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BackgroundVasculogenic Mimicry (VM) can reduce the efficacy of anti-angiogenesis and promote distant metastasis in hepatocellular carcinoma (HCC). Our previous studies have found that Celastrus orbiculatus extract (COE) can inhibit the VM formation in HCC by reducing EphA2 expression. However the underlying mechanism related to EphA2 in VM formation is unclear.PurposeThis study aimed to confirm that EphA2 is one of the potential targets of COE, and to explore the effect of EphA2 in VM formation in hypoxia context in HCC.MethodsTCM Systems Pharmacology database and proteomics analysis were used to explore the key targets of COE in HCC treatment. CD31-PAS double staining and VE-CAD staining were used to indicate vasculogenic mimicry. The localization of EphA2 and VE-CAD was examined through fluorescent microscopy. CCK8 assay, cell invasion assay, and tube formation assay were used to indicate the formation of VM under hypoxic conditions. The regulatory relationship of EphA2 upstream and downstream molecules were evaluated through COIP and Western Blot. The nude mouse xenograft tumor models were used to observe the VM formation after knocking down or overexpressing EphA2.ResultsEphA2 is identified to the target of COE, and the driving gene of HCC. In HCC surgical specimens, EphA2 expression is closely associated with the VM formation of HCC. COE-regulated EphA2 is involved in hypoxia-induced VM formation in HCC cells in vitro. EphA2 is regulated by HIF directly or indirectly by C-MYC. Overexpression of EphA2 can promote the VM formation of HCC in nude mice, while knocking down EphA2 can inhibit the VM formation.ConclusionEphA2, as a target of COE, plays a crucial regulatory role in the formation of vasculogenic mimicry in HCC, involving upstream HIF/MYC transcriptional promotion and downstream PI3K/FAK/VE-CAD expression regulation.

Background: The current prophylactic tuberculosis vaccine Bacille Calmette-Guérin (BCG), was derived in the 1920s, but the humoral immune responses induced by BCG vaccination have not been fully elucidated to date. In this study, our aim was to reveal the profiles of antibody responses induced by BCG vaccination in adults and identify the potential biomarkers for evaluating the BCG vaccination response. Methods: Proteome microarrays were performed to reveal the serum profiles of antibody responses induced by BCG vaccination in adults. ELISA was used to validate the potential biomarkers in validation cohort (79 healthy controls and 58 BCG-vaccinated subjects). Then combined panel was established by logistic regression analysis based on OD values of potential biomarkers. Results: Multiple antigens elicited stronger serum IgG or IgM antibody responses in BCG vaccinated subjects than healthy subjects at 12 weeks post BCG vaccination; among the antigens, Rv0060, Rv2026c and Rv3379c were further verified using 137 serum samples and presented the moderate performance in assessment of the BCG vaccination response by receiver operating characteristic analysis. Furthermore, a combined panel exhibited an improved AUC of 0.923, and the sensitivity and specificity were 77.59 % and 91.14 %, respectively. In addition, the antibody response against Rv0060, Rv2026c and Rv3379c was related to the clinical background to a certain extent. Conclusions: The novel antigens identified in our study could offer better knowledge towards developing a more efficacious vaccine based on humoral immune responses, and they could be potential biomarkers in assessments of BCG vaccination responses.

An electron vortex beam (EVB) carrying orbital angular momentum (OAM) plays a key role in a series of fundamental scientific researches, such as chiral energy-loss spectroscopy and magnetic dichroism spectroscopy. So far, almost all the experimentally created EVBs manifest isotropic doughnut intensity patterns. Here, based on the correlation between local divergence angle of electron beam and phase gradient along azimuthal direction, we show that free electrons can be tailored to EVBs with customizable intensity patterns independent of the carried OAM. As proof-of-concept, by using computer generated hologram and designing phase masks to shape the incident free electrons in the transmission electron microscope, three structured EVBs carrying identical OAM are tailored to exhibit completely different intensity patterns. Furthermore, through the modal decomposition, we quantitatively investigate their OAM spectral distributions and reveal that structured EVBs present a superposition of a series of different eigenstates induced by the locally varied geometries. These results not only generalize the concept of EVB, but also demonstrate an extra highly controllable degree of freedom for electron beam manipulation in addition to OAM.

