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Abstract Whether small nucleolar RNAs (snoRNAs) are involved in the regulation of liver cancer stem cells (CSCs) self-renewal and serve as therapeutic targets remains largely unclear. Here we show that a functional snoRNA (SNORD88B) is robustly expressed in Hepatocellular carcinoma (HCC) tumors and liver CSCs. SNORD88B deficiency abolishes the self-renewal of liver CSCs and hepatocarcinogenesis. Mechanistically, SNORD88B anchors WRN in the nucleolus, promoting XRCC5 interacts with STK4 promoter to suppress its transcription, leading to inactivation of Hippo signaling. Moreover, low expression of STK4 and high expression of XRCC5 are positively correlated with HCC poor prognosis. Additionally, snord88b knockout suppresses mouse liver tumorigenesis. Notably, co-administration of SNORD88B antisense oligonucleotides (ASOs) with MST1 agonist adapalene (ADA) exert synergistic antitumor effects and increase overall murine survival. Our findings delineate that SNORD88B drives self-renewal of liver CSCs and accelerates HCC tumorigenesis via non-canonical mechanism, providing potential targets for liver cancer therapy by eliminating liver CSCs.

Ensuring a low cross-polarization level (CPL) is imperative in the design of antennas with a low sidelobe level (SLL). This paper introduces an innovative approach for designing wideband, high-gain, low-sidelobe, and low-cross-polarization reflectarray (RA) and transmitarray (TA) antennas. The methodology leverages a groundbreaking metasurface endowed with the capability for independent amplitude and phase manipulation in both transmission and reflection modes. Initial characterization robustly verifies the metasurface’s proficiency in independently controlling amplitude and phase in reflection and transmission modes. Importantly, the study demonstrates that this metasurface enables the straightforward attainment of low CPL in the design of low-SLL RA and TA antennas. The study progresses to the design, fabrication, and testing of three RA and TA antennas. The obtained simulated and measured results affirm their exceptional performance in terms of wideband, high-gain, low-SLL, and low-CPL characteristics.

Abstract Supercoupling effect is an exotic and counterintuitive physical phenomenon of epsilon-near-zero (ENZ) media, in which the light can be “squeezed” and tunneled through flexible channels substantially narrower than its wavelength. Theoretically, ENZ channels with infinitely small widths perform ideal supercoupling with full energy transmission and zero-phase advance. As a feasible solution to demonstrate ENZ supercoupling through a finite-width channel, photonic doping can assist the light in squeezing, but the resonant dopant introduces inevitable losses. Here, we propose an approach of transmission-type photonic doping to achieve proximate ideal ENZ supercoupling. In contrast to the conventional resonance-type photonic doping, our proposed transmission-type doping replaces high-quality-factor two-dimensional resonant doping modes with low-quality-factor one-dimensional modes, such that obviously high transmission efficiency and zero-phase advance in ENZ supercoupling is achieved and observed in experiments. Benefiting from the high-efficiency ENZ supercoupling, waveguides with near-total energy transmission can be engineered with arbitrary dimensions and shapes, serving as flexible power conduits in the paradigm of waveguide integrated circuits for future millimeter-wave and terahertz integrated circuit innovations.

Electric vehicles can reduce the dependence on limited resources such as oil, which is conducive to the development of clean energy. An accurate battery state of health (SOH) is beneficial for the safety of electric vehicles. A multi-feature and Convolutional Neural Network–Bidirectional Long Short-Term Memory–Multi-head Attention (CNN-BiLSTM-MHA)-based lithium-ion battery SOH estimation method is proposed in this paper. First, the voltage, energy, and temperature data of the battery in the constant current charging phase are measured. Then, based on the voltage and energy data, the incremental energy analysis (IEA) is performed to calculate the incremental energy (IE) curve. The IE curve features including IE, peak value, average value, and standard deviation are extracted and combined with the thermal features of the battery to form a complete multi-feature sequence. A CNN-BiLSTM-MHA model is set up to map the features to the battery SOH. Experiments were conducted using batteries with different charging currents, and the results showed that even if the nonlinearity of battery SOH degradation is significant, this method can still achieve a fast and accurate estimation of the battery SOH. The Mean Absolute Error (MAE) is 0.1982%, 0.1873%, 0.1652%, and 0.1968%, and the Root-Mean-Square Error (RMSE) is 0.2921%, 0.2997%, 0.2130%, and 0.2625%, respectively. The average Coefficient of Determination (R2) is above 96%. Compared to the BiLSTM model, the training time is reduced by an average of about 36%.

