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Abstract Epithelial–mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells plays key roles in the pathogenesis of multiple vitreoretinal diseases, leading to profound and permanent vision loss. Circular RNAs (circRNAs) are widespread and functional endogenous RNAs that could regulate gene expression in eukaryotes. The functions of circRNAs in mediating EMT has been reported in several diseases. In the current study, we investigated the role of circRNA HIPK3 (circHIPK3) in EMT process of RPE cells (RPE-EMT). circHIPK3 is one abundant circRNA generated from the second exon of HIPK3 mRNA. We found that circHIPK3 expression was significantly increased in TGF-β1-induced RPE-EMT model. Silencing of circHIPK3 attenuated TGF-β1-induced RPE-EMT process, whereas forced expression of circHIPK3 could trigger EMT in RPE cells. Mechanistically, circHIPK3 regulates RPE-EMT process via sponging multiple microRNAs (miRNAs). This study provides novel insights into the mechanism of RPE-EMT. Targeting circHIPK3 might serve as a therapeutic strategy in RPE-EMT associated vitreoretinal diseases.

Abstract Combing macroscopic experimental method and mesoscopic numerical method, this study analyses the strain-softening behaviours of granite and sandstone. From the macroscopic perspective, the stress–strain curves of granite and sandstone under different confining pressures are studied by laboratory triaxial compression test. Variations of post-peak reduction modulus and critical plastic shear strain versus confining stress are obtained. Evolution of strength parameters at peak, residual and strain-softening stage are proposed. Then a method to develop the strain-softening model of hard and soft rocks is presented. From the mesoscopic perspective, based on the laboratory test results, the parameters of discrete element method PFC for the samples of the granite and sandstone are calibrated. Comparing the basically consistent results of laboratory experiment and numerical simulation, the feasibility of discrete element method is verified. Evolutions of mesoscopic crack propagation and mesoscopic particle displacement field in the complete failure process are analysed. Typical stresses of granite sample and sandstone sample in the failure stage are investigated. Above combined macroscopic experimental method and mesoscopic numerical method systematically analyse the characteristics of hard rock and soft rock in the strain-softening stage. Failure process and mechanical property of hard rock and soft rock are revealed at the macroscopic and mesoscopic levels. The initiation and propagation process of micro-cracks in rock are thoroughly investigated. The research results provide a scientific foundation for the analyse of strain-softening behaviour of hard rock and soft rock. The result shows that both the mesoscopic numerical method and macroscopic experimental method indicate that the failure pattern of sandstone is influenced by both confining pressure and axial stress, while granite is mainly affected by axial stress.

Abstract Melatonin supplementation during in vitro maturation (IVM) improves porcine oocyte maturation and embryonic development by exerting antioxidative effects. Nevertheless, the mechanism by which melatonin prevents polyspermy after in vitro fertilization (IVF) remains unclear. Here, we examined the effects of melatonin on cytoplasmic maturation and the incidence of polyspermic penetration in porcine oocytes. No statistically significant difference was observed in the rate of first polar body formation between the groups (Control, Melatonin, Melatonin + Luzindole, and Melatonin + 4-P-PDOT). Interestingly, melatonin supplementation significantly improved the cytoplasmic maturation of porcine oocytes by enhancing the normal distribution of organelles (Golgi apparatus, endoplasmic reticulum and mitochondria) and upregulating organelle-related gene expressions (P

Abstract Sinonasal squamous cell carcinoma (SNSCC) is an aggressive cancer affecting the nasal and sinus regions, with its progression factors, particularly genetic ones, not yet fully understood. Here, we first conducted a retrospective study with 219 SNSCC patients to identify clinical factors affecting SNSCC prognosis. Additionally, we mined a vast literature dataset to uncover genetic factors associated with SNSCC progression. Based on this data, we constructed SNSCC prognosis pathways and performed a gene set enrichment analysis (GSEA). Clear operative margins were linked to a 73.5–86.3% improvement in overall survival and a 73.5–88.9% lower risk of recurrence. Nasal cavity-originated cases exhibited a 67.6–97.4% decrease in mortality and an 80.7–96.7% lower recurrence rate. Patients at T1-2 staging had a 65.0–80.6% reduced risk of death and recurrence compared to those at T3 stage. Additionally, we identified 53 genes associated with SNSCC, with 14 also implicated in primary tumor site, T stage, and operative margin. These genes, including EGFR, PIK3CA, ERBB2, PTEN, BCL2, BRAF, KRAS, and PRL, form a complex SNSCC-prognosis pathway and were significantly enriched in 42 KEGG pathways and Gene Ontology (GO) terms (FDR-corrected p-value

