A novel spherical GelMA-HAMA hydrogel encapsulating APET×2 polypeptide and CFIm25-targeting sgRNA for immune microenvironment modulation and nucleus pulposus regeneration in intervertebral discs.

METHODS: Single-cell transcriptomics and high-throughput transcriptomics were used to screen factors significantly correlated with intervertebral disc degeneration (IDD). Expression changes of CFIm25 were determined via RT-qPCR and Western blot. NP cells were isolated from mouse intervertebral discs and induced to degrade with TNF-α and IL-1ß. CFIm25 was knocked out using CRISPR-Cas9, and CFIm25 knockout and overexpressing nucleus pulposus (NP) cell lines were generated through lentiviral transfection. Proteoglycan expression, protein expression, inflammatory factor expression, cell viability, proliferation, migration, gene expression, and protein expression were analyzed using various assays (alcian blue staining, immunofluorescence, ELISA, CCK-8, EDU labeling, transwell migration, scratch assay, RT-qPCR, Western blot). The GelMA-HAMA hydrogel loaded with APET×2 polypeptide and sgRNA was designed, and its effects on NP regeneration were assessed through in vitro and mouse model experiments. The progression of IDD in mice was evaluated using X-ray, H&E staining, and Safranin O-Fast Green staining. Immunohistochemistry was performed to determine protein expression in NP tissue. Proteomic analysis combined with in vitro and in vivo experiments was conducted to elucidate the mechanisms of hydrogel action. RESULTS: CFIm25 was upregulated in IDD NP tissue and significantly correlated with disease progression. Inhibition of CFIm25 improved NP cell degeneration, enhanced cell proliferation, and migration. The hydrogel effectively knocked down CFIm25 expression, improved NP cell degeneration, promoted cell proliferation and migration, and mitigated IDD progression in a mouse model. The hydrogel inhibited inflammatory factor expression (IL-6, iNOS, IL-1ß, TNF-α) by targeting the p38/NF-κB signaling pathway, increased collagen COLII and proteoglycan Aggrecan expression, and suppressed NP degeneration-related factors (COX-2, MMP-3). CONCLUSION: The study highlighted the crucial role of CFIm25 in IDD and introduced a promising therapeutic strategy using a porous spherical GelMA-HAMA hydrogel loaded with APET×2 polypeptide and sgRNA. This innovative approach offers new possibilities for treating degenerated intervertebral discs.

Worldwide burden of liver cancer due to metabolic dysfunction-associated steatohepatitis from 1990 to 2019: insights from the Global Burden of Disease study.

Introduction: Metabolic dysfunction-associated steatohepatitis (MASH) is increasingly becoming a prevalent cause of hepatocellular carcinoma (HCC). Our study examines the burden of MASH-related HCC globally, regionally, and nationally, along with associated risk factors from 1990 to 2019, considering variables such as age, sex, and socioeconomic status. Objective: We aimed to report the global, regional, and national burden of liver cancer due to MASH and its attributable risk factors between 1990 and 2019, by age, sex, and sociodemographic index (SDI). Methods: Utilizing the Global Burden of Disease 2019 project, we analyzed data on prevalence, mortality, and disability-adjusted life years (DALYs) for liver cancer attributable to MASH across 204 countries. We provided counts and rates per 100,000 population, including 95% uncertainty intervals. Results: In 2019, there were 46.8 thousand cases of MASH-related HCC, leading to 34.7 thousand deaths, and 795.8 thousand DALYs globally. While the prevalence increased by 19.8% since 1990, the death and DALY rates decreased by 5.3% and 15.1%, respectively. The highest prevalence was in High-income Asia Pacific, with the greatest increases observed in Australasia, Central Asia, and High-income North America. Southern Sub-Saharan Africa reported the highest death rate, while the lowest rates were in parts of Latin America, Central Sub-Saharan Africa, and Eastern Europe. DALY rates were the highest in Southern Sub-Saharan Africa and the lowest in Tropical Latin America. Discussion: The burden of MASH-related HCC is expected to rise slightly over the next decade. This disease, which is not associated with the SDI, remains a major public health problem. In addition, the escalating rates of obesity, demographic shifts, and an aging population could position MASH as a leading factor in liver cancer cases, surpassing viral hepatitis. It is imperative, therefore, that the forthcoming years see the implementation of strategic interventions aimed at the early detection and prevention of liver cancer associated with MASH.