Lung ischemia–reperfusion injury (IRI) stands as the primary culprit behind primary graft dysfunction (PGD) after lung transplantation, yet viable therapeutic options are lacking. In the present study, we used a murine hilar clamp (1 h) and reperfusion (3 h) model to study IRI. The left lung tissues were harvested for metabolomics, transcriptomics, and single-cell RNA sequencing. Metabolomics of plasma from human lung transplantation recipients was also performed. Lung histology, pulmonary function, pulmonary edema, and survival analysis were measured in mice. Integrative analysis of metabolomics and transcriptomics revealed a marked up-regulation of arachidonate 12-lipoxygenase (ALOX12) and its metabolite 12-hydroxyeicosatetraenoic acid (12-HETE), which played a pivotal role in promoting ferroptosis and neutrophil extracellular trap (NET) formation during lung IRI. Additionally, single-cell RNA sequencing revealed that ferroptosis predominantly occurred in pulmonary endothelial cells. Importantly, Alox12-knockout (KO) mice exhibited a notable decrease in ferroptosis, NET formation, and tissue injury. To investigate the interplay between endothelial ferroptosis and NET formation, a hypoxia/reoxygenation (HR) cell model using 2 human endothelial cell lines was established. By incubating conditioned medium from HR cell model with neutrophils, we found that the liberation of high mobility group box 1 (HMGB1) from endothelial cells undergoing ferroptosis facilitated the formation of NETs by activating the TLR4/MYD88 pathway. Last, the administration of ML355, a targeted inhibitor of Alox12, mitigated lung IRI in both murine hilar clamp/reperfusion and rat left lung transplant models. Collectively, our study indicates ALOX12 as a promising therapeutic strategy for lung IRI.

Background: Currently, the mechanism(s) underlying corticogenesis is still under characterization.Methods: We curated the most comprehensive single-cell RNA-seq (scRNA-seq) datasets from mouse and human fetal cortexes for data analysis and confirmed the findings with co-immunostaining experiments.Results: By analyzing the developmental trajectories with scRNA-seq datasets in mice, we identified a specific developmental sub-path contributed by a cell-population expressing both deep- and upper-layer neurons (DLNs and ULNs) specific markers, which occurred on E13.5 but was absent in adults. In this cell-population, the percentages of cells expressing DLN and ULN markers decreased and increased, respectively, during the development suggesting direct neuronal transition (namely D-T-U). Whilst genes significantly highly/uniquely expressed in D-T-U cell population were significantly enriched in PTN/MDK signaling pathways related to cell migration. Both findings were further confirmed by co-immunostaining with DLNs, ULNs and D-T-U specific markers across different timepoints. Furthermore, six genes (co-expressed with D-T-U specific markers in mice) showing a potential opposite temporal expression between human and mouse during fetal cortical development were associated with neuronal migration and cognitive functions. In adult prefrontal cortexes (PFC), D-T-U specific genes were expressed in neurons from different layers between humans and mice.Conclusion: Our study characterizes a specific cell population D-T-U showing direct DLNs to ULNs neuronal transition and migration during fetal cortical development in mice. It is potentially associated with the difference of cortical development in humans and mice.

Chronic restraint stress induces anxiety-like behaviors and colitis susceptibility, which is mediated by c-Jun in AgRP neurons.

Abstract Purpose To investigate the factors influencing and long-term effects of manual myotomy (MM) occurring during physiotherapy for congenital muscular torticollis (CMT). Methods We retrospectively collected the clinical data of children with CMT receiving physiotherapy between 2008 and 2018. The children were divided into manual myotomy (MM) and non-manual myotomy (NMM) groups according to whether MM occurred during treatment. We assessed physiotherapy outcomes in children with CMT using craniofacial asymmetry parameters and the Cheng–Tang rating score. By measuring the ear-eye distance, ear-nose distance, eye-mouth distance, ear-mouth distance, half-head circumference, and half-head top at two sides to evaluate craniofacial asymmetry. Based on the Cheng–Tang assessment criteria, we recorded the range of rotation, range of lateral flexion, the status of the contracted muscle, the hardness of the mass, the extent of head tilting during activities and sleeping, the status of daily activities, face size, type of head shape, cranial changes, and subjective head tilting to assess the effectiveness of treatment. Clinical data and outcome indicators (craniofacial asymmetry parameters and Cheng–Tang rating score) were compared. Results The MM group had a significantly higher total Cheng–Tang rating score than the NMM group (P

