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Abstract Frequency combs, specialized laser sources emitting multiple equidistant frequency lines, have revolutionized science and technology with unprecedented precision and versatility. Recently, integrated frequency combs are emerging as scalable solutions for on-chip photonics. Here, we demonstrate a fully integrated superconducting microcomb that is easy to manufacture, simple to operate, and consumes ultra-low power. Our turnkey apparatus comprises a basic nonlinear superconducting device, a Josephson junction, directly coupled to a superconducting microstrip resonator. We showcase coherent comb generation through self-started mode-locking. Therefore, comb emission is initiated solely by activating a DC bias source, with power consumption as low as tens of picowatts. The resulting comb spectrum resides in the microwave domain and spans multiple octaves. The linewidths of all comb lines can be narrowed down to 1 Hz through a unique coherent injection-locking technique. Our work represents a critical step towards fully integrated microwave photonics and offers the potential for integrated quantum processors.

Abnormal expression of connexin 43 (Cx43) contributes to the development and progression of cancer. However, its regulation is complex and dependent on the environment. The expression of Cx43 in triple-negative cancer lesions was analyzed by immunohistochemistry and optical coherence tomography using experimental models and clinical samples. The model of TGFβ1-SMad3-in-αv signal axis was established and verified by experiments. The results show that Cx43 plays a key role in the regulation of triple-negative cancer metastasis. In vivo, over-expressed Cx43 decreased tumor volume and inhibited ITGαV, TGF-β1, Smad3 and N-cadherin expressions, but enhanced the E-cadherin. Cx43 had the lowest expression in the TNBC samples, especially in lymph node metastatic TNBC patients and had a negative correlation with ITG alpha V, TGF-β1 and Smad3.The study demonstrated Cx43 controlled metastatic behavior through TGF-β1 -Smad3-ITG αV signaling axis in MDA-MB-231 cells, providing evidence for Cx43’s function in TNBC. The optical image diagnosis method can realize the identification and quantitative evaluation of early cancer triple negative, and provide a new strategy and means for the treatment of cancer triple negative.

Abstract The metasurface platform with time-varying characteristics has emerged as a promising avenue for exploring exotic physics associated with Floquet materials and for designing photonic devices like linear frequency converters. However, the limited availability of materials with ultrafast responses hinders their applications in the terahertz range. Here we present a time-varying metasurface comprising an array of superconductor-metal hybrid meta-molecules. Each meta-molecule consists of two meta-atoms that are “bonded” together by double superconducting microbridges. Through experimental investigations, we demonstrate high-efficiency linear terahertz frequency conversion by rapidly breaking the bond using a coherent ultrashort terahertz pump pulse. The frequency and relative phase of the converted wave exhibit strong dependence on the pump-probe delay, indicating phase controllable wave conversion. The dynamics of the meta-molecules during the frequency conversion process are comprehensively understood using a time-varying coupled mode model. This research not only opens up new possibilities for developing innovative terahertz sources but also provides opportunities for exploring topological dynamics and Floquet physics within metasurfaces.

Alternative splicing (AS) is a prevalent post-transcriptional regulatory mechanism in eukaryotes and plays a crucial role in plant disease resistance. Here, we used the Illumina Novaseq sequencing platform to conduct transcriptome sequencing on canola (Brassica napus) leaves infected with the blackleg pathogen (Leptosphaeria biglobosa strain nm−1) at 0 h, 72 h, 120 h, and 168 h post-inoculation to investigate the mechanism of AS coordination with transcriptional regulation in canola’s response to blackleg disease. The rMATS software (4.1.0) was employed to analyze different AS events in samples taken at 72 h, 120 h, and 168 h. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to elucidate the biological functions of differentially spliced genes at various time points, while Weighted Gene Co-expression Network Analysis (WGCNA) was used to identify key modules and hub genes. As a result, our analysis reveals 16908 AS events across three time points, with 221 being differently spliced. Intron retention (RI) was the most common AS event, accounting for approximately 55% of all events, while alternative 5′ splice site events were least common, comprising only 2%. Furthermore, a total of 213 significantly differentially spliced genes were identified, which were enriched in functions related to protein kinase activity, transferase activity, and pathways such as MAPK signaling pathway—plant and plant hormone signal transduction. WGCNA identified three key modules and ten hub genes, including calcium-binding transcription activator 1, LRR class receptor serine/threonine protein kinase FEI 2, PLATZ transcription factor family proteins, serine/threonine protein kinase PRP4, and E3 ubiquitin ligase SUD1, all of which are associated with canola resistance to L. biglobosa. Thus, this study provides a theoretical basis for identifying disease-resistance genes involved in AS and for exploring the functions of AS gene isoforms in canola.