Abstract We perform a high-precision computation of the three-loop three-point form factor of the stress-tensor supermultiplet in N $$ \mathcal{N} $$ = 4 SYM. Both the leading-color and sub-leading-color form factors are expanded in terms of simple integrals. We compute the complete set of integrals at a special kinematic point with very high precision using AMFlow. The high-precision leading-color result enables us to obtain the analytic form of a numerical constant in the three-loop BDS ansatz, which is previously known only numerically. The high-precision values of the non-leading-color finite remainder as well as all integrals are also presented, which can be valuable for future use.

Abstract Background Computed tomography (CT) plays a great role in characterizing and quantifying changes in lung structure and function of chronic obstructive pulmonary disease (COPD). This study aimed to explore the performance of CT-based whole lung radiomic in discriminating COPD patients and non-COPD patients. Methods This retrospective study was performed on 2785 patients who underwent pulmonary function examination in 5 hospitals and were divided into non-COPD group and COPD group. The radiomic features of the whole lung volume were extracted. Least absolute shrinkage and selection operator (LASSO) logistic regression was applied for feature selection and radiomic signature construction. A radiomic nomogram was established by combining the radiomic score and clinical factors. Receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) were used to evaluate the predictive performance of the radiomic nomogram in the training, internal validation, and independent external validation cohorts. Results Eighteen radiomic features were collected from the whole lung volume to construct a radiomic model. The area under the curve (AUC) of the radiomic model in the training, internal, and independent external validation cohorts were 0.888 [95% confidence interval (CI) 0.869–0.906], 0.874 (95%CI 0.844–0.904) and 0.846 (95%CI 0.822–0.870), respectively. All were higher than the clinical model (AUC were 0.732, 0.714, and 0.777, respectively, P

Abstract The next generation of high-capacity, multi-task optical informatics requires sophisticated manipulation of multiple degrees of freedom (DoFs) of light, especially when they are coupled in a non-separable way. Vector beam, as a typical non-separable state between the spin and orbital angular momentum DoFs, mathematically akin to entangled qubits, has inspired multifarious theories and applications in both quantum and classical regimes. Although qubit rotation is a vital and ubiquitous operation in quantum informatics, its classical analogue is rarely studied. Here, we demonstrate the logical rotation of vectorial non-separable states via the uniform self-assembled chiral superstructures, with favorable controllability, high compactness and exemption from formidable alignment. Photonic band engineering of such 1D chiral photonic crystal renders the incident-angle-dependent evolution of the spatially-variant polarizations. The logical rotation angle of a non-separable state can be tuned in a wide range over 4π by this single homogeneous device, flexibly providing a set of distinguished logic gates. Potential applications, including angular motion tracking and proof-of-principle logic network, are demonstrated by specific configuration. This work brings important insight into soft matter photonics and present an elegant strategy to harness high-dimensional photonic states.

Abstract For classical waves, phase matching is vital for enabling efficient energy transfer in many scenarios, such as waveguide coupling and nonlinear optical frequency conversion. Here, we propose a temporal quasi-phase matching method and realize robust and complete acoustical energy transfer between arbitrarily detuned cavities. In a set of three cavities, A, B, and C, the time-varying coupling is established between adjacent elements. Analogy to the concept of stimulated Raman adiabatic passage, amplitudes of the two couplings are modulated as time-delayed Gaussian functions, and the couplings’ signs are periodically flipped to eliminate temporal phase mismatching. As a result, robust and complete acoustic energy transfer from A to C is achieved. The non-reciprocal frequency conversion properties of our design are demonstrated. Our research takes a pivotal step towards expanding wave steering through time-dependent modulations and is promising to extend the frequency conversion based on state evolution in various linear Hermitian systems to nonlinear and non-Hermitian regimes.