Highly selective and efficient Pb2+ capture using PO4-loaded 3D-NiFe layer double hydroxides derived from MIL-88A.

Lead (Pb) contamination in water requires improved decontamination technologies. The addition of phosphate to precipitate Pb2+ is a widely used method for remediating Pb in soil and water, though it has certain limitations. This study focuses on novel 3D mesoporous layered double hydroxide (LDH) sorbents functionalized with phosphate anions for Pb2+ removal from contaminated waters. Our innovative strategy involves converting a sacrificial template metal-organic frameworks (MOFs) structure (MIL-88A(Fe)) into NixFe LDH, followed by an anion exchange reaction with phosphate anions. This process preserves the 3D microrod architecture of MIL-88A and prevents deleterious LDH particle aggregation. The synthesis results in stable microrod crystals, 1-2 µm long, composed of 3D assemblies of NixFe-PO4 LDH nanoplatelets with a specific surface area exceeding 110 m2/g. The novel LDH materials display fast adsorption kinetics (pseudo-second order model) and remarkably high Pb2+ removal performances (Langmuir isotherm model) with a capacity of 538 mg/g, surpassing other reported adsorbents. LDH-PO4 exhibits high selectivity for Pb2+ over competing ions like Ni2+ and Cd2+ (selectivity order is: Pb2+ > Ni2+ > Cd2+). Removal of Pb2+ from NixFeLDH/88A-PO4 involves various mechanisms, including surface complexation and surface precipitation of lead phosphate or lead hydroxide phases as revealed by structural characterization techniques.

Deep neural network-enabled multifunctional switchable terahertz metamaterial devices.

Under the support of deep neural networks (DNN), a multifunctional switchable terahertz metamaterial (THz MMs) device is designed and optimized. This device not only achieves ideal ultra-wideband (UWB) absorption in the THz frequency range but enables dual-functional polarization transformation over UWB. When vanadium dioxide (VO2) is in the metallic state, the device as a UWB absorber with an absorption rate exceeding 90% in the 2.43-10 THz range, with a relative bandwidth (RBW) of 145.2%, and its wideband absorption performance is insensitive to polarization. When VO2 is in the insulating state, the device can switch to a polarization converter, achieving conversions from linear to cross polarization and from linear to circular polarization in the ranges of 4.58-10 THz and 4.16-4.43 THz, respectively. Within the 4.58-10 THz range, the polarization conversion ratio approaches 100% with an RBW of 74.3%, the polarization rotation angle is near 90°. Within the 4.16-4.43 THz range, the RBW is 6.29% and the ellipticity ratio approaches 1, Moreover, the effects of incident angle and polarization angle on the operational characteristics are studied. This THz MMs due to its advantages of wide angle, broad bandwidth, and high efficiency, provides valuable references for the research of new multifunctional THz devices. It has great application potential in short-range wireless THz communication, ultrafast optical switches, high-temperature resistant switches, transient spectroscopy, and optical polarization control devices.

Biomimetic Leaf-Shaped Wedge Structure with Mixed Wettability for Fog Harvesting.

Water scarcity is a pressing issue in arid and semi-arid regions, making fog harvesting a promising method for water collection. However, enhancing the rate of fog harvesting remains a challenge. Controlling the movement of droplets on functional surfaces is crucial for the development of effective water-harvesting devices. In this study, a three-dimensional (3D) fog-harvesting device with mixed wettability is fabricated using a combination of physical and chemical techniques. With inspiration drawn from natural organisms, such as the desert beetle and Nephrolepis cordifolia, which can both live in low humidity, a copper substrate with a leaf-shaped wedge superhydrophilic structure and flat superhydrophobic regions is fabricated for fog harvesting. The modified surface results in a maximum 49.89% improvement in fog-harvesting efficiency compared to the original copper substrate. The synergistic effect of the 3D structure and mixed wettability of this study offers an idea for improving fog collection efficiency, with potential implications for energy sustainability water resources.