Abstract Background This study analyzed the clinical features and biomarkers of alcohol-associated liver disease (ALD) to investigate the diagnostic value of age, bilirubin, international normalized ratio (INR), and creatinine (ABIC) score to triglyceride (TG) ratio (ABIC/TG) in ALD-associated primary liver carcinoma (PLC). Materials and methods Data were collected from 410 participants with ALD, and the epidemiological and clinical records of 266 participants were analyzed. Participants were divided into ALD-without-PLC and ALD-associated-PLC groups. Relationships between clinical characteristics, biomarkers and ALD-associated PLC were estimated. Serum lipid levels and liver function were compared between ALD patients without PLC and patients with ALD-associated PLC. Scoring systems were calculated to investigate ALD severity. The robustness of the relationship was analyzed by the receiver operating characteristic (ROC) curve. Results Age and dyslipidemia were more strongly associated with ALD-associated PLC than with ALD-without PLC, with AORs of 2.39 and 0.25, respectively, with P less than 0.05. Drinking time and average daily intake, ABIC score, and ABIC/TG ratio were significantly higher in the ALD-associated-PLC group than in the ALD-without-PLC group. The AUC for the ABIC/TG ratio predicting the incidence of PLC was 0.80 (P

Abstract Superconducting nanocircuits, which are usually fabricated from superconductor films, are the core of superconducting electronic devices. While emerging transition-metal dichalcogenide superconductors (TMDSCs) with exotic properties show promise for exploiting new superconducting mechanisms and applications, their environmental instability leads to a substantial challenge for the nondestructive preparation of TMDSC nanocircuits. Here, we report a universal strategy to fabricate TMDSC nanopatterns via a topotactic conversion method using prepatterned metals as precursors. Typically, robust NbSe2 meandering nanowires can be controllably manufactured on a wafer scale, by which a superconducting nanowire circuit is principally demonstrated toward potential single photon detection. Moreover, versatile superconducting nanocircuits, e.g., periodical circle/triangle hole arrays and spiral nanowires, can be prepared with selected TMD materials (NbS2, TiSe2, or MoTe2). This work provides a generic approach for fabricating nondestructive TMDSC nanocircuits with precise control, which paves the way for the application of TMDSCs in future electronics.

Hydrogels are three-dimensional crosslinked functional materials with water-absorbing and swelling properties. Many hydrogels can store a variety of small functional molecules to structurally and functionally mimic the natural extracellular matrix; hence, they have been extensively studied for biomedical applications. Polyamidoamine (PAMAM) dendrimers have an ethylenediamine core and a large number of peripheral amino groups, which can be used to engineer various polymer hydrogels. In this review, an update on the progress of using PAMAM dendrimers for multifunctional hydrogel design was given. The synthesis of these hydrogels, which includes click chemistry reactions, aza-Michael addition, Schiff base reactions, amidation reactions, enzymatic reactions, and radical polymerization, together with research progress in terms of their application in the fields of drug delivery, tissue engineering, drug-free tumor therapy, and other related fields, was discussed in detail. Furthermore, the biomedical applications of PAMAM-engineered nano-hydrogels, which combine the advantages of dendrimers, hydrogels, and nanoparticles, were also summarized. This review will help researchers to design and develop more functional hydrogel materials based on PAMAM dendrimers.