Abstract Background With breast cancer becoming the most diagnosed cancer in the world, the number of breast cancer-afflicted mothers with adolescent daughters is also rising. Further, adolescent daughters’ mothers serve as role models for in identity formation processes, especially concerning gender and sexuality. Nevertheless, breast cancer threats mother’s health, including such a key symbol of her womanhood—the breast—which may adversely affect the development of an adolescent daughter’s own sense of personal identity and womanhood. However, few researchers and practitioners have paid attention to mother-daughter interactions in the context of breast cancer. Therefore, this study aimed to uncover the nuances of the interactive challenges with adolescent daughters from breast cancer-afflicted mothers’ perspective. Methods We conducted a qualitative study following the sample saturation principle, collecting data through semi-structured interviews with 21 breast cancer patients who met the inclusion criteria. We utilized thematic analysis and partially integrated the Foucauldian discourse approach to analyze the data. Results Three major themes emerged from the data: (1) mothers are lost in chaos (inability to handle the shock of cancer, feelings of powerlessness about the uncertainty of their life span, and confusion about how to respond to daughter’s curiosity); (2) mothers struggle to maintain balance (torn between protecting daughters and letting them be independent, and making a tough choice between being a mother or a patient); and (3) mothers are immersed in guilt (increasing daughters’ risk of cancer, influencing daughters’ development, and imposing burdens on daughters). Conclusions Our research explored the interactive experience of breast cancer-afflicted mothers and adolescent daughters. The insights uncovered by this study will help mothers enhance interaction with their daughters and assist health practitioners in devising interventions.

This paper reports an experimental observation of irrotational, inviscid, and incompressible electromagnetic power flow within an epsilon-near-zero medium, exhibiting an analogy to an ideal fluid.

ABSTRACT: Beam synthesizing antenna arrays are essentially demanded for on-chip millimeter wave and terahertz systems. In order to achieve a particular radiation beam, specific amplitude and phase distributions are required for all the array elements, which is conventionally realized through a properly designed feeding network. In the current work, a low-loss feeding network design approach based on epsilon-near-zero (ENZ) medium was proposed for large-scale antenna arrays with different beam requirements. Due to the infinite wavelength within the ENZ medium, a newly-discovered stair-like resonant mode was adopted for assigning a uniform phase distribution to each element, while the amplitudes and positions of these elements were optimized for generating particular beams. To implement the design philosophy in a low-loss manner, a hollow air-filled waveguide near cutoff frequency was employed to emulate the ENZ medium, and the bulk silicon microelectromechanical systems (MEMS) micromachining technology was utilized for chip-scale integration. As a specific example, a low-sidelobe antenna array at 60.0 GHz was designed, which realized an impedance bandwidth of 2.57%, a gain of 13.6 dBi and a sidelobe level as low as -20.0 dB within the size of 0.5 × 3.4λ02. This method is also compatible with a variety of applications, such as the high-directivity antenna array, non-diffractive Bessel beam antenna array, and so on. Based on this innovative concept of applying ENZ medium to the on-chip antenna array, it shows the advantages of simple structure and low loss for on-chip beam synthesis without complex lossy feeding networks.

Abstract Owing to the persistent inflammatory microenvironment and unsubstantial dermal tissues, chronic diabetic wounds do not heal easily and their recurrence rate is high. Therefore, a dermal substitute that can induce rapid tissue regeneration and inhibit scar formation is urgently required to address this concern. In this study, we established biologically active dermal substitutes (BADS) by combining novel animal tissue‐derived collagen dermal‐replacement scaffolds (CDRS) and bone marrow mesenchymal stem cells (BMSCs) for the healing and recurrence treatments of chronic diabetic wounds. The collagen scaffolds derived from bovine skin (CBS) displayed good physicochemical properties and superior biocompatibility. CBS loaded with BMSCs (CBS‐MCSs) could inhibit M1 macrophage polarization in vitro. Decreased MMP‐9 and increased Col3 at the protein level were detected in CBS‐MSCs‐treated M1 macrophages, which may be attributed to the suppression of the TNF‐α/NF‐κB signaling pathway (downregulating phospho‐IKKα/β/total IKKα/β, phospho‐IκB/total IκB, and phospho‐NFκB/total NFκB) in M1 macrophages. Moreover, CBS‐MSCs could benefit the transformation of M1 (downregulating iNOS) to M2 (upregulating CD206) macrophages. Wound‐healing evaluations demonstrated that CBS‐MSCs regulated the polarization of macrophages and the balance of inflammatory factors (pro‐inflammatory: IL‐1β, TNF‐α, and MMP‐9; anti‐inflammatory: IL‐10 and TGF‐β3) in db/db mice. Furthermore, CBS‐MSCs facilitated the noncontractile and re‐epithelialized processes, granulation tissue regeneration, and neovascularization of chronic diabetic wounds. Thus, CBS‐MSCs have a potential value for clinical application in promoting the healing of chronic diabetic wounds and preventing the recurrence of ulcers.