Abstract Metasurfaces are capable of fully reshaping the wavefronts of incident beams in desired manners. However, the requirement for external light excitation and the resonant nature of their meta-atoms, make challenging their on-chip integration. Here, we introduce the concept and design of a fresh class of metasurfaces, driven by unidirectional guided waves, capable of arbitrary wavefront control based on the unique dispersion properties of unidirectional guided waves rather than resonant meta-atoms. Upon experimentally demonstrating the feasibility of our designs in the microwave regime, we numerically validate the introduced principle through the design of several microwave meta-devices using metal-air-gyromagnetic unidirectional surface magneto-plasmons, agilely converting unidirectional guided modes into the wavefronts of 3D Bessel beams, focused waves, and controllable vortex beams. We, further, numerically demonstrate sub-diffraction focusing, which is beyond the capability of conventional metasurfaces. Our unfamiliar yet practical designs may enable full, broadband manipulation of electromagnetic waves on deep subwavelength scales.

Abstract Primary gastric adenosquamous carcinoma (PGASC) is a rare type of gastric cancer with limited research and poorly understood clinicopathological features. This study investigated the clinicopathological features and outcomes of PGASC. Patients with PGASC from Union Hospital, Tongji Medical College, Huazhong University of Science and Technology and from the published literature were enrolled in this study. Survival curves were generated using the Kaplan–Meier method, and prognostic factors were identified through Cox proportional hazards regression models. This study identified 76 eligible cases of PGASC, with 45 cases from published literature and 31 from our center. The most prevalent symptoms were abdominal pain and dysphagia, with a median age of 62 years (range: 29–84 years). The primary lesions were predominantly in the proximal stomach, with a median tumor size of 6.5 cm (range: 1.5–16.0 cm). Tumor stages II, III, and IV were detected in 12 (16.7%), 43 (59.7%), and 17 (23.6%) patients, respectively. Most tumors were poorly differentiated in both the squamous cell carcinoma (SCC) component and adenocarcinoma (AC) component. The median survival time was 17 months (range: 2–122 months). The 1, 3, and 5-year overall survival (OS) was 60.7%, 31.1%, and 24.1%, respectively. Multivariate analysis revealed that OS was independently predicted by the proportion of SCC component, differentiation of AC component, and tumor stage. PGASC is a rare disease with a poor prognosis. A high proportion of SCC components, low differentiated AC components, and advanced tumor were associated with worse survival in patients with PGASC. Adjuvant therapy did not improve survival time.

Abstract This study aimed to evaluate the association between low-density lipoprotein cholesterol (LDL-C) and serum uric acid to serum creatinine (SUA/SCr) ratio in male gout patients at different BMIs. This real-world study included 956 male gout patients aged 18–83 years. We retrospectively analyzed the medical records of Chinese male gout patients from 2017 to 2019. The correlation between LDL-C and SUA/SCr was tested after adjusting for confounding factors. We found a nonlinear relationship between LDL-C and SUA/SCr in the whole study population. Stratification analysis showed that there was actually a nonlinear relationship between LDL-C and SUA/SCr in men with a BMI of 24–28, the inflection point of LDL-C was 1.8 mmol/L, when LDL-C was greater than 1.8 mmol/L, there was a positive correlation between LDL-C levels and SUA/SCr (β = 0.67, 95% CI 0.35–0.98, P

Abstract Computational methods have been proposed to leverage spatially resolved transcriptomic data, pinpointing genes with spatial expression patterns and delineating tissue domains. However, existing approaches fall short in uniformly quantifying spatially variable genes (SVGs). Moreover, from a methodological viewpoint, while SVGs are naturally associated with depicting spatial domains, they are technically dissociated in most methods. Here, we present a framework (PROST) for the quantitative recognition of spatial transcriptomic patterns, consisting of (i) quantitatively characterizing spatial variations in gene expression patterns through the PROST Index; and (ii) unsupervised clustering of spatial domains via a self-attention mechanism. We demonstrate that PROST performs superior SVG identification and domain segmentation with various spatial resolutions, from multicellular to cellular levels. Importantly, PROST Index can be applied to prioritize spatial expression variations, facilitating the exploration of biological insights. Together, our study provides a flexible and robust framework for analyzing diverse spatial transcriptomic data.

