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Abstract In the field of information processing, all-optical routers are significant for achieving high-speed, high-capacity signal processing and transmission. In this study, we developed three types of structurally simple and flexible routers using the deep diffractive neural network (D2NN), capable of routing incident light based on wavelength and polarization. First, we implemented a polarization router for routing two orthogonally polarized light beams. The second type is the wavelength router that can route light with wavelengths of 1550, 1300, and 1100 nm, demonstrating outstanding performance with insertion loss as low as 0.013 dB and an extinction ratio of up to 18.96 dB, while also maintaining excellent polarization preservation. The final router is the polarization-wavelength composite router, capable of routing six types of input light formed by pairwise combinations of three wavelengths (1550, 1300, and 1100 nm) and two orthogonal linearly polarized lights, thereby enhancing the information processing capability of the device. These devices feature compact structures, maintaining high contrast while exhibiting low loss and passive characteristics, making them suitable for integration into future optical components. This study introduces new avenues and methodologies to enhance performance and broaden the applications of future optical information processing systems. Graphical Abstract

Abstract The topological photonics plays an important role in the fields of fundamental physics and photonic devices. The traditional method of designing topological system is based on the momentum space, which is not a direct and convenient way to grasp the topological properties, especially for the perturbative structures or coupled systems. Here, we propose an interdisciplinary approach to study the topological systems in real space through combining the information entropy and topological photonics. As a proof of concept, the Kagome model has been analyzed with information entropy. We reveal that the bandgap closing does not correspond to the topological edge state disappearing. This method can be used to identify the topological phase conveniently and directly, even the systems with perturbations or couplings. As a promotional validation, Su–Schrieffer–Heeger model and the valley-Hall photonic crystal have also been studied based on the information entropy method. This work provides a method to study topological photonic phase based on information theory, and brings inspiration to analyze the physical properties by taking advantage of interdisciplinarity. Graphical Abstract

Abstract Objective To evaluate the efficacy of urethral-sparing laparoscopic simple prostatectomy (US-LSP) for the treatment of large-volume (>80 ml) benign prostatic hyperplasia (BPH) with asymptomatic urethral stricture (urethral lumen > 16 Fr) after urethral stricture surgery. Methods We retrospectively analyzed clinical data of 39 large-volume BPH patients with asymptomatic urethral stricture after urethral stricture surgery who underwent US-LSP from January 2016 to October 2021. Postoperative follow-ups were scheduled at 1, 3, and 6 months. Results All patients affected by significant BPH-related lower urinary tract symptoms (LUTS) including 22 cases with asymptomatic anterior urethral stricture and 17 cases with asymptomatic posterior urethral stricture. Median operative time was 118 min (interquartile range [IQR]100–145). Median estimated blood loss was 224 ml (IQR: 190–255). 33 patients(84.6%) avoided continuous bladder irrigation. Postoperative complications occurred in 5 patients (12.8%), including 4 cases with Clavien-Dindo grade 1 and grade 2 and 1 case with grade 3a. During follow-up, US-LSP presented statistically significant improvements in LUTS compared to baseline (P

Abstract Background Molecular subtyping is expected to enable precise treatment. However, reliable subtyping strategies for clinical application remains defective and controversial. Given the significance of tumor immune dysfunction and exclusion (TIDE), we aimed to develop a novel TIDE-based subtyping strategy to guide personalized immunotherapy in the bladder cancer (BC). Methods Transcriptome data of BC was used to evaluate the heterogeneity and the status of TIDE patterns. Subsequently, consensus clustering was applied to classify BC patients based on TIDE marker-genes. Patients’ clinicopathological, molecular features and signaling pathways of the different TIDE subtypes were well characterized. We also utilize the deconvolution algorithms to analyze the tumor microenvironment, and further explore the sensitivity and mechanisms of each subtype to immunotherapy. Furthermore, BC patient clinical information, real-world BC samples and urine samples were collected for the validation of our findings, which were used for RNA-seq analysis, H&E staining, immunohistochemistry and immunofluorescence staining, and enzyme-linked immunosorbent assay. Finally, we also explored the conservation of our novel TIDE subtypes in pan-cancers. Results We identified 69 TIDE biomarker genes and classified BC samples into three subtypes using consensus clustering. Subtype I showed the lowest TIDE status and malignancy with the best prognosis and highest sensitivity to immune checkpoint blockade (ICB) treatment, which was enriched of metabolic related signaling pathways. Subtype III represented the highest TIDE status and malignancy with the poorest prognosis and resistance to ICB treatment, resulting from its inhibitory immune microenvironment and T cell terminal exhaustion. Subtype II was in a transitional state with intermediate TIDE level, malignancy, and prognosis. We further confirmed the existence and characteristics of our novel TIDE subtypes using real-world BC samples and collected patient clinical data. This subtyping method was proved to be more efficient than previous known methods in identifying non-responders to immunotherapy. We also propose that combining our TIDE subtypes with known biomarkers can potentially improve the sensitivity and specificity of these biomarkers. Moreover, besides guiding ICB treatment, this classification approach can assist in selecting the frontline or recommended drugs. Finally, we confirmed that the TIDE subtypes are conserved across the pan-tumors. Conclusions Our novel TIDE-based subtyping method can serve as a powerful clinical tool for BC and pan-cancer patients, and potentially guiding personalized therapy decisions for selecting potential beneficiaries and excluding resistant patients of ICB therapy.

Median arcuate ligament (MAL) syndrome, otherwise known as celiac artery compression syndrome, is rare and is characterized by celiac artery compression by the median arcuate ligament. We report a unique case of MAL syndrome with recurrent myocardial infarction as the primary manifestation, and offer new pathophysiological insights. A man in his early 50s experienced recurrent upper abdominal pain, electrocardiographic changes, and elevated troponin concentrations, which suggested myocardial infarction. Contrast-enhanced computed tomography showed considerable celiac artery stenosis due to MAL syndrome. The patient was diagnosed with MAL syndrome and acute myocardial infarction. He declined revascularization owing to economic constraints, and opted to have conservative treatment with Chinese herbal extracts and medications. He succumbed to sudden cardiac death during a subsequent abdominal pain episode. The findings from this case show that MAL syndrome can present with recurrent myocardial infarction rather than typical intestinal angina symptoms. The pathophysiological link may involve intestinal and cardiac ischemia. An accurate diagnosis and appropriate management of MAL syndrome require careful evaluation and investigation.