State of charge (SOC) is a very important variable for using batteries safely and reliably. To improve the accuracy of SOC estimation, a novel variational extended Kalman filter (EKF) technique based on least square error method is herein provided by establishing a second-order equivalent circuit model for the battery. It was found that when SOC decreased, resistance polarization occurred in the electrochemical model, and the parameters in the equivalent RC model varied. To decrease the modeling error in the equivalent circuit model, the system parameters were identified online depending on the SOC’s estimated result. Through the SOC-estimation process, the variation theorem was introduced, which enabled the system parameters to track the real situations based on the output measured. The experiment results reveal the comparison of the SOC-estimation results of the variational EKF algorithm, the traditional EKF algorithm, the recursive least square (RLS) EKF algorithm, and the forgotten factor recursive least square (FFRLS) EKF algorithm based on different indices, including the mean square error (MSE) and the mean absolute error (MAE). The variational EKF algorithm provided in this paper has higher estimation accuracy and robustness than the traditional EKF, which verifies the superiority and effectiveness of the proposed method.

The multiple photonic dopants contained in an epsilon-near-zero medium can serve as non-interacting resonators, and offer an opportunity for the independent control of electromagnetic waves at various frequencies.

This paper proposes an unconventional type of antennas that are composed by epsilon-near-zero (ENZ) media. The operating frequencies of such antennas are independent of their geometries, and are determined by material dispersion.

Hexagonal optical lattices (HOLs) are formed when three beams with oblique incidence coherently interfere with each other. Theoretical model considering the orientation of three fundamental Gaussian beams is established to describe all kinds of patterns of HOLs. The formula describing the size and shape of the HOLs are also given. The nested Mach-Zehnder interferometer is employed to generate HOLs in experiment. The relations between the geometry parameters (size and shape) of HOLs and orientations of three beams are experimentally and numerically investigated. The experimental generated HOLs can be well simulated using our theory. Our study about HOLs generated by three-beam interference can be used to fabricate periodic structure modulation for the refractive index of a nonlinear media or create two-dimensional photonic crystals.

Abstract Background Birth defects pose a major challenge to infant health. Thus far, however, the causes of most birth defects remain cryptic. Over the past few decades, considerable effort has been expended on disclosing the underlying mechanisms related to birth defects, yielding myriad treatises and data. To meet the increasing requirements for data resources, we developed a freely accessible birth defect multi-omics database (BDdb, http://t21omics.cngb.org ) consisting of multi-omics data and potential disease biomarkers. Results In total, omics datasets from 136 Gene Expression Omnibus (GEO) Series records, including 5245 samples, as well as 869 biomarkers of 22 birth defects in six different species, were integrated into the BDdb. The database provides a user-friendly interface for searching, browsing, and downloading data of interest. The BDdb also enables users to explore the correlations among different sequencing methods, such as chromatin immunoprecipitation sequencing (ChIP-Seq) and RNA sequencing (RNA-Seq) from different studies, to obtain the information on gene expression patterns from diverse aspects. Conclusion To the best of our knowledge, the BDdb is the first comprehensive database associated with birth defects, which should benefit the diagnosis and prevention of birth defects.

Metabolic adaptation has been reported to promote cancer, yet the underlying mechanisms are not clear. Here, the authors show that m1A methylation in tRNA regulates cholesterol metabolism in liver cancer stem cells and m1A inhibition decreases tumourigenesis in preclinical models of hepatocellular carcinoma.

