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Simple Summary: Ductal carcinoma in situ (DCIS) patients have an excellent overall survival rate and over-treatment is always a cause for concern due to potential side-effects. Standard clinicopathological parameters have limited value in predicting breast cancer events (BCEs) and stratification of high and low risk patients. Herein, we have developed a deep learning (DL) classification framework to predict BCEs in DCIS patients. A generative adversarial network (GAN) augmented deep learning (DL) classification of histological features associated with aggressive disease was trained on hematoxylin and eosin (H & E) tissue microarray (TMA) images of DCIS to predict BCEs. The area under the curve (AUC) for BCE's in the validation set was 0.82. Early and accurate prediction of DCIS BCEs would facilitate a personalized approach to therapy. Standard clinicopathological parameters (age, growth pattern, tumor size, margin status, and grade) have been shown to have limited value in predicting recurrence in ductal carcinoma in situ (DCIS) patients. Early and accurate recurrence prediction would facilitate a more aggressive treatment policy for high-risk patients (mastectomy or adjuvant radiation therapy), and simultaneously reduce over-treatment of low-risk patients. Generative adversarial networks (GAN) are a class of DL models in which two adversarial neural networks, generator and discriminator, compete with each other to generate high quality images. In this work, we have developed a deep learning (DL) classification network that predicts breast cancer events (BCEs) in DCIS patients using hematoxylin and eosin (H & E) images. The DL classification model was trained on 67 patients using image patches from the actual DCIS cores and GAN generated image patches to predict breast cancer events (BCEs). The hold-out validation dataset (n = 66) had an AUC of 0.82. Bayesian analysis further confirmed the independence of the model from classical clinicopathological parameters. DL models of H & E images may be used as a risk stratification strategy for DCIS patients to personalize therapy. [ABSTRACT FROM AUTHOR]

PTEN-induced kinase-1 (PINK1) is the initiator of the canonical mitophagy pathway. Our aim was to study the immunoexpression of PINK1 in surgical specimens from ninety patients with metastatic colorectal adenocarcinoma (CRC) to the liver (CRLM). Tissue arrays were produced, and immunohistochemical studies were analyzed by the H-Score method. The mean immunoexpression of PINK1 in normal tissues was between 40 to 100 points. In tumoral tissues, positive PINK1 immunoexpression was observed in all samples, and no differences were noted between CRCs. In CRLMs, a significant under-expression was noted for PINK1 from the rectum (71.3 ± 30.8; p < 0.042) compared to other sites. Altered PINK1 immunoexpression in CRCs, either higher than 100 points or lower than 40 points, was associated with worse overall survival (OS) (p < 0.012) due to a shorter post-metastatic survival (PMS) (p < 0.023), and it was found to be a significant independent predictor of prognosis in a multivariate model for OS and PMS (HR = 1.972, 95% CI 0.971–4.005; p = 0.022. HR = 2.023, 95% CI 1.003–4.091; p = 0.037, respectively). In conclusion, altered PINK1 immunoexpression determined in CRCs with resected CRLM predicts a worse prognosis, possibly due to the abnormal function of mitophagy. [ABSTRACT FROM AUTHOR]

Background & Objective: Tissue microarray (TMA) is a method of harvesting small tissue cores from a number of donor paraffin tissue blocks and arraying them in a recipient paraffin block. It has numerous advantages and applications but is expensive. This study aimed to develop a simple yet efficient method of manual, small-format TMA block construction. Methods: Disposable skin punch biopsy needles were used to manually core out 4-mm cylinders from the archival donor blocks comprising tissue from 60 thyroidectomy specimens. These cores were oriented in the embedding cassette in accordance with the grid design. The molten wax was slowly dispensed and allowed to be set. Sectioning, mounting, and hematoxylin and eosin (H&E) staining were performed by a conventional method. Immunohistochemical studies, using HBME-1, CK19, and S100 antibodies, were also performed on these tissue array sections. Results: There was no core loss during processing. Technical issues like core tilt and floatation were easily tackled. Morphological identification, histological typing, and immunohistochemical analysis could be satisfactorily performed in these TMA sections. Donor blocks did not break after punching. Conclusion: This TMA construction method is simple, feasible, easily reproducible, and time-saving. It can serve as an excellent cost-effective alternative for resource-poor laboratories for carrying out immunohistochemical studies. [ABSTRACT FROM AUTHOR]

The demand for unprecedented data and ubiquitous wireless connections have led to the adoption of new types of transmitters and receivers. Additionally, different new types of devices and technologies need to be proposed for such demand. Reconfigurable intelligent surface (RIS) is going to play a very significant role in the upcoming beyond-5G/6G communications. It is envisioned that not only the RIS will be deployed to assist and create a smart wireless environment for the upcoming communications, but also the receiver and transmitter can be fabricated using RIS to make a smart and intelligent transmitter and receiver. Thus, the latency of upcoming communications can be reduced very significantly using RIS, which is a very important factor. Artificial intelligence assists communications and shall be adopted widely for the next generation networks. In this paper, radiation pattern measurement results of our previously published RIS have been provided. This work is the extension work of our previously proposed RIS. The polarization-independent passive type of RIS working in the sub-6 GHz frequency band using low-cost FR4-substrate was designed. Each unit cell with dimensions of 42 mm × 42 mm had a single-layer substrate backed by a copper plate. A 10 × 10-unit cell array was fabricated to check the performance of the RIS. Such types of unit cells and RIS were designed to set up initial measurement facilities in our laboratory for any kinds of RIS measurements. [ABSTRACT FROM AUTHOR]

The neural crest is a vertebrate-specific embryonic stem cell population that gives rise to a vast array of cell types throughout the animal body plan. These cells are first born at the edges of the central nervous system, from which they migrate extensively and differentiate into multiple cellular derivatives. Given the unique set of structures these cells comprise, the origin of the neural crest is thought to have important implications for the evolution and diversification of the vertebrate clade. In jawed vertebrates, neural crest cells exist as distinct subpopulations along the anterior-posterior axis. These subpopulations differ in terms of their respective differentiation potential and cellular derivatives. Thus, the modern neural crest is characterized as multipotent, migratory, and regionally segregated throughout the embryo. Here, we retrace the evolutionary origins of the neural crest, from the appearance of conserved regulatory circuitry in basal chordates to the emergence of neural crest subpopulations in higher vertebrates. Finally, we discuss a stepwise trajectory by which these cells may have arisen and diversified throughout vertebrate evolution. [ABSTRACT FROM AUTHOR]

Background: Our previous studies have identified CA916798 as a chemotherapy resistance-associated gene in lung cancer. However, the histopathological relevance and biological function of CA916798 in lung adenocarcinoma (LUAD) remains to be delineated. In this study, we further investigated and explored the clinical and biological significance of CA916798 in LUAD. Methods: The relationship between CA916798 and clinical features of LUAD was analyzed by tissue array and online database. CCK8 and flow cytometry were used to measure cell proliferation and cell cycle of LUAD after knockdown of CA916798 gene. qRT-PCR and western blotting were used to detect the changes of cell cycle-related genes after knockdown or overexpression of CA916798. The tumorigenesis of LUAD cells was evaluated with or without engineering manipulation of CA916798 gene expression. Response to Gefitinib was evaluated using LUAD cells with forced expression or knockdown of CA916798. Results: The analysis on LUAD samples showed that high expression of CA916798 was tightly correlated with pathological progression and poor prognosis of LUAD patients. A critical methylation site in promoter region of CA916798 gene was identified to be related with CA916798 gene expression. Forced expression of CA916798 relieved the inhibitory effects of WEE1 on CDK1 and facilitated cell cycle progression from G2 phase to M phase. However, knockdown of CA916798 enhanced WEE1 function and resulted in G2/M phase arrest. Consistently, chemical suppression of CDK1 dramatically inhibited G2/M phase transition in LUAD cells with high expression of CA916798. Finally, we found that CA916798 was highly expressed in Gefitinib-resistant LUAD cells. Exogenous expression of CA916798 was sufficient to endow Gefitinib resistance with tumor cells, but interference of CA916798 expression largely rescued response of tumor cells to Gefitinib. Conclusions: CA916798 played oncogenic roles and was correlated with the development of Gefitinib resistance in LUAD cells. Therefore, CA916798 could be considered as a promising prognostic marker and a therapeutic target for LUAD. [ABSTRACT FROM AUTHOR]