Abstract Modulation of topological phase transition has been pursued by researchers in both condensed matter and optics research fields, and has been realized in Euclidean systems, such as topological photonic crystals, topological metamaterials, and coupled resonator arrays. However, the spin-controlled topological phase transition in non-Euclidean space has not yet been explored. Here, we propose a non-Euclidean configuration based on Möbius rings, and we demonstrate the spin-controlled transition between the topological edge state and the bulk state. The Möbius ring, which is designed to have an 8π period, has a square cross section at the twist beginning and the length/width evolves adiabatically along the loop, accompanied by conversion from transverse electric to transverse magnetic modes resulting from the spin-locked effect. The 8π period Möbius rings are used to construct Su–Schrieffer–Heeger configuration, and the configuration can support the topological edge states excited by circularly polarized light, and meanwhile a transition from the topological edge state to the bulk state can be realized by controlling circular polarization. In addition, the spin-controlled topological phase transition in non-Euclidean space is feasible for both Hermitian and non-Hermitian cases in 2D systems. This work provides a new degree of polarization to control topological photonic states based on the spin of Möbius rings and opens a way to tune the topological phase in non-Euclidean space. Graphical abstract

Abstract Background Prostate cancer (PCA) is the fifth leading cause of cancer-related deaths worldwide, with limited treatment options in the advanced stages. The immunosuppressive tumor microenvironment (TME) of PCA results in lower sensitivity to immunotherapy. Although molecular subtyping is expected to offer important clues for precision treatment of PCA, there is currently a shortage of dependable and effective molecular typing methods available for clinical practice. Therefore, we aim to propose a novel stemness-based classification approach to guide personalized clinical treatments, including immunotherapy. Methods An integrative multi-omics analysis of PCA was performed to evaluate stemness-level heterogeneities. Unsupervised hierarchical clustering was used to classify PCAs based on stemness signature genes. To make stemness-based patient classification more clinically applicable, a stemness subtype predictor was jointly developed by using four PCA datasets and 76 machine learning algorithms. Results We identified stemness signatures of PCA comprising 18 signaling pathways, by which we classified PCA samples into three stemness subtypes via unsupervised hierarchical clustering: low stemness (LS), medium stemness (MS), and high stemness (HS) subtypes. HS patients are sensitive to androgen deprivation therapy, taxanes, and immunotherapy and have the highest stemness, malignancy, tumor mutation load (TMB) levels, worst prognosis, and immunosuppression. LS patients are sensitive to platinum-based chemotherapy but resistant to immunotherapy and have the lowest stemness, malignancy, and TMB levels, best prognosis, and the highest immune infiltration. MS patients represent an intermediate status of stemness, malignancy, and TMB levels with a moderate prognosis. We further demonstrated that these three stemness subtypes are conserved across pan-tumor. Additionally, the 9-gene stemness subtype predictor we developed has a comparable capability to 18 signaling pathways to make tumor diagnosis and to predict tumor recurrence, metastasis, progression, prognosis, and efficacy of different treatments. Conclusions The three stemness subtypes we identified have the potential to be a powerful tool for clinical tumor molecular classification in PCA and pan-cancer, and to guide the selection of immunotherapy or other sensitive treatments for tumor patients.

Abstract Nonreciprocal interlayer coupling is difficult to practically implement in bilayer non-Hermitian topological photonic systems. In this work, we identify a similarity transformation between the Hamiltonians of systems with nonreciprocal interlayer coupling and on-site gain/loss. The similarity transformation is widely applicable, and we show its application in one- and two-dimensional bilayer topological systems as examples. The bilayer non-Hermitian system with nonreciprocal interlayer coupling, whose topological number can be defined using the gauge-smoothed Wilson loop, is topologically equivalent to the bilayer system with on-site gain/loss. We also show that the topological number of bilayer non-Hermitian C6v-typed domain-induced topological interface states can be defined in the same way as in the case of the bilayer non-Hermitian Su–Schrieffer–Heeger model. Our results show the relations between two microscopic provenances of the non-Hermiticity and provide a universal and convenient scheme for constructing and studying nonreciprocal interlayer coupling in bilayer non-Hermitian topological systems. This scheme is useful for observation of non-Hermitian skin effect in three-dimensional systems. Graphical Abstract

In this study, we monitored changes in fruit hardness, cell wall-modifying enzyme activities such as polygalacturonase (PG), pectin methylesterase (PME), pectin lyases (PL) and β-galactosidase (β-Gal), and physiochemical properties of three cell wall polysaccharides including water soluble polysaccharide (WSP), trans-1,2-cyclohexanediaminetetraacetic acid (CDTA)-soluble polysaccharide (CSP) and Na2CO3-soluble polysaccharide (NSP) in ‘Yate’ kiwifruits during postharvest cold storage. Results showed that postharvest kiwifruits went through a ‘fast-slow’ softening process. PG activity showed a maximum value of 670.76 U/mg after 10 days of storage. PL and PME activities showed a maximum increase over the first five days of storage, reaching up to 3.41 and 9.17 U/mg, respectively. Particularly, β-Gal activity continuously increased during storage and showed a negative correlation with fruit hardness (r = −0.888). The pectin contents of WSP, CSP and NSP increased significantly with storage time. Moreover, the results of high performance gel permeation chromatography (GPC) showed that the weight average molecular mass of WSP increased, that of CSP initially decreased and then increased, and that of NSP gradually decreased during storage. Furthermore, a decrease in the area and an increase in the lamellarity of WSP were observed by scanning electron microscopy (SEM), whereas CSP was found to be soft and muslin-like after 15 days of storage, and the cluster-like accumulation of NSP was gradually dispersed with more debris being observed. These results may provide a solid theoretical basis for elucidating the exact mechanism of kiwifruit softening.