Abstract We investigated the relationship between dyslipidemia and drug-induced liver injury (DILI), especially the level of triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C) in severe DILI. In this single-centered retrospective study, of 326 patients with DILI, 221 patients were analyzed. Control groups include medication using group and acute hepatitis B group. The relationship between dyslipidemia and DILI was estimated. Demographic and clinical features were analyzed. Dyslipidemia and TG/HDL-C ratios were compared between DILI and control groups, DILI mild group and severe group. The area under the receiver-operating characteristic curve (AUC) was used to evaluate the credibility of the relationship and to find cut-off points. Dyslipidemia is related to DILI when compared with medication using control group (AOR 4.60; 95% CI 2.81–7.54; P

Abstract Fiber components form the standard not only in modern telecommunication but also for future quantum information technology. For high-performance single-photon detection, superconducting nanowire single-photon detectors (SPDs) are typically fabricated on a silicon chip and fiber-coupled for easy handling and usage. The fiber-to-chip interface hinders the SPD from being an all-fiber device for full utilization of its excellent performance. Here, we report a scheme of SPD that is directly fabricated on the fiber tip. A bury-and-planar fabrication technique is developed to improve the roughness of the substrate for all-fiber detectors’ performance for single-photon detection with amorphous molybdenum silicide (MoSi) nanowires. The low material selectivity and universal planar process enable fabrication and packaging on a large scale. Such a detector responds to a broad wavelength range from 405 nm to 1550 nm at a dark count rate of 100 cps. The relaxation time of the response pulse is ~ 15 ns, which is comparable to that of on-chip SPDs. Therefore, this device is free from fiber-to-chip coupling and easy packaging for all-fiber quantum information systems.

Abstract This study aims to evaluate levels of D-dimer and serum lipid in different types of pancreatitis, and the relationship between D-dimer and dyslipidemia, especially triglyceride to HDL-C ratio (TG/HDL-C) in different types of pancreatitis. We analyzed the D-dimer and dyslipidemia levels in acute pancreatitis (AP), recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP). A single-centered retrospective study was conducted on 1013 patients diagnosed with AP, RAP or CP. Only patients hospitalized within 24 h of onset were included, and 204 patients were enrolled in pancreatitis groups. 68 normal persons without pancreatitis, malignant diseases, pregnancy, or organ failure, who had health check-ups, were enrolled in the control group. Blood samples were taken within 24 h of admission. The relevant information on epidemiology and etiology was collected. D-dimer and serum lipid levels in different types of pancreatitis were analyzed. Furthermore, the area under the receiver-operating characteristic curve (AUC) was used to estimate the validity of the predictor and to define optimal cut-off points for prediction. We found that D-dimer and TG/HDL-C ratio could distinguish mild AP (MAP) and non-MAP in AP and RAP patients. The D-dimer level was related to TG/HDL-C ratio and severity of pancreatitis, with the coefficient correlation of 0.379 and 0.427(p

Abstract A simple method for preparing superconducting NbN thin films on flexible dielectric substrates with controllable thickness was developed. The structure and surface characteristics and superconducting properties of the flexible film were studied by X-ray diffraction (XRD), atomic force microscopy (AFM) and physical property measurement system (PPMS). We found that NbN films on the flexible substrate show certain preferred orientations through the self-buffering effect of the amorphous NbN layer. The zero resistance superconducting transition temperature (TC0) for 10 nm thick NbN films is 8.3 K, and the TC0 for 30 nm thick NbN films in a magnetic field of 9 T remains above 7 K. This flexible film can be transferred to any substrate and adapted to different shape applications. It can also be further processed into single-layer or multilayer flexible superconducting devices.

IntroductionWe investigated the epidemiology of Cytochrome P450 (CYP) 3A4 genotype and the relationship between CYP3A4 genotype and alcohol drinking habits.Materials and methodsA single-centered retrospective study was conducted on 630 patients who underwent CYP3A4*1G genetic testing. Their relevant information on epidemiology and etiology was collected. Laboratory testing, including CYP3A4*1G genotype, liver function tests, and serum lipid measurements were performed. Bi-variate logistic regressions were used to examine the relationship between variables. The relationship between alcohol drinking and CYP3A4*1G genotype was estimated. Demographic and clinical features were analyzed. Participants with drinking history were divided into non-heavy drinking and heavy drinking groups. Liver function and dyslipidemia of participants with drinking histories were compared between CYP3A4*1G mutation (GA+AA) and wild-type (GG) groups.ResultsParticipants with CYP3A4*1G mutation(GA+AA) had an increased adjusted odds ratio (AOR) of 2.56 (95% CI, 1.4-4.65; P = 0.00) for alcohol abuse when compared with participants without CYP3A4 mutation (GG). In the subgroup of participants with alcohol abuse, there are no significant differences in liver injury levels and serum lipid levels between CYP3A4*1G mutant and wild-type groups. Patients with CYP3A4*1G mutation had an increased AOR of cardiac-vascular diseases and malignant diseases compared with patients without CYP3A4*1G mutation. The epidemiology had no difference between GA and AA group.ConclusionThe study indicated that there was association between alcohol drinking and CYP3A4*1G genetic mutation. In the subgroup of participants with alcohol abuse, there are no significant differences in liver injury and dyslipidemia between CYP3A4*1G mutant and wild-type groups. CYP3A4*1G mutation was also related to cardiac-vascular diseases and malignant diseases.

