforced and a eutectic mixture of Al2O3-ZrO2-reinforced AISI 304 stainless-steel composites were numerically analyzed and experimentally validated. The thermal analysis results show that the geometry of the melt pool is significantly dependent on reinforcing particles, owing to the variations in the melting point and the thermal conductivity of the powder mixture. With the use of a eutectic mixture of Al2O3-ZrO2 instead of an Al2O3 reinforcing particle, the maximum temperature of the melt pool was increased. Meanwhile, a negligible corresponding relationship was observed between the cooling rate of both reinforcements. Therefore, it was identified that the liquid lifetime of the melt pool has the effect on the melting behavior, rather than the cooling rate, and the liquid lifetime increases with the eutectic ratio of Al2O3-ZrO2 reinforcement. The temperature gradient at the top surface reduces with the use of an Al2O3-ZrO2 reinforcement particle due to the wider melt pool. Inversely, the temperature gradient in the thickness direction increases with the use of an Al2O3-ZrO2 reinforcement particle. The results of melt-pool behaviors will provide a deep understanding of the effect of reinforcing particles on the dimensional accuracies and properties of fabricated AISI 304 stainless-steel composites.

For the last couple of decades, natural products, either applied singly or in conjunction with other cancer therapies including chemotherapy and radiotherapy, have allowed us to combat different types of human cancers through the inhibition of their initiation and progression. The principal sources of these useful compounds are isolated from plants that were described in traditional medicines for their curative potential. Leelamine, derived from the bark of pine trees, was previously reported as having a weak agonistic effect on cannabinoid receptors and limited inhibitory effects on pyruvate dehydrogenase kinases (PDKs). It has been reported to possess a strong lysosomotropic property; this feature enables its assembly inside the acidic compartments within a cell, such as lysosomes, which may eventually hinder endocytosis. In this review, we briefly highlight the varied antineoplastic actions of leelamine that have found implications in pharmacological research, and the numerous intracellular targets affected by this agent that can effectively negate the oncogenic process.

The selective laser-melting (SLM) process can be applied to the additive building of complex metal parts using melting metal powder with laser scanning. A metal mesh is a common type of metal screen consisting of parallel rows and intersecting columns. It is widely used in the agricultural, industrial, transportation, and machine protection sectors. This study investigated the fabrication of parts containing a mesh pattern from the SLM of AISI 304 stainless steel powder. The formation of a mesh pattern has a strong potential to increase the functionality and cost-effectiveness of the SLM process. To fabricate a single-layered thin mesh pattern, laser layering has been conducted on a copper base plate. The high thermal conductivity of copper allows heat to pass through it quickly, and prevents the adhesion of a thin laser-melted layer. The effects of the process conditions such as the laser scan speed and scanning path on the size and dimensional accuracy of the fabricated mesh patterns were characterized. As the analysis results indicate, a part with a mesh pattern was successfully obtained, and the application of the proposed method was shown to be feasible with a high degree of reliability.

Oxymatrine (OMT) is a major alkaloid found in radix Sophorae flavescentis extract and has been reported to exhibit various pharmacological activities. We elucidated the detailed molecular mechanism(s) underlying the therapeutic actions of OMT in non-small cell lung cancer (NSCLC) cells and a xenograft mouse model. Because the STAT5 signaling cascade has a significant role in regulating cell proliferation and survival in tumor cells, we hypothesized that OMT may disrupt this signaling cascade to exert its anticancer effects. We found that OMT can inhibit the constitutive activation of STAT5 by suppressing the activation of JAK1/2 and c-Src, nuclear localization, as well as STAT5 binding to DNA in A549 cells and abrogated IL-6-induced STAT5 phosphorylation in H1299 cells. We also report that a sub-optimal concentration of OMT when used in combination with a low dose of paclitaxel produced significant anti-cancer effects by inhibiting cell proliferation and causing substantial apoptosis. In a preclinical lung cancer mouse model, OMT when used in combination with paclitaxel produced a significant reduction in tumor volume. These results suggest that OMT in combination with paclitaxel can cause an attenuation of lung cancer growth both in vitro and in vivo.

Farnesol, an acyclic sesquiterpene alcohol, is predominantly found in essential oils of various plants in nature. It has been reported to exhibit anti-cancer and anti-inflammatory effects, and also alleviate allergic asthma, gliosis, and edema. In numerous tumor cell lines, farnesol can modulate various tumorigenic proteins and/or modulates diverse signal transduction cascades. It can also induce apoptosis and downregulate cell proliferation, angiogenesis, and cell survival. To exert its anti-inflammatory/anti-oncogenic effects, farnesol can modulate Ras protein and nuclear factor kappa-light-chain-enhancer of activated B cells activation to downregulate the expression of various inflammatory mediators such as cyclooxygenase-2, inducible nitric oxide synthase, tumor necrosis factor alpha, and interleukin-6. In this review, we describe the potential mechanisms of action underlying the therapeutic effects of farnesol against cancers and inflammatory disorders. Furthermore, these findings support the clinical development of farnesol as a potential pharmacological agent in clinical studies.