Abstract Optical neural networks (ONNs) herald a new era in information and communication technologies and have implemented various intelligent applications. In an ONN, the activation function (AF) is a crucial component determining the network performances and on-chip AF devices are still in development. Here, we first demonstrate on-chip reconfigurable AF devices with phase activation fulfilled by dual-functional graphene/silicon (Gra/Si) heterojunctions. With optical modulation and detection in one device, time delays are shorter, energy consumption is lower, reconfigurability is higher and the device footprint is smaller than other on-chip AF strategies. The experimental modulation voltage (power) of our Gra/Si heterojunction achieves as low as 1 V (0.5 mW), superior to many pure silicon counterparts. In the photodetection aspect, a high responsivity of over 200 mA/W is realized. Special nonlinear functions generated are fed into a complex-valued ONN to challenge handwritten letters and image recognition tasks, showing improved accuracy and potential of high-efficient, all-component-integration on-chip ONN. Our results offer new insights for on-chip ONN devices and pave the way to high-performance integrated optoelectronic computing circuits.

In order to study the influence of heat treatment on the dynamic properties of fine-grained granite, an improved split Hopkinson pressure bar (SHPB) system was used to conduct impact compression tests on the granite specimens treated at 20~1000 °C under three loading rates. The experimental results show that the shape of the impact stress–strain curve is affected by the loading rate and heat treatment temperature. Under the same loading rate, the average strain rate, peak strain, and maximum strain of granite specimen exhibit a trend of “slow increasing (20~200 °C)—slow decreasing (200~400 °C)—slow increasing (400~500 °C)”. The peak stress and elastic modulus show the opposite trend. The average strain rate, peak strain, and maximum strain of the granite specimen treated at 600 °C increase significantly. The peak stress and elastic modulus decrease significantly. Within the heat treatment temperature range of 600~800 °C, the dynamic properties of granite deteriorate slowly. The average strain rate, peak strain, and maximum strain of the granite specimens treated at 900 °C and 1000 °C increase sharply, while the peak stress decreases sharply. Within the heat treatment temperature range of 600–1000 °C, the elastic modulus of the granite specimen shows an approximately linear decreasing trend. There are no changes in the mineral composition of granite within the heat treatment temperature range of 20–1000 °C. After heat treatment at 600 °C, the width of internal cracks in granite increases significantly. The width of internal cracks in the heat-treated granites at 900 °C and 1000 °C increases sharply. The change in the dynamic properties of granite is determined by the internal microstructure of the heat-treated granite at different temperatures.

The Symmetry Editorial Office retracts the article titled “RETRACTED: Hybrid Thermal-Chemical Enhanced Oil Recovery Methods; An Experimental Study for Tight Reservoirs” [...]

Abstract Low-loss dielectric modes are important features and functional bases of fundamental optical components in on-chip optical devices. However, dielectric near-field modes are challenging to reveal with high spatiotemporal resolution and fast direct imaging. Herein, we present a method to address this issue by applying time-resolved photoemission electron microscopy to a low-dimensional wide-bandgap semiconductor, hexagonal boron nitride (hBN). Taking a low-loss dielectric planar waveguide as a fundamental structure, static vector near-field vortices with different topological charges and the spatiotemporal evolution of waveguide modes are directly revealed. With the lowest-order vortex structure, strong nanofocusing in real space is realized, while near-vertical photoemission in momentum space and narrow spread in energy space are simultaneously observed due to the atomically flat surface of hBN and the small photoemission horizon set by the limited photon energies. Our approach provides a strategy for the realization of flat photoemission emitters.

Computational thinking (CT) is an imperative competency in the 21st century. Mindtools can assist students in understanding concepts and decomposing tasks during CT development through programming. However, students may encounter challenges in complex CT problem-solving tasks due to being confused when using mindtools without proper guidance. Research evidence shows the potential of reflection in complex CT problem-solving by regulating cognitive activities. Accordingly, this study designed a reflection-guided visualized mindtool strategy to address CT development challenges. A quasi-experiment and lag sequential analysis were conducted by recruiting 97 junior high school students to examine the effects of the proposed strategy on CT development and to explore students’ behavior patterns. Results revealed that the proposed approach improved students’ CT performance, CT disposition, meta-cognitive awareness, and learning motivation. Students learning with the proposed strategy exhibited more key behaviors of facilitating CT problem-solving (e.g., generalizing the knowledge, re-designing the algorithm scheme, and evaluating the feasibility of their proposed schemes) than students in the control group, revealing the essential process of CT development and enlightening teachers on guiding students to produce such learning processes when cultivating CT.

PurposeThe intent of this paper is to understand the effect of Physical Activity on university students' Subjective Well-being and to explore whether Perceived Health, Social Support, and Self-esteem play roles as mediating variables.MethodsSelf-reported data from 404 college students (147 males and 257 females) were analyzed using structural equation modeling (SEM). The relationships between the study variables were tested by mediation models and 5,000 bootstrap samples using AMOS version 24.Results(1) The six hypotheses were supported in the measurement model in the results (P

The basic indexes of all-optical integrated photonic circuits include high-density integration, ultrafast response and ultra-low energy consumption. Traditional methods mainly adopt conventional micro/nano-structures. The overall size of the circuit is large, usually reaches hundreds of microns. Besides, it is difficult to balance the ultrafast response and ultra-low energy consumption problem, and the crosstalk between two traditional devices is difficult to overcome. Here, we propose and experimentally demonstrate an approach based on inverse design method to realize a high-density, ultrafast and ultra-low energy consumption integrated photonic circuit with two all-optical switches controlling the input states of an all-optical XOR logic gate. The feature size of the whole circuit is only 2.5 μm × 7 μm, and that of a single device is 2 μm × 2 μm. The distance between two adjacent devices is as small as 1.5 μm, within wavelength magnitude scale. Theoretical response time of the circuit is 150 fs, and the threshold energy is within 10 fJ/bit. We have also considered the crosstalk problem. The circuit also realizes a function of identifying two-digit logic signal results. Our work provides a new idea for the design of ultrafast, ultra-low energy consumption all-optical devices and the implementation of high-density photonic integrated circuits.