Abstract Endowing flexible and adaptable fiber devices with light-emitting capabilities has the potential to revolutionize the current design philosophy of intelligent, wearable interactive devices. However, significant challenges remain in developing fiber devices when it comes to achieving uniform and customizable light effects while utilizing lightweight hardware. Here, we introduce a mass-produced, wearable, and interactive photochromic fiber that provides uniform multicolored light control. We designed independent waveguides inside the fiber to maintain total internal reflection of light as it traverses the fiber. The impact of excessive light leakage on the overall illuminance can be reduced by utilizing the saturable absorption effect of fluorescent materials to ensure light emission uniformity along the transmission direction. In addition, we coupled various fluorescent composite materials inside the fiber to achieve artificially controllable spectral radiation of multiple color systems in a single fiber. We prepared fibers on mass-produced kilometer-long using the thermal drawing method. The fibers can be directly integrated into daily wearable devices or clothing in various patterns and combined with other signal input components to control and display patterns as needed. This work provides a new perspective and inspiration to the existing field of fiber display interaction, paving the way for future human–machine integration.

Abstract Branched flows occur ubiquitously in various wave systems, when the propagating waves encounter weak correlated scattering potentials. Here we report the experimental realization of electrical tuning of the branched flow of light using a nematic liquid crystal (NLC) system. We create the physical realization of the weakly correlated disordered potentials of light via the inhomogeneous orientations of the NLC. We demonstrate that the branched flow of light can be switched on and off as well as tuned continuously through the electro-optical properties of NLC film. We further show that the branched flow can be manipulated by the polarization of the incident light due to the optical anisotropy of the NLC film. The nature of the branched flow of light is revealed via the unconventional intensity statistics and the rapid fidelity decay along the light propagation. Our study unveils an excellent platform for the tuning of the branched flow of light which creates a testbed for fundamental physics and offers a new way for steering light.

Bound states in the continuum (BICs) with exceptionally high quality factors ($Q$ factors) have become focal points in photonic device research, finding applications in nonlinear enhancement, laser generation, sensing, and beyond. In this study, we systematically investigate the intricate relationship between the in-plane symmetry groups of photonic crystals and symmetry-protected BICs (SP-BICs) using a rigorous group theory approach. By modifying the spatial distribution of refractive indices to perturb the $C_{2}$ and $C_{3}$ symmetries within a $C_{6v}$ photonic crystal slab, we introduce a novel method to enable precise tuning of BIC resonances, including the BIC frequency, $Q$ factor, and polarization state. The proposed group theory approach and tuning mechanism establish a pioneering pathway for the design and tunability of BICs, opening avenues for the development of advanced photonic devices with tailored functionalities such as tunable lasers and optical sensors with enhanced performance.

Abstract Liquid crystals are a vital component of modern photonics, and recent studies have demonstrated the exceptional sensing properties of stimuli-responsive cholesteric liquid crystals. However, existing cholesteric liquid crystal-based sensors often rely on the naked eye perceptibility of structural color or the measurement of wavelength changes by spectrometric tools, which limits their practical applications. Therefore, developing a platform that produces recognizable sensing signals is critical. In this study, we present a visual sensing platform based on geometric phase encoding of stimuli-responsive cholesteric liquid crystal polymers that generates real-time visual patterns, rather than frequency changes. To demonstrate this platform’s effectiveness, we used a humidity-responsive cholesteric liquid crystal polymer film encoded with a q-plate pattern, which revealed that humidity causes a shape change in the vortex beam reflected from the encoded cholesteric liquid crystal polymers. Moreover, we developed a prototype platform towards remote humidity monitoring benefiting from the high directionality and long-range transmission properties of laser beams carrying orbital angular momentum. Our approach provides a novel sensing platform for cholesteric liquid crystals-based sensors that offers promising practical applications. The ability to generate recognizable sensing signals through visual patterns offers a new level of practicality in the sensing field with stimuli-responsive cholesteric liquid crystals. This platform might have significant implications for a broad readership and will be of interest to researchers working in the field of photonics and sensing technology.

