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Abstract Tumor cells must rewire nucleotide synthesis to satisfy the demands of unbridled proliferation. Meanwhile, they exhibit augmented reactive oxygen species (ROS) production which paradoxically damages DNA and free deoxy-ribonucleoside triphosphates (dNTPs). How these metabolic processes are integrated to fuel tumorigenesis remains to be investigated. MYC family oncoproteins coordinate nucleotide synthesis and ROS generation to drive the development of numerous cancers. We herein perform a Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-based functional screen targeting metabolic genes and identified nudix hydrolase 1 (NUDT1) as a MYC-driven dependency. Mechanistically, MYC orchestrates the balance of two metabolic pathways that act in parallel, the NADPH oxidase 4 (NOX4)-ROS pathway and the Polo like kinase 1 (PLK1)-NUDT1 nucleotide-sanitizing pathway. We describe LC-1-40 as a potent, on-target degrader that depletes NUDT1 in vivo. Administration of LC-1-40 elicits excessive nucleotide oxidation, cytotoxicity and therapeutic responses in patient-derived xenografts. Thus, pharmacological targeting of NUDT1 represents an actionable MYC-driven metabolic liability.

Intervertebral disc degeneration (IVDD) is rising worldwide and leading to significant health issues and financial strain for patients. Traditional treatments for IVDD can alleviate pain but do not reverse disease progression, and surgical removal of the damaged disc may be required for advanced disease. The inflammatory microenvironment is a key driver in the development of disc degeneration. Suitable anti-inflammatory substances are critical for controlling inflammation in IVDD. Several treatment options, including glucocorticoids, non-steroidal anti-inflammatory drugs, and biotherapy, are being studied for their potential to reduce inflammation. However, anti-inflammatories often have a short half-life when applied directly and are quickly excreted, thus limiting their therapeutic effects. Biomaterial-based platforms are being explored as anti-inflammation therapeutic strategies for IVDD treatment. This review introduces the pathophysiology of IVDD and discusses anti-inflammatory therapeutics and the components of these unique biomaterial platforms as comprehensive treatment systems. We discuss the strengths, shortcomings, and development prospects for various biomaterials platforms used to modulate the inflammatory microenvironment, thus providing guidance for future breakthroughs in IVDD treatment.

The security of underwater acoustic communication networks is an important guarantee for information sharing and cooperative operation of underwater communication. Existing technologies mainly study authentication protocol and data encryption, focusing on improving the security of the network but ignoring the efficiency and energy consumption of the network. To avoid network congestion caused by the above methods, this paper, inspired by research in mobile smart devices and other fields, proposed to integrate voiceprint authentication into the identity authentication system of underwater communication networks, and it designed a recognition method based on voiceprint features of communication payloads. This method used the attention mechanism and merged nonlinear cepstrum features and phase spectrum features to reduce the influence of complex marine environment noise. In addition, it identified the target through the AlexNet network. To verify the effectiveness of this method, this paper collected underwater acoustic communication signals, verified the difference and effectiveness of the proposed voiceprint feature recognition, and demonstrated the feasibility and reliability of the proposed method. The research in the paper provides a new idea for solving the identity authentication of underwater acoustic communication networks, which serves as a reference for enhancing security and realizing high-quality information sharing and high-efficiency cooperative control of underwater acoustic communication networks.

The adaptive optics system (AOS) incorporating a modulated pyramid wavefront sensor (PWFS) represents a key area of exploration in current research aimed at enhancing the capabilities of future extremely large astronomical telescopes. However, incorporating a conventional modulated PWFS into an AOS presents several challenges, including complex optical pathways, intricate alignment procedures, and issues related to deviation in the exit pupil image. This paper introduces a novel discrete modulated operation method for the pyramid wavefront sensor, while the sensor concept has been already presented in authors’ last paper, termed the DM-PWFS. The DM-PWFS integrates the modulation mirror with the pyramidal prism, reducing the number of conjugate planes in the system and significantly simplifying the optical pathways and alignment processes. Moreover, the M-PWFS replaces the traditional method of incident light modulation by modulating the center point of pyramidal prism, ensuring that the primary optical axis remains stationary during modulation and effectively eliminating the impact of pupil image deviation. The theoretical model and geometrical optical analysis explain the wavefront sensing principle of the DM-PWFS. Simulation analysis discusses the system parameters and dynamic performance of the DM-PWFS. Experimental results demonstrate that an AOS equipped with the DM-PWFS successfully corrects wavefront distortion, achieving a residual wavefront Root Mean Square (RMS) value of approximately 0.02λ and a focal plane image Strehl Ratio value of around 0.83.

Nowadays, numerous countries are facing the challenge of aging population. Additionally, the number of people with reduced mobility due to physical illness is increasing. In response to this issue, robots used for walking assistance and sit-to-stand (STS) transition have been introduced in nursing to assist these individuals with walking. Given the shared characteristics of these robots, this paper collectively refers to them as Walking Support Robots (WSR). Additionally, service robots with assisting functions have been included in the scope of this review. WSR are a crucial element of modern nursing assistants and have received significant research attention. Unlike passive walkers that require much user’s strength to move, WSR can autonomously perceive the state of the user and environment, and select appropriate control strategies to assist the user in maintaining balance and movement. This paper offers a comprehensive review of recent literature on WSR, encompassing an analysis of structure design, perception methods, control strategies and safety & comfort features. In conclusion, it summarizes the key findings, current challenges and discusses potential future research directions in this field.

Purpose: We aimed to develop an artificial intelligence-based myopic maculopathy grading method using EfficientNet to overcome the delayed grading and diagnosis of different myopic maculopathy degrees. Methods: The cooperative hospital provided 4642 healthy and myopic maculopathy color fundus photographs, comprising the four degrees of myopic maculopathy and healthy fundi. The myopic maculopathy grading models were trained using EfficientNet-B0 to EfficientNet-B7 models. The diagnostic results were compared with those of the VGG16 and ResNet50 classification models. The leading evaluation indicators were sensitivity, specificity, F1 score, area under the receiver operating characteristic (ROC) curve area under curve (AUC), 95% confidence interval, kappa value, and accuracy. The ROC curves of the ten grading models were also compared. Results: We used 1199 color fundus photographs to evaluate the myopic maculopathy grading models. The size of the EfficientNet-B0 myopic maculopathy grading model was 15.6 MB, and it had the highest kappa value (88.32%) and accuracy (83.58%). The model's sensitivities to diagnose tessellated fundus (TF), diffuse chorioretinal atrophy (DCA), patchy chorioretinal atrophy (PCA), and macular atrophy (MA) were 96.86%, 75.98%, 64.67%, and 88.75%, respectively. The specificity was above 93%, and the AUCs were 0.992, 0.960, 0.964, and 0.989, respectively. Conclusion: The EfficientNet models were used to design grading diagnostic models for myopic maculopathy. Based on the collected fundus images, the models could diagnose a healthy fundus and four types of myopic maculopathy. The models might help ophthalmologists to make preliminary diagnoses of different degrees of myopic maculopathy.

As an important part of proliferation and discharge, crustaceans can effectively conserve and supplement fishery resources in natural waters. Based on the data of crustacean proliferation and release in Zhejiang Province from 2017 to 2021 and related literature, this paper systematically reviewed the annual variation trend of crustacean release type and quantity, release capital, and the spatial and quantitative distribution of release area and release specifications. The results show that: from 2017 to 2021, six species of crustacean proliferate in Zhejiang Province, including Penaeus japonicus, Portunus trituberculatus and Penaeus chinensis, etc.. A total of 5220, 455, 000 were released, and the investment was 33, 202, 000 yuan. Among them, the largest amount of release and investment was Japanese prawnaeus, the least amount of release was green crab, and the least amount of investment was Prawnaeus puerarii. The release area involved Wenzhou, Ningbo, Taizhou, Zhoushan and other cities, and the distribution of release was unbalanced between regions, and mainly concentrated in small and medium sizes. In this paper, some specific suggestions will be put forward on problems such as insufficient assessment of the effect of crustacean release species, poor release effect of some proliferating species, and few reserve species of crustacean release in the coastal waters of Zhejiang Province, so as to provide a basis for improving the scientific management of crustacean release species in the future.