The two-dimensional electron gas (2DEG) generated at the LaAlO3/SrTiO3 interface has been in the focus of oxides research since its first discovery. Although oxygen vacancies play an important role in the generation of the insulator-to-metal transition of the SrTiO3 bare surface, their contribution at the LaAlO3/SrTiO3 interface remains unclear. In this work, we investigated a LaAlO3/SrTiO3 heterostructure with regional distribution of defect-based localized polar sites at the interface. Using static and time-resolved threshold photoemission electron microscopy, we prove that oxygen vacancies are induced near those polar sites, resulting in the increase of carrier density of the 2DEG states. In addition, oxygen-related surface states were uncovered, which we attributed to the release of lattice oxygen during the formation of oxygen vacancies. Such effects are mainly found spatially located around the defect sites at the buried interface, while other regions remain unaffected. Our results confirm that the itinerant electrons induced by oxygen vacancies can coexist with the charge transfer mechanism in the LaAlO3/SrTiO3 heterostructure, together leading to the formation of the metallic interface. These observations provide fundamental insights into the nature of LaAlO3/SrTiO3 interface based 2DEG and unique perspectives for potential applications.

ObjectivesTo evaluate the effects of mirabegron in the treatment of overactive bladder syndrome (OAB) after radical prostatectomy (RP).Patients and methodsA total of 108 post-operative RP patients were randomly assigned to either the mirabegron (study) or the placebo (control) group. The Overactive Bladder Syndrome Self-Assessment Scale (OABSS) was selected as the primary endpoint, and the International Prostate Symptom Score (IPSS) and Quality of Life (QOL) score were selected as secondary endpoints. Statistical analysis was performed using IBM SPSS Statistics 26, and the treatment effects were compared between the two groups using independent samples t-test.ResultsIn total, 55 patients were included in the study group and 53 patients in the control group. The mean age was(70.08 ± 7.54)years. There was no statistical difference in the baseline data between the two groups. OABSS scores decreased significantly in the study group compared to the control group during drug treatment (6.67 ± 1.06 vs. 9.14 ± 1.83, p < 0.01) and were better than the control group during the follow-up at week 8 and week 12. In addition, the decrease in IPSS scores (11.29 ± 3.89 and 15.34 ± 3.54, p

Here the authors provide the experimental observation of a topological rainbow in a silicon-based nanophotonic chip. The system is robust against disorders allows to separate and trap topological photonic states of different wavelength into different positions.

The rapid development of information technology has fueled an ever-increasing demand for ultrafast and ultralow-energy-consumption computing. Existing computing instruments are pre-dominantly electronic processors, which use electrons as information carriers and possess von Neumann architecture featured by physical separation of storage and processing. The scaling of computing speed is limited not only by data transfer between memory and processing units, but also by RC delay associated with integrated circuits. Moreover, excessive heating due to Ohmic losses is becoming a severe bottleneck for both speed and power consumption scaling. Using photons as information carriers is a promising alternative. Owing to the weak third-order optical nonlinearity of conventional materials, building integrated photonic computing chips under traditional von Neumann architecture has been a challenge. Here, we report a new all-optical computing framework to realize ultrafast and ultralow-energy-consumption all-optical computing based on convolutional neural networks. The device is constructed from cascaded silicon Y-shaped waveguides with side-coupled silicon waveguide segments which we termed “weight modulators” to enable complete phase and amplitude control in each waveguide branch. The generic device concept can be used for equation solving, multifunctional logic operations as well as many other mathematical operations. Multiple computing functions including transcendental equation solvers, multifarious logic gate operators, and half-adders were experimentally demonstrated to validate the all-optical computing performances. The time-of-flight of light through the network structure corresponds to an ultrafast computing time of the order of several picoseconds with an ultralow energy consumption of dozens of femtojoules per bit. Our approach can be further expanded to fulfill other complex computing tasks based on non-von Neumann architectures and thus paves a new way for on-chip all-optical computing.

Galanin is a neurohormone as well as a neurotransmitter and plays versatile physiological roles for the neuroendocrine axis, such as regulating food intake, insulin level and somatostatin release. It is expressed in the central nervous system, including hypothalamus, pituitary, and the spinal cord, and colocalises with other neuronal peptides within neurons. Structural analyses reveal that the human galanin precursor is 104 amino acid (aa) residues in length, consisting of a mature galanin peptide (aa 33-62), and galanin message-associated peptide (GMAP; aa 63-104) at the C-terminus. GMAP appears to exhibit distinctive biological effects on anti-fungal activity and the spinal flexor reflex. Galanin-like peptide (GALP) has a similar structure to galanin and acts as a hypothalamic neuropeptide to mediate metabolism and reproduction, food intake, and body weight. Alarin, a differentially spliced variant of GALP, is specifically involved in vasoactive effect in the skin and ganglionic differentiation in neuroblastic tumors. Dysregulation of galanin, GALP and alarin has been implicated in various neuroendocrine conditions such as nociception, Alzheimer’s disease, seizures, eating disorders, alcoholism, diabetes, and spinal cord conditions. Further delineation of the common and distinctive effects and mechanisms of various types of galanin family proteins could facilitate the design of therapeutic approaches for neuroendocrine diseases and spinal cord injury.

Abstract The aim of this study is to investigate the feasibility and efficacy of a novel biomimetic poly‐l‐lactide (PLLA) nanofiber membrane in repairing anterior urethral strictures from both preclinic and clinic. Biomimetic PLLA membrane was fabricated layer by layer according to the structure of human extracellular matrix. Microstructure, tensile strength, and suture retention strength were fully assessed. Before the clinical application, the safety and toxicology test of the biomimetic PLLA membrane was performed in vitro and in experimental animals. The patients underwent urethroplasty used dorsal onlay or lateral onlay technique. Then, they were followed up for 1 month, 3 months, 6 months, and then annually after the surgery. The mechanical experiments showed well property for application. Biomimetic PLLA membrane was safe according to the in vitro and animal studies. Then, a total of 25 patients (mean age 48.96 years) were included in the study from September 2016 to December 2018. After a mean follow‐up of 33.56 months, 20 patients successfully treated with biomimetic PLLA membrane. Five patients (2 bulbar and 3 penile) suffered postoperational urethral stricture recurrence. None of infection or urinary fistula or any other adverse events related to the use of biomimetic PLLA membrane were observed during the follow‐up period for all patients. The preliminary result confirmed the feasibility and efficacy of the biomimetic PLLA membrane as a novel material for anterior urethral repair. The long‐term effects with more patients should be investigated in further studies.