Background: Bushenhuoxue (BSHX) formula, a ten-compound herbal decoction, is widely used to treat postmenopausal osteoporosis (PMOP) in China. However, the mechanism is not clear yet. Methods: The underlying biological processes and signaling pathways were predicted by network pharmacology. In vivo experimental study, 24 female C57BL/6 J mice were randomly divided into sham, ovariectomized (OVX) and BSHX formula groups. Mice in the latter two groups were subjected to bilateral ovariectomy, and mice in the BSHX formula group were extra treated by BSHX formula at an oral dosage of 0.2 mL/10 g for 8 weeks. The femur samples were harvested for tissue analyses including μCT assay, histology and immunohistochemical (IHC) staining of VEGF signaling. Results: A total of 218 active ingredients and 274 related targets were identified in BSHX formula. After matching with 292 targets of PMOP, 64 overlapping genes were obtained. GO and KEGG enrichment analyses on these 64 genes revealed that angiogenesis and VEGF signaling were considered as the potential therapeutic mechanism of BSHX formula against PMOP. Animal experiments showed that mice in the BSHX formula-treated group presented increased bone mass, microstructural parameters, blood vessel numbers and an activation of VEGF signaling (VEGF, COX2, eNOS and CD31) compared to the OVX mice. Conclusion: This study revealed that BSHX formula exerts anti-PMOP effects possibly through activating VEGF signaling-mediated angiogenesis. [ABSTRACT FROM AUTHOR]

Study Design.: We performed histologic, immunohistochemical, immunoblot examination and suspension array analyses of cytokine expression in cultured cells derived from human cervical ossification of the posterior longitudinal ligament (OPLL). Objective.: To determine the roles of interleukin-6 (IL-6) during the maturation of osteoblasts and chondrocytes associated with the development of OPLL. Summary of Background Data.: Ectopic OPLL affects ~3% of the general population, with a higher incidence in Asian ethnic groups. Alterations in cytokine profiles may influence osteoblast differentiation, but the mechanisms and signaling pathways associated with the ossification process remain unclear. Methods.: Samples were collected from 14 patients with OPLL who had undergone spinal surgery and seven with cervical spondylotic myelopathy without OPLL. Tissue sections were used for histologic and immunohistochemical studies, and primary cells from ligamentum samples were used for cytokine array and immunoblotting. A suspension array was used to measure the concentrations of 27 inflammatory cytokines or growth factors. Results.: Suspension array and immunoblot analyses revealed significantly elevated levels of IL-6 in OPLL patients. Alterations in IL-6 concentrations were found to alter the expression of the genes Sox9 , Runx2 , and SIRT1. In addition, immunohistochemical analysis revealed that these factors are present in mesenchymal cells within the degenerative portion of the ligament matrix that is adjacent to the ossification front. Conclusions.: IL-6 plays a profound role in the osteoblast differentiation process along with the induction of chondrocyte hypertrophy and cell apoptosis in the early stages of ossification in OPLL. These changes in cytokine profiles are essential factors for regulation of the ectopic ossified plaque in OPLL. [ABSTRACT FROM AUTHOR]

Objective: For patients with advanced or metastatic renal cell carcinoma (RCC), the dose of targeted agents was recommended in combination with immune checkpoint inhibitors. We performed a network meta‐analysis to describe a categorized safety ranking profile and assess the adaptability of the combination options of targeted agents. Methods: The targeted agents refer to vascular endothelial growth factor tyrosine kinase inhibitors (VEGF‐TKIs) and mammalian target of rapamycin (mTOR) inhibitors. Randomized controlled trials comparing these drugs were enrolled in a Bayesian model network meta‐analysis. Results: Nineteen clinical trials with 11 treatments and 10,615 patients were included. For grade ≥ 3 adverse events (AEs), compared with placebo, lenvatinib plus everolimus showed worse safety than all other treatments except for lenvatinib (placebo vs. OR 0.23, 95% CI 0.07–0.78). Everolimus was generally the safest agent (OR 1.23, 95% CI 0.50–3.14). Sorafenib arose the least renal AEs (placebo vs. OR 0.85, 95% CI 0.06–11.64), whereas lenvatinib plus everolimus had the highest risk of renal toxicity (placebo vs. 0.17 95% CI 0.01–1.02). For gastrointestinal symptoms, everolimus was related to much lower toxicity than other agents. In the respiratory safety analysis, tivozanib (placebo vs. OR 0.15, 95% CI 0.07–0.31) and axitinib (OR 5.43, 95% CI 3.26–9.22) were the riskiest agents. In terms of hepatobiliary (placebo vs. OR 0.44, 95% CI 0.09–2.10) and hemotoxicity (placebo vs. OR 1.03, 95% CI 0.14–7.68) related AEs, lenvatinib was found to be the safest treatment compared to placebo. Conclusions: Everolimus, with the best safety of grade ≥ 3, gastrointestinal, and respiratory AEs, was more likely to be considered for combination therapies. Lenvatinib appears to be the safest for blood/lymphatic and hepatobiliary AEs. For patients with renal disorders, sorafenib arises the least renal toxicity AEs. This study will guide treatment options and optimize the trial design for advanced or metastatic RCC. [ABSTRACT FROM AUTHOR]

While loss-of-function mutations in the murine dominant white spotting/Kit (W) locus affect a diverse array of cell lineages and organs, the brain, organ with the highest expression show the least number of defective phenotypes. We performed transcriptome analysis of the brains of KitW embryos and found prominent gene expression changes specifically in the E12.5 KitW/W homozygous mutant. Although other potentially effective changes in gene expression were observed, uniform downregulation of ribosomal protein genes and oxidative phosphorylation pathway genes specifically observed in the E12.5 brain may comprise a genetic compensation system exerting protective metabolic effects against the deleterious effect of KitW/W mutation in the developing brain. [ABSTRACT FROM AUTHOR]

Stem cells play a crucial role in re-establishing homeostasis in the body, and the search for mechanisms by which they interact with the host to exert their therapeutic effects remains a key question currently being addressed. Considering their significant regenerative/therapeutic potential, research on mesenchymal stem cells (MSCs) has experienced an unprecedented advance in recent years, becoming the focus of extensive works worldwide to develop cell-based approaches for a variety of diseases. Initial evidence for the effectiveness of MSCs therapy comes from the restoration of dynamic microenvironmental homeostasis and endogenous stem cell function in recipient tissues by systemically delivered MSCs. The specific mechanisms by which the effects are exerted remain to be investigated in depth. Importantly, the profound cell-host interplay leaves persistent therapeutic benefits that remain detectable long after the disappearance of transplanted MSCs. In this review, we summarize recent advances on the role of MSCs in multiple disease models, provide insights into the mechanisms by which MSCs interact with endogenous stem cells to exert therapeutic effects, and refine the interconnections between MSCs and cells fused to damaged sites or differentiated into functional cells early in therapy. [ABSTRACT FROM AUTHOR]

Background: Lung cancer is a fatal disease that kills approximately 85% of those diagnosed with it. In recent years, advances in medical imaging have greatly improved the acquisition, storage, and visualization of various pathologies, making it a necessary component in medicine today. Objective: Develop a computer-aided diagnostic system to detect lung cancer early by segmenting tumor and non-tumor tissue on Tissue Micro Array Analysis (TMA) histopathological images. Method: The prototype computer-aided diagnostic system was developed to segment tumor areas, non-tumor areas, and fundus on TMA histopathological images. Results: The system achieved an average accuracy of 83.4% and an F-measurement of 84.4% in segmenting tumor and non-tumor tissue. Conclusion: The computer-aided diagnostic system provides a second diagnostic opinion to specialists, allowing for more precise diagnoses and more appropriate treatments for lung cancer. [ABSTRACT FROM AUTHOR]

Urine-based cytology is non-invasive and widely used for clinical diagnosis of urothelial carcinoma (UC), but its sensitivity is less than 40% for low-grade UC detection. As such, there is a need for new diagnostic and prognostic biomarkers of UC. CUB domain containing protein 1 (CDCP1) is a type I transmembrane glycoprotein highly expressed in various cancers. Using tissue array analysis, we demonstrated that CDCP1 expression in UC patients (n = 133), especially in those with low-grade UC, was significantly higher than in 16 normal persons. In addition, CDCP1 expression in urinary UC cells could also be detected by using immunocytochemistry method (n = 11). Furthermore, in 5637-CD cells, overexpression of CDCP1 affected the expression of epithelial mesenchymal transition-related markers and increased matrix metalloproteinase 2 expression and migration ability. Conversely, the knockdown of CDCP1 in T24 cells had the opposite effects. Using specific inhibitors, we demonstrated the involvement of c-Src/PKCδ signaling in the CDCP1-regulated migration of UC. In conclusion, our data suggest that CDCP1 contributes to the malignant progression of UC and may have the potential as a urine-based biomarker for detecting low-grade UC. However, a cohort study needs to be conducted. [ABSTRACT FROM AUTHOR]