Abstract Dielectric metasurfaces, composed of planar arrays of subwavelength dielectric structures that collectively mimic the operation of conventional bulk optical elements, have revolutionized the field of optics by their potential in constructing high-efficiency and multi-functional optoelectronic systems on chip. The performance of a dielectric metasurface is largely determined by its constituent material, which is highly desired to have a high refractive index, low optical loss and wide bandgap, and at the same time, be fabrication friendly. Here, we present a new material platform based on tantalum pentoxide (Ta2O5) for implementing high-performance dielectric metasurface optics over the ultraviolet and visible spectral region. This wide-bandgap dielectric, exhibiting a high refractive index exceeding 2.1 and negligible extinction coefficient across a broad spectrum, can be easily deposited over large areas with good quality using straightforward physical vapor deposition, and patterned into high-aspect-ratio subwavelength nanostructures through commonly-available fluorine-gas-based reactive ion etching. We implement a series of high-efficiency ultraviolet and visible metasurfaces with representative light-field modulation functionalities including polarization-independent high-numerical-aperture lensing, spin-selective hologram projection, and vivid structural color generation, and the devices exhibit operational efficiencies up to 80%. Our work overcomes limitations faced by scalability of commonly-employed metasurface dielectrics and their operation into the visible and ultraviolet spectral range, and provides a novel route towards realization of high-performance, robust and foundry-manufacturable metasurface optics.

Purpose: The aim was to determine the combined value of serological lipid metabolism and an orbital MRI quantitative parameter in predicting the effectiveness of glucocorticoid (GC) therapy in patients with thyroid eye disease (TED). Methods: This study retrospectively enrolled 46 patients with active and moderate-to-severe TED (GC-effective group, n = 29; GC-ineffective group, n = 17). Serological lipid metabolism, the orbital MRI-based minimum signal intensity ratio of extraocular muscles (EOM-SIRmin), as well as other clinical parameters before GC therapy were collected and compared between the two groups. Multivariate logistic regression and receiver operating characteristic curve analysis were adopted to identify independent predictable variables and assess their predictive performances. Results: Compared to the GC-ineffective group, the GC-effective group showed lower serum total cholesterol levels (P = 0.006), lower serum low-density lipoprotein cholesterol levels (P = 0.019), higher EOM-SIRmin values (P = 0.005), and shorter disease durations (P = 0.017). Serum total cholesterol and EOM-SIRmin were found to be independent predictors of GC-effective TED through multivariate analysis (odds ratios = 0.253 and 2.036 per 0.1 units, respectively) (both P < 0.05). The integration of serum total cholesterol ≤4.8 mmol/L and EOM-SIRmin ≥ 1.12 had a better predictive efficacy (area under the curve, 0.834) than EOM-SIRmin alone, with a sensitivity of 75.9% and a specificity of 82.4% (P = 0.031). Conclusion: Serological lipid metabolism, combined with an orbital MRI-derived parameter, was a useful marker for predicting the effectiveness of GCs in patients with active and moderate-to-severe TED.

Abstract Several observational studies have revealed an association between autoimmune diseases (AIDs) and colorectal cancer (CRC), although their causal association remained controversial. Therefore, our study used a two-sample Mendelian randomization (MR) analysis to verify the causal association between AIDs and CRC. We employed three common MR approaches, including inverse variance weighted (IVW), weighted median, and MR-Egger methods, to assess the causal association between type 1 diabetes (T1D), systemic lupus erythematosus, rheumatoid arthritis, psoriasis, multiple sclerosis, juvenile idiopathic arthritis, celiac disease, and primary sclerosing cholangitis (PSC) and CRC. The reverse MR analysis was performed to assess the possibility of reverse causation. To evaluate the validity of the analysis, we also performed sensitivity analysis, such as the heterogeneity test, the horizontal pleiotropy test, and the leave-one-out sensitivity analysis, and validated the results in the validation cohort. Our results showed that genetically predicted T1D was nominally associated with a lower risk of CRC (IVW OR = 0.965, 95% CI = 0.939–0.992, P = 0.012). However, genetic susceptibility to psoriasis nominally increased the risk of CRC (IVW OR = 1.026, 95% CI = 1.002–1.050, P = 0.037). Genetically predicted PSC had a significant causal effect on the increasing risk of CRC (IVW OR = 1.038, 95% CI = 1.016–1.060, P = 5.85 × 10−4). Furthermore, the MR analysis between PSC and the CRC validation cohort indicated consistent results. We found no causal association between genetically predicted other five AIDs and CRC (P > 0.05). The results of reverse MR analysis showed that genetically predicted CRC had no causal effect on T1D, psoriasis, and PSC (P > 0.05). The sensitivity analysis demonstrated that the results of the MR analysis were reliable. Our findings help to understand the causal association between AIDs and CRC, which deserves further investigation.

Composite robots often encounter difficulties due to changes in illumination, external disturbances, reflective surface effects, and cumulative errors. These challenges significantly hinder their capabilities in environmental perception and the accuracy and reliability of pose estimation. We propose a nonlinear optimization approach to overcome these issues to develop an integrated localization and navigation framework, IIVL-LM (IMU, Infrared, Vision, and LiDAR Fusion for Localization and Mapping). This framework achieves tightly coupled integration at the data level using inputs from an IMU (Inertial Measurement Unit), an infrared camera, an RGB (Red, Green and Blue) camera, and LiDAR. We propose a real-time luminance calculation model and verify its conversion accuracy. Additionally, we designed a fast approximation method for the nonlinear weighted fusion of features from infrared and RGB frames based on luminance values. Finally, we optimize the VIO (Visual-Inertial Odometry) module in the R3LIVE++ (Robust, Real-time, Radiance Reconstruction with LiDAR-Inertial-Visual state Estimation) framework based on the infrared camera’s capability to acquire depth information. In a controlled study, using a simulated indoor rescue scenario dataset, the IIVL-LM system demonstrated significant performance enhancements in challenging luminance conditions, particularly in low-light environments. Specifically, the average RMSE ATE (Root Mean Square Error of absolute trajectory Error) improved by 23% to 39%, with reductions from 0.006 to 0.013. At the same time, we conducted comparative experiments using the publicly available TUM-VI (Technical University of Munich Visual-Inertial Dataset) without the infrared image input. It was found that no leading results were achieved, which verifies the importance of infrared image fusion. By maintaining the active engagement of at least three sensors at all times, the IIVL-LM system significantly boosts its robustness in both unknown and expansive environments while ensuring high precision. This enhancement is particularly critical for applications in complex environments, such as indoor rescue operations.

Artemisia ordosica polysaccharides (AOP) can promote animal growth, improve intestinal morphology, regulate immunity, and enhance antioxidant capacity. To investigate the antioxidant capacity of AOP, three experiments were conducted. (1) Different concentrations of AOP (0, 50, 100, 150, 200, and 250 μg/mL) and 1 µg/mL VA on peripheral blood lymphocytes (PBLs) treated with/without lipopolysaccharides (LPS) were investigated to select the optimum concentration. The results showed that 150 μg/mL AOP had significant antioxidation activity. (2) The PBLs was randomly divided into eight treatments with six replicates, namely CON, AOP, LPS, ML385 (Nrf2 inhibitor), AOP + LPS, AOP + ML385, LPS + ML385 and LPS + ML385 + AOP. The results showed that under a normal condition or stress condition, AOP presented antioxidation activity via upregulating Nrf2/Keap1 pathway-related gene expression. (3) The PBLs was randomly divided into eight treatments with six replicates, namely CON, AOP, LPS, PDTC (NF-κB inhibitor), AOP + LPS, AOP + PDTC, LPS + PDTC and LPS + PDTC + AOP. The results showed that under a normal condition, AOP presented antioxidation activity via increasing TLR4/NF-κB pathway-related gene expression; under a stress condition, AOP alleviated oxidative damage caused by LPS via suppressing TLR4/NF-κB pathway-related gene expression.