Most patients with clear cell renal cell carcinoma (ccRCC) have an impaired response to immune checkpoint blockade (ICB) therapy. Few biomarkers can predict responsiveness, and there is insufficient evidence to extend them to ccRCC clinical use. To explore subtypes and signatures of immunocytes with good predictive performance for ICB outcomes in the ccRCC context, we reanalyzed two ccRCC single-cell RNA sequencing (scRNA-seq) datasets from patients receiving ICB treatment. A subtype of proliferative CD4+ T cells and regulatory T cells and a subtype of antigen-presenting monocytes that have good predictive capability and are correlated with ICB outcomes were identified. These findings were corroborated in independent ccRCC ICB pretreatment bulk RNA-seq datasets. By incorporating the cluster-specific marker genes of these three immunocyte subtypes, we developed a prediction model, which reached an AUC of 93% for the CheckMate cohort (172 samples). Our study shows that the ICB response prediction model can serve as a valuable clinical decision-making tool for guiding ICB treatment of ccRCC patients.

TAFA chemokine like family member 4 (TAFA4, also named FAM19A4) is a member of the TAFA chemokine like ligand or FAM19A family, which includes TAFA1, TAFA2, TAFA3, TAFA4, and TAFA5 (or FAM19A1, FAM19A2, FAM19A3, FAM19A4, and FAM19A5). They are also referred to as neurokines and are involved in the regulation of a diverse range of cellular processes, including chemotaxis of macrophages, phagocytosis, and release of reactive oxygen species (ROS). TAFA4 is a marker of C-low-threshold mechanoreceptors and is expressed predominantly in nociceptors, such as dorsal root ganglia (DRG). TAFA4 has been implicated in the sensory perception of pain in the spinal cord. Mice with deficiency of TAFA4 demonstrate altered excitability in lamina IIi neurons in DRG in addition to increased mechanical and chemical nociception following inflammation or injury. As a secreted protein, TAFA4 binds to cell surface receptor formyl peptide receptor 1 (FPR1), a G protein-coupled receptor to mediate the chemoattraction of macrophages, phagocytosis, and the inflammatory profile of macrophages. It also interacts with cell surface neurexin to mediate signalling across the synapse. Further understanding the mechanisms by which this conserved protein family regulates diverse biological processes such as in neuronal functions, inflammation, and tissue fibrosis will help to design therapeutic targets for the treatment of TAFA related diseases such as spinal cord injury and neuro-inflammatory disorders.

Summary: Generally, mammals are unable to regenerate complex tissues and organs however the deer antler provides a rare anomaly to this rule. This osseous cranial appendage which is located on the frontal bone of male deer is capable of stem cell-based organogenesis, annual casting, and cyclic de novo regeneration. A series of recent studies have classified this form of regeneration as epimorphic stem cell based. Antler renewal is initiated by the activation of neural crest derived pedicle periosteal cells (PPCs) found residing within the pedicle periosteum (PP), these PPCs have the potential to differentiate into multiple lineages. Other antler stem cells (ASCs) are the reserve mesenchymal cells (RMCs) located in the antlers tip, which develop into cartilage tissue. Antlerogenic periosteal cells (APCs) found within the antlerogenic periosteum (AP) form the tissues of both the pedicle and first set of antlers. Antler stem cells (ASCs) further appear to progress through various stages of activation, this coordinated transition is considered imperative for stem cell-based mammalian regeneration. The latest developments have shown that the rapid elongation of the main beam and antler branches are a controlled form of tumour growth, regulated by the tumour suppressing genes TP73 and ADAMTS18. Both osteoclastogenesis, as well as osteogenic and chondrogenic differentiation are also involved. While there remains much to uncover this review both summarises and comprehensively evaluates our existing knowledge of tissue regeneration in the deer antler. This will assist in achieving the goal of in vitro organ regeneration in humans by furthering the field of modern regenerative medicine. The Translational potential of this article: As a unique stem cell-based organ regeneration process in mammals, the deer antler represents a prime model system for investigating mechanisms of regeneration in mammalian tissues. Novel ASCs could provide cell-based therapies for regenerative medicine and bone remodelling for clinical application. A greater understanding of this process and a more in-depth defining of ASCs will potentiate improved clinical outcomes.

Cascaded nanophotonic devices play a vital role in all-optical connection, all-optical computation and all-optical network. However, there is almost no effective method for the direct design of on-chip cascaded nanophotonic devices, since current study of nanophotonic devices mostly focuses on single device. Here, on-chip cascaded nanophotonic devices are designed based on an intelligent algorithm by combining genetic algorithm, simulated annealing algorithm and finite element method for the first time, and verified experimentally by using silicon-based planar structures. The cascaded devices consist of a bandpass filter and a wavelength router operating in optical communication range. The operation bandwidth of the bandpass filter is 408 nm with transmission more than 80%, within which the communication wavelengths of 1,300 nm and 1,550 nm are routed into different output ports through the wavelength router component. The footprint is only 3.62 μm2 for the bandpass filter and only 2.56 μm2 for the wavelength router, which are easy for integration with planar structures and ultrasmall size. This work provides a highly-efficient scheme for the realization of on-chip cascaded nanophotonic devices on the same chip, and lays a foundation for the realization of photonic chip based on intelligent algorithm.