Abstract Unidirectional surface waves in nonreciprocal plasmonic platforms with nonlocal effects have been a topic of significant interest and some controversy. In this study, we present a scheme to achieve unidirectional surface magnetoplasmons (USMPs) with large modal areas at terahertz frequencies. Such large-area USMPs (LUSMPs) exist in a metal-UENZ (uniaxial- $$\varepsilon $$ ε -near-zero)-Si-InSb structure under external magnetic field, where the effect of nonlocality is included. The field of the LUSMP extends almost uniformly in the UENZ layer with a thickness of wavelength scale, thus its modal size can be represented by the UENZ-layer thickness. Due to the modal energy primarily distributed in the thick UENZ layer, the nonlocality-induced leakage of the LUSMP is significantly reduced by an order of magnitude, compared to previous USMP existing at interface between InSb and opaque isotropic medium. Due to their large modal sizes, such LUSMPs can be efficiently excited by terahertz radiations directly from free space. In addition, LUSMPs offer high degree of freedom for manipulating terahertz waves, such as energy squeezing and trapping. Based on LUSMPs, a terahertz free-space isolator is also developed. Our findings have important implications to the development of innovative plasmonic devices in terahertz regime.

Abstract The existing biomarkers are insufficient for predicting the prognosis of pancreatic ductal adenocarcinoma (PDAC). Intraductal papillary mucinous neoplasm (IPMN) is a precursor to PDAC; therefore, identifying biomarkers from differentially expressed genes (DEGs) of PDAC and IPMN is a new and reliable strategy for predicting the prognosis of PDAC. In this study, four datasets were downloaded from the Gene Expression Omnibus database and standardized using the R package ‘limma.’ A total of 51 IPMN and 81 PDAC samples were analyzed, and 341 DEGs in PDAC and IPMN were identified; DEGs were involved in the extracellular matrix and tumor microenvironment. An acceptable survival prognosis was demonstrated by SDC1 and ITGA2, which were highly expressed during in vitro PDAC cell proliferation, apoptosis, and migration. SDC1 high was enriched in interferon alpha (IFN-α) response and ITGA2 high was primarily detected in epithelial-mesenchymal transition (EMT), which was verified using western blotting. We concluded that SDC1 and ITGA2 are potential prognostic biomarkers for PDAC associated with IPMN. Downregulation of SDC1 and ITGA2 expression in PDAC occurs via a mechanism involving possible regulation of IFN-α response, EMT, and immunity, which may act as new targets for PDAC therapy.

Abstract Circulating microRNAs (miRNAs) have been considered potential markers for the early detection of malignant colorectal cancer (CRC). We aimed to identify a group of miRNAs for the early detection of CRC and assess their predictive ability in a community-based population in China. A nested case‒control study consisting of 97 incident colorectal cancer cases and 103 frequency-matched healthy controls was conducted. The data were randomly assigned into a training set (60%) and a test set (40%). We selected and detected 10 kinds of miRNAs in plasma samples. Multivariate logistic regression analysis was used to identify miRNAs associated with colorectal cancer risk in the training set and test set. Then, we evaluated the predictive ability of the identified miRNAs by the receiver operating characteristic curve (ROC). In this study, three miRNAs (miRNA-29a, miRNA-125b, miRNA-145) were significantly associated with colorectal cancer risk in both the training set and test set. The sensitivity of the identified miRNAs ranged from 0.854 to 0.961. After adding the identified miRNAs, the AUC (area under the curve) value significantly increased from 0.61 to 0.71 compared with the basic model consisting of only basic demographic information. We identified a three-plasma miRNA signature that may serve as a novel non-invasive biomarker in early CRC detection and in predicting individual CRC risk in the generation population.