A FIFO is a special type of buffer that controls the data flow between the sender and receiver. It is used to monitor the serial data flow and to avoid mismatch conditions. In general, the dual-ported memory cell array suffers from dynamic power dissipation. In this research article, a 128 x 128-bit Synchronous First-In-First-Out (FIFO) buffer is designed for dual-ported memory cell array with pipeline architecture using clock gating technique, which reduces power dissipation significantly. The FIFO-based dual-ported memory cell array will store a large amount of data and minimize the clock skew. A circular FIFO used in dual-ported memory is organized in a circular queue fashion with two pointers for write and read. Conventional FIFO designs use more power and hardware area on the silicon chip. The FIFO-based pipelining and clock gating approach will improve throughput while reducing dynamic power. The proposed FIFO design is simulated and implemented using the Cadence-Encounter tool using 180nm and 45nm Technology. The parameters power consumption, cell utilization, and clock frequency have been analyzed. The synchronous FIFO design reduces the area by 70.3%, power dissipation by 10.6%, and operates at clock frequency up to 322 MHz. [ABSTRACT FROM AUTHOR]

Inspired by nature, it is envisaged that a nanorough surface exhibits bactericidal properties by rupturing bacterial cells. In order to study the interaction mechanism between the cell membrane of a bacteria and a nanospike at the contact point, a finite element model was developed using the ABAQUS software package. The model, which saw a quarter of a gram-negative bacteria (Escherichia coli) cell membrane adhered to a 3 × 6 array of nanospikes, was validated by the published results, which show a reasonably good agreement with the model. The stress and strain development in the cell membrane was modeled and were observed to be spatially linear and temporally nonlinear. From the study, it was observed that the bacterial cell wall was deformed around the location of the nanospike tips as full contact was generated. Around the contact point, the principal stress reached above the critical stress leading to a creep deformation that is expected to cause cell rupture by penetrating the nanospike, and the mechanism is envisaged to be somewhat similar to that of a paper punching machine. The obtained results in this project can provide an insight on how bacterial cells of a specific species are deformed when they adhere to nanospikes, and how it is ruptured using this mechanism. [ABSTRACT FROM AUTHOR]

Spexin2 (SPX2), a paralog of SPX1, is a newly identified gene in non-mammalian vertebrates. Limited studies in fish have evidenced its important role in food intake and energy balance modulation. However, little is known about its biological functions in birds. Using the chicken (c-) as a model, we cloned the full-length cDNA of SPX2 by using RACE-PCR. It is 1189 base pair (bp) in length and predicted to generate a protein of 75 amino acids that contains a 14 amino acids mature peptide. Tissue distribution analysis showed that cSPX2 transcripts were detected in a wide array of tissues, with abundant expression in the pituitary, testis, and adrenal gland. cSPX2 was also observed to be ubiquitously expressed in chicken brain regions, with the highest expression in the hypothalamus. Its expression was significantly upregulated in the hypothalamus after 24 or 36 h of food deprivation, and the feeding behavior of chicks was obviously suppressed after peripheral injection with cSPX2. Mechanistically, further studies evidenced that cSPX2 acts as a satiety factor via upregulating cocaine and amphetamine regulated transcript (CART) and downregulating agouti-related neuropeptide (AGRP) in hypothalamus. Using a pGL4-SRE-luciferase reporter system, cSPX2 was demonstrated to effectively activate a chicken galanin II type receptor (cGALR2), a cGALR2-like receptor (cGALR2L), and a galanin III type receptor (cGALR3), with the highest binding affinity for cGALR2L. Collectively, we firstly identified that cSPX2 serves as a novel appetite monitor in chicken. Our findings will help clarify the physiological functions of SPX2 in birds as well as its functional evolution in vertebrates. [ABSTRACT FROM AUTHOR]

Background: Dendrobium nobile (D. nobile), a traditional Chinese medicine, has received attention as an anti-tumor drug, but its mechanism is still unclear. In this study, we applied network pharmacology, bioinformatics, and in vitro experiments to explore the effect and mechanism of Dendrobin A, the active ingredient of D. nobile, against pancreatic ductal adenocarcinoma (PDAC). Methods: The databases of SwissTargetPrediction and PharmMapper were used to obtain the potential targets of Dendrobin A, and the differentially expressed genes (DEGs) between PDAC and normal pancreatic tissues were obtained from The Cancer Genome Atlas and Genotype-Tissue Expression databases. The protein-protein interaction (PPI) network for Dendrobin A anti-PDAC targets was constructed based on the STRING database. Molecular docking was used to assess Dendrobin A anti-PDAC targets. PLAU, one of the key targets of Dendrobin A anti-PDAC, was immunohistochemically stained in clinical tissue arrays. Finally, in vitro experiments were used to validate the effects of Dendrobin A on PLAU expression and the proliferation, apoptosis, cell cycle, migration, and invasion of PDAC cells. Results: A total of 90 genes for Dendrobin A anti-PDAC were screened, and a PPI network for Dendrobin A anti-PDAC targets was constructed. Notably, a scale-free module with 19 genes in the PPI indicated that the PPI is highly credible. Among these 19 genes, PLAU was positively correlated with the cachexia status while negatively correlated with the overall survival of PDAC patients. Through molecular docking, Dendrobin A was found to bind to PLAU, and the Dendrobin A treatment led to an attenuated PLAU expression in PDAC cells. Based on clinical tissue arrays, PLAU protein was highly expressed in PDAC cells compared to normal controls, and PLAU protein levels were associated with the differentiation and lymph node metastatic status of PDAC. In vitro experiments further showed that Dendrobin A treatment significantly inhibited the proliferation, migration, and invasion, inducing apoptosis and arresting the cell cycle of PDAC cells at the G2/M phase. Conclusion: Dendrobin A, a representative active ingredient of D. nobile, can effectively fight against PDAC by targeting PLAU. Our results provide the foundation for future PDAC treatment based on D. nobile. [ABSTRACT FROM AUTHOR]

Random Access Memory (RAM) refers to the main memory of a computer. For the central processor unit (CPU) to operate quickly and effectively, it stores operating system software, applications, and other data. Unfortunately, single event upset and other high-soft error problems plague standard static RAM (SRAMs) in aircraft applications (SEU). Many Radiation-Hardened-Based Designs (RHBD) and Radiation-Hardened-Polar Designs (RHPD), such as the 12T We-Quatro and twelve-transistor (12T) Dice SRAM cells, have been created to address the soft error issues. However, they consume more total and static power, as well as have more delay and area. In this article, an RHPD and RHBD 12T SRAM cell is proposed to reduce power dissipation and area overhead. Compared to RHPD, the RHBD 12T SRAM cell devours less total and static power, and RHPD cells have less delay. The proposed SRAM cell is implemented in the 32 × 32 array architecture. The power consumption of a 32 × 32 SRAM array with a 12T RHBD SRAM cell is 1.33mW, which is 10.1% less than a 32 × 32 SRAM array with a 12T RHPD SRAM array is 4.23mW. Cadence virtuoso 6.1.5 at 45 nm Generic Process Design Kit (GPDK) technology file is used to simulate the comparative analysis for the SRAM cell. [ABSTRACT FROM AUTHOR]

Previously, two PMP cell lines, N14A and N15A, have been reported as the immortalized cell lines using a lentivirus with the entire SV40 genome, enabling the cells to achieve passaging for over 20 passages [29]. The NCC-PMP1-C1 cell line is the first PMP cell line derived from metastasized tissue and is a potential resource for basic and pre-clinical research on metastasized PMP. Third, NCC-PMP1-C1 cells comprised the first PMP cell line derived from a metastatic tumor of a patient with PMP. [Extracted from the article]

We created an ultra-thin, triple-band incident angle-insensitive perfect metamaterial absorber (MMA) with a metallic patch and a continuous metal ground isolated by a central dielectric substrate. The top metallic patch, placed across the edges of the 0.58 mm thickness Rogers RO4003C (lossy) substrate, forms the bulk of the projected absorber's ultra-thin layer. Nonetheless, absorption is exceedingly strong, covering C-band, X-band and K-band and reaching levels of 97.8%, 99.9%, and 99.9%, respectively, under normal and even oblique (0° to 45°) incident conditions. In chosen ranges of frequency of 6.24, 10.608, and 18.624 GHz for both TM and TE mode, the displayed Q-factors were 62.4, 17.68, and 26.61, respectively. We correspondingly calculated the RAB (relative absorption bandwidth) to evaluate absorption performance. An equivalent circuit proved its performance capabilities, indicating that it would produce a high-quality MMA from ADS software. Furthermore, the absorber's performance has been verified in free space on a sample being tested using a different array of unit cells. Moreover, the proposed structures with HFSS simulators to display the MMA's absolute absorption at each absorption peak are somewhat inconsistent with the results of the CST simulator. Because of its superior performance, the ultra-thin absorber is suited for a wide range of applications, including satellite applications such as radar systems, stealth technology, imaging, and electromagnetic interference reduction. [ABSTRACT FROM AUTHOR]