Micro-Opto-Electro-Mechanical Systems for High-Precision Displacement Sensing: A Review.

High-precision displacement sensing has been widely used across both scientific research and industrial applications. The recent interests in developing micro-opto-electro-mechanical systems (MOEMS) have given rise to an excellent platform for miniaturized displacement sensors. Advancement in this field during past years is now yielding integrated high-precision sensors which show great potential in applications ranging from photoacoustic spectroscopy to high-precision positioning and automation. In this review, we briefly summarize different techniques for high-precision displacement sensing based on MOEMS and discuss the challenges for future improvement.

Comparative morphology of the cruciate ligaments: A radiological study.

Background: The anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) are important structures to maintain knee stability. The present study aimed to further enrich understandings of the morphology of the cruciate ligaments and explore the relationship between the diameter of ACL and PCL. Method: This study collected valid MRI samples of 50 male and 50 female normal right knee joints and measured the diameter of each point of the ACL and PCL through the 3D Slicer. Results: The diameter of the ACL in the sagittal MRI of the normal right knee joint was significantly different from the diameter of each point of the PCL. The average diameter of each point of the ACL was larger than the diameter of the corresponding point of the PCL. Males and females had statistical differences in their PCL origin point, PCL midpoint, ACL origin point, ACL midpoint, and ACL insertion point diameters under sagittal MRI examination. The average diameter of males was greater than the average diameter of females at the above corresponding sites. In sagittal MRI scans of the normal right knee joint, we observed that only the origin point of the PCL exhibited a moderate correlation with the midpoint and insertion point of the ACL in terms of their respective diameters. Conclusion: The correlation between diameters of normal ACL and PCL in knee joint MRI was moderate and may help clinicians determine appropriate graft for cruciate ligament reconstruction surgery quickly for severe cruciate ligament injuries.

A miniaturized tunable optical attenuator with ultrawide bandwidth based on evanescent-field coupling between nanofibers.

We propose a novel miniaturized optical attenuator based on the evanescent-field coupling between two nanofibers. Benefiting from a wavelength-dependent waveguiding property of the coupled structure, a tunable attenuation with maximum extinction ratio of ~ 20 dB is demonstrated with an ultrawide optical bandwidth up to 0.7 µm in experiment. The wavelength-depended waveguiding properties of both one single nanofiber and coupled nanofibers are investigated in both theory and simulation. Using an adiabatic coupling structure, an attenuation range from - 0.16 dB to - 18.46 dB is obtained within a spectrum from 1.2 µm to 1.7 µm experimentally. Moreover, the simulated results indicate that, the attenuation only shows a slight change of ~ 0.1 dB with a lateral misalignment of 0.5 µm between the two nanofibers, indicating a high tolerance of this attenuator to the lateral misalignment. Considering the wide bandwidth as well as the ultracompact structure, this attenuator shows high potential in applications such as all-fiber optical sensing and communicating.

ezSingleCell: an integrated one-stop single-cell and spatial omics analysis platform for bench scientists.

ezSingleCell is an interactive and easy-to-use application for analysing various single-cell and spatial omics data types without requiring prior programing knowledge. It combines the best-performing publicly available methods for in-depth data analysis, integration, and interactive data visualization. ezSingleCell consists of five modules, each designed to be a comprehensive workflow for one data type or task. In addition, ezSingleCell allows crosstalk between different modules within a unified interface. Acceptable input data can be in a variety of formats while the output consists of publication ready figures and tables. In-depth manuals and video tutorials are available to guide users on the analysis workflows and parameter adjustments to suit their study aims. ezSingleCell's streamlined interface can analyse a standard scRNA-seq dataset of 3000 cells in less than five minutes. ezSingleCell is available in two forms: an installation-free web application ( https://immunesinglecell.org/ezsc/ ) or a software package with a shinyApp interface ( https://github.com/JinmiaoChenLab/ezSingleCell2 ) for offline analysis.