Abstract The convergence-confinement method (CCM) is a simplified widely utilised tool for assessing the interplay between the rock mass behaviour and the support effect, so it is quite helpful for tunnel support design purposes. However, the direct application of this technique has shown some limitations, many of which are directly related to the three-dimensionality issue. Indeed, the CCM tries to solve the three-dimensional (3D) problem of tunnel advance deformation and support response, by means of a series of two-dimensional (2D) plane strain analyses. So, regardless purely elastic cases, certain deviation is observed when comparing CCM and 3D numerical modelling results. The reasons behind this deviation have been studied from different points of views, but they seem to be still not well understood. With the aim of advancing towards a better knowledge of this issue, this paper discusses the limitation of CCM to correctly reflect the 3D tunnelling effect by comparing CCM and 3D numerical deformation, support pressure and liner load results in a typical tunnel case for various geological conditions. The reasons for CCM results in different rock deformation and support pressure in comparing to the 3D numerical modelling are explained. Some guidelines are eventually given recommending when the use of CCM can be acceptable according to the rock mass strength and tunnel depth, and when a more rigorous 3D approach is convenient.

Abstract The regression analysis method is being widely adopted to analyse the tunnel strain, most of which ignore the strain-softening effect of the rock mass and fail to consider the influence of support pressure, initial stress state, and rock mass strength classification in one fitting equation. This study aims to overcome these deficiencies with a regression model used to estimate the tunnel strain. A group of geological strength indexes (GSI) are configured to quantify the input strength parameters and deformation moduli for the rock mass with a quality ranging from poor to excellent. A specific semi-analytical procedure is developed to calculate the tunnel strain around a circular opening, which is validated by comparison with those using existing methods. A nonlinear regression model is then established to analyse the obtained tunnel strain, combining twelve fitting equations to relate the tunnel strain and the factors including the support pressure, GSI, initial stress state, and critical softening parameter. Particularly, three equations are for the estimation of the critical tunnel strain, critical support pressure, and tunnel strain under elastic behaviour, respectively; and the other nine equations are for the tunnel strain with different strain-softening behaviours. The relative significance between the GSI, the initial stress and the support pressure on the tunnel strain is assessed.

In strongly correlated materials multiple electronic phases can form simultaneously in real space, offering the potential of devices with multiple electronic properties, if such phase separation can be controlled. Here, Li et al study this electronic phase separation in LaMnO3/CaMnO3/PrMnO3 superlattice, and find a nano-network electronic phase separation resulting from local strain relaxation that persists through thermal cycling.

Abstract To establish a prognostic model based on immune-related microRNA (miRNA) for pancreatic carcinoma. Weighted correlation network analysis (WGCNA) was performed using the "WGCNA" package to find the key module genes involved in pancreatic carcinoma. Spearman correlation analysis was conducted to screen immune-related miRNAs. Uni- and multi-variate COX regression analyses were carried out to identify miRNAs prognostic for overall survival (OS) of pancreatic carcinoma, which were then combined to generate a prognostic model. Kaplan–Meier survival analysis, receiver operating characteristic (ROC) analysis, distribution plot of survival status in patients and regression analysis were collectively performed to study the accuracy of the model in prognosis. Target genes of the miRNAs in the model were intersected with the key module genes, and a miRNA–mRNA network was generated and visualized by Cytoscape3.8.0. TIMER analysis was conducted to study the abundance of immune infiltrates in tumor microenvironment of pancreatic carcinoma. Expression levels of immune checkpoint genes in subgroups stratified by the model were compared by Wilcoxon test. Gene Set Enrichment Analysis (GSEA) was performed to analyze the enriched signaling pathways between subgroups. Differential analysis revealed 1826 genes differentially up-regulated in pancreatic carcinoma and 1276 genes differentially down-regulated. A total of 700 immune-related miRNAs were obtained, of which 7 miRNAs were significantly associated with OS of patients and used to establish a prognostic model with accurate predictive performance. There were 99 mRNAs overlapped from the 318 target genes of the 7 miRNAs and the key modules genes analyzed by WGCNA. Patient samples were categorized as high or low risk according to the prognostic model, which were significantly associated with dendritic cell infiltration and expression of immune checkpoint genes (TNFSF9, TNFRSF9, KIR3DL1, HAVCR2, CD276 and CD80). GSEA showed remarkably enriched signaling pathways in the two subgroups. This study identified an immune-related 7-miRNA based prognostic model for pancreatic carcinoma, which could be used as a reliable tool for prognosis.