Simple Summary: Jaw osteosarcoma (JO) differs from its long-bones counterpart in many ways. The pathophysiology of this disease is still unknown, but the tumor microenvironment seems to play an important role in the progression of the disease and might offer new therapeutic perspectives. Through an immunohistochemical study performed on 50 biopsies of JO, we investigated various parameters associated with bone resorption, vascular and immune infiltrates. We demonstrated a strong and significant correlation between CD163 staining and lower survival in patients. Also, high levels of RANK and RANKL were found in the tumor samples and correlated with lower disease-free survival, while the T cells markers (CD4+ and CD8+) and the immune checkpoint PD-1/PD-L1 were poorly detected in the samples. Background—The purpose of this study was to investigate the bone resorption, as well as the vascular and immune microenvironment, of jaw osteosarcomas (JO) and to correlate these features with patient clinical outcomes. Methods—We studied 50 JO biopsy samples by immunohistochemical analysis of tissue microarrays (TMAs). We investigated the bone remodeling markers RANK/RANKL/OPG, the endothelial glycoprotein CD146, and biomarkers of the immune environment (CD163 and CD68 of macrophages, CD4+ and CD8+ of tumor-infiltrating lymphocytes (TILs), and an immune checkpoint PD-1/PD-L1). The biomarkers were analyzed for their influence on progression (recurrence and metastasis), overall survival (OS), and disease-free survival (DFS). Results—A strong and significant correlation has been found between CD163 staining and lower OS and DFS. The level of CD4+ and CD8+ staining was low and non-significantly associated with survival outcomes. High levels of RANK and RANKL were found in the tumor samples and correlated with lower DFS. Conclusion—Our findings suggest that CD163+ TAMs represent markers of poor prognosis in JO. Targeting TAMs could represent a valuable therapeutic strategy in JO. [ABSTRACT FROM AUTHOR]

RhoGDI2 is a guanine nucleotide dissociation inhibitor (GDI) specific for the Rho family of small GTPases. It is highly expressed in hematopoietic cells but is also present in a large array of other cell types. RhoGDI2 has been implicated in multiple human cancers and immunity regulation, where it can display a dual role. Despite its involvement in various biological processes, we still do not have a clear understanding of its mechanistic functions. This review sheds a light on the dual opposite role of RhoGDI2 in cancer, highlights its underappreciated role in immunity and proposes ways to explain its intricate regulatory functions. [ABSTRACT FROM AUTHOR]

Bacteria coat themselves with a dense array of cell envelope glycans that enhance bacterial fitness and promote survival. Despite the importance of bacterial glycans, their systematic study and perturbation remains challenging. Chemical tools have made important inroads toward understanding and altering bacterial glycans. This review describes how pioneering discoveries from Prof. Carolyn Bertozzi's laboratory inspired our laboratory to develop sugar probes to facilitate the study of bacterial glycans. As described below, we used metabolic glycan labelling to install bioorthogonal reporters into bacterial glycans, ultimately permitting the discovery of a protein glycosylation system, the identification of glycosylation genes, and the development of metabolic glycan inhibitors. Our results have provided an approach to screen bacterial glycans and gain insight into their function, even in the absence of detailed structural information. [ABSTRACT FROM AUTHOR]

Self-organization of cells into higher-order structures is key for multicellular organisms, for example via repetitive replication of template-like founder cells or syncytial energids. Yet, very similar spatial arrangements of cell-like compartments ('protocells') are also seen in a minimal model system of Xenopus egg extracts in the absence of template structures and chromatin, with dynamic microtubule assemblies driving the self-organization process. Quantifying geometrical features over time, we show here that protocell patterns are highly organized with a spatial arrangement and coarsening dynamics similar to that of two-dimensional foams but without the long-range ordering expected for hexagonal patterns. These features remain invariant when enforcing smaller protocells by adding taxol, i.e. patterns are dominated by a single, microtubulederived length scale. Comparing our data to generic models, we conclude that protocell patterns emerge by simultaneous formation of randomly assembling protocells that grow at a uniform rate towards a frustrated arrangement before fusion of adjacent protocells eventually drives coarsening. The similarity of protocell patterns to arrays of energids and cells in developing organisms, but also to epithelial monolayers, suggests generic mechanical cues to drive selforganized space compartmentalization. [ABSTRACT FROM AUTHOR]

Simple Summary: Adenocarcinomas represent nearly 40% of all cancer types, and account for more than 70% of cancer-related deaths. Labyrinthin (LAB) is a novel cancer neoantigen expressed on the surface of adenocarcinoma cells of various cancer types. Several treatment strategies are being developed for targeting LAB as a pan-adenocarcinoma target. This study aimed to develop an immunohistochemistry (IHC) assay to detect LAB expression on archival tumor specimens of non-small-cell lung cancer (NSCLC) and characterize the clinical significance of LAB expression. We also explored LAB mRNA expression by RNA sequencing using NSCLC data in The Cancer Genome Atlas (TCGA), and correlated with clinical phenotype and outcome. Further study is warranted to validate LAB IHC and LAB RNA expression as independent biomarkers for selecting patients for cancer therapy targeting LAB. To determine Labyrinthin (LAB) expression in non-small-cell lung cancer (NSCLC), we immunostained and scored for LAB immunohistochemistry (IHC) expression on sections of tissue microarrays (TMAs) prepared from 256 archival tissue blocks of NSCLC. Propensity-score-weighted Kaplan–Meier curves and weighted Cox models were used to associate LAB expression with overall survival. LAB mRNA expression was assessed in The Cancer Genome Atlas (TCGA) and correlated with clinical phenotype and outcome. Positive LAB IHC expression (>5% of tumor cells) was detected in 208/256 (81.3%) of NSCLC samples, and found in both lung adenocarcinomas (LUAD) and lung squamous cell cancer (LUSC). LAB positivity was associated with poor overall survival (HR = 3.56, 95% CI: 2.3–5.4; p < 0.0001) and high tumor differentiation grade or metastasis compared with negative LAB expression. Univariant and multivariate survival analyses demonstrated LAB expression as an independent prognostic factor for NSCLC patients. LAB RNA expression in TCGA-LUAD was higher in primary and advanced-stage tumors than in normal tissue, and was associated with poorer overall survival. No significant differences or associations were found with LAB RNA expression in TCGA-LUSC. The LAB IHC assay is being used to identify candidate cancer patients for the first-in-human phase I trial evaluating the LAB vaccines (UCDCC#296, NCT051013560). [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic ductal adenocarcinoma (PDAC) accounts for more than 90% of all pancreatic malignancies, and has a generally poor prognosis. Although it is the most common neoplastic disease of the pancreas, differential diagnosis is hindered by the lack of accurate and reliable diagnostic assays. Identification of molecular signatures for PDAC diagnosis offers a solution to improve the clinical and patient management. However, comprehensive omics profiling is time- and relatively cost-intensive and limited by tissue heterogeneity. Thus, it is not implemented in clinical routine. In this study, we investigate the feasibility of MALDI-MSI in combination with a neural-network-based analysis for accurate classification of pancreatic-ductal-adenocarcinoma patients. We provide evidence of the usefulness of this technology to support PDAC assessment which is promising for pathological aid. Despite numerous diagnostic and therapeutic advances, pancreatic ductal adenocarcinoma (PDAC) has a high mortality rate, and is the fourth leading cause of cancer death in developing countries. Besides its increasing prevalence, pancreatic malignancies are characterized by poor prognosis. Omics technologies have potential relevance for PDAC assessment but are time-intensive and relatively cost-intensive and limited by tissue heterogeneity. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) can obtain spatially distinct peptide-signatures and enables tumor classification within a feasible time with relatively low cost. While MALDI-MSI data sets are inherently large, machine learning methods have the potential to greatly decrease processing time. We present a pilot study investigating the potential of MALDI-MSI in combination with neural networks, for classification of pancreatic ductal adenocarcinoma. Neural-network models were trained to distinguish between pancreatic ductal adenocarcinoma and other pancreatic cancer types. The proposed methods are able to correctly classify the PDAC types with an accuracy of up to 86% and a sensitivity of 82%. This study demonstrates that machine learning tools are able to identify different pancreatic carcinoma from complex MALDI data, enabling fast prediction of large data sets. Our results encourage a more frequent use of MALDI-MSI and machine learning in histopathological studies in the future. [ABSTRACT FROM AUTHOR]