Computational thinking (CT) is important for students because it is one of the 21st century’s skills. Reverse engineering pedagogy (REP) can improve students’ CT due to its ability to develop students’ cooperativity, algorithmic thinking, creativity, and problem-solving in discipline education. Thus, this study aimed to explore the effect of REP on primary school students’ CT skills in STEM learning activities. A total of 101 fifth graders in a primary school participated in the study for one semester (16 weeks), including 51 students in the experimental group (EG) with REP, and 50 students in the control group (CG) with the demonstration method (DM). The computational thinking scale (CTS) was used to measure the CT skills of students in the pretest and posttest. The Wilcoxon signed-rank test and the Mann-Whitney U test were used to analyze the data. The results verified that REP had a fine effect on the improvement of students’ CT skills compared to the DM. The findings can provide some ideas for researchers to develop students’ CT skills in STEM learning activities. Teachers can use different teaching methods to reasonably arrange teaching activities to develop primary school students’ CT skills.

In nonlinear optical systems, the optical superposition principle breaks down. The system’s response (including electric polarization, current density, etc) is not proportional to the stimulus it receives. Over the past half century, nonlinear optics has grown from an individual frequency doubling experiment into a broad academic field. The nonlinear optics has not only brought new physics and phenomena, but also has become an enabling technology for numerous areas that are vital to our lives, such as communications, health, advanced manufacturing, et al . This Roadmap surveys some of the recent emerging fields of the nonlinear optics, with a special attention to studies in China. Each section provides an overview of the current and future challenges within a part of the field, highlighting the most exciting opportunities for future research and developments.

Humanin (HN) belongs to a member of mitochondrial-derived peptides (MDPs) which are encoded by mitochondrial genes. HN shares sequence homology with thirteen HN-like proteins, named MTRNR2L1 to MTRNR2L13, which encompass 24–28 amino acid residues in length. HN mediates mitochondrial status and cell survival by acting via an intracellular mechanism, or as a secreted factor via extracellular signals. Intracellularly, it binds Bcl2-associated X protein (BAX), Bim and tBid, and IGFBP3 to inhibit caspase activity and cell apoptosis. When released from cells as a secreted peptide, HN interacts with G protein-coupled formyl peptide receptor-like 1 (FPRL1/2) to mediate apoptosis signal-regulating kinase (ASK) and c-Jun N-terminal kinase (JNK) signalling pathways. Additionally, it interacts with CNTFR-α/gp130/WSX-1 trimeric receptors to induce JAK2/STA3 signalling cascades. HN also binds soluble extracellular proteins such as VSTM2L and IGFBP3 to modulate cytoprotection. It is reported that HN plays a role in neuronal disorders such as Alzheimer’s disease, as well as in diabetes mellitus, infertility, and cardiac diseases. Its roles in the skeletal system are emerging, where it appears to be involved with the regulation of osteoclasts, osteoblasts, and chondrocytes. Understanding the molecular structure and role of HN in neural and skeletal diseases is vital to the application of HN in tissue regeneration.

Active control of light polarization is necessary for the development of laser physics, optical communications, and also the molecular dynamics. Conventional polarization control methods suffer from low speed, and the existing all‐optical switching based on nonlinear materials solely has a lot of conducting restrictions, impeding its practical utilizations. Herein, an all‐optical polarization switching in the near‐IR range, composed of the plasmonic gratings deposited on an indium tin oxide (ITO) film with epsilon‐near‐zero response, is realized. A sub‐1 ps response speed and the 19° rotation of the polarization ellipse are determined with the excitation power of 1.37 GW cm−2. The device is demonstrated to output the varied signal with tuning the incident polarization and intensity in a spectral range from 1200 to 1500 nm. The ultrafast processing speed, broadband, and diverse tunability ensure the designed device a promising and necessary element for practically integrating into the next‐generation signal‐processing systems with high performance and large capacity.

Higher-order topological insulators have attracted great interest for their unconventional bulk-boundary correspondence especially gapless corner states. Here, we realize topological biphoton corner states in two-dimensional lattices. In addition to the striking state localization, the correlations in topologically nontrivial cases are more than 60 times higher than those in trivial cases and the visibility of Hong-Ou-Mandel interference for output topological corner-entangled states is higher than 90.3%. We confirm that the second-order photonic topological insulators support stable biphoton states that can maintain spatial distributions in high-dimensional Hilbert space, which have potential applications in quantum algorithms, simulation, and computation.

BackgroundStudies have explored the relationship between social class and health for decades. However, the underlying mechanism between the two remains not fully understood. This study aimed to explore whether health self-management had a mediating role between social class and health under the framework of Socio-cultural Self Model.Methods663 adults, randomly sampled from six communities in Southwest China, completed the survey for this study. Social class was assessed using individuals' income, education, occupation. Health self-management was assessed through evaluation of the health self-management behavior, health self-management cognition, health self-management environment. Physical health and mental health were measured by the Chinese version of Short-Form (36-item) Health Survey, which contains Physical Functioning, Role-Physical, Role-Emotional, Vitality, Mental Health, Social Function, Bodily Pain and General Health. Pearson's correlation was used to examine the associations between major variables. Mediation analyses were performed to explore the mediating role of health self-management.ResultsSocial class positively predicted self-rated health. The lower the social class, the lower the self-reported physical and mental health. Health self-management partially mediated the relationship between social class and self-rated health. That is, the health self-management ability of the lower class, such as access to healthy and nutritious food and evaluate their own health status, is worse than that of the higher class, which leads to physical and mental health inequality between the high and the low classes.ConclusionHealth self-management mediated the relationship between social class and health. Promoting health self-management abilities are conducive to improving both physical and mental health.

The mid-infrared (MIR, 2–20 μm) waveband is of great interest for integrated photonics in many applications such as on-chip spectroscopic chemical sensing, and optical communication. Thermo-optic switches are essential to large-scale integrated photonic circuits at MIR wavebands. However, current technologies require a thick cladding layer, high driving voltages or may introduce high losses in MIR wavelengths, limiting the performance. This paper has demonstrated thermo-optic (TO) switches operating at 2 μm by integrating graphene onto silicon-on-insulator (SOI) structures. The remarkable thermal and optical properties of graphene make it an excellent heater material platform. The lower loss of graphene at MIR wavelength can reduce the required cladding thickness for the thermo-optics phase shifter from micrometers to tens of nanometers, resulting in a lower driving voltage and power consumption. The modulation efficiency of the microring resonator (MRR) switch was 0.11 nm/mW. The power consumption for 8-dB extinction ratio was 5.18 mW (0.8 V modulation voltage), and the rise/fall time was 3.72/3.96 μs. Furthermore, we demonstrated a 2 × 2 Mach-Zehnder interferometer (MZI) TO switch with a high extinction ratio of more than 27 dB and a switching rise/fall time of 4.92/4.97 μs. A comprehensive analysis of the device performance affected by the device structure and the graphene Fermi level was also performed. The theoretical figure of merit (2.644 mW−1μs−1) of graphene heaters is three orders of magnitude higher than that of metal heaters. Such results indicate graphene is an exceptional nanomaterial for future MIR optical interconnects.