Abstract Two-dimensional (2D) materials are promising candidates for uses in next-generation electronic and optoelectronic devices. However, only a few high-quality 2D materials have been mechanically exfoliated to date. One of the critical issues is that the exfoliability of 2D materials from their bulk precursors is unknown. To assess the exfoliability of potential 2D materials from their bulk counterparts, we derived an elasticity-based-exfoliability measure based on an exfoliation mechanics model. The proposed measure has a clear physical meaning and is universally applicable to all material systems. We used this measure to calculate the exfoliability of 10,812 crystals having a first-principles calculated elastic tensor. By setting the threshold values for easy and potential exfoliation based on already-exfoliated materials, we predicted 58 easily exfoliable bulk crystals and 90 potentially exfoliable bulk crystals for 2D materials. As evidence, a topology-based algorithm indicates that there is no interlayer bonding topology for 93% predicted exfoliable bulk crystals, and the analysis on packing ratios shows that 99% predicted exfoliable bulk crystals exhibit a relatively low packing ratio value. Moreover, literature survey shows that 34 predicted exfoliable bulk crystals have been experimentally exfoliated into 2D materials. In addition, the characteristics of these predicted 2D materials were discussed for practical use of such materials.

Abstract This study explored the dosimetric difference between hypofractionated whole-breast irradiation (HFWBI) with sequential boost (SEB) and simultaneous integrated boost (SIB) based on supine and prone positions to identify the superior boost mode and superior position. Thirty breast cancer patients eligible for HFWBI after breast-conserving surgery were enrolled. All patients underwent 3DCT simulation scanning in both supine and prone positions. For the SEB-HFWBI plan, the dose prescribed for the planning target volume (PTV) of whole breast (WB) was 2.67 Gy per fraction with a total of 15 fractions, followed by a sequential boost of 3.2 Gy per fraction to the PTV of tumor bed (TB) in 3 fractions. For the SIB-HFWBI plan, the dose prescribed for the PTV of WB was 2.67 Gy per fraction with a total of 15 fractions, with a simultaneously integrated boost of 3.2 Gy per fraction to the PTV of TB with a total of 15 fractions. Regardless of the position, for the PTV of TB, the conformal index (CI) in the SIB-HFWBI plans was greater than those in the SEB-HFWBI plans (T = − 8.114, − 8.114; both P

Abstract Determining the etiology of end-stage renal disease (ESRD) constitutes a great challenge in the context of renal transplantation. Evidence is lacking on the genetic findings for adult renal transplant recipients through exome sequencing (ES). Adult patients on kidney transplant waitlist were recruited from 2017 to 2019. Trio-ES was conducted for the families who had multiple affected individuals with nephropathy or clinical suspicion of a genetic kidney disease owing to early onset or extrarenal features. Pathogenic variants were confirmed in 62 from 115 families post sequencing for 421 individuals including 195 health family members as potential living donors. Seventeen distinct genetic disorders were identified confirming the priori diagnosis in 33 (28.7%) families, modified or reclassified the clinical diagnosis in 27 (23.5%) families, and established a diagnosis in two families with ESRD of unknown etiology. In 14.8% of the families, we detected promising variants of uncertain significance in candidate genes associated with renal development or renal disease. Furthermore, we reported the secondary findings of oncogenes in 4.4% of the patients and known single-nucleotide polymorphisms associated with pharmacokinetics in our cohort to predict the drug levels of tacrolimus and mycophenolate. The diagnostic utility of the genetic findings has provided new clinical insight in most families that help with preplanned renal transplantation.