BackgroundSkin cutaneous melanoma (SKCM) is the most lethal skin cancer with an increasing incidence worldwide. The poor prognosis of SKCM urgently requires us to discover prognostic biomarkers for accurate therapy. As a regulator of DNA replication, TIMELESS (TIM) has been found to be highly expressed in various malignancies but rarely reported in SKCM. The objective of this study was to evaluate the relationship between TIM and SKCM tumorigenesis and prognosis.MethodsWe obtained RNA sequencing data from TCGA and GTEx to analyze TIM expression and differentially expressed genes (DEGs). Subsequently, GO/KEGG, GSEA, immune cell infiltration analysis, and protein-protein interaction (PPI) network were used to perform the functional enrichment analysis of TIM-related DEGs. Moreover, the receiver operating characteristic (ROC) curves, Cox regression analysis, Kaplan–Meier (K-M) analysis, and nomograms were applied to figure out the clinical significance of TIM in SKCM. In addition, we investigated the relationship between TIM promoter methylation and SKCM prognosis through the UALCAN database. Finally, the immunohistochemical (IHC) results of normal skin and SKCM were analyzed to determine expression differences.ResultsTIM was significantly elevated in various malignancies, including SKCM, and high expression of TIM was associated with poor prognosis. Moreover, a total of 402 DEGs were identified between the two distinct TIM expression groups, and functional annotation showed enrichment with positive regulation of cell cycle and classic oncogenic pathways in the high TIM expression phenotype, while keratinization pathways were negatively regulated and enriched. Further analysis showed that TIM was correlated with infiltration of multiple immune cells. Finally, IHC validated the differential expression of TIM in SKCM.ConclusionTIM might play a pivotal role in tumorigenesis of SKCM and is closely related to its prognosis.

Abstract Background Leucine deprivation modulates the dietary amino acid composition, reducing the fat content and improving the glucose tolerance, thus protecting the organism against obesity. However, a complete deprivation of leucine can lead to an extremely rapid fat loss in mice, accompanied by prolonged adverse effects such as weakness and mental fatigue. Therefore, in this study we aimed to seek the optimal concentration of dietary leucine that can reduce fat mass and improve the metabolism without the onset of severe effects. Methods To investigate whether there is a better concentration of diet leucine restriction (LR), based on the diet we conducted (A10021B), that can reduce fat mass and improve metabolism status without taking many negative effects, we fed 8 weeks old male C57Bl/6J mice with increasing degrees of leucine restriction diet 0% LR (control group), 25% LR, 50% LR, and 75% LR groups (4–6 mice each group). Fat mass and blood glucose levels were measured. The expression levels of genes involved in lipid metabolism in white adipose tissue (WAT) and liver, and proteins in insulin signaling were assessed in WAT, liver and muscle. Results We found that the 50% LR group is the most proper group here at the lowest leucine effective concentration, which reduced fat mass (p

Abstract Background The biological role of miR-203 and the underlying mechanisms on the proliferation of epidermal stem cells (ESCs) have not yet been reported during the progression of chronic wound healing in diabetes mellitus. Our previous studies have observed that the expression of miR-203 showed a marked upregulation and ESC proliferation capacity was impaired in diabetes mellitus skin wounds in rats. Methods Wound models were established in normal rats and rats with type 2 diabetes. Expression level of miR-203 and the alteration of ESCs’ number and function were detected. ESCs were isolated from the back skin of fetal rats to assess the effects of glucose in vitro. An antagomir to miR-203 was used to assess its effect on ESCs. Using microarray analysis, we further identified potential target genes and signaling pathways of miR-203. Results We found that high glucose significantly upregulated the expression of miR-203 and subsequently reduced the number of ESCs and impaired their proliferation capacity. Meanwhile, over-expression of miR-203 reduced the ESCs’ numbers and impaired the proliferation capacity via downregulation of the Notch and Wnt signaling pathways. Conversely, inhibition of miR-203 enhanced the proliferation capacity. Additionally, silencing miR-203 in skin of rats with type 2 diabetes accelerated wound healing and improved healing quality via the upregulation of the Notch and Wnt signaling pathways. Finally, over-expression of miR-203 downregulated genes ROCK2, MAPK8, MAPK9, and PRKCA. Conclusion Our findings demonstrated that induced expression of miR-203 by high glucose in type 2 diabetic rats decreased the number of ESCs and impaired ESC proliferation capacity via downregulating genes related to Notch and Wnt signaling pathways, resulting in a delayed wound healing.

Ethereum smart contracts are programs that can be collectively executed by a network of mutually untrusted nodes. Smart contracts handle and transfer assets of values, offering strong incentives for malicious attacks. Intrusion attacks are a popular type of malicious attacks. ContractGuard, the first intrusion detection system (IDS) was proposed to defend Ethereum smart contracts against such attacks. Like IDSs for conventional programs, ContractGuard detects intrusion attempts as abnormal control flow. However, existing IDS techniques or tools are inapplicable to Ethereum smart contracts due to Ethereum’s decentralized nature and its highly restrictive execution environment. To address these issues, ContractGuard was designed by embedding it in the contracts. At runtime, ContractGuard protects the smart contract by monitoring the context-tagged acyclic path of the smart contract. As ContractGuard involves deployment overhead and deployment overhead. It was optimized under the Ethereum Gas-oriented performance model to reduce the overheads. The experimental results show that this work can effectively detect 83% of vulnerabilities, ContractGuard only adds to 36.14% of the deployment overhead and 28.27% of the runtime overhead.