In this study, we demonstrate an Nb5N6 terahertz (THz) detector with radio frequency (RF) choke-enhanced dipole antenna structure for 0.3 THz detection. The maximum electric field intensity of 218 V/m is obtained by optimizing the parameters of the dipole antenna with RF choke. Compared to a dipole antenna without RF choke, the electric field intensity of that with RF choke is improved by 2.6 times. The RF choke-enhanced dipole antenna-coupled Nb5N6 THz detector is fabricated and characterized. The measured maximum responsivity of the detector is 1100 V/W at 0.308 THz, and the corresponding noise equivalent power (NEP) is 6.4 × 10–12 W/Hz1/2. The measured response time of the Nb5N6 THz detector is as low as 8.46 μs. Furthermore, the Nb5N6 THz detector is applied to a homemade THz transmission imaging system for demonstrating its performance. The THz imaging results of a blade and access card show that the contrast of the blade image is sharp and the components hidden within the access card are clearly visible. This indicates that the Nb5N6 THz detector can be used in THz imaging, particularly in THz active imaging, which will have greater application prospects.

The immune inflammatory response changes rapidly with the progression of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and is responsible for clearance of the virus and further recovery from the infection. However, the intensified immune and inflammatory response in the development of the disease may lead to more serious and fatal consequences, which indicates that immune indicators have the potential to predict serious cases.

Objectives: COVID-19 is highly infectious and has been widely spread worldwide, with more than 159 million confirmed cases and more than 3 million deaths as of May 11, 2021. It has become a serious public health event threatening people’s lives and safety. Due to the rapid transmission and long incubation period, shortage of medical resources would easily occur in the short term of discovering disease cases. Therefore, we aimed to construct an artificial intelligent framework to rapidly distinguish patients with COVID-19 from common pneumonia and non-pneumonia populations based on computed tomography (CT) images. Furthermore, we explored artificial intelligence (AI) algorithms to integrate CT features and laboratory findings on admission to predict the clinical classification of COVID-19. This will ease the burden of doctors in this emergency period and aid them to perform timely and appropriate treatment on patients.Methods: We collected all CT images and clinical data of novel coronavirus pneumonia cases in Inner Mongolia, including domestic cases and those imported from abroad; then, three models based on transfer learning to distinguish COVID-19 from other pneumonia and non-pneumonia population were developed. In addition, CT features and laboratory findings on admission were combined to predict clinical types of COVID-19 using AI algorithms. Lastly, Spearman’s correlation test was applied to study correlations of CT characteristics and laboratory findings.Results: Among three models to distinguish COVID-19 based on CT, vgg19 showed excellent diagnostic performance, with area under the curve (AUC) of the receiver operating characteristic (ROC) curve at 95%. Together with laboratory findings, we were able to predict clinical types of COVID-19 with AUC of the ROC curve at 90%. Furthermore, biochemical markers, such as C-reactive protein (CRP), LYM, and lactic dehydrogenase (LDH) were identified and correlated with CT features.Conclusion: We developed an AI model to identify patients who were positive for COVID-19 according to the results of the first CT examination after admission and predict the progression combined with laboratory findings. In addition, we obtained important clinical characteristics that correlated with the CT image features. Together, our AI system could rapidly diagnose COVID-19 and predict clinical types to assist clinicians perform appropriate clinical management.