Abstract Superhydrophobic sponges have considerable potential for oil/water separation. Most of the methods used for superhydrophobic modification of sponges require toxic or harmful solvents, which have the drawbacks of hazardous to environment, expensive, and complex to utilize. Moreover, the hydrophobic layer on the surface of sponge is often easily destroyed. In this paper, a highly efficient superhydrophobic sponge with excellent reusability was developed by using a facile, simple and environmentally friendly dopamine biomimetic bonding method. Different types of sponges, such as melamine, polyethylene or polyurethane sponge wastes, were used as raw materials to prepare superhydrophobic sponges, which possess the advantages of inexpensive and abundant. The effects of different dopamine polymerization time and different hydrophobic agent dosage on the hydrophobicity and oil absorption capacity of melamine sponges were optimized. The study results showed that the water contact angle of the superhydrophobic sponge could reach 153° with excellent organic solvent absorption capacity of 165.9 g/g. Furthermore, the superhydrophobic sponge retained approximately 92.1% of its initial absorption capacity after 35 reutilization cycles. More importantly, the dopamine biomimetic bonding superhydrophobic modification method can be used for different types of sponges. Therefore, a universally applicable, facile, simple and environmentally friendly superhydrophobic modification method for sponges was developed.

Abstract Lateral heterostructures of two-dimensional (2D) materials, integrating different phases or materials into a single piece of nanosheet, have attracted intensive research interests for electronic devices. Extending the 2D lateral heterostructures to spintronics demands more diverse electromagnetic properties of 2D materials. In this paper, using density functional theory calculations, we survey all IV, V, and VI group transition metal dichalcogenides (TMDs) and discover that CrS2 has the most diverse electronic and magnetic properties: antiferromagnetic (AFM) metallic 1T phase, non-magnetic (NM) semiconductor 2H phase, and ferromagnetic (FM) semiconductor 1T′ phase with a Curie temperature of ~1000 K. Interestingly, we find that a tensile or compressive strain can turn the 1T′ phase into a spin-up or spin-down half-metal. Such strain tunability can be attributed to the lattice deformation under tensile/compressive strain that selectively promotes the spin-up/spin-down VBM (valence band bottom) orbital interactions. The diverse electromagnetic properties and the strain tunability enable strain-controlled spintronic devices using a single piece of CrS2 nanosheet with improved energy efficiency. As a demo, a prototypical design of the spin-valve logic device is presented. It offers a promising solution to address the challenge of high energy consumption in miniaturized spintronic devices.

Abstract The generation of hydrogel droplets using droplet microfluidics has emerged as a powerful tool with many applications in biology and medicine. Here, a microfluidic system to control the position of particles (beads or astrocyte cells) in hydrogel droplets using bulk acoustic standing waves is presented. The chip consisted of a droplet generator and a 380 µm wide acoustic focusing channel. Droplets comprising hydrogel precursor solution (polyethylene glycol tetraacrylate or a combination of polyethylene glycol tetraacrylate and gelatine methacrylate), photoinitiator and particles were generated. The droplets passed along the acoustic focusing channel where a half wavelength acoustic standing wave field was generated, and the particles were focused to the centre line of the droplets (i.e. the pressure nodal line) by the acoustic force. The droplets were cross-linked by exposure to UV-light, freezing the particles in their positions. With the acoustics applied, 89 ± 19% of the particles (polystyrene beads, 10 µm diameter) were positioned in an area ± 10% from the centre line. As proof-of-principle for biological particles, astrocytes were focused in hydrogel droplets using the same principle. The viability of the astrocytes after 7 days in culture was 72 ± 22% when exposed to the acoustic focusing compared with 70 ± 19% for samples not exposed to the acoustic focusing. This technology provides a platform to control the spatial position of bioparticles in hydrogel droplets, and opens up for the generation of more complex biological hydrogel structures.

Measurement(s) color Technology Type(s) satellite imaging Factor Type(s) temporal interval Sample Characteristic - Environment water body • lake Sample Characteristic - Location global Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.13257218

Pollen is an abundant material; but, currently has limited applications. Here, the authors turn pollen grains into soft microgel by de-esterification of pectin molecules and explore the mechanical and structural changes of the pollen grains using physical and modelling approaches.

Organic materials hold great potential of for spintronic applications. Here the authors show electronic phase dependent magnetoresistance (MR) effect in LPCMO/Alq3/Co junctions with large MR up to 440% at 10 K as well as electrical Hanle effect as the Hallmark of the spin injection.