This paper reviews recent biomechanical studies on heart valve flutter. The function of the heart valves is essential for maintaining effective blood circulation. Heart valve flutter is a kind of small vibration phenomenon like a flag fluttering in the wind, which is related to many factors such as a thrombus, valve calcification, regurgitation, and hemolysis and material fatigue. This vibration phenomenon is particularly prevalent in valve replacement patients. The biomechanical implications of flutter are profound and can lead to micro-trauma of valve tissue, accelerating its degeneration process and increasing the risk of thrombosis. We conducted a systematic review along with a critical appraisal of published studies on heart valve flutter. In this review, we summarize and analyze the existing literature; discuss the detection methods of frequency and amplitude of heart valve flutter, and its potential effects on valve function, such as thrombosis and valve degeneration; and discuss some possible ways to avoid flutter. These findings are important for optimizing valve design, diagnosing diseases, and developing treatment strategies.

This paper introduces an optimization method for multi-robot automated control welding based on a Particle Swarm Genetic Algorithm (PSGA), aiming to address issues such as high costs, large footprint, and excessive production cycles in multi-robot welding production lines. The method first constructs a multi-axis robotic kinematic model to provide constraint conditions. Then, the PSO (particle swarm optimization) algorithm, which integrates penalty functions into the fitness evaluation, is used to determine the optimal welding path by simulating collective behavior within a group. The GA (genetic algorithm) encodes the position of the welding robot bases into chromosomes to find the optimal layout for coordinated control of multiple robots. The entire process is optimized according to welding standards and requirements. Additionally, a comprehensive production line performance estimation model was used to quantitatively analyze the new scheme. The results show that the optimized production line’s balance rate increased by 10%, the balance loss rate decreased by 10%, the smoothness index increased by 37.8%, the space costs reduced by 44.4%, the equipment demand reduced by 41.1%, the labor demand reduced by 50%, the total costs reduced by 10%, and the average product cycle time was reduced by 5.07 s. Finally, we tested the algorithm in various complex scenarios and compared its performance against mainstream algorithms within the context of this study. The results demonstrated that the optimized production line significantly improved efficiency while maintaining safety standards.

When mineral resources are extracted using underground mining methods in hilly regions, landslides or slope failures can be induced frequently. In this study, slope collapse disasters in mountain mining areas were analyzed. The model test and numerical simulation of the slope impacted by repeated mining were carried out. The crack evolution and failure process were analyzed to reveal the instability mechanism. The results show that the rock mass would topple to the inside of the slope first, when the subsidence of overlying rock was induced by the mining of the upper coal seam. When repeated mining was performed in the lower coal seam, the mining induced macro-cracks that could connect with natural fissures, inducing the outward displacement of the slope. Then, the rock mass at the foot of the slope has to bear the upper load, which is also squeezed out by the collapsed rock mass, forming the potential slip zone. Finally, the instability is caused by the shear slip of the slope toe rock mass. Therefore, the instability evolution of the slope under underground repeated mining disturbance can be divided into four stages as follows: roof caving and overlaying rock subsidence, joint rock toppling, fracture penetration, and slope toe shearing and slope slipping.

The precise detection of liquid flow and viscosity is a crucial challenge in industrial processes and environmental monitoring due to the variety of liquid samples and the complex reflective properties of energetic liquids. Traditional methods often struggle to maintain accuracy under such conditions. This study addresses the complexity arising from sample diversity and the reflective properties of energetic liquids by introducing a novel model based on computer vision and deep learning. We propose the DBN-AGS-FLSS, an integrated deep learning model for high-precision, real-time liquid surface pointer detection. The model combines Deep Belief Networks (DBN), Feedback Least-Squares SVM classifiers (FLSS), and Adaptive Genetic Selectors (AGS). Enhanced by bilateral filtering and adaptive contrast enhancement algorithms, the model significantly improves image clarity and detection accuracy. The use of a feedback mechanism for reverse judgment dynamically optimizes model parameters, enhancing system accuracy and robustness. The model achieved an accuracy, precision, F1 score, and recall of 99.37%, 99.36%, 99.16%, and 99.36%, respectively, with an inference speed of only 1.5 ms/frame. Experimental results demonstrate the model’s superior performance across various complex detection scenarios, validating its practicality and reliability. This study opens new avenues for industrial applications, especially in real-time monitoring and automated systems, and provides valuable reference for future advancements in computer vision-based detection technologies.

Within the area of environmental perception, automatic navigation, object detection, and computer vision are crucial and demanding fields with many applications in modern industries, such as multi-target long-term visual tracking in automated production, defect detection, and driverless robotic vehicles. The performance of computer vision has greatly improved recently thanks to developments in deep learning algorithms and hardware computing capabilities, which have spawned the creation of a large number of related applications. At the same time, with the rapid increase in autonomous systems in the market, energy consumption has become an increasingly critical issue in computer vision and SLAM (Simultaneous Localization and Mapping) algorithms. This paper presents the results of a detailed review of over 100 papers published over the course of two decades (1999–2024), with a primary focus on the technical advancement in computer vision. To elucidate the foundational principles, an examination of typical visual algorithms based on traditional correlation filtering was initially conducted. Subsequently, a comprehensive overview of the state-of-the-art advancements in deep learning-based computer vision techniques was compiled. Furthermore, a comparative analysis of conventional and novel algorithms was undertaken to discuss the future trends and directions of computer vision. Lastly, the feasibility of employing visual SLAM algorithms in the context of autonomous vehicles was explored. Additionally, in the context of intelligent robots for low-carbon, unmanned factories, we discussed model optimization techniques such as pruning and quantization, highlighting their importance in enhancing energy efficiency. We conducted a comprehensive comparison of the performance and energy consumption of various computer vision algorithms, with a detailed exploration of how to balance these factors and a discussion of potential future development trends.

Radiative natural convection is of vital importance in the process of energy storage, power generation, and thermal storage technology. As the attenuation coefficients of many heat transfer media in these fields are high enough to be considered as optically thick media, like nanofluids or molten salts in concentrated solar power or phase change thermal storage, Rosseland approximation is commonly used. In this paper, we delve into the impact of thermal radiation on the Rayleigh-Bénard (RB) convection. Theoretical analysis has been conducted by modifying the Grossmann-Lohse (GL) model. Based on turbulent dissipation theory, the corresponding scaling laws in four main regimes are proposed. Direct numerical simulation (DNS) was also performed, revealing that radiation exerts a notable influence on both flow and heat transfer, particularly on the formation of large-scale circulation. By comparing with DNS results, it is found that due to the presence of radiation, the modified Nu scaling law in small Pr range of the GL model is more suitable for predicting the transport characteristics of optical thick media with large Pr. The maximum deviation between the results of DNS and prediction model is about 10%, suggesting the summarized scaling law can effectively predict the Nu of radiative RB convection.

A surprising “planar” thermal Hall effect, whereby the field is parallel to the current, has recently been observed in a few magnetic insulators; this effect has been attributed to exotic excitations such as Majorana fermions or chiral magnons. Here, we investigate the possibility of a planar thermal Hall effect in three different cuprate materials, in which the conventional thermal Hall conductivity κ_{xy} (with an out-of-plane field perpendicular to the current) is dominated by either electrons or phonons. Our measurements show that the planar κ_{xy} from electrons in cuprates is zero, as expected from the absence of a Lorentz force in the planar configuration. By contrast, we observe a sizable planar κ_{xy} in those samples where the thermal Hall response is due to phonons, even though it should, in principle, be forbidden by the high crystal symmetry. Our findings call for a careful reexamination of the mechanisms responsible for the phonon thermal Hall effect in insulators.