Design of Broadband High-Frequency Multi-Throw RF-MEMS Switches.

This paper introduces a broadband triple-pole triple-throw (3P3T) RF MEMS switch with a frequency range from DC to 380 GHz. The switch achieves precise signal control and efficient modulation through its six-port design. It achieves an insertion loss of -0.66 dB across its frequency range, with isolation and return loss metrics of -32 dB and -15 dB, respectively. With its low actuation voltage of 6.8 V and rapid response time of 2.28 µs, the switch exemplifies power-efficient and prompt switching performance. The compact design is ideal for integration into space-conscious systems. This switch is pivotal for 6G research and has potential applications in satellite communications, military radar systems, and next-generation radio applications that require multi-antenna access.

3DOF displacement sensor based on the self-imaging effect of optical micro-gratings.

In recent years, there has been an increasing demand for a multiple degrees of freedom (DOF) measurement system with high performance and high integration. Here, we report a 3DOF displacement sensor based on the self-imaging effect of optical micro-gratings. The optical field distribution behind a micro-grating with a period of 3 µm is analyzed theoretically. The transmission properties of a double-grating structure are investigated in theory. In the experiment, 3DOF displacement measurement within a range of 1 mm is demonstrated. Using an interpolation circuit with a subdividing factor of 1000, displacement measurement with a theoretical resolution of 3 nm is realized. The experimental resolution is ∼8n m. An error within 2 µm is obtained experimentally within a range of 1 mm for 3DOF measurement. With a few optical components such as a beam splitter prism and beam expanders, the sensor shows potential in developing ultra-compact multi-DOF displacement measuring systems. Together with a nanometric resolution, the 3DOF displacement sensor has shown great potential in applications such as high-precision mechanical engineering and semiconductor processing.

A 60 GHz Slotted Array Horn Antenna for Radar Sensing Applications in Future Global Industrial Scenarios.

This paper presents the design of a 60 GHz millimeter-wave (MMW) slot array horn antenna based on the substrate-integrated waveguide (SIW) structure. The novelty of this device resides in the achievement of a broad impedance bandwidth and high gain performance by meticulously engineering the radiation band structure and slot array. The antenna demonstrates an impressive impedance bandwidth of 14.96 GHz (24.93%), accompanied by a remarkable maximum reflection coefficient of -39.47 dB. Furthermore, the antenna boasts a gain of 10.01 dBi, showcasing its outstanding performance as a high-frequency antenna with a wide bandwidth and high gain. To validate its capabilities, we fabricated and experimentally characterized a prototype of the antenna using a probe test structure. The measurement results closely align with the simulation results, affirming the suitability of the designed antenna for radar sensing applications in future global industrial scenarios.

Intelligent devices for assessing essential tremor: a comprehensive review.

Essential tremor (ET) stands as the most prevalent movement disorder, characterized by rhythmic and involuntary shaking of body parts. Achieving an accurate and comprehensive assessment of tremor severity is crucial for effectively diagnosing and managing ET. Traditional methods rely on clinical observation and rating scales, which may introduce subjective biases and hinder continuous evaluation of disease progression. Recent research has explored new approaches to quantifying ET. A promising method involves the use of intelligent devices to facilitate objective and quantitative measurements. These devices include inertial measurement units, electromyography, video equipment, and electronic handwriting boards, and more. Their deployment enables real-time monitoring of human activity data, featuring portability and efficiency. This capability allows for more extensive research in this field and supports the shift from in-lab/clinic to in-home monitoring of ET symptoms. Therefore, this review provides an in-depth analysis of the application, current development, potential characteristics, and roles of intelligent devices in assessing ET.

Finely-Tuning Chemiluminescent Color of CdTe Nanocrystals and Its Application for Near-Infrared Semi-Automatic Immunoassay.