Abstract A microwave one-way waveguide of three-dimensional configuration is proposed and investigated theoretically. In this waveguide there exists a complete one-way propagation band, where the mode propagates only in one direction and can be immune to backscattering. By terminating the one-way waveguide with metal slab, one-way propagating waves in this waveguide system can be stopped at the terminal end without any backscattering. Meanwhile, a hotspot with extremely enhanced magnetic-field amplitude is generated in this 3D waveguide system. For an incident microwave pulse, the trapped wave packet can be compressed to deep subwavelength scale besides the magnetic field enhancement. Moreover, the magnetic field enhancement of trapped waves can be further largely increased by tapering laterally the waveguide system. The approach for trapping microwaves has promising applications in magnetic sensing and magnetic non-linearity.

β2-adrenergic receptor (β2AR) can be phosphorylated by G protein receptor kinases and second messenger-dependent kinases. Here, the authors demonstrate that these phosphorylation events are specific to functionally distinct and spatially segregated subpopulations of β2AR that co-exist in a single cell.

Abstract The mechanism by which TSC2 inactivation or deficiency contributes to the pathology of tuberous sclerosis complex (TSC) is not fully clear. We show that renal angiomyolipomas from TSC patients and kidney cortex from Tsc2+/− mice exhibit elevated levels of reactive oxygen species (ROS). Downregulation of tuberin (protein encoded by TSC2 gene) in renal proximal tubular epithelial cells significantly increased ROS concomitant with enhanced Nox4. Similarly, we found elevated levels of Nox4 in the renal cortex of Tsc2+/− mice and in the renal angiomyolipomas from TSC patients. Tuberin deficiency is associated with activation of mTORC1. Rapamycin, shRNAs targeting raptor, or inhibition of S6 kinase significantly inhibited the expression of Nox4, resulting in attenuation of production of ROS in tuberin-downregulated proximal tubular epithelial cells. In contrast, activation of mTORC1 increased Nox4 and ROS. These results indicate that Nox4 may be a potential target for tuberin-deficiency-derived diseases. Using a xenograft model from tuberin-null tubular cells in nude mice, both anti-sense Nox4 and GKT137831, a specific inhibitor of Nox1/4, significantly inhibited the tumor growth. Thus, our results demonstrate the presence of an antagonistic relationship between tuberin and Nox4 to drive oncogenesis in the tuberin deficiency syndrome and identify Nox4 as a target to develop a therapy for TSC.

Tumor associated macrophages (TAMs) promote cancer progression. Here, the author show that caspase-1 promotes TAMs differentiation by attenuating medium-chain acyl-CoA dehydrogenase activity and that inhibition of this axis results in suppression of tumour growth in a transgenic mouse model of breast cancer.

Abstract Connexins play essential roles in lens homeostasis and development. Here, we identified a new role for Cx50 that mediates cell-cell adhesion function. Cx50 enhanced the adhesive capability of AQP0. Interestingly, the expression of Cx50 alone promoted cell adhesion at a comparable level to AQP0; however, this cell adhesive function was not observed with other lens connexins, Cx43 and Cx46. Moreover, the adhesive property occurred in both homotypic with Cx50 expressed in both pairing cells and heterotypic with Cx50 in only one pairing cell, and this function appears to be unrelated to its role in forming gap junction channels. Cx50 KO lenses exhibited increased intercellular spaces between lens fiber cells. The second extracellular loop domain (E2) is primarily responsible for this adhesive function. Treatment with a fusion protein containing E2 domain inhibited cell adhesion. Furthermore, disruption of cell adhesion by the E2 domains impaired primary lens cell differentiation. Five critical amino acid residues in the E2 domain primarily are involved in cell adhesive function as well as lens epithelial-fiber differentiation. Together, these results suggest that in addition to forming gap junction channels, Cx50 acts as an adhesive molecule that is critical in maintaining lens fiber integrity and epithelial-fiber differentiation.

Aurora kinase A is a mitotic kinase that facilitates G2/M events. Here the authors show that in breast cancer cells Aurora kinase A has a kinase-independent function in the nucleus by activating the MYC promoter in cooperation with hnRNP K, enhancing the breast cancer stem cell phenotype.