Superconducting series nanowire single-photon detectors (SNDs) have been used for resolving photon numbers. But it can also exhibit a higher counting rate than a single superconducting nanowire single-photon detector (SNSPD), because the serial architecture allows multiple detectors working in parallel and the inductance of each pixel is reduced. In this paper, we found each pixel of the SND could reset fast although the whole detector took a much longer time for recovering. Therefore, the speed of an SND with a large kinetic inductance of 1.25 μH was characterized and compared to a standard SNSPD with the same total inductance. By measuring the detected photon rate over the input photon rate, we obtained a photon counting rate enhancement by 7.5 times. Meanwhile, the timing jitter of the SND was 63 ps at single photon detection regime. Our results show that the series structure and the readout scheme are quite practical in realizing high speed single-photon detectors besides resolving photon numbers.

Niobium nitride (NbN) nanowires have a high repetition rate and efficiency, making them ideal for superconducting nanowire single photon detectors (SNSPDs). However, it is difficult to fabricate NbN arrays over large areas, which is critical for various applications. This paper describes a 4 × 4 NbN SNSPD array (16 pixels) and optical coupling with a 300-μm-diameter multimode fiber using beam compression technology. This is the first NbN SNSPD coupled with such large-diameter fibers. The designed pixels are positioned as closely as possible (pixel filling factor about 98.5%), almost without dead area between them. This results in a system efficiency of 46% and a quantum efficiency of 94.5% for photons (λ = 1064 nm) coupled from multimode fibers. An intrinsic time resolution of less than 69 ps can be obtained. The proposed high-performance single photon detector is suitable for satellite laser ranging. Furthermore, the proposed system is feasible for large SNSPD arrays with NbN, paving the way for the development of efficient photon cameras with NbN nanowires.

Photon-number-resolving (PNR) is an important functionality in many applications. The traditional single photon detectors (SNSPDs) operated with the conventional readout scheme does not have the PNR functionality. In this paper, we demonstrate a superconducting photon-number-resolving detector operating at the visible wavelength regime, based on the serial connection of six superconducting nanowires. The results of our 6-element PNR device show clear evidence of n-photons differentiation with n ranging from 1 to 6. The system detection efficiency reaches 54% with the dark counts rate below 10 Hz at 660 nm. The demonstrated 6-element PNR device does not require a complex readout circuit compared with the SNSPD array device, and is expected to have wider applications in addition to imaging and communication.

Existing video steganography puts much emphasis on the design of algorithms such as mapping rules or distortion functions, thereby ignoring the selection of cover to embed secret information. However, this is just one of the major differences between image steganography and video steganography. In addition, since HEVC is the latest standard in the video codec field, it is of important academic significance and applied value to study HEVC-based steganography. This paper proposes a novel video steganography in HEVC, based on intra-prediction mode (IPM). Firstly, this paper analyzes the probability distribution of 4 × 4 IPMs. Then a cover selection rule combined with the Coding Unit (CU) and Prediction Unit (PU) coding information is proposed, which can improve the security performance of a stego video stream. In addition, matrix coding is used as a coding example to implement the steganography on HEVC video streams. Experimental results show that the proposed algorithm can not only maintain the video quality and the security performance but is also easy to implement. Furthermore, the proposed cover selection rule can also be integrated into other HEVC IPM based steganography.

We experimentally studied a series of terahertz (THz) metamaterials with asymmetric resonator structures made from superconducting niobium nitride or gold films. Fano and toroidal dipole resonances are excited in superconducting metamaterials and their quality factors are higher in comparison with those of gold samples. Superconducting samples possess good tuning behaviors for both Fano and toroidal dipole resonance frequencies due to the change of kinetic inductance under different temperatures. The superconducting samples also exhibit good slow light effect due to the sharp dispersion in transmission spectra. These tunable and low loss metamaterials possess great significance to the development of THz nonlinear and slow light devices.

We present the nonlinear response of superconducting niobium nitride (NbN) thin film and NbN metamaterial with different thicknesses under intense terahertz pulses. For NbN thin film, nonlinearity emerges and superconductivity is suppressed with increasing incident terahertz electric field, and the suppression extent weakens as the film thickness increases from 15 to 50 nm. As the variation in intense terahertz fields alters the intrinsic conductivity in NbN, a consequent remarkable amplitude modulation in NbN metamaterial is observed due to the strong nonlinearity. Absorbed photo density in either NbN film or NbN metamaterial is estimated and used to understand the mechanism of nonlinear response. With a thicker NbN film element of 200 nm, the resonance of the metamaterial shows similar nonlinear modulation accompanied by a lower loss and a higher quality factor compared with a thinner NbN film element of 50 nm, which demonstrates the innovative implementation of strongly enhanced nonlinearity with thick superconducting film elements and the potential for novel applications using nonlinear metamaterial.