Chemiluminescence (CL), especially commercialized CL immunoassay (CLIA), is normally performed within the eye-visible region of the spectrum by exploiting the electronic-transition-related emission of the molecule luminophore. Herein, dual-stabilizers-capped CdTe nanocrystals (NCs) is employed as a model of nanoparticulated luminophore to finely tune the CL color with superior color purity. Initialized by oxidizing the CdTe NCs with potassium periodate (KIO4), intermediates of the reactive oxygen species (ROS) tend to charge CdTe NCs in both series-connection and parallel-connection routes and dominate the charge-transfer CL of CdTe NCs. The CdTe NCs/KIO4 system can exhibit color-tunable CL with the maximum emission wavelength shifted from 694 nm to 801 nm, and the red-shift span is over 100 nm. Both PL and CL of each of the CdTe NCs are bandgap-engineered; the change in the NCs surface state via CL reaction enables CL of each of the CdTe NCs to be red-shifted for ∼20 nm to PL, while the change in the NCs surface state via labeling CdTe NCs to secondary-antibody (Ab2) enables CL of the CdTe NCs-Ab2 conjugates to be red-shifted for another ∼20 nm to bare CdTe NCs. The CL of CdTe753-Ab2/KIO4 is ∼791 nm, which can perform near-infrared CL immunoassay and semi-automatically determined procalcitonin (PCT) on commercialized in vitro diagnosis (IVD) instruments.

Tyrosine hydroxylase inhibits HCC progression by downregulating TGFß/Smad signaling.

The alteration of metabolic processes has been found to have significant impacts on the development of hepatocellular carcinoma (HCC). Nevertheless, the effects of dysfunction of tyrosine metabolism on the development of HCC remains to be discovered. This research demonstrated that tyrosine hydroxylase (TH), which responsible for the initial and limiting step in the bio-generation of the neuro-transmitters dopamine and adrenaline, et al. was shown to be reduced in HCC. Increased expression of TH was found facilitates the survival of HCC patients. In addition, decreased TH indicated larger tumor size, much more numbers of tumor, higher level of AFP, and the presence of cirrhosis. TH effectively impairs the growth and metastasis of HCC cells, a process dependent on the phosphorylation of serine residues (S19/S40). TH directly binds to Smad2 and hinders the cascade activation of TGFß/Smad signaling with the treatment of TGFß1. In summary, our study uncovered the non-metabolic functions of TH in the development of HCC and proposes that TH might be a promising biomarker for diagnosis as well as an innovative target for metastatic HCC.

Enhancing the Consistency and Performance of Graphene-Based Devices via Al Intermediate-Layer-Assisted Transfer and Patterning.

Graphene has garnered widespread attention, and its use is being explored for various electronic devices due to its exceptional material properties. However, the use of polymers (PMMA, photoresists, etc.) during graphene transfer and patterning processes inevitably leaves residues on graphene surface, which can decrease the performance and yield of graphene-based devices. This paper proposes a new transfer and patterning process that utilizes an Al intermediate layer to separate graphene from polymers. Through DFT calculations, the binding energy of graphene-Al was found to be only -0.48 eV, much lower than that of PMMA and photoresist with graphene, making it easier to remove Al from graphene. Subsequently, this was confirmed through XPS analysis. A morphological characterization demonstrated that the graphene patterns prepared using the Al intermediate layer process exhibited higher surface quality, with significantly reduced roughness. It is noteworthy that the devices obtained with the proposed method exhibited a notable enhancement in both consistency and sensitivity during electrical testing (increase of 67.14% in temperature sensitivity). The low-cost and pollution-free graphene-processing method proposed in this study will facilitate the further commercialization of graphene-based devices.

Linearization signal conditioning circuit for tri-axial micro-grating MOEMS accelerometer.