The effective clearance of apoptotic cells is essential for maintaining central nervous system (CNS) homeostasis and restoring homeostasis after injury. In most cases of physiological apoptotic cell death, efferocytosis prevents inflammation and other pathological conditions. When apoptotic cells are not effectively cleared, destruction of the integrity of the apoptotic cell membrane integrity, leakage of intracellular contents, and secondary necrosis may occur. Efferocytosis is the mechanism by which efferocytes quickly remove apoptotic cells from tissues before they undergo secondary necrosis. Cells with efferocytosis functions, mainly microglia, help to eliminate apoptotic cells from the CNS. Here, we discuss the impacts of efferocytosis on homeostasis, the mechanism of efferocytosis, the associations of efferocytosis failure and CNS diseases, and the current clinical applications of efferocytosis. We also identify efferocytosis as a novel potential target for exploring the causes and treatments of CNS diseases.

Due to the important application in the study of vibrational circular dichroism and helical dichroism of chiral molecules, the tunable vortex beam at mid-infrared region has attracted increasing attention. Based on orbital angular momentum (OAM) conservation in nonlinear interactions, the vortex pumped singly resonant optical parametric oscillator (SRO) is recognized as a versatile source of coherent vortex radiation providing high power and broad wavelength coverage from a single device. However, the low parametric gain and high oscillation threshold under continuous wave (cw) pumping has so far been the most challenging factor in generating cw tunable vortex beams. To predict the output characteristic of vortex pumped SRO, a theoretical model describing the vortex pumped SRO is needed. In this study, the theoretical model describing the vortex pumped SRO is set up under collimated Gaussian beam approximation. Output characteristics of different SROs are simulated numerically. By proper selection of pump scheme (such as double-pass pumping scheme), the vortex pumped mid-infrared SRO can oscillate at a relatively low pump power. By controlling the gain (mode overlap ratio between the pump and resonant wave in the nonlinear crystal) and loss (employing a spot-defect mirror with different defect size as the output coupler) of the resonant signal mode in the SRO, the OAM of the pump beam can be directionally transferred to a specific down converted beam. The transfer mechanism of the OAM among the pump light and the down-converted beams and factors affecting the transfer are studied. Our study provides the guidelines for the design and optimization of vortex pumped SRO under cw operation.

Here, the authors demonstrate substrate-integrated photonic doping, enabling the implementation of near-zero-index media within a printed circuit board integrated design. They illustrate the potential by designing and numerically demonstrating a dielectric sensor, an acousto-microwave modulator and a flexible transmission line.

Spiral phase plate (SPP) is the widely used method in the generation of vortex beam (VB) with fixed topological charges (TCs) for specific wavelength. Although VB with large TCs can be directly generated by using the SPP with high vortex order. The fabrication of high-quality SPPs with high vortex orders usually requires complex manufacturing process and high machining accuracy. An alternative method to generate VBs with large TCs is cascaded multiple SPPs with low order. In this study, we numerically calculate the transmitted light field of cascaded multiple SPPs according to the Huygens–Fresnel diffraction integral, and perform the experimental verifications. Based on cascading 6 SPPs (3 SPPs with TCs of 2, and 3 SPPs with TCs 4, respectively), an VB with TCs as high as 18 is generated. Furthermore, The TCs of the generated VB are detected by coaxial and off-axis interfering with fundamental Gaussian beam or its conjugate beam, respectively. The generated fork and spiral patterns allow us to distinguish the value and sign of TCs carried by the VB. The experimental results coincide well with the theoretical simulations. The fork pattern shows better resolution than the spiral one, and the petal pattern with small spiral allows us to distinguish large TCs with a higher resolution.