One silsesquioxane-polythiophene hybrid copolymer, with combined star-like structure and intramolecular heterogeneity, was synthesized and sufficiently characterized via various methods, including FTIR, NMR, and SEC measurements. According to the exploration and characterization results, it was much more efficient at modifying SWNTs than its linear analogs in aqueous solution. The hydrophobic silsesquioxane core and PEDOT chains could locally anchor to the surface of the nanotubes, while the soluble flexible copolymer chains extended into the solution and rigid conjugated chains provided some π-π stacking effect to enhance adhesive force with the conjugated structure of the carbon nanotube, imparting steric stabilization to nanotube dispersion. The noncovalent interaction with SWNTs and solubility in aqueous solution improved the electrochemical characteristics of the modified-SWNT composite and availed for the preparation of a flexible and transparent electroactive film. Accordingly, this kind of silsesquioxane-polythiophene hybrid copolymer will be forwarded to apply to the assembling of flexible optoelectronic devices.

Nitrite in a water environment is very harmful to humans and aquatic animals. A novel aerobic denitrifying bacterium able to utilize NO2--N as the only nitrogen source was isolated for the purpose of removing nitrite from water, which was identified as Acinetobacter sp. and named as YT03. The growth and denitrification activity of strain YT03 was assessed comprehensively. Results showed that the nitrite in water with an initial concentration of 10 mg L–1 could be completely removed within 6 h by strain YT03, and the optimal conditions for strain YT03 to remove nitrite were as follows: sodium succinate as the carbon source, C/N ratio of 16, pH of 6.5, temperature of 30°C, and shaking speed of 250 rpm. An RNA-Seq transcriptome analysis was used to find genes associated with nitrite removal. Compared with the removal of ammonia nitrogen, 47 genes were significantly differentially expressed, including 20 up-regulated and 27 down-regulated genes, mainly involved in the transport process, biosynthetic process, and so on. And among the differentially expressed genes, C4-dicarboxylate transporter (DctA) and nitrate/nitrite transporter (Nrt) might be of importance for the efficient utilization of carbon and nitrogen sources in aerobic nitrite denitrification with sodium succinate by strain YT03.

The topological nanophotonic wavelength router, which can steer light with different wavelength signals into different topological channels, plays a key role in optical information processing. However, no effective method has been found to realize such a topological nanophotonic device. Here, an on-chip topological nanophotonic wavelength router working in an optical telecom band is designed based on a topology optimization algorithm and experimentally demonstrated. Valley photonic crystal is used to provide a topological state in the optical telecom band. The measured topological wavelength router has narrow signal peaks and is easy for integration. This work offers an efficient scheme for the realization of topological devices and lays a foundation for the future application of topological photonics.

The orbital angular momentum (OAM) of the structure light is viewed as a candidate for enhancing the capacity of information processing. Microring has advantages in realizing the compact lasers required for on-chip applications. However, as the clockwise and counterclockwise whispering gallery modes (WGM) appear simultaneously, the emitted light from the normal microring does not possess net OAM. Here, we propose an OAM laser based on the standing-wave WGMs containing clockwise and counterclockwise WGM components. Due to the inhomogeneous intensity distribution of the standing-wave WGM, the single-mode lasing for the OAM light can be realized. Besides, the OAM of the emitted light can be designed on demand. The principle and properties of the proposed laser are demonstrated by numerical simulations. This work paves the way for exploring a single-mode OAM laser based on the plasmonic standing-wave WGMs at the microscale, which can be served as a basic building block for on-chip optical devices.

Phase-change materials (PCMs) are important photonic materials that have the advantages of a rapid and reversible phase change, a great difference in the optical properties between the crystalline and amorphous states, scalability, and nonvolatility. With the constant development in the PCM platform and integration of multiple material platforms, more and more reconfigurable photonic devices and their dynamic regulation have been theoretically proposed and experimentally demonstrated, showing the great potential of PCMs in integrated photonic chips. Here, we review the recent developments in PCMs and discuss their potential for photonic devices. A universal overview of the mechanism of the phase transition and models of PCMs is presented. PCMs have injected new life into on-chip photonic integrated circuits, which generally contain an optical switch, an optical logical gate, and an optical modulator. Photonic neural networks based on PCMs are another interesting application of PCMs. Finally, the future development prospects and problems that need to be solved are discussed. PCMs are likely to have wide applications in future intelligent photonic systems.

A four-layer tri-wavelength silica antireflective (AR) coating with 100% transmittance simultaneously at 1064 nm, 532 nm and 355 nm was designed based on the vector method combined with absentee layer. The type of this AR coating is λ/2-λ/4-λ/2-λ/4 (λ0 = 532 nm): 1.0|L A1 H A2|1.46 with nL = 1.19, nA1 = 1.31, nH = 1.44 and nA2 = 1.33. Keywords: Antireflective coating, Tri-wavelength, Vector design, Absentee layer

This paper investigates the degree to which different variables affect the completion of a Massive Open Online Course (MOOC). Data on those variables, such as age, gender, English proficiency, education level, and motivation for course enrollment were first collected through a pre-course survey. Next, course completion records were collected via the Coursera database. Finally, multiple binomial logistic regression models were used to identify factors related to MOOC completion. Although students were grouped according to their preferences, working in groups did not affect students’ likelihood for MOOC completion. Also, other variables such as age, the institution hosting the MOOC, academic program alignment with students’ needs, and students’ intention to complete the course all affected their probability of MOOC completion. This study contributes to the literature by indicating the factors that influence the probability of MOOC completion. Results show that older participants (age > 50 years old) have higher probability of completing the MOOC. Students’ MOOC completion also increases when the MOOC provides experiences that add to students’ current academic backgrounds and when they are hosted by institutions with a strong academic reputation. Based on these factors, this study contributes to research methods in MOOCs by proposing a model that is aligned with the most important factors predicting completion as recommended by the current MOOC literature. For the next phase of assigning learners to work in groups, findings from this study also suggest that MOOC instructors should provide assistance for group work and monitor students’ collaborative processes.