Shallow purple soils (Entisols) were widely distributed in hilly areas of southwest China and were easily subjected to drought due to the weak soil water retention capacity, which largely reduced the crop productivity. However, the impact of solum thickness on ecological traits and water use strategies of crops remain poorly understood under the shallow Entisol environment. In this study, water use patterns and physiological adaptation of maize with different solum thicknesses were investigated to ascertain the optimum solum thickness based on an in-situ experiment. Isotopic (2H and 18O) tracing technique was used to investigate the water sources for maize growth in sloping croplands with solum of 20 cm (C1), 40 cm (C2), 60 cm (C3), 80 cm (C4), 100 cm (C5) thickness. The morphological and physiological characteristics were also discussed under different soil moisture regimes. The results showed the soil water storage capacity significantly increased with solum thickness. The isotopes of xylem water in shallow solum (≦40 cm) were more enriched, indicating more contributions from the bottom soil water, especially under dry regimes (62.3% for C1, 42.8% for C2, at Jul. 09). The water sources utilized by maize in the treatments with solum thickness greater than 60 cm were relatively evenly distributed throughout the soil profile (mean 19.3%, 19.6% and 17.6%, respectively, in the 0–10 cm, 10–20 cm, 20–40 cm soil layer), and the water niche breadth increased with the solum thickness. Maize in shallow solum (≦40 cm) had lower biomass and higher specific leaf area (SLA) to reduce transpiration rate and improved water use efficiency (WUEi) (highest for C1, P60 cm) had significantly higher yields than in shallower solum (P

Abstract Diseases like obesity and intestinal inflammation diseases are accompanied by dysbiosis of the gut microbiota (DSGM), which leads to various complications, including systemic metabolic disorders. DSGM reportedly impairs the fertility of male mice; however, the regulatory mechanism is unclear. Exosomes are molecular mediators of intercellular communication, but the regulation of spermatogenesis by non‐reproductive tissue‐originated exosomes remains unknown. The present study shows that DSGM altered the miRNA expression profile of mouse circulating exosomes and impaired spermatogenesis. Moreover, the single‐cell sequencing results indicate that circulating exosomes from mice with DSGM impaired spermatogenesis, while circulating exosomes from wild mice improved spermatogenesis by promoting meiosis. Further study demonstrates that DSGM leads to abnormal upregulation of miR‐211‐5p in gut‐derived circulating exosomes, which inhibited the expression of meiosis‐specific with coiled‐coil domain (Meioc) in the testes and impaired spermatogenesis by disturbing meiosis process. In summary, this study defines the important role of gut‐derived exosomes in connecting the “gut‐testis” axis.

Abstract Preeclampsia (PE) is considered as a disease of placental origin. However, the specific mechanism of placental abnormalities remains elusive. This study identified thrombospondin‐1 (THBS1) is downregulated in preeclamptic placentae and negatively correlated with blood pressure. Functional studies show that THBS1 knockdown inhibits proliferation, migration, and invasion and increases the cycle arrest and apoptosis rate of HTR8/SVneo cells. Importantly, THBS1 silencing induces necroptosis in HTR8/SVneo cells, accompanied by the release of damage‐associated molecular patterns (DAMPs). Necroptosis inhibitors necrostatin‐1 and GSK′872 restore the trophoblast survival while pan‐caspase inhibitor Z‐VAD‐FMK has no effect. Mechanistically, the results show that THBS1 interacts with transforming growth factor B‐activated kinase 1 (TAK1), which is a central modulator of necroptosis quiescence and affects its stability. Moreover, THBS1 silencing up‐regulates the expression of neuronal precursor cell‐expressed developmentally down‐regulated 4 (NEDD4), which acts as an E3 ligase of TAK1 and catalyzes K48‐linked ubiquitination of TAK1 in HTR8/SVneo cells. Besides, THBS1 attenuates PE phenotypes and improves the placental necroptosis in vivo. Taken together, the down‐regulation of THBS1 destabilizes TAK1 by activating NEDD4‐mediated, K48‐linked TAK1 ubiquitination and promotes necroptosis and DAMPs release in trophoblast cells, thus participating in the pathogenesis of PE.

Abstract Spinal cord injury (SCI) has no effective treatment modalities. It faces a significant global therapeutical challenge, given its features of poor axon regeneration, progressive local inflammation, and inefficient systemic drug delivery due to the blood–spinal cord barrier (BSCB). To address these challenges, a new nano complex that achieves targeted drug delivery to the damaged spinal cord is proposed, which contains a mesoporous silica nanoparticle core loaded with microRNA and a cloaking layer of human umbilical cord mesenchymal stem cell membrane modified with rabies virus glycoprotein (RVG). The nano complex more readily crosses the damaged BSCB with its exosome‐resembling properties, including appropriate size and a low‐immunogenic cell membrane disguise and accumulates in the injury center because of RVG, where it releases abundant microRNAs to elicit axon sprouting and rehabilitate the inflammatory microenvironment. Culturing with nano complexes promotes axonal growth in neurons and M2 polarization in microglia. Furthermore, it showed that SCI mice treated with this nano complex by tail vein injection display significant improvement in axon regrowth, microenvironment regulation, and functional restoration. The efficacy and biocompatibility of the targeted delivery of microRNA by nano complexes demonstrate their immense potential as a noninvasive treatment for SCI.

Abstract Peptide and protein postmodification have gained significant attention due to their extensive impact on biomolecule engineering and drug discovery, of which cysteine‐specific modification strategies are prominent due to their inherent nucleophilicity and low abundance. Herein, the study introduces a novel approach utilizing multifunctional 5‐substituted 1,2,3‐triazine derivatives to achieve multifaceted bioconjugation targeting cysteine‐containing peptides and proteins. On the one hand, this represents an inaugural instance of employing 1,2,3‐triazine in biomolecular‐specific modification within a physiological solution. On the other hand, as a powerful combination of precision modification and biorthogonality, this strategy allows for the one‐pot dual‐orthogonal functionalization of biomolecules utilizing the aldehyde group generated simultaneously. 1,2,3‐Triazine derivatives with diverse functional groups allow conjugation to peptides or proteins, while bi‐triazines enable peptide cyclization and dimerization. The examination of the stability of bi‐triazines revealed their potential for reversible peptide modification. This work establishes a comprehensive platform for identifying cysteine‐selective modifications, providing new avenues for peptide‐based drug development, protein bioconjugation, and chemical biology research.

Objective: The goal of the research is to investigate the link between serum potassium levels and death after 28 days in sepsis patients, utilizing an extensive sample of patients from the multi-center Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Current research on serum potassium levels and 28-day mortality in sepsis patients is questionable. This study adds to the growing body of evidence linking serum potassium levels to the 28-day possibility of death in patients with sepsis. Methods: We collected 349,08 patients with sepsis from the retrospective cohort MIMIC-IV database, using serum potassium level on the first day of admission to the intensive care unit as the exposure variable and mortality at 28 days as the outcome variable. And controlled for confounding characteristics including gender, age, ethnicity, and vital signs during admission. Results: Serum potassium has a U-shaped connection with 28-day mortality in patients suffering from sepsis. The turning point was 4.10 mmol/L (95 % confidence interval: 4.03 to 4.22). Serum potassium and 28-day mortality were negatively linked on the inflection point’s left side (OR: 0.72; 95 % CI: 0.63 to 0.83, P

Polycyclic aromatic hydrocarbons (PAHs) and carbon dioxide primarily originate from the combustion of fossil fuels and biomass. The implementation of the Chinese “double carbon strategy” is expected to impact the distribution of PAH emissions, consequently influencing the spatial distribution trend of PAHs in surface soil. Therefore, it is crucial to quantitatively evaluate the effectiveness of the Chinese “double carbon strategy” on soil PAH pollution for the purpose of “the reduction of pollution and carbon emissions”. This study utilized 15,088 individual PAH concentration data from 943 soil samples collected between 2003 and 2020 in China, in conjunction with PAH emissions at a 10 km resolution, for meta-analysis. The calculated PAH emissions in this study are in line with the global PAH emission inventory (PKU-PAH-2007), with a relative standard deviation at the provincial level of less than 25 %. Subsequently, a novel method was developed using emission density and Kow of PAHs to predict PAH concentrations in surface soil based on a least-squares regression model. Compared to other environmental models, the method established in this study significantly reduced the percent sample deviation to less than 70 %. Furthermore, energy consumption data for China were simulated based on the implementation plan of the “double carbon strategy” to project PAH emissions and soil PAH levels for the years 2030 and 2060. The predicted PAH emissions in China were estimated to decrease to 41,300 t in 2030 and 10,406.5 t in 2060 from 78,815 t in 2020. Moreover, the heavily contaminated areas of soil PAHs (i.e., total PAH concentrations in soil exceeding 1000 μg kg−1) were projected to decrease by 45 % and 82 % in 2030 and 2060, respectively, compared to levels in 2020. These findings suggest that the implementation of the “double carbon strategy” can fundamentally reduce the pollution of PAHs in surface soil of China.