Abstract The iron oxide nanoparticles (IONPs), possessing both magnetic behavior and semiconductor property, have been extensively used in multifunctional biomedical fields due to their biocompatible, biodegradable and low toxicity, such as anticancer, antibacterial, cell labelling activities. Nevertheless, there are few IONPs in clinical use at present. Some IONPs approved for clinical use have been withdrawn due to insufficient understanding of its biomedical applications. Therefore, a systematic summary of IONPs’ preparation and biomedical applications is crucial for the next step of entering clinical practice from experimental stage. This review summarized the existing research in the past decade on the biological interaction of IONPs with animal/cells models, and their clinical applications in human. This review aims to provide cutting-edge knowledge involved with IONPs’ biological effects in vivo and in vitro, and improve their smarter design and application in biomedical research and clinic trials. Graphical Abstract

Objective To preliminarily summarize the epidemiological and clinical characteristics of functional movement disorder (FMD) based on movement disorders clinic in China. Methods and Results A total of 593 patients with movement disorders newly diagnosed in movement disorders clinic of 22 clinical medical centers from August to September in 2023 were included, including 37 patients (6.24%) with FMD and 556 patients (93.76%) with organic movement disorder. Comparison of the epidemiological characteristics of the 2 groups, the proportions of corona virus disease (COVID⁃19) infection (χ2 = 4.217, P = 0.040) and psychopsychological symptoms (χ2 = 18.694, P = 0.000) in the FMD group were higher than those in the organic movement disorder group, while age (t = 3.757, P = 0.000), age of onset (t = 3.720, P = 0.000) and proportion of hypertension (χ2 = 4.736, P = 0.030) were lower than those in the organic movement disorder group. Comparison of the clinical characteristics of the 2 groups, the FMD group had higher proportions of tremor (χ2 = 3.955, P = 0.047) and myoclonus (Fisher′s exact probability: P = 0.011) than the organic movement disorder group, and the proportions of parkinsonism (χ2 = 8.491, P = 0.004) and gait disorder (χ2 = 5.028, P = 0.025) were lower than those in the organic movement disorder group. Conclusions The age and age of onset, as well as the proportions of COVID⁃19 infection, hypertension, psychopsychological symptoms, tremor, myoclonus, parkinsonism and gait disorder with FMD were different from those with organic movement disorder in China.

Inflammatory bowel disease (IBD) is a systemic disorder affecting intestinal tract and other organs outside the gut, known as extraintestinal manifestations (EIMs). These EIMs are complex and diverse, and early treatment may reduce teratogenic rates and improve quality of life. However, our understanding of EIMs in IBD is currently limited by a lack of mechanistic insight. Fortunately, advances in our understanding of intestinal microecology are allowing us to uncover the underlying mechanisms of EIMs. The gut microbiota can drive aberrant immune activation and intestinal inflammation. Intriguingly, chronic inflammation can also shape the microbiome in reverse and aggravate dysbiosis. Recent research has revealed that microbiome-derived signal molecules play a crucial role in catalyzing enterocolitis and altering mucosal barrier function. Furthermore, gut microbiota-associated antigens can translocate from the intestine to extraintestinal sites, leading to systemic inflammatory responses. The microbiome is showing its potential in treating IBD and EIMs, and microbial engineering approaches, such as probiotic engineering and engineered fecal microbiota transplantation, are exhibiting great promise for IBD therapeutics.