It is essential to have an adequate understanding of the fluid-structure in a porous medium since this gives direct information about the processes necessary to extract the liquid and the likely yield. The concept of symmetry is one of the petroleum engineering issues that has been used to provide an analytical analysis for modeling fluid dynamics through porous media, which can be beneficial to validate the experimental field data. Tight reservoirs regarding their unique reservoir characterization have always been considered as a challenging issue in the petroleum industries. In this paper, different injectivity scenarios which included chemical and thermal methods were taken into consideration to compare the efficiency of each method on the oil recovery enhancement. According to the results of this experiment, the recovery factor for foams and brine injection is about 80%, while it is relatively 66% and 58% for brine-carbon dioxide and brine-nitrogen, respectively. Consequently, foam injection after water flooding would be an effective method to produce more oil volumes in tight reservoirs. Moreover, KCl regarding its more considerable wettability changes has provided more oil production rather than other scenarios.

Owing to the unique properties of evanescent fields, surface waves show great applications in near field enhancement and in breaking the resolution limit. In this work, we found the amorphous-state Bi2Te3 film deposited by pulsed laser deposition exhibits surface wave properties in an ultrawide waveband ranging from the visible to near-infrared regions. We analyze the surface wave in three ways: the propagation form, localized form, and coupling with a gold nanobar. This work not only breaks the strict limit of a Bi2Te3 topological crystalline insulator but also widens the wavelength region of surface waves compared with a previous report.

In this study, a blended synchronous learning environment (BSLE) was created to support a group of graduate students when they were taking a course. Instruction was delivered to both face-to-face (F2F) and online students simultaneously. The purpose of this paper is to present how this BSLE was gradually designed, implemented, and improved by following the educational design research approach. Results showed that the BSLE environment had the capability to support online and classroom students at the same time and provide equivalent learning experiences for them, but challenges emerged in the process. Design principles were summarized to guide researchers or teachers when they design similar learning environments.

We propose a scheme of unidirectional transmission in a 1D nonlinear topological photonic crystal based on the topological edge state and three order optical nonlinearity. The 1D photonic crystals consists of a nonlinear photonic crystal L and a linear photonic crystal R. In the backward direction, light is totally reflected for the photons transmission prohibited by the bandgap. While in the forward direction, light interacts with the nonlinear photonic crystal L by optical Kerr effect, bringing a topological phase reversal and results the topological edge mode arising at the interface which could transmit photons through the bandgaps both of the photonic crystal L and R. When the signal power intensity larger than a moderate low threshold value of 10.0 MW/cm2, the transmission contrast ratio could remain at 30 steadily.

Poor compatibility between nanocellulose crystals (NCCs) and major polymers has limited the application of NCC as bio-reinforcements. In this work, an effective and ultra-fast method was investigated to significantly improve the hydrophobicity of NCC by using poly(methylhydrogen)siloxane (PMHS) as modifier. PMHS possessed amounts of reactive −Si−H groups and hydrophobic −CH3 groups. The former groups were reactive with the hydroxyl groups of NCC, while the latter groups afforded NCC very low surface energy. As the weight ratio of PMHS to NCC was only 0.0005%, the hydrophobicity of NCC was significantly improved by increasing the water contact angle of NCC from 0° to 134°. The effect of weight ratio of PMHS to NCC and the hydrogen content of −Si−H in PMHS on the hydrophobicity and thermal stability was investigated in detail by Fourier transform infrared spectroscopy (FTIR), (X-ray Diffraction) XRD and (thermogravimetric analysis) TGA. The results indicated that PMHS chains were covalently grafted onto NCC and PMHS modification improved the thermal stability of NCC.

The concept of a traditional return period has long been questioned in non-stationary studies, and the risk of failure was recommended to evaluate the design events in flood modeling. However, few studies have been done in terms of multivariate cases. To investigate the impact of non-stationarity on the streamflow series, the Yichang station in the Yangtze River was taken as a case study. A time varying copula model was constructed for bivariate modeling of flood peak and 7-day flood volume, and the non-stationary return period and risk of failure were applied to compare the results between stationary and non-stationary models. The results demonstrated that the streamflow series at the Yichang station showed significant non-stationary properties. The flood peak and volume series presented decreasing trends in their location parameters and the dependence structure between them also weakened over time. The conclusions of the bivariate non-stationary return period and risk of failure were different depending on the design flood event. In the event that both flood peak and volume are exceeding, the flood risk is smaller with the non-stationary model, which is a joint effect of the time varying marginal distribution and copula function. While in the event that either flood peak or volume exceed, the effect of non-stationary properties is almost negligible. As for the design values, the non-stationary model is characterized by a higher flood peak and lower flood volume. These conclusions may be helpful in long-term decision making in the Yangtze River basin under non-stationary conditions.

Dodecyltrimethoxysilane (DTMOS), which is a silanation modifier, was grafted onto nanocellulose crystals (NCC) through a two-step method using KH560 (ɤ-(2,3-epoxyproxy)propytrimethoxysilane) as a linker to improve the hydrophobicity of NCC. The reaction mechanism of NCC with KH560 and DTMOS and its surface chemical characteristics were investigated using Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) and HCl–acetone titration. These analyses confirmed that KH560 was grafted onto the surface of NCC through the ring-opening reaction, before DTMOS was covalently grafted onto the surface of NCC using KH560 as a linker. The grafting of NCC with DTMOS resulted in an improvement in its hydrophobicity due to an increase in its water contact angle from 0° to about 140°. In addition, the modified NCC also possessed enhanced thermal stability.