As a local specialty of Tibet, Qingke baijiu (QB) is made from highland barley, and is referred to as the manufacturing process of light-aroma baijiu. Using highland barley in the Qu-making and the high-temperature stacking process of sauce-aroma baijiu results in a novel Qingke baijiu (NQB). This study analyzed two kinds of NQBs by GC-MS, GC×GC-MS, and GC-O-MS, and compared them with QB, light-aroma, strong-aroma, and sauce-aroma baijiu. A total of 346 volatile compounds and 60 aroma-active compounds were detected in NQB. There were 14 compounds with FD≥27 and OAVs ≥1. Although NQB and QB shared 39 volatile compounds, NQB has more than three times the overall concentration of volatile compounds than QB. In contrast to QB, NQB exhibited a richer flavor profile and a more intense fruity, floral, and acidic aroma. Meanwhile, the distilled grains and sorghum aroma were comparatively diminished.

Background Osteosarcoma is the most common primary malignant bone tumor, but its pathogenesis remains unclear. Ubiquitin-specific processing peptidase 22 (USP22) is reported to be highly expressed and associated with tumor malignancy and prognosis in cancers. However, the role and mechanism of USP22 in osteosarcoma is not fully understood. This study aims to investigate the function and potential mechanism of USP22 in osteosarcoma using bioinformatics analysis combined with experimental validation. Methods We first integrated transcriptomic datasets and clinical information of osteosarcoma from GEO and TCGA databases to assess the expression and prognostic value of USP22 in osteosarcoma. Then, differential expression analysis and weighted gene co-expression network analysis (WGCNA) were conducted to identify USP22-related co-expressed genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to explore the biological functions and signaling pathways of USP22 co-expressed genes. To validate the accuracy of bioinformatics analyses, we downregulated USP22 expression in osteosarcoma cell line Sao-2 using siRNA and assessed its effect on cell proliferation, migration, invasion, apoptosis, and regulation of key signaling pathways. Results We found that USP22 was highly expressed in osteosarcoma tissues and correlated with poor prognosis in osteosarcoma patients. USP22 also showed potential as a diagnostic marker for osteosarcoma. In addition, 344 USP22-related co-expressed genes were identified, mainly involved in signaling pathways such as glycolysis, oxidative phosphorylation, spliceosome, thermogenesis, and cell cycle. The in vitro experiments confirmed the accuracy and reliability of bioinformatics analyses. We found that downregulation of USP22 could inhibit Sao-2 cell proliferation, migration, invasion, and induce apoptosis. Furthermore, downregulation of USP22 significantly reduced aerobic glycolysis levels in Sao-2 cells and inhibited the expression of key enzymes and transporters in aerobic glycolysis pathways such as HK2, PKM2, and GLUT1. Conclusions USP22 plays a critical role in the occurrence, development, and prognosis of osteosarcoma. USP22 could influence Sao-2 cell proliferation, apoptosis, migration, and invasion by regulating the glycolysis pathway, thereby promoting osteosarcoma progression. Therefore, USP22 may be a potential therapeutic target for the treatment of osteosarcoma.

Epilepsy is a chronic, relapsing neurological disorder, and current treatments focus primarily on neurons, yet one-third of patients still develop drug-resistant epilepsy. Therefore, there is an urgent need to explore new therapeutic targets. Interestingly, astrocytes can transfer their healthy mitochondria into neighboring neurons, thus preventing neuronal damage. Astrocyte mitochondria have been shown to have a therapeutic role in stroke and neurodegenerative diseases. However, their therapeutic effect in epilepsy and its related mechanisms have been less studied. In this review, we mainly summarize the regulatory role of astrocyte mitochondria in glutamate, calcium ion, and adenosine triphosphate (ATP) homeostasis and outline the protective role of astrocyte mitochondria in nervous system diseases, revealing a new target for epilepsy treatment.

Cancer targeted therapy is essential to minimize damage to normal cells and improve treatment outcomes. The elevated activity of Cystathionine beta-synthase (CBS), an enzyme responsible for producing endogenous hydrogen sulfide (H2S), plays a significant role in promoting tumor growth, invasiveness, and metastatic potential. Consequently, the selective inhibition of CBS could represent a promising therapeutic strategy for cancer. Currently, there is much interest in combining paclitaxel with other drugs for cancer treatment. This study aimed to investigate the efficacy of combining benserazide, a CBS inhibitor, with paclitaxel in treating tumors. Firstly, we demonstrated CBS is indeed involved in the progression of multiple cancers. Then it was observed that the total binding free energy between the protein and the small molecule is −98.241 kJ/mol. The release of H2S in the group treated with 100 μM benserazide was reduced by approximately 90% compared to the negative control, and the thermal denaturation curve of the complex protein shifted to the right, suggesting that benserazide binds to and blocks the CBS protein. Next, it was found that compared to paclitaxel monotherapy, the combination of benserazide with paclitaxel demonstrated stronger antitumor activity in KYSE450, A549, and HCT8 cells, accompanied by reduced cell viability, cell migration and invasion, as well as diminished angiogenic and lymphangiogenic capabilities. In vivo studies showed that the combined administration of benserazide and paclitaxel significantly reduced the volume and weight of axillary lymph nodes in comparison to the control group and single administration group. Further mechanistic studies revealed that the combination of benserazide and paclitaxel significantly suppressed the S-sulfhydration of SIRT1 protein, thereby inhibiting the expression of SIRT1 protein and activating SIRT1 downstream Notch1/Hes1 signaling pathway in KYSE450, A549, and HCT8 cells. Meanwhile, we observed that benserazide combined with paclitaxel induced a more significant downregulation of HIF-1α, VEGF-A, VEGF-C, and VEGF-D proteins expression levels in KYSE450, A549, and HCT8 cells compared to paclitaxel alone. These findings indicated that benserazide enhances the anticancer effects of paclitaxel via inhibiting the S-sulfhydration of SIRT1 and down-regulating HIF-1α/VEGF signaling pathway. This study suggests that benserazide may have potential as a chemosensitizer in cancer treatment.

Abstract Urgent research into innovative severe acute respiratory coronavirus‐2 (SARS‐CoV‐2) vaccines that may successfully prevent various emerging emerged variants, particularly the Omicron variant and its subvariants, is necessary. Here, we designed a chimeric adenovirus‐vectored vaccine named Ad5‐Beta/Delta. This vaccine was created by incorporating the receptor‐binding domain from the Delta variant, which has the L452R and T478K mutations, into the complete spike protein of the Beta variant. Both intramuscular (IM) and intranasal (IN) vaccination with Ad5‐Beta/Deta vaccine induced robust broad‐spectrum neutralization against Omicron BA.5‐included variants. IN immunization with Ad5‐Beta/Delta vaccine exhibited superior mucosal immunity, manifested by higher secretory IgA antibodies and more tissue‐resident memory T cells (TRM) in respiratory tract. The combination of IM and IN delivery of the Ad5‐Beta/Delta vaccine was capable of synergically eliciting stronger systemic and mucosal immune responses. Furthermore, the Ad5‐Beta/Delta vaccination demonstrated more effective boosting implications after two dosages of mRNA or subunit recombinant protein vaccine, indicating its capacity for utilization as a booster shot in the heterologous vaccination. These outcomes quantified Ad5‐Beta/Delta vaccine as a favorable vaccine can provide protective immunity versus SARS‐CoV‐2 pre‐Omicron variants of concern and BA.5‐included Omicron subvariants.