Simple Summary: Here, we examined the presence and clinical relevance of A20 in oral squamous cell carcinoma (OSCC). Using a tissue microarray (TMA), immunohistochemical A20 expression as well as tumor-infiltrating lymphocytes (TIL) were analyzed. Hereby, A20 expression was significantly increased in TILs and patients with elevated A20 expression in stromal CD3+ cells showed ameliorated survival in uni- as well as multivariable analyses. A20, known as a potent inhibitor of NF-κB signaling, has been characterized in numerous clinical as well as preclinical studies. Recently, especially in various malignant diseases, the prognostic and therapeutic relevance of A20 was investigated. In oral squamous cell carcinoma (OSCC) however, the characterization of A20 is uncharted territory. We analyzed a tissue microarray (TMA) of 229 surgically-treated OSCC patients (2003–2013). Immunohistochemical (IHC) stainings were performed for A20 and CD3; additionally, standard haematoxylin-eosin staining was applied. IHC findings were correlated with a comprehensive dataset, comprising clinical and pathohistological information. A20 expression was analyzed in tumor cells as well as in tumor infiltrating lymphocytes (TILs) and correlated with the overall survival (OS) and recurrence-free survival (RFS) using uni- and multivariable Cox regression. The median follow-up time was 10.9 years and the A20 expression was significantly decreased in CD3+ TILs compared to mucosa-infiltrating lymphocytes (MILs). In the Kaplan–Meier analyses, higher A20 expression in TILs was correlated with better OS (p = 0.017) and RFS (p = 0.020). In the multivariable survival analysis, A20 overexpression correlated with improved OS (HR: 0.582; 95% CI 0.388–0.873, p = 0.009) and RFS (HR 0.605; 95% CI 0.411–0.889, p = 0.011). Our results indicate a novel prognostic role for A20 in OSCC. Due to its elevated expression in TILs, further research is highly desirable, which therefore could offer new therapeutic opportunities for patients suffering from OSCC. [ABSTRACT FROM AUTHOR]

Despite the remarkable advantages of luminescent solar concentrators (LSCs), their application has not been of interest in ultrahigh efficient photovoltaic modules such as multi‐junctions and related two‐terminal tandems due to challenging issues limiting the cell capability and impeding the output current. Here type of multi‐junction LSC photovoltaics is presented that consists of transfer‐printed arrays of InGaP/GaAs solar cells and strategically tailored luminescent waveguides. A coplanar waveguide with the non‐self‐aligned quantum dot luminophores enables simultaneous absorptions of the directly illuminated solar flux and the indirectly waveguided LSC flux, where cell deployment and luminophore spectrum are systematically tuned for balanced enhancement of the subcell photocurrents. Through systematic comparisons across various LSC configurations supported by both experimental and theoretical quantifications, the power conversion efficiency of flexible modules with InGaP/GaAs cell arrays is improved from 1.67% to 2.22% by the optimal LSC, where the module area is 14.4 times larger than the total cell area. The details of optical and mechanical studies provide a further comprehensive understanding of the suggested approach toward multi‐junction LSC photovoltaics. [ABSTRACT FROM AUTHOR]

Given that, even after multimodal therapy, early-stage lung cancer (LC) often recurs, novel prognostic markers to help guide therapy are highly desired. The mRNA levels of cell division cycle 25C (CDC25C), a phosphatase that regulates G2/M cell cycle transition in malignant cells, correlate with poor clinical outcomes in lung adenocarcinoma (LUAD). However, whether CDC25C protein detected by immunohistochemistry can serve as a prognostic marker in LUAD is yet unknown. We stained an LC tissue array and a cohort of 61 LUAD tissue sections for CDC25C and searched for correlations between CDC25C staining score and the pathological characteristics of the tumors and the patients' clinical outcomes. Clinical data were retrieved from our prospectively maintained departmental database. We found that high expression of CDC25C was predominant among poorly differentiated LUAD (p < 0.001) and in LUAD > 1cm (p < 0.05). Further, high expression of CDC25C was associated with reduced disease-free survival (p = 0.03, median follow-up of 39 months) and with a trend for reduced overall survival (p = 0.08). Therefore, high expression of CDC25C protein in LUAD is associated with aggressive histological features and with poor outcomes. Larger studies are required to further validate CDC25C as a prognostic marker in LUAD. [ABSTRACT FROM AUTHOR]

This work introduces a miniaturized metasurface (MS) energy harvester operating at 5.54 GHz with a high capture efficiency and a wide incident angle. The proposed MS structure is comprised of an ensemble of electric ring resonator (ERR) array. The MS's impedance is engineered to match free space, so that the incident electromagnetic (EM) power is efficiently captured with minimal reflection and delivered to the optimal resistor load through an optimally positioned metallic-via. According to the simulation results obtained by CST Microwave Studio, the proposed MS harvester achieves higher conversion efficiency of about 91% under normal incidence and more than 78% across a wider incident angle up to 60°. In order to verify the simulation results, a 5×5 cell array of the proposed MS harvester is fabricated and tested. The simulation and experimental results are well match. The proposed MS configuration can be attractive for high-efficiency and compact wireless sensor network harvesting systems. [ABSTRACT FROM AUTHOR]

Background: Metastatic colonization is one of the critical steps in tumor metastasis. A pre-metastatic niche is required for metastatic colonization and is determined by tumor-stroma interactions, yet the mechanistic underpinnings remain incompletely understood. Methods: PCR-based miRNome profiling, qPCR, immunofluorescent analyses evaluated the expression of exosomal miR-141 and cell-to-cell communication. LC-MS/MS proteomic profiling and Dual-Luciferase analyses identified YAP1 as the direct target of miR-141. Human cytokine profiling, ChIP, luciferase reporter assays, and subcellular fractionation analyses confirmed YAP1 in modulating GROα production. A series of in vitro tumorigenic assays, an ex vivo model and Yap1 stromal conditional knockout (cKO) mouse model demonstrated the roles of miR-141/YAP1/GROα/CXCR1/2 signaling cascade. RNAi, CRISPR/Cas9 and CRISPRi systems were used for gene silencing. Blood sera, OvCa tumor tissue samples, and tissue array were included for clinical correlations. Results: Hsa-miR-141-3p (miR-141), an exosomal miRNA, is highly secreted by ovarian cancer cells and reprograms stromal fibroblasts into proinflammatory cancer-associated fibroblasts (CAFs), facilitating metastatic colonization. A mechanistic study showed that miR-141 targeted YAP1, a critical effector of the Hippo pathway, reducing the nuclear YAP1/TAZ ratio and enhancing GROα production from stromal fibroblasts. Stromal-specific knockout (cKO) of Yap1 in murine models shaped the GROα-enriched microenvironment, facilitating in vivo tumor colonization, but this effect was reversed after Cxcr1/2 depletion in OvCa cells. The YAP1/GROα correlation was demonstrated in clinical samples, highlighting the clinical relevance of this research and providing a potential therapeutic intervention for impeding premetastatic niche formation and metastatic progression of ovarian cancers. Conclusions: This study uncovers miR-141 as an OvCa-derived exosomal microRNA mediating the tumor-stroma interactions and the formation of tumor-promoting stromal niche through activating YAP1/GROα/CXCRs signaling cascade, providing new insight into therapy for OvCa patients with peritoneal metastases. [ABSTRACT FROM AUTHOR]

Background: Excess body weight has been found to associate with an increased risk of lymphomas and some metabolic pathways are currently recognized in lymphomagenesis. Bioactive lipid metabolites such as sphingosine-1-phosphate (S1P) have been proposed to play an important role linking obesity and lymphomas. However, the underlying mechanism(s) of S1P signaling in obesity-lymphomagenesis have not been well addressed. Methods: The gene expression of sphingosine kinase (SPHK), lymphoma prognosis, and S1P production were analyzed using Gene Expression Omnibus (GEO) and human lymphoma tissue array. Obesity-lymphoma mouse models and lymphoma cell lines were used to investigate the S1P/SPHK-YAP axis contributing to obesity-lymphomagenesis. By using the mouse models and a monocyte cell line, S1P-mediated polarization of macrophages in the tumor microenvironment were investigated. Results: In human study, up-regulated S1P/SPHK1 was found in human lymphomas, while obesity negatively impacted progression-free survival and overall survival in lymphoma patients. In animal study, obesity-lymphoma mice showed an aggressive tumor growth pattern. Both in vivo and in vitro data suggested the existence of S1P-YAP axis in lymphoma cells, while the S1P-ALOX15 signaling mediated macrophage polarization towards TAMs exacerbated the lymphomagenesis. In addition, treatment with resveratrol in obesity-lymphoma mice showed profound effects of anti-lymphomagenesis, via down-regulating S1P-YAP axis and modulating polarization of macrophages. Conclusion: S1P/S1PR initiated the feedback loops, whereby S1P-S1PR1/S1PR3-YAP signaling mediated lymphomagenesis contributing to tumor aggressive growth, while S1P-ALOX15 signaling mediated TAMs contributing to immunosuppressive microenvironment in obesity-lymphoma. S1P-targeted therapy could be potentially effective and immune-enhancive against obesity-lymphomagenesis. Highlights: • Obesity negatively impacted progression-free survival and overall survival in lymphoma patients while an aggressive tumor growth pattern was found in obesity-lymphoma mice. • S1P-S1PR1/S1PR3-YAP signaling mediated lymphomagenesis contributing to tumor aggressive growth in obesity-lymphoma. • S1P-ALOX15 signaling mediated TAMs contributing to immunosuppressive microenvironment in obesity-lymphoma. • S1P-targeted therapy could be potentially effective and immune-enhancive against obesity-lymphomagenesis. [ABSTRACT FROM AUTHOR]