β-thalassemia, caused by mutations in the human hemoglobin β (HBB) gene, is one of the most common genetic diseases in the world. The HBB −28(A>G) mutation is one of the five most common mutations in Chinese patients with β-thalassemia. However, few studies have been conducted to understand how this mutation affects the expression of pathogenesis-related genes, including globin genes, due to limited homozygote clinical materials. Therefore, we developed an efficient technique using CRISPR/Cas9 combined with asymmetric single-stranded oligodeoxynucleotides (assODNs) to generate a K562 cell model with HBB −28(A>G) named K562–28(A>G). Then, we systematically analyzed the differences between K562–28(A>G) and K562 at the transcriptome level by high-throughput RNA-seq before and after erythroid differentiation. We found that the HBB −28(A>G) mutation not only disturbed the transcription of HBB, but also decreased the expression of HBG, which may further aggravate the thalassemia phenotype and partially explain the more severe clinical outcome of β-thalassemia patients with the HBB −28(A>G) mutation. Moreover, we found that the K562–28(A>G) cell line is more sensitive to hypoxia and shows a defective erythrogenic program compared with K562 before differentiation. Importantly, all abovementioned abnormalities in K562–28(A>G) were reversed after correction of this mutation with CRISPR/Cas9 and assODNs, confirming the specificity of these phenotypes. Overall, this is the first time to analyze the effects of the HBB −28(A>G) mutation at the whole-transcriptome level based on isogenic cell lines, providing a landscape for further investigation of the mechanism of β-thalassemia with the HBB −28(A>G) mutation.

Introduction Early screening for diabetic retinopathy (DR) with an efficient and scalable method is highly needed to reduce blindness, due to the growing epidemic of diabetes. The aim of the study was to validate an artificial intelligence-enabled DR screening and to investigate the prevalence of DR in adult patients with diabetes in China.Research design and methods The study was prospectively conducted at 155 diabetes centers in China. A non-mydriatic, macula-centered fundus photograph per eye was collected and graded through a deep learning (DL)-based, five-stage DR classification. Images from a randomly selected one-third of participants were used for the DL algorithm validation.Results In total, 47 269 patients (mean (SD) age, 54.29 (11.60) years) were enrolled. 15 805 randomly selected participants were reviewed by a panel of specialists for DL algorithm validation. The DR grading algorithms had a 83.3% (95% CI: 81.9% to 84.6%) sensitivity and a 92.5% (95% CI: 92.1% to 92.9%) specificity to detect referable DR. The five-stage DR classification performance (concordance: 83.0%) is comparable to the interobserver variability of specialists (concordance: 84.3%). The estimated prevalence in patients with diabetes detected by DL algorithm for any DR, referable DR and vision-threatening DR were 28.8% (95% CI: 28.4% to 29.3%), 24.4% (95% CI: 24.0% to 24.8%) and 10.8% (95% CI: 10.5% to 11.1%), respectively. The prevalence was higher in female, elderly, longer diabetes duration and higher glycated hemoglobin groups.Conclusion This study performed, a nationwide, multicenter, DL-based DR screening and the results indicated the importance and feasibility of DR screening in clinical practice with this system deployed at diabetes centers.Trial registration number NCT04240652.

Background/Aims: Little is known how miR-203 is involved in epidermal stem cells (ESCs) differentiation and scar formation. Methods: We first used luciferase assay to determine the interaction of miR-203 with the 3’-UTR in regulation of Hes1 expression. We then used flow cytometry to analyze the effects of miR-203 expression on the differentiation of ESCs to MFB by determination of CK15 ratio and α-SMA. To confirm the results of flow cytometry analysis, we used Western blot to examine the expression of α-SMA, Collagen I (Col I), and Collagen III (Col III), as well as the expression of Notch1, Jagged1, and Hes1 in ESCs after the treatment of pre-miR-203 or anti-miR-203. Finally, we examined the effects local anti-miR-203 treatment on would closure and scar formation using a mouse skin wound model. Results: Pre-miR-203 treatment increased ESCs differentiation to MFB cells, as indicated by decreased CK15 ratio and increased MFB biomarkers. This phenomenon was reversed by overexpression of Hes1 in ESCs. In addition, skin incision increased expression of miR-203 in wound tissue. Local treatment of anti-miR-203 could accelerate wound closure and reduce scar formation in vivo, which was associated with increased re-epithelialization, skin attachment regeneration, and collagen reassignment. Finally, we confirmed that anti-miR-203 treatment could inhibit ESCs differentiation in vivo via increasing Hesl expression. Conclusion: Taken together, our results suggested that overexpression of miR-203 in ESCs after skin wound may be a critical mechanism underlying the scar formation.