BackgroundAdrenocortical carcinoma (ACC) is an aggressive endocrine malignancy with limited therapeutic options. Treating advanced ACC with mitotane, the cornerstone therapy, remains challenging, thus underscoring the significance to predict mitotane response prior to treatment and seek other effective therapeutic strategies.ObjectiveWe aimed to determine the efficacy of mitotane via an in vitro assay using patient-derived ACC cells (PDCs), identify molecular biomarkers associated with mitotane response and preliminarily explore potential agents for ACC.MethodsIn vitro mitotane sensitivity testing was performed in 17 PDCs and high-throughput screening against 40 compounds was conducted in 8 PDCs. Genetic features were evaluated in 9 samples using exomic and transcriptomic sequencing.ResultsPDCs exhibited variable sensitivity to mitotane treatment. The median cell viability inhibition rate was 48.4% (IQR: 39.3-59.3%) and -1.2% (IQR: -26.4-22.1%) in responders (n=8) and non-responders (n=9), respectively. Median IC50 and AUC were remarkably lower in responders (IC50: 53.4 µM vs 74.7 µM, P

Osteoarthritis (OA) is characterized by cartilage degradation, inflammatory responses, and osteophyte formation. Matrix metalloproteinase 13 (MMP13) is a hallmark of OA development, and increased MMP13 expression is closely associated with extracellular matrix degradation. MMP13 expression varies significantly at different stages of OA progression. While cyclooxygenase 2 (COX-2) inhibitors are commonly used to treat OA, their long-term systemic administration increases the risks of adverse effects. Therefore, with the aim of achieving localized and responsive delivery of the COX-2 inhibitor celecoxib, the current study investigated an innovative MMP13-responsive micro-nano hydrogel microsphere system. Celecoxib-loaded cationic liposomes are non-covalently attached within the microsphere, enabling controlled drug release for OA treatment. In an OA environment with elevated MMP13 expression, the system is degraded via the action of MMP13 substrate peptide (MMP13sp), facilitating accelerated release of drug-loaded liposomes to improve the inflammatory microenvironment and treat OA rapidly. Compared to a phosphate-buffered saline solution with hyaluronidase (HAase), the prepared hyaluronic acid methacrylate microspheres HAMA/MMP13sp/Lipo@celecoxib exhibited rapid degradation in a solution containing a physiological concentration of MMP13/HAase, demonstrating specific enzyme responsiveness for precise anti-inflammatory drug release. The MMP13-responsive hydrogel microsphere system achieves intelligent and controllable drug release in OA, effectively decelerating disease progression and promoting articular cartilage repair.

In recent years, a novel two-dimensional semiconductor ZrX2 (X = Cl, Br, and I) has been found to have excellent optoelectronic properties and has attracted much attention. In this paper, the elastic properties of two-dimensional Janus ZrXY (X/Y = Cl, Br, and I, X ≠ Y) are studied by first principles, including elastic parameters, such as elastic tensor components, Young’s modulus, Poisson’s ratio, and stability. Research has found that the lattice parameters of two-dimensional Janus ZrXY are still influenced by the atomic radius. The Janus structure shows excellent dynamic stability both before and after its construction. Based on the elastic theory, the mechanical stability of the two-dimensional Janus ZrXY was proved indirectly. After constructing the two-dimensional Janus ZrXY structure with different planes, the elastic tensor component increases to a certain extent, and Young’s modulus and Poisson’s ratio increase, but the anisotropy of Young’s modulus and Poisson’s ratio decreases significantly.

Abstract Chronic inflammation is increasingly considered as the most important component of vascular aging, contributing to the progression of age‐related cardiovascular diseases. To delay the process of vascular aging, anti‐inflammation may be an effective measure. The anti‐inflammatory factor annexin A1 (ANXA1) is shown to participate in several age‐related diseases; however, its function during vascular aging remains unclear. Here, an ANXA1 knockout (ANXA1−/−) and an endothelial cell‐specific ANXA1 deletion mouse (ANXA1△EC) model are used to investigate the role of ANXA1 in vascular aging. ANXA1 depletion exacerbates vascular remodeling and dysfunction while upregulates age‐ and inflammation‐related protein expression. Conversely, Ac2‐26 (a mimetic peptide of ANXA1) supplementation reverses this phenomenon. Furthermore, long‐term tumor necrosis factor‐alpha (TNF‐α) induction of human umbilical vein endothelial cells (HUVECs) increases cell senescence. Finally, the senescence‐associated secretory phenotype and senescence‐related protein expression, rates of senescence‐β‐galactosidase positivity, cell cycle arrest, cell migration, and tube formation ability are observed in both ANXA1‐knockdown HUVECs and overexpressed ANXA1‐TNF‐α induced senescent HUVECs. They also explore the impact of formyl peptide receptor 2 (a receptor of ANXA1) in an ANXA1 overexpression inflammatory model. These data provide compelling evidence that age‐related inflammation in arteries contributes to senescent endothelial cells that promote vascular aging.

Abstract Organic solar cells (OSCs) have demonstrated over 19% power conversion efficiency (PCE) with the help of material innovation and device optimization. Co‐working with newly designed materials, traditional solvent additives, 1‐chloronaphthalene (CN), and 1,8‐diodooctane (DIO) are still powerful in morphology modulation towards satisfying efficiencies. Here, we chose recently reported high‐performance polymer donors (PM6 & D18‐Fu) and small molecular acceptors (Y6 & L8‐BO) as active layer materials and processed them by different conditions (CN or DIO or none). Based on corresponding 12 groups of device results, and their film morphology characterizations (both ex‐situ and in‐situ ones), the property‐performance relationships are revealed case by case. It is thereby supposed to be taken as a successful attempt to demonstrate the importance and complexity of donor‐acceptor‐additive interaction, since the device performance and physics analyses are also tightly combined with morphology variation. Furthermore, ternary blend construction for PCE improvement provides an approaching 19% level and showcases the potential of understanding‐guided‐optimization (UGO) in the future of OSCs.

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) recently caused a global pandemic, resulting in more than 702 million people being infected and over 6.9 million deaths. Patients with coronavirus disease (COVID‐19) may suffer from diarrhea, sleep disorders, depression, and even cognitive impairment, which is associated with long COVID during recovery. However, there remains no consensus on effective treatment methods. Studies have found that patients with COVID‐19 have alterations in microbiota and their metabolites, particularly in the gut, which may be involved in the regulation of immune responses. Consumption of probiotics may alleviate the discomfort caused by inflammation and oxidative stress. However, the pathophysiological process underlying the alleviation of COVID‐19‐related symptoms and complications by targeting the microbiota remains unclear. In the current study, we summarize the latest research and evidence on the COVID‐19 pandemic, together with symptoms of SARS‐CoV‐2 and vaccine use, with a focus on the relationship between microbiota alterations and COVID‐19‐related symptoms and vaccine use. This work provides evidence that probiotic‐based interventions may improve COVID‐19 symptoms by regulating gut microbiota and systemic immunity. Probiotics may also be used as adjuvants to improve vaccine efficacy.