BACKGROUND: Sperm-associated antigen 5 (SPAG5) has been identified as a novel driver oncogene involved in multiple cancers; however, its role in lung adenocarcinoma (LUAD) needs further investigation. Our study aims to elucidate the potential significance of SPAG5 in LUAD prognosis and its implications for the efficacy of immunotherapy. METHODS: In this study, we used bioinformatics analysis and tissue microarray (TMA) staining to examine the potential role of SPAG5 in LUAD survival and response to immunotherapy. We used the Oncomine, TIMER2.0, Gene Expression Profiling Interactive Analysis (GEPIA), Sangerbox, PredicScan, and Kaplan-Meier Plotter databases to examine the expression and prognostic role of SPAG5 in the LUAD of The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and other databases. We also used Cancer Single-cell State Atlas (CancerSEA) and Tumor Immune Estimation Resource (TIMER2.0) to analyze the association of SPAG5 with malignant phenotype and tumor immune microenvironment. Furthermore, Immune Cell Abundance Identifier (ImmuCellAI) analysis of TCGA sequencing data was used to predict the role of SPAG5 in determining the response to immune checkpoint blockade (ICB) treatment in LUAD. Co-expression analysis of programmed death-ligand 1 (PD-L1) and SPAG5 was performed using LUAD TMA immunohistochemistry (IHC) analysis. RESULTS: Our findings indicate that SPAG5 is overexpressed in LUAD and is positively correlated with advanced clinical stage, poor overall survival, relapse-free survival, and progression-free survival outcomes. SPAG5 may be involved in regulating the cell cycle, proliferation, invasion, DNA damage and repair, and tumor immunosuppression. Furthermore, TMA IHC analysis showed a positive correlation between PD-L1 expression in LUAD and SPAG5 which suggests that SPAG5 may serve as a potential predictor of response to ICB therapy in LUAD. CONCLUSIONS: Our results highlight the role of SAPG5 in promoting a tumor malignancy phenotype and immunosuppression in LUAD and suggest that SPAG5 may serve as a potential response marker for ICB therapy. [ABSTRACT FROM AUTHOR]

Objective: This study was designed to identify changes in the expression of proteins occurring during the progression of oral squamous cell carcinoma (OSCC) and to validate their impact on patient prognosis. Materials and Methods: The human OSCC cell line UPCI‐SCC‐040 was treated in vitro with TGF‐β1, and transcriptome analysis of differentially expressed genes (DEGs) revealed putative candidates relative to untreated cells. The respective protein expression levels of the most important genes were immunohistochemically validated on a tissue microarray (TMA) containing tissue samples from 39 patients with OSCC and were correlated with disease‐free survival (DFS) as the primary clinical endpoint. Results: Our univariate Cox proportional hazard regression (CR) analysis revealed significant correlations among positive N stage (local lymph node metastasis, p =.04), stearoyl‐CoA desaturase‐1 (p <.01), sclerostin (p =.01), and CD137L expression (p =.04) and DFS. Stearoyl‐CoA desaturase‐1 and sclerostin remained the main prognostic factors (p <.01) in the multiple CR model. Conclusion: We identified changes in differentially expressed genes during OSCC progression in vitro and translated the impact of the most deregulated genes on patient prognosis. Stearoyl‐CoA desaturase‐1 and sclerostin acted as independent prognostic factors in OSCC and could also be interesting candidates for new cancer targeted therapeutic approaches. [ABSTRACT FROM AUTHOR]

Simple Summary: The lung is the second most common site of metastases in colorectal cancer (CRC). The aim of our study was to evaluate the prognostic value of CD3+ and CD8+ T-cell density based immune cell score (ICS) and PD-1/PD-L1 expression in resected pulmonary metastases of microsatellite stable CRC. The T-cell infiltration was higher in the first pulmonary metastases compared to primary tumour. Pulmonary metastases with high ICS had improved survival compared to low ICS after adjusting for confounders. High tumour cell PD-L1 expression was associated with favourable prognosis. Our results might have clinical feasibility in planning future therapies. The objective of this study was to evaluate the prognostic value of CD3+ and CD8+ based immune cell score (ICS), programmed death -1 (PD-1) and programmed death ligand -1 (PD-L1) in pulmonary metastases of proficient mismatch repair colorectal cancer (CRC) patients. A total of 101 pulmonary metastases and 62 primary CRC tumours were stained for CD3+, CD8+, PD-1 and PD-L1 expression. The prognostic value of ICS, PD-1/PD-L1 expression in 67 first pulmonary metastases and 61 primary CRC tumour was analysed. Comparative analysis was also performed between primary tumours and pulmonary metastases, as well as between T-cell densities and PD-1/PD-L1 expression. The 5-year overall survival rates of low, intermediate, and high ICS in pulmonary metastases were 10.0%, 25.5% and 47.0% (p = 0.046), respectively. Patients with high vs. low ICS in pulmonary metastases had a significantly better 5-year survival (adjusted HR 0.25, 95% CI 0.09–0.75, p = 0.013). High tumour cell PD-L1 expression in the pulmonary metastases was associated with improved survival (p = 0.024). Primary tumour CD8+ expression was significantly correlated with all T-cell densities in pulmonary metastases. Conclusion: The ICS evaluated from the resected pulmonary metastases of CRC showed significant prognostic value. High PD-L1 expression in pulmonary metastases is associated with favourable prognosis. [ABSTRACT FROM AUTHOR]

Chondrosarcoma is the second most common type of bone cancer. Surgical resection is the best choice for clinical treatment. High-grade chondrosarcoma is destructive and is more possible to metastasis, which is difficult to remove using surgery. Doxorubicin (Dox) is the most commonly used chemotherapy drug in the clinical setting; however, drug resistance is a major obstacle to effective treatment. In the present study, we compared Dox-resistant SW1353 cells to their parental cells using RNA sequencing (RNA-Seq). We found that the apelin (APLN) pathway was highly activated in resistant cells. In addition, tissue array analysis also showed that APLN was higher in high-grade tissues compared to low-grade tissues. APLN is a member of the adipokine family, which is a novel secreted peptide with multifunctional and biological activities. Previously, studies have shown that inhibition of the APLN axis may have a therapeutic benefit in cancers. However, the role of APLN in chondrosarcoma is completely unclear, and no related studies have been reported. During in vitro experiments, APLN was also observed to be highly expressed and secreted in Dox-resistant cells. Once APLN was knocked down, it could effectively improve its sensitivity to Dox. We also explored possible upstream regulatory microRNAs (miRNAs) of APLN through bioinformatics tools and the results disclosed that miR-631 was the most likely regulator of APLN. Furthermore, the expression of miR-631 was lower in the resistant cells, but overexpression of miR-631 in the Dox-resistant cell lines significantly increased the Dox sensitivity. These results were also observed in another chondrosarcoma cell line, JJ012 cells. Taken together, these findings will provide rationale for the development of drug resistance biomarkers and therapeutic strategies for APLN pathway inhibitors to improve the survival of patients with chondrosarcoma. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Infiltrating tumor border configuration (ITBC) portends a poor prognosis compared with pushing tumor border configuration (PTBC) in colorectal cancer. The tumor and its surrounding immune microenvironment of tumor border configuration is not well-characterized. We aim to elucidate the differences in expression of molecular markers between the 2 groups using tissue microarray (TMA). STUDY DESIGN: Immunohistochemistry was performed on TMAs of surgical pathology specimens obtained from colorectal cancer patients consecutively operated at our institution from 2004 to 2015. TMAs were stained for immune cells (CD8, FOXP3, LAG3, PU1, CD163, and PDL1); HLA II, beta 2 microglobulin, and HC10 on tumor cells; BRAFV600E mutation; and DNA mismatch repair proteins (MMR) status. Patients who received neoadjuvant therapy were excluded. RESULTS: There were 646 tumors with ITBC and 310 tumors with PTBC. There was a significantly lower expression (p < 0.05) of immune components, namely CD8, FOXP3, LAG3, PU1, PDL1 immune cells, and Beta-2 Microglobulin on tumor cells in the tumors with ITBC compared with PTBC, except CD163 immune cells, and HC10 and HLAII on tumor cells. Tumors with ITBC were less likely to be associated with BRAFV600E mutations and deficient MMR proteins (p < 0.001). On analyzing MMR-proficient tumors separately, we could not find any difference in the expression of any molecular marker (including BRAF), except a lower expression of PDL1 immune cells in tumors with ITBC (p < 0.001). CONCLUSIONS: Colorectal tumors with ITBC are associated with a generalized low immune microenvironment and low rates of BRAFV600E mutation compared with tumors with PTBC. However, the molecular expression of tumor border configuration seems confounded by the MMR molecular signature. MMR-proficient colorectal tumors with ITBC are associated with a lower expression of only PDL1 immune cells among all immune markers examined. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the mineral density of enamel and dentin tissues of healthy individuals using threedimensional cone-beam computed tomography. Material and Methods: CBCT images of 15 healthy individuals, previously obtained for various reasons, were used in this study. In HU measurements, mineral density measurements were made from three different regions of enamel and three different regions of dentin, and the values obtained were compared. Enamel and dentin mineralization density measurements were measured from six regions, namely the crown cutting edge, buccal middle and cervical region for enamel, and the crown cutting edge, cervical region and root apex for dentin. In the comparisons of groups, the parametric One-Way ANOVA variance analysis method was applied. In the paired comparisons between the groups, the Tukey HSD test was applied as the multiple comparison post hoc test. A value of p<0.05 was accepted as statistically significant. Results:Mineralization density of tooth enamel and dentin tissues was quantitatively different in the maxilla and mandible in anterior and posterior teeth. Conclusion: In all the teeth, there were statistically significant decreases in the mineral density values of enamel and dentin tissue from occlusal towards the cemento-enamel junction. Statistically significant decreases were observed in the mineral density values of enamel and dentin tissue from the anterior region towards the posterior region in the teeth in both the upper and lower jaws. [ABSTRACT FROM AUTHOR]