In this paper, we have designed an ultra-wideband electromagnetic (EM) absorber based on the concept of metasurface Salisbury screen (MSS), which features low profile, light weight, simple configuration, and robust angular performance. The metasurface with extremely simple patch pattern is utilized to generate diverse controllable reflection phases, in place of the non-dispersive metallic plate used in conventional absorbers, thus achieving a multi-octave ultra-wideband EM wave absorption. Equivalent circuit model is established to analyze the performance of the MSS elements, and then the genetic algorithm and simulated annealing algorithm are employed to optimize the MSS element geometries and their spatial distribution. The proposed and fabricated MSS, with a polarization-insensitive absorption over 88% from 3.74 to 18.5 GHz verified by experiments, shows a considerable bandwidth improvement compared with the conventional Salisbury screen of same thickness which has 88% absorption band from 4.8 to 11.5 GHz. Furthermore, the MSS can still provide ultra-wideband absorption with high efficiency for large incident angle, for example, higher than 82% for 45° incidence. The proposed concept could provide opportunities for flexibly designing ultra-wideband EM absorbers, exhibiting promising potentials for many practical applications, such as electromagnetic compatibility, stealth technique, and so on.

A high-order moment recursive state estimator is designed to achieve the minimum mean square error estimation of a Markov jump linear system (MJLS) whose state distribution obeys a generalized Gaussian distribution (GGD). The operation properties of the cumulant generating function are explored to transform the stochastic MJLS into a high-order component form. Based on the transformed high-order moment deterministic system, a Kalman filter is applied to estimate the high-order moment information of the state variable, such as the skewness and kurtosis of the GGD. This method allows for the estimation of the Gaussian distribution, such as the two special cases, mean and variance. A comparison with the existing results of the mean error estimation demonstrates the higher estimation accuracy for the simulation. The application of the proposed method to economic and power systems demonstrates its effectiveness and advantages.

Power optimization is an important part of network-on-chip(NoC) design. This paper proposes an improved algorithm based on genetic algorithm on how to properly map IP (Intellectual Property) cores to 3D NoC. First, in view of the randomness of the traditional genetic algorithm in individual selection, an improved greedy algorithm is used in the initial population generation stage to make the generated individuals reach the optimal. Secondly, in view of the weak local optimization ability of the traditional genetic algorithm and prone to premature problems, the simulated annealing algorithm is added in the crossover operation stage to make the offspring reach the global optimum. The experimental results show that compared with the traditional genetic algorithm, the algorithm has better convergence and low power consumption performance, which can quickly search for a better solution, in the case of a large number of cores (124 IP cores), the average power consumption can be reduced by 42.2%.

Abstract Background Basic fibroblast growth factor (bFGF) plays an important role in promoting wound healing and reducing scar, but the possible molecular mechanisms are still unclear. Our previous studies have found that activating the Notch1/Jagged1 pathway can inhibit the differentiation of epidermal stem cells (ESCs) to myofibroblasts (MFB). Herein, we document that bFGF reduces scar by inhibiting the differentiation of ESCs to MFB via activating the Notch1/Jagged1 pathway. Methods In in-vitro study, ESCs were isolated from 10 neonatal SD rats (1–3 days old), cultured in keratinocyte serum-free medium, and divided into six groups: bFGF group, bFGF + SU5402 group, bFGF + DAPT group, siJagged1 group, bFGF + siJagged1 group, and control group. Jagged1 of the ESCs in the siJagged1 group and bFGF + siJagged1 group was knocked down by small-interfering RNA transfection. Expression of ESC markers (CK15/CK10), MFB markers (α-SMA, Collagen I, Collagen III), and Notch1/Jagged1 components (Jagged1, Notch1, Hes1) was detected by FCM, qRT-PCR, and western blot analysis to study the relationships of bFGF, ESCs, and Notch1/Jagged1 pathway. In in-vivo study, the wound healing time and scar hyperplasia were observed on rabbit ear scar models. The quality of wound healing was estimated by hematoxylin and eosin staining and Masson staining. Expression of ESC markers, MFB markers and Notch1/Jagged1 components was elucidated by immunohistochemistry, immunofluorescence, and western blot analysis. Results The in-vitro study showed that bFGF could significantly upregulate the expression of ESC markers and Notch1/Jagged1 components, while downregulating the expression of MFB markers at the same time. However, these effects could be obviously decreased when we knocked down Jagged1 or added DAPT. Similarly, in in-vivo study, bFGF also exhibited its functions in inhibiting the differentiation of rabbit ESCs to MFB by activating the Notch1/Jagged1 pathway, which improved the wound healing quality and alleviated scar significantly. Conclusion These results provide evidence that bFGF can reduce scar by inhibiting the differentiation of ESCs to MFB via the Notch1/Jagged1 pathway, and present a new promising potential direction for the treatment of scar.