Abstract High metastatic propensity of osteosarcoma leads to its therapeutic failure and poor prognosis. Although nuclear activation miRNAs (NamiRNAs) are reported to activate gene transcription via targeting enhancer and further promote tumor metastasis, it remains uncertain whether NamiRNAs regulate osteosarcoma metastasis and their exact mechanism. Here, we found that extracellular vesicles of the malignant osteosarcoma cells (143B) remarkably increased the migratory abilities of MNNG cells representing the benign osteosarcoma cells by two folds, which attributed to their high miR‐1246 levels. Specially, miR‐1246 located in nucleus could activate the migration gene expression (such as MMP1) to accelerate MNNG cell migration through elevating the enhancer activities via increasing H3K27ac enrichment. Instead, MMP1 expression was dramatically inhibited after Argonaute 2 (AGO2) knockdown. Notably, in vitro assays demonstrated that AGO2 recognized the hybrids of miR‐1246 and its enhancer DNA via PAZ domains to prevent their degradation from RNase H and these protective roles of AGO2 may favor the gene activation by miR‐1246 in vivo. Collectively, our findings suggest that miR‐1246 could facilitate osteosarcoma metastasis through interacting with enhancer to activate gene expression dependent on AGO2, highlighting the nuclear AGO2 as a guardian for NamiRNA‐targeted gene activation and the potential of miR‐1246 for osteosarcoma metastasis therapy.

Nocardia seriolae is the primary pathogen causing nocardiosis in various fish species, leads to significant economic losses in the aquaculture industry. In this study, 10 bacterial strains isolated from Micropterus salmoides and Channa argus infected with nocardiosis, were identified as N. seriolae by physiological and biochemical identification, as well as 16S rDNA sequencing. Moreover, the key virulence-related genes such as ESX-1, T7SS-2, T7SS-3, EspG1, sodC, sod2 and ESAT6 were all positive, and showing high homology among different strains. Pathogenicity testing revealed mortality rates ranging from 70 to 100%, accompanied by the presence of white nodules in the viscera of deceased fish. The drug sensitivity test demonstrated that LY21811, the most lethal strain, exhibited high sensitivity to nine types of antibiotics, including azithromycin, doxycycline, florfenicol and compound sulfamethoxazole, yet showed complete resistance to β-lactam antibiotics. Additionally, the tannic acid also demonstrated potent inhibitory effects against LY21811, with a minimum inhibitory concentration of 0.0625 mg/mL. These results showed that N. seriolae originated from M. salmoides and C. argus in Zhejiang Province were highly conserved, demonstrating a high homogeneity in genetic characteristics, pathogenicity and antimicrobial susceptibilities. These results provide a foundation for further research on the pathogenic characteristics and disease prevention of N. seriolae infections.

Abstract In this article, the construction principle of rotary engine and sliding vane internal combustion engine is carefully analyzed, and the concept of micro‐rotary cam internal combustion engine is proposed by integrating and innovating on them. Overall design, theoretical analysis, and model making of miniature rotary cam internal combustion engine and its supporting system. The effects of different air intake modes and different ignition advance angles on the combustion and emission characteristics of internal combustion engines were studied. Through the study of the flow field, combustion and emission characteristics of small rotating internal combustion engines, it is found that the intake form has a great influence on the cylinder smoothness of rotating internal combustion engines. The vortex formed by the end cover inlet air in the middle of the combustion chamber can fully mix the fuel and air in the cylinder, and the mixture is evenly distributed in the combustion chamber to effectively promote the spread of flame. Compared with the surrounding air intake structure, the heat release should be increased by 4.3%, and the total amount of HC and CO generated was 26.8% and 15.7% less, respectively. By studying the turbulent kinetic energy, combustion heat release, peak temperature and pressure in the cylinder, fuel consumption rate and emission characteristics of small rotary internal combustion engine, it is found that when the ignition advance angle of the small rotating internal combustion engine is 5°, the peak pressure in the cylinder is increased by 2.3% compared with other schemes, the fuel consumption rate is high, and the combustion is more complete. In addition, in terms of emission characteristics, the amount of CO and HC generated when the ignition advance angle is 5° are reduced by 35% and 35.3%, respectively.

Background: While hepatocellular carcinoma (HCC) represents a highly heterogeneous disease with variable oncogenesis mechanisms and biological features, little is understood about differences in distant metastasis (DM) and prognosis between early-onset and late-onset HCC. This study defined early-onset disease as cancer diagnosed at age younger than 50 years and aimed to present a comprehensive analysis to characterize these disparities based on age. Methods: Information of HCC patients was retrospectively collected from the SEER database and our hospital. Patient demographics, tumor characteristics, and survival were compared between the two groups. A 1:1 propensity score matching (PSM) was adopted to adjust confounding factors. Logistic and cox analysis were utilized to explore risk factors of DM and prognosis, respectively. Besides, the survival differences were assessed by the Kaplan–Meier curve and log-rank test. Results: In total, 19187 HCC patients obtained from the SEER database and 129 HCC patients obtained from our own center were enrolled. Among 19187 patients with HCC, 3376 were identified in the matched cohort, including 1688 early-onset patients and 1688 late-onset patients. Compared with late-onset HCC, early-onset HCC was more likely to occur in female (25.2% vs. 22.9%, P = 0.030), have large tumors (>10.0 cm, 24.1% vs. 14.6%, P = 0.000), harbor poorly differentiated/undifferentiated cancers (17.0% vs. 14.0%, P = 0.003), present advanced clinical stage (T3+T4, 33.7% vs. 28.5%; N1, 9.2% vs. 6.7%; P = 0.000), and develop DM (13.0% vs. 9.5%, P = 0.000). After adjustment for confounders by PSM, we discovered that early-onset HCC remained an independent risk factor for DM. However, combined with Kaplan–Meier curve and cox analysis, early-onset HCC was an independent favorable predictor of survival. We validated these data on an independent cohort from our hospital. Conclusion: In this population-based study, despite developing DM more frequently, early-onset HCC exhibited a superior prognosis than late-onset HCC. Nevertheless, further research is warranted to understand the underlying aetiologic basis for the disparities.

Summary: The question of whether serofast status of syphilis patients indicates an ongoing low-grade Treponema pallidum (T. pallidum) infection remains unanswered. To address this, we developed a machine learning model to identify T. pallidum in cell-free DNA (cfDNA) using next-generation sequencing (NGS). Our findings showed that a TP_rate cut-off of 0.033 demonstrated superior diagnostic performance for syphilis, with a specificity of 92.3% and a sensitivity of 71.4% (AUROC = 0.92). This diagnosis model predicted that 20 out of 92 serofast patients had a persistent low-level infection. Based on these predictions, re-treatment was administered to these patients and its efficacy was evaluated. The results showed a statistically significant decrease in RPR titers in the prediction-positive group compared to the prediction-negative group after re-treatment (p

In this study, the enteric swelling layer of capsules was prepared by optimizing the ratio of pullulan to gellan gum. The enteric-coating solution was prepared by dissolving polyacrylic acid resin III in 85 % ethanol, and the two were combined to form pullulan enteric-coated capsules (PECs). To elaborate further, Pullulan enteric-coated thin films (PEFs) were fabricated using the casting method, and their oxygen permeability (OP) and water vapor permeability (WVP) were assessed. Enteric capsules were prepared employing a secondary impregnation method. The cap gap and surface roughness of the capsules were characterized using Scanning Electron Microscopy (SEM) and Atomic Force Microscopy (AFM). The water content and hygroscopicity of the capsules were examined by employing the drying weight loss method. The pullulan-based enteric capsules (PECs) exhibited attributes such as low water content, hygroscopicity, brittleness, leakage resistance, and high impermeability. Finally, the in vitro release of aspirin from the enteric capsules was investigated. Results demonstrated the excellent combination of the enteric-coating layer and the swelling layer in the PECs. Compared with Gelatin enteric-coated capsules (GECs) on the market, it had a smaller cap gap, lower brittleness, weaker moisture absorption, and a good dissolution effect. Thus, it met the requirements of Chinese pharmacopeia, i.e., the ability to maintain integrity for 2 h in simulated gastric fluid and a drug-release rate reaching 80 % within 30 min in simulated intestinal fluid. This capsule also exhibited certain characteristics of a pulsatile drug-delivery system. This work proposed a potential method of preparing enteric hard capsules by using pullulan combined with polyacrylic acid resin III.