A simple and label-free optical biosensor is developed for selective insulin sensing with a detection limit of 0.1 nM based on conformational change of an aptamer at aqueous-liquid crystal interface. [Display omitted] Insulin is a critical predictor for the function of pancreatic islet beta cells, which plays a crucial role in diagnosing diabetes and diabetes-related disorders. Herein, we propose and validate a label-free and cost-effective aptamer-based optical LC biosensor for detection of insulin based on the directional recognition of biomolecular binding events at a responsive aqueous-liquid crystal (LC) interface. The binding of insulin and aptamer adsorbed on CTAB triggers a conformational change of the aptamer from G-quadruplex to stretched structure, inducing homeotropic to planar alignment and correspondingly dark to bright optical image change of the LC films. The molecular dynamic (MD) simulation validates that the orientational transition is associated with the interaction energy changes at the interface, which is in coordination with the optical observation. This LC biosensor takes advantages of simple preparation, easy operation, rapid sensing, high specificity for insulin determination in the range of 0.1–1.0 nM within 5 min. This sensor is also applicable for insulin detection in diluted human urine and serum. Additionally, the optical cell arrays allow to detection multiple samples of the same/different biomarkers at the same time. Such a strategy offers a potential basis for monitoring other clinical biomarkers, and for point-of-care testing (POCT) as well. [ABSTRACT FROM AUTHOR]

We present a supramolecular sensor array based on a series of heteromultivalent macrocyclic coassemblies using amphiphilic calixarenes and cyclodextrin as the building blocks for cell recognition. The corresponding cross-reactivity between the coassemblies and cells served as the unique fingerprint for cell classification, and successfully identified the normal cell lines, cancerous cell lines, and cross-contaminated cells. [ABSTRACT FROM AUTHOR]

In this work, we reported a theoretical model for a novel piezoelectric micromachined ultrasonic transducer (PMUT). The sensing cells with hexagonal transduction diaphragms in the PMUT array are designed and arranged in a bioinspired honeycomb structure. Based on the classical piece-wise approach commonly used for PMUT with circular diaphragm, an enhanced theoretical model is developed. In this model, the deflection of the honeycomb diaphragm is analytically determined by the volume deflection, rather than the path deflection commonly used in the previous models. The hexagonal diaphragm is converted as a circular one, whose radius is derived by correcting the characteristic size of the hexagonal diaphragm multiplied by a correction factor. The calculated parameters by the reported theoretical model of a transduction cell in the PMUT array, such as resonant frequency and static deflection, matched well with the data obtained by finite element analysis and experiment. Special investigations are made on the effects of top electrode coverage and transduction layer thickness towards PMUT’s performance. The reported theoretical model in this work is suitable not only for PMUTs with circular and hexagonal transduction cells, but also for square and other arbitrary shape diaphragms. This enhanced theoretical model provides an interesting insight on design optimizations of PMUT with various transduction cell geometries. [2022-0093] [ABSTRACT FROM AUTHOR]

To establish a simple model for predicting postoperative acute kidney injury (AKI) requiring renal replacement therapy (RRT) in patients with renal insufficiency (CKD stages 3–4) who underwent cardiac surgery. A total of 330 patients were enrolled. Among them, 226 were randomly selected for the development group and the remaining 104 for the validation group. The primary outcome was AKI requiring RRT. A nomogram was constructed based on the multivariate analysis with variables selected by the application of the least absolute shrinkage and selection operator. Meanwhile, the discrimination, calibration, and clinical power of the new model were assessed and compared with those of the Cleveland Clinic score and Simplified Renal Index (SRI) score in the validation group. Results: The rate of RRT in the development group was 10.6% (n = 24), while the rate in the validation group was 14.4% (n = 15). The new model included four variables such as postoperative creatinine, aortic cross‐clamping time, emergency, and preoperative cystatin C, with a C-index of 0.851 (95% CI, 0.779–0.924). In the validation group, the areas under the receiver operating characteristic curves for the new model, SRI score, and Cleveland Clinic score were 0.813, 0.791, and 0.786, respectively. Furthermore, the new model demonstrated greater clinical net benefits compared with the Cleveland Clinic score or SRI score. We developed and validated a powerful predictive model for predicting severe AKI after cardiac surgery in patients with renal insufficiency, which would be helpful to assess the risk for severe AKI requiring RRT. [ABSTRACT FROM AUTHOR]

This letter proposes a novel capacitor-less dynamic random-access memory composed of a 3D stacked cell array. To perform selective program and erase operations in the 3D cell array, a back-gate-sharing and channel-separating architecture are adopted. The operation of the unit cell is demonstrated through 3D technology computer-aided design simulations. The proposed device uses a simple process to optimize the back gate (e.g., modifying the thickness of materials or using different types of materials). Through optimization of the back gate, a sensing margin and retention time of 52 $\mu \text{A}$ and 475 ms, respectively, are achieved at 300 K in a scaled cell with a gate length of 30 nm and channel radius of 30 nm. Because this device has a cell array similar to that of a 3D NAND flash memory, it can be manufactured using the same process and equipment in a cost-effective manner. In addition, it can be adopted in processing-in-memory applications to provide high-performance and high-density hybrid memory functionality when used in conjunction with NAND flash memories. [ABSTRACT FROM AUTHOR]

Luminal Androgen Receptor (LAR) triple-negative breast cancers (TNBC) express androgen receptors (AR), exhibit high frequency of PIK3CA mutations and intact RB. Herein, we investigated combined blockade of the CDK4/6 and PI3K signaling with palbociclib, alpelisib, and capivasertib, which inhibit CDK4/6, PI3Kα, and AKT1-3, respectively. The combination of palbociclib/capivasertib, but not palbociclib/alpelisib, synergistically inhibited proliferation of MDA-MB-453 and MFM-223 LAR cells [synergy score 7.34 (p = 5.81x10−11) and 4.78 (p = 0.012), respectively]. The AR antagonist enzalutamide was inactive against MDA-MB-453, MFM-223, and CAL148 cells and did not enhance the efficacy of either combination. Palbociclib/capivasertib inhibited growth of LAR patient-derived xenografts more potently than palbociclib/alpelisib. Treatment of LAR cells with palbociclib suppressed phosphorylated-RB and resulted in adaptive phosphorylation/activation of S473 pAKT and AKT substrates GSK3β, PRAS40, and FoxO3a. Capivasertib blocked palbociclib-induced phosphorylation of AKT substrates more potently than alpelisib. Treatment with PI3Kβ inhibitors did not block phosphorylation of AKT substrates, suggesting that PI3Kβ did not mediate the adaptive response to CDK4/6 inhibition. Phosphokinase arrays of MDA-MB-453 cells treated with palbociclib showed time-dependent upregulation of PDGFRβ, GSK3β, STAT3, and STAT6. RNA silencing of PDGFRβ in palbociclib-treated MDA-MB-453 and MFM-223 cells blocked the upregulation of S473 pAKT, suggesting that the adaptive response to CDK4/6 blockade involves PDGFRβ signaling. Finally, treatment with palbociclib and the PDGFR inhibitor CP637451 arrested growth of MDA-MB-453 and MFM-223 cells to the same degree as palbociclib/capivasertib. These findings support testing the combination of CDK4/6 and AKT inhibitors in patients with LAR TNBC, and further investigation of PDGFR antagonists in this breast cancer subtype. • The combination of CDK4/6and AKT inhibitors (CDK4/6i, AKTi) results in synergistic inhibition of cell proliferation in Luminal Androgen Receptor (LAR) subtype triple-negative breast cancer cells. • CDK4/6i and AKTi effectively inhibit tumor growth in LAR TNBC patient-derived and cell-derived xenografts. • CDK4/6 blockade induces adaptive activation of AKT in LAR preclinical models, which is more effectively suppressed by an AKTi than a PI3K inhibitor. • PDGFRβ plays a compensatory role by activating AKT after treatment with CDK4/6i. [ABSTRACT FROM AUTHOR]