This paper proposes what we believe to be a novel linearization signal conditioning circuit for a tri-axial micro-grating micro-opto-electro-mechanical systems (MOEMS) accelerometer. The output of a micro-grating accelerometer varies as a sine/cosine function of the acceleration. The proposed circuit utilizes a subdivision interpolation technique to process these nonlinear intensity variations and render a linear digital output across the full range. Such a linearization circuit was achieved through a 90-degree phase-shift circuit, high-precision DC bias-voltage and subdivision interpolation circuits to reduce the influence of phase, magnitude, and offset errors of the sine-cosine signals on the interpolation factor, improving the resolution and accuracy of acceleration detection. Experimental results demonstrated that the micro-grating MOEMS accelerometer achieves a resolution of sub-mg, cross-axis errors of 3.57%, 1.22% and 0.89% for x-, y- and z-aixs, respectively. The bias instabilities and velocity random walks for the vertical and lateral accelerometer are superior to 26 µg and 38.7 µg/√Hz. The tri-axial micro-grating MOEMS accelerometer exhibits significant potential for applications requiring high sensitivity and large operation ranges, including the automotive industry and military equipment.

Wet Chemical Synthesis of Ultrathin γ-Ga2O3 Quantum Wires Enabling Far-UVC Photodetection with Ultrahigh Selectivity and Sensitivity.

As compared to solar-blind ultraviolet (UV) photodetectors (PDs), far-UVC PDs not only show some irreplaceable advantages but also are more challenging to be developed. To solve this challenge, we report herein a soft template-assisted solvothermal route to synthesize ultrathin γ-Ga2O3 quantum wires (UQWs) with diameters down to 1-2 nm. These UQWs all exhibit a cluster-like absorption feature with a strong peak located between 190 and 230 nm and an edge below 250 nm, allowing highly selective absorption to far-UVC light. Notably, their normalized absorption coefficients were experimentally and theoretically confirmed to increase obviously with decreasing their diameters. Self-powered photoelectrochemical-type PDs based on Ga2O3 QWs of 1.7 nm diameter were therefore fabricated, exhibiting an excellent far-UVC detection performance with an unprecedented ultrahigh spectral selectivity (R210 nm/R250 nm = 452). As a proof of concept, this paper offers a new idea for developing ultrawide bandgap semiconductor materials and devices by leveraging a strong quantum confinement effect.

Genkwanin alleviates intervertebral disc degeneration via regulating ITGA2/PI3K/AKT pathway and inhibiting apoptosis and senescence.

Intervertebral disc degeneration (IVDD) is a progressive degenerative disease influenced by various factors. Genkwanin, a known anti-inflammatory flavonoid, has not been explored for its potential in IVDD management. This study aims to investigate the effects and mechanisms of genkwanin on IVDD. In vitro, cell experiments revealed that genkwanin dose-dependently inhibited Interleukin-1ß-induced expression levels of inflammatory factors (Interleukin-6, inducible nitric oxide synthase, cyclooxygenase-2) and degradation metabolic protein (matrix metalloproteinase-13). Concurrently, genkwanin upregulated the expression of synthetic metabolism genes (type II collagen, aggrecan). Moreover, genkwanin effectively reduced the phosphorylation of phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin, mitogen-activated protein kinase (MAPK), and nuclear factor-κB (NF-κB) pathways. Transcriptome sequencing analysis identified integrin α2 (ITGA2) as a potential target of genkwanin, and silencing ITGA2 reversed the activation of PI3K/AKT pathway induced by Interleukin-1ß. Furthermore, genkwanin alleviated Interleukin-1ß-induced senescence and apoptosis in nucleus pulposus cells. In vivo animal experiments demonstrated that genkwanin mitigated the progression of IVDD in the rat model through imaging and histological examinations. In conclusion, This study suggest that genkwanin inhibits inflammation in nucleus pulposus cells, promotes extracellular matrix remodeling, suppresses cellular senescence and apoptosis, through the ITGA2/PI3K/AKT, NF-κB and MAPK signaling pathways. These findings indicate that genkwanin may be a promising therapeutic candidate for IVDD.

Potential-selective electrochemiluminescence of AgInS2/ZnS nanocrystals and its immunoassay application.

Potential-selective electrochemiluminescence (ECL) with tunable maximum-emission-potential ranging from 0.95 to 0.30 V is achieved using AgInS2/ZnS nanocrystals, which is promising in the design of multiplexed bioassay on commercialized ECL setups. The model system AgInS2/ZnS/N2H4 exhibits efficient ECL around 0.30 V and can be exploited for sensitive immunoassays with less electrochemical interference and crosstalk.