C22H26O6, orthorhombic, P212121 (no. 19), a = 7.6648(5) Å, b = 11.2663(6) Å, c = 22.7321(7) Å, V = 1963.0(2) Å3, Z = 4, Rgt (F) = 0.0652, wRref (F 2) = 0.1399, T = 273(2) K.

ABSTRACT Importance Central line‐associated bloodstream infection (CLABSI) is one of the most serious complications of central venous access devices. Reducing the risk of CLABSI is of utmost significance in efforts to improve neonatal mortality rates and enhance long‐term prognosis. Objective To determine the dwell time and incidence of CLABSI of umbilical venous catheterization (UVC) for preterm infants in China. Methods Preterm infants with UVC admitted to 44 tertiary neonatal intensive care units in 24 provinces in China were enrolled. Study period was from November 2019 to August 2021. The end point of observations was 48 h after umbilical venous (UV) catheter removal. The primary outcomes were dwell time of UV catheter and UVC‐associated CLABSI. Data between infants with UV catheter dwell time ≤7 days and >7 days, and with birth weight (BW) ≤1000 g and >1000 g were compared. Results In total, 2172 neonates were enrolled (gestational age 30.0 ± 2.4 weeks, BW 1258.5 ± 392.8 g). The median UV catheter dwell time was 7 (6–10) days. The incidence of UVC‐associated CLABSI was 3.03/1000 UV catheter days. For infants with UV catheter dwell time ≤7 days and >7 days, the UVC‐associated CLABSI incidence was 3.71 and 2.65 per 1000 UV catheter days, respectively, P = 0.23. For infants with UVC dwell times of 3–6, 7–12, and 13–15 days, the UVC‐associated CLABSI rates were 0.14%, 0.68%, and 2.48% (P 1000 g (P = 0.60). Interpretation The median dwell time of UV catheter was 7 days, and the incidence of UVC‐associated CLABSI was 3.03/1000 catheter days in China. The daily risk of UVC‐associated CLABSI and other complications increased with the dwell time.

Abstract Background The association between air pollution and retinal diseases such as age-related macular degeneration (AMD) has been demonstrated, but the pathogenic correlation is unknown. Damage to the outer blood–retinal barrier (oBRB), which consists of the retinal pigment epithelium (RPE) and choriocapillaris, is crucial in the development of fundus diseases. Objectives To describe the effects of airborne fine particulate matter (PM2.5) on the oBRB and disease susceptibilities. Methods A PM2.5-exposed mice model was established through the administration of eye drops containing PM2.5. Optical coherence tomography angiography, transmission electron microscope, RPE immunofluorescence staining and Western blotting were applied to study the oBRB changes. A co-culture model of ARPE-19 cells with stretching vascular endothelial cells was established to identify the role of choroidal vasodilatation in PM2.5-associated RPE damage. Results Acute exposure to PM2.5 resulted in choroidal vasodilatation, RPE tight junctions impairment, and ultimately an increased risk of retinal edema in mice. These manifestations are very similar to the pachychoroid disease represented by central serous chorioretinopathy (CSC). After continuous PM2.5 exposure, the damage to the RPE was gradually repaired, but AMD-related early retinal degenerative changes appeared under continuous choroidal inflammation. Conclusion This study reveals oBRB pathological changes under different exposure durations, providing a valuable reference for the prevention of PM2.5-related fundus diseases and public health policy formulation. Graphical abstract

In this work, a novel heterojunction composite Ag2S/KTaxNb1-xO3 was designed and synthesized through a combination of hydrothermal and precipitation procedures. The Ta/Nb ratio of the KTaxNb1-xO3 and the Ag2S content were optimized. The best 0.5% Ag2S/KTa0.5Nb0.5O3 (KTN) sample presents an enhanced photocatalytic performance in ammonia synthesis than KTN and Ag2S. Under simulated sunlight, the NH3 generation rate of 0.5% Ag2S/KTN reaches 2.0 times that of pure KTN. Under visible light, the reaction rate ratio of the two catalysts is 6.0. XRD, XPS, and TEM analysis revealed that Ag2S was intimately decorated on the KTN nanocubes surface, which promoted the electron transfer between the two semiconductors. The band structure investigation indicated that the Ag2S/KTN heterojunction established a type-II band alignment with intimate contact, thus realizing the effective transfer and separation of photogenerated carriers. The change in charge separation was considered as the main reason for the enhanced photocatalytic performance. Interestingly, the Ag2S/KTN composite exhibited higher NH3 generation performance under the combined action of ultrasonic vibration and simulated sunlight. The enhanced piezo-photocatalytic performance can be ascribed that the piezoelectric effect of KTN improved the bulk separation of charge carriers in KTN. This study not only provides a potential catalyst for photocatalytic nitrogen fixation but also shows new ideas for the design of highly efficient catalysts via semiconductor modification and external field coupling.

Abstract Background Chinese wheat mosaic virus (CWMV) often causes severe damage to wheat (Triticum aestivum L.) growth and yield. It is well known that a successful infection in plants depends on a complex interaction between the host plant and the pathogen. Post-translational modification (PTM) of proteins is considered to be one of the main processes that decides the outcome of the plant-pathogen arms race during this interaction. Although numerous studies have investigated PTM in various organisms, there has been no large-scale phosphoproteomic analysis of virus-infected wheat plants. We therefore aimed to investigate the CWMV infection-induced phosphoproteomics changes in wheat by high-resolution liquid chromatography-tandem mass spectroscopy (LC–MS/MS) using affinity-enriched peptides followed by comprehensive bioinformatics analysis. Results Through this study, a total of 4095 phosphorylation sites have been identified in 1968 proteins, and 11.6% of the phosphorylated proteins exhibited significant changes (PSPCs) in their phosphorylation levels upon CWMV infection. The result of Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that most of the PSPCs were associated with photosynthesis, plant-pathogen interactions, and MAPK signaling pathways. The protein–protein interaction (PPI) network analysis result showed that these PSPCs were mainly participated in the regulation of biosynthesis and metabolism, protein kinase activities, and transcription factors. Furthermore, the phosphorylation levels of TaChi1 and TaP5CS, two plant immunity-related enzymes, were significantly changed upon CWMV infection, resulting in a significant decrease in CWMV accumulation in the infected plants. Conclusions Our results indicate that phosphorylation modification of protein plays a critical role in wheat resistance to CWMV infection. Upon CWMV infection, wheat plants will regulate the levels of extra- and intra-cellular signals and modifications of enzyme activities via protein phosphorylation. This novel information about the strategies used by wheat to resist CWMV infection will help researchers to breed new CWMV-resistant cultivars and to better understand the arms race between wheat and CWMV.

Abstract Early pressure injury (PI) progression is associated with multi-circulatory disorders and they interplay with each other, resulting in a lack of a satisfactory diagnostic method. We generated early PI and blanchable erythema hairless rat models. Transparent disc method and capillary refilling time test (CRTT) results were recorded with ultraviolet camera to capture the dynamics changes, and the blanching index and refilling index were set for comprehensive analysis. The deteriorated areas of early PI showed non-blanchable erythema (NBE) and an increase in erythema at 0.5 and 6 h with the transparent disc method. CRTT showed a marked refilling delay at 12 h. The comprehensive analysis of blanching index and refilling index showed a significant change in erythema from NBE at 0.5 h and ischemia progressing to hemorrhage at 18 h. There was also a marked difference in the deteriorating and improving areas within the same erythema. Pathological analysis showed inflammatory cell infiltration, with marked edema accompanied by increased hemorrhage and tissue necrosis. Furthermore, small arteries and veins with thrombosis and microthrombi were observed. Consistent ischemia after decompression and subsequent hemorrhage are important indicators, and comprehensive analysis can help increase the positive diagnosis rate over that for other circulatory disorders alone.