• Identified molecular interplay between sarcopenia and osteoporosis. • Discovered biomarkers for osteosarcopenia using proteomics. • Revealed critical pathways affecting muscle and bone health. • Integrated transcriptomics and proteomics enhance disease understanding. • Suggested new targets for therapeutic intervention. Osteoporosis and sarcopenia are common age-related conditions characterized by the progressive loss of bone density and muscle mass, respectively. Their co-occurrence, often referred to as osteosarcopenia, presents significant challenges in elderly care due to increased fragility and functional impairment. Existing studies have identified shared pathological mechanisms between these conditions, including inflammation, hormonal imbalances, and metabolic dysregulation, but a comprehensive understanding of their molecular interplay remains incomplete. This study aims to deepen our understanding of the molecular interactions between sarcopenia and osteoporosis through an integrated omics approach, revealing potential therapeutic targets and biomarkers. Employing a combination of proteomics and transcriptomics analyses, this study analyzed bone and muscle tissue samples from patients diagnosed with osteoporosis and osteosarcopenia. Techniques included high-throughput sequencing and label-free proteomics, supported by advanced bioinformatics tools for data analysis and functional annotation of genes and proteins. The study found marked differences in gene and protein expressions between osteoporosis and osteosarcopenia tissues. Specifically, genes like PDIA5, TUBB1, and CYFIP2 in bone, along with MYH7 and NCAM1 in muscle, exhibited differential expression at both mRNA and protein levels. Pathway analyses revealed the significance of oxidative-reduction balance, cellular metabolism, and immune response in the progression of these conditions. Importantly, the study pinpointed osteoclast differentiation and NF-kappa B signaling pathways as critical in the molecular dynamics of osteosarcopenia, suggesting potential targets for therapy. This study utilized transcriptomics and proteomics to identify key genes and proteins impacting sarcopenia and osteoporosis, employing advanced network tools to delineate interaction networks and crucial signaling pathways. It highlighted genes like PDIA5 and TUBB1, consistently expressed in both analyses, involved in pathways such as osteoclast differentiation and cytokine interactions. These insights enhance understanding of the molecular interplay in bone and muscle degeneration with aging, suggesting directions for future research into therapeutic interventions and prevention strategies for age-related degenerative diseases. [ABSTRACT FROM AUTHOR]

A wideband transmissive surface with identical slots on 15 × 15 unit cells proposes in this article. The high gain transmitarray antenna presents using Huygens' principle at 15 GHz. The transmitarray surface consists of trilayer H-shaped slots on the middle of four symmetric slots on the edges of the unit cells. The placed slots induce Huygens' resonances at three frequencies, 13.5 GHz, 15 GHz and 16.7 GHz which is caused by electric and magnetic surface currents on the transmitarray surface. This makes a wide bandwidth for the antenna performance. 360° phase distribution is obtained by increasing the H-shaped slots legs. Since no dielectric substrate used between layers, the transmission coefficient is near 1 (0 dB) through the whole range. For experimental results, the trilayer artificial metallic surfaces with substrateless conductive slotted unit cells is fabricated. The test results presented the transmitarray antenna peak gain is measured 28.6 dB at operating frequency, 15 GHz. Ultra wide band antenna with 3 dB gain bandwidth of 30% and high aperture efficiency of 42.66%. • The main highlights, advantages and novel issues of the presented paper are as follows: • A low profile, wide band and high gain transmitarray antenna for Ku band, consists of tri-layer substrate-less 15 × 15 Huygens' metasurface unit cells. • The equivalent circuit model is examined to attain the optimized values of proposed metasurface unit cell array dimensions. • The transmission phase and magnitude presented transmitarray aperture have been simulated by parametric analysis of proposed unit cell, realized 360° transmission phase scan and nearly full transmission (0 dB). • The Huygens' principle was presented to validate the three resonant frequencies, which is caused by electric and magnetic surface currents on the transmitarray surface. [ABSTRACT FROM AUTHOR]

The study extends the locally-exact homogenization theory (LEHT) to determine the effective parameters and localized multiphysics fields of unidirectional piezoelectric nanocomposites with energetic surfaces. The interface is simulated using the generalized Gurtin-Murdoch model for piezoelectric nanocomposites, taking into account the discontinuities between surface stresses and electrical displacement. By characterizing hexagonal and square repeating unit cells (RUC), the interactions across a fiber's or pore's interface in piezoelectric nanocomposites with energetic surfaces have been analyzed. The extended LEHT possesses the advantages of fast convergence, excellent stability, and computational efficiency due to its avoidance of mesh discretization and pointwise satisfaction of interfacial conditions. To verify the validity of the present theory, this paper also derives the Eshelby solution for piezoelectric nanocomposite with energetic surfaces. The reliability and accuracy of the present theory are demonstrated by comparing the present results from the Eshelby solution and the finite element method (FEM) with generally good agreement. On this basis, the influence of microstructural effects, such as phase volume fractions and geometrical arrangement, on the effective and local responses of piezoelectric nanocomposites with energetic surfaces are investigated. The results show that effective piezoelectric/dielectric moduli and electric displacement field for piezoelectric nanocomposites are significantly affected by the size effect, along with several other parameters such as unit cell arrays and fiber/pore volume fractions. Those results highlight the significance of neighboring pore or fiber interactions for piezoelectric nanocomposites, which are often overlooked in traditional micromechanics models and are challenging to be captured using numerical methods. • The extended locally-exact homogenization theory (LEHT) is developed to determine the effective and localized multiphysics responses of unidirectional piezoelectric nanocomposites with energetic surfaces. • The generalized Gurtin-Murdoch model is employed to account for the discontinuities of both surface stresses and electrical displacement for microstructural interface of piezoelectric nanocomposites. • Several additional microstructural effects are investigated for piezoelectric nanocomposites, such as phase volume fraction and geometric arrangement. [ABSTRACT FROM AUTHOR]

The rapid advancement of single-cell transcriptomics in neurology has allowed for profiling of post-mortem human brain tissue across multiple diseases. Over the past 3 years, several studies have examined tissue from donors with and without diagnoses of Alzheimer's disease, highlighting key changes in cell type composition and molecular signatures associated with pathology and, in some cases, cognitive decline. Although all of these studies have generated single-cell/nucleus RNA-seq or ATAC-seq data from the full array of major cell classes in the brain, they have each focused on changes in specific cell types. Here, we synthesize the main findings from these studies and contextualize them in the overall space of large-scale omics studies of Alzheimer's disease. Finally, we touch upon new horizons in the field, in particular advancements in high-resolution spatial interrogation of tissue and multi-modal efforts—and how they are likely to further advance mechanistic and target-selection studies on Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Background: Tumor infiltration with cytotoxic CD8+ T-cells is associated with a favorable outcome in several neoplasms, including thyroid cancer. The chemokine axis CXCR4/SDF-1 correlates with more aggressive tumors, but little is known concerning the prognostic relevance in relation to the tumor immune microenvironment of differentiated thyroid cancer (DTC). Methods: A tissue microarray (TMA) of 37 tumor specimens of primary DTC was analyzed by immunohistochemistry (IHC) for the expression of CD8+, CXCR4, phosphorylated CXCR4 and SDF-1. A survival analysis was performed on a larger collective (n = 456) at RNA level using data from The Cancer Genome Atlas (TCGA) papillary thyroid cancer cohort. Results: Among the 37 patients in the TMA-cohort, the density of CD8+ was higher in patients with less advanced primary tumors (median cells/TMA-punch: 12.5 (IQR: 6.5, 12.5) in T1–2 tumors vs. 5 (IQR: 3, 8) in T3–4 tumors, p = 0.05). In the TCGA-cohort, CXCR4 expression was higher in patients with cervical lymph node metastasis compared to N0 or Nx stage (CXCR4high/low 116/78 vs. 97/116 vs. 14/35, respectively, p = 0.001). Spearman's correlation analysis of the TMA-cohort demonstrated that SDF-1 was significantly correlated with CXCR4 (r = 0.4, p = 0.01) and pCXCR4 (r = 0.5, p = 0.002). In the TCGA-cohort, density of CD8+ correlated with CXCR4 and SDF-1 expression (r = 0.58, p < 0.001; r = 0.4, p < 0.001). The combined marker analysis of the TCGA cohort demonstrated that high expression of both, CXCR4 and SDF-1 was associated with reduced overall survival in the CD8 negative TCGA cohort (p = 0.004). Conclusion: These findings suggest that the prognostic significance of CXCR4 and SDF-1 in differentiated thyroid cancer depends on the density of CD8 positive T-lymphocytes. Further studies with larger sample sizes are needed to support our findings and inform future investigations of new treatment and diagnostic options for a more personalized approach for patients with differentiated thyroid cancer. [ABSTRACT FROM AUTHOR]