BackgroundIndividuals with high autistic traits exhibit characteristics like those of individuals with autism, including impairments in sociability and communication skills. Whether individuals with high autistic traits exhibit less cooperation remains debated.MethodsThis study employed the prisoner’s dilemma game (PDG) to measure cooperation in 56 dyads, including 27 with high-low (HL) autistic traits and 29 with low-low (LL) autistic traits, using functional near-infrared spectroscopy (fNIRS) hyperscanning technique. Cognitive and emotional empathy were also measured.ResultsIndividuals with high autistic traits had a lower unilateral cooperation rate than did those with low autistic traits; The HL autistic dyads exhibited a lower mutual cooperation rate and reduced interpersonal brain synchronization (IBS) in the right inferior parietal lobule (r-IPL) and right temporoparietal junction (r-TPJ) compared with the LL autistic dyads; Individuals with high autistic traits had significantly lower cognitive empathy scores than did those with low autistic traits, and the cognitive empathy scores had a marginally significant positive correlation with the unilateral cooperation rate and a marginally significant negative correlation with the activation of the right inferior frontal gyrus (r-IFG); Emotional empathy scores did not significantly differ between the high and low autistic groups, and there was a significant positive correlation between emotional empathy scores and the activation of the r-IFG in individuals with high autistic traits.ConclusionThis study revealed abnormal cooperation in individuals with high autistic traits from unilateral and mutual behavior neural perspectives, potentially linked to a disability of cognitive empathy.

Abstract Gallbladder cancer (GBC) is a highly aggressive malignancy lacking clinically available targeted therapeutic agents. Super‐enhancers (SEs) are crucial epigenetic cis‐regulatory elements whose extensive reprogramming drives aberrant transcription in cancers. To study SE in GBC, the genomic distribution of H3K27ac is profiled in multiple GBC tissue and cell line samples to establish the SE landscape and its associated core regulatory circuitry (CRC). The biliary lineage factor SOX9 and Wnt pathway effector TCF7L2, two master transcription factor (TF) candidates identified by CRC analysis, are verified to co‐occupy each other's SE region, forming a mutually autoregulatory loop to drive oncogenic SE reprogramming in a subset of GBC. The SOX9/TCF7L2 double‐high GBC cells are highly dependent on the two TFs and enriched of SE‐associated gene signatures related to stemness, ErbB and Wnt pathways. Patients with more such GBC cells exhibited significantly worse prognosis. Furthermore, SOX9/TCF7L2 double‐high GBC preclinical models are found to be susceptible to SE‐targeted CDK7 inhibition therapy in vitro and in vivo. Together, this study provides novel insights into the epigenetic mechanisms underlying the oncogenesis of a subset of GBCs with poorer prognosis and illustrates promising prognostic stratification and therapeutic strategies for treating those GBC patients in future clinical trials.

ABSTRACTIn this study, Al-Zn-Mg-Cu alloy components were prepared using wire arc additive manufacturing (WAAM). Through multi-scale characterisation technology, performance testing and slow strain rate tensile (SSRT) testing, the microstructure, mechanical properties and stress corrosion cracking (SCC) susceptibility of WAAM Al-Zn-Mg-Cu components were studied, revealing the generation mechanism of inhomogeneity and anisotropy. The results show that with the increase of WAAM thermal cycles, the matrix precipitates (MPs), grain boundary precipitates (GBPs) and precipitation-free zones (PFZ) evolve in different paths and increase to varying degrees, resulting in performance decrease and increase in stress corrosion susceptibility, so the inhomogeneity is mainly attributed to differences in precipitated phases. The Inter-layer inclined to the scanning direction and the Inner-layer inclined to the building direction led to anisotropy in tensile strength and SCC behaviour, so the anisotropy is mainly attributed to the grain orientation and fracture mode.