Background Peutz-Jeghers syndrome (PJS) is a rare genetic disorder characterized by the development of pigmented spots, gastrointestinal polyps and increased susceptibility to cancers. Currently, most studies have investigated intestinal microbiota through fecal microbiota, and there are few reports about mucosa-associated microbiota. It remains valuable to search for the key intestinal microbiota or abnormal metabolic pathways linked to PJS. Aim This study aimed to assess the structure and composition of mucosa-associated microbiota in patients with PJS and to explore the potential influence of intestinal microbiota disorders and metabolite changes on PJS. Methods The bacterial composition was analyzed in 13 PJS patients and 12 controls using 16S rRNA gene sequencing (Illumina MiSeq) for bacteria. Differential analyses of the intestinal microbiota were performed from the phylum to species level. Liquid chromatography-tandem mass spectrometry (LC-MS) was used to detect the differentially abundant metabolites of PJS patients and controls to identify different metabolites and metabolic biomarkers of small intestinal mucosa samples. Results High-throughput sequencing confirmed the special characteristics and biodiversity of the mucosa microflora in patients with PJS. They had lower bacterial biodiversity than controls. The abundance of intestinal mucosal microflora was significantly lower than that of fecal microflora. In addition, lipid metabolism, amino acid metabolism, carbohydrate metabolism, nucleotide metabolism and other pathways were significantly different from those of controls, which were associated with the development of the enteric nervous system, intestinal inflammation and development of tumors. Conclusion This is the first report on the mucosa-associated microbiota and metabolite profile of subjects with PJS, which may be meaningful to provide a structural basis for further research on intestinal microecology in PJS. Keywords: Peutz-Jeghers syndrome, Metabolomics, LC-MS, Mucosa-associated microbiota, Bacteria, Author(s): Sui Wang[sup.2], Guan-Jun Kou[sup.1], Xiao-Han Zhao[sup.1], Gang Huang[sup.1], Jue-Xin Wang[sup.1], Lin Tian[sup.1], Xiu-Li Zuo[sup.1], Yan-Qing Li[sup.1], Jia-Yong Wang[sup.3] and Yan-Bo Yu[sup.1] Introduction Peutz-Jeghers syndrome (PJS) is a rare genetic [...]

ObjectiveTo investigate the clinical characteristics and risk factors of patients with SARS-CoV-2 Omicron variant infection complicated with cardiovascular diseases.MethodsA retrospective analysis of general clinical data was conducted on patients with SARS-CoV-2 omicron infection complicated with hypertension, coronary heart disease, and heart failure admitted to one hospital in Guangdong Province from December 1, 2022, to February 28, 2023. Clinical symptoms, laboratory tests, imaging examinations, treatment, and clinical outcomes were collected. Multivariate logistic regression analysis was used to analyze the risk factors for mortality in patients with SARS-CoV-2 Omicron variant infection complicated with cardiovascular diseases. ROC curves were drawn to evaluate the predictive value of CRP, D-dimer, and CK-MB in predicting the risk of death.ResultsA total of 364 confirmed cases were included, divided into the asymptomatic group, mild to moderate group, and severe to critically ill group based on the symptoms of COVID-19. There were 216 males (59.34%) and 148 females (40.66%), with a median age of 75 years. The differences between the three groups in terms of sex and age were statistically significant (p

Fast motion and high adaptability are crucial for the practical applications of miniature robots. However, combining these capabilities into a single robot skillfully is challenging, particularly in the domain of miniature structural design. Inspired by the amphibious motion of crocodiles in nature, a hollow piezoelectric miniature robot (HPMR) is proposed. The key benefit of the HPMR is to concurrently output the oscillating motion of the driving foot (oscillating mode) and the rotating motion of the internal rotor (rotating mode). That is, the mode of single‐energy‐input‐multimotion output allows the robot to balance the requirements of speed and adaptability. In the oscillating mode, HPMR can run at speeds of up to 12.3 BL s−1 and realize a displacement resolution of 0.3 μm. Following the conical rotor assembly, the rotor can operate at a speed of 890 rpm, with a displacement resolution of 7.28 mrad. In the rotating mode, the robot demonstrates its multitasking ability in moving amphibiously, carrying loads, running on surfaces with varying roughness, crossing obstacles, and resisting shocks. The results show that the HPMR is capable of fast, high‐resolution moving combined with high adaptability, opening up the possibility of using it for mobile detection tasks in real‐world settings.