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Abstract Langerhans cell histiocytosis (LCH) is the most common histiocytic disorder in children, and liver involvement in LCH is rare. This retrospective study reported the clinical features and prognosis of patients with hepatic LCH. Liver involvement was defined by histopathological findings, liver dysfunction or abnormalities, or ultrasound imaging. A total of 130 patients (14.5%) with hepatic LCH out of 899 in the LCH population were enrolled. Patients with liver involvement had greater frequencies of skin, lung, hearing system, and haematologic system involvement, and hemophagocytic lymphohistiocytosis (P

The vertically integrated emission rate, centroid altitude, peak emission rate, and peak height of the hydroxyl (OH) airglow were calculated from Thermosphere Ionosphere Mesosphere Energetics and Dynamics (TIMED)/Sounding of the Atmosphere using Broadband Emission Radiometry (SABER) observations to study the seasonal and interannual variations in the intensity and location of the OH emission. The emission rate is inversely proportional to the height of the emission, with the semiannual oscillation dominating at low latitudes and the annual oscillation dominating at higher latitudes. The OH emission is modulated by the quasibiennial oscillation at the equator, and the quasibiennial oscillation signal is weak at other latitudes. We represented the vertical transport of atomic oxygen by using atomic oxygen concentrations obtained from a global atmospheric model, the Specified Dynamics Whole Atmosphere Community Climate Model with thermosphere and ionosphere eXtension simulations. Compared with the amplitudes of the migrating diurnal tide (DW1) calculated from temperature data observed by TIMED/SABER, we found that both the vertical transport of atomic oxygen and DW1 amplitudes in the equatorial region exhibit semiannual oscillation and quasibiennial oscillation, which have a strong correlation with the variations in the amplitude and phase of semiannual oscillation and quasibiennial oscillation in OH emission. It is likely that the DW1 affects the vertical transport of atomic oxygen that is involved in the reaction to produce O3, thus affecting the OH emission. We analyzed the relationship between OH emission and solar activity by using the solar radio flux at 10.7 cm as a proxy for solar activity. The results showed that the OH emission is well correlated with solar activity, and the modulation of OH emission by solar activity has a significant latitudinal variation. The small correlation between emission height and solar activity indicates that solar activity modulates OH emission mainly through chemical rather than dynamic processes.

Abstract Uniaxial compression tests and cyclic loading acoustic emission tests were conducted on 20%, 40%, 60%, 80%, dry and saturated muddy sandstone by using a creep impact loading system to investigate the mechanical properties and acoustic emission characteristics of soft rocks with different water contents under dynamic disturbance. The mechanical properties and acoustic emission characteristics of muddy sandstones at different water contents were analysed. Results of experimental studies show that water is a key factor in the mechanical properties of rocks, softening them, increasing their porosity, reducing their brittleness and increasing their plasticity. Under uniaxial compression, the macroscopic damage characteristics of the muddy sandstone change from mono-bevel shear damage and ‘X’ type conjugate bevel shear damage to a roadway bottom-drum type damage as the water content increases. Dynamic perturbation has a strengthening effect on the mechanical properties of samples with 60% and less water content, and a weakening effect on samples with 80% and more water content, but the weakening effect is not obvious. Macroscopic damage characteristics of dry samples remain unchanged, water samples from shear damage and tensile–shear composite damage gradually transformed into cleavage damage, until saturation transformation monoclinic shear damage. The evolution of acoustic emission energy and event number is mainly divided into four stages: loading stage (I), dynamic loading stage (II), yield failure stage (III), and post-peak stage (IV), the acoustic emission characteristics of the stages were different for different water contents. The characteristic value of acoustic emission key point frequency gradually decreases, and the damage degree of the specimen increases, corresponding to low water content—high main frequency—low damage and high water content—low main frequency—high damage.

The 2D limit equilibrium method is widely used for slope stability analysis. However, with the advancement of dump engineering, composite slopes often exhibit significant 3D mechanical effects. Consequently, it is of significant importance to develop an effective 3D stability calculation method for composite slopes to enhance the design and stability control of open-pit slope engineering. Using the composite slope formed by the mining stope and inner dump in Baiyinhua No. 1 and No. 2 open-pit coal mine as a case study, this research investigates the failure mode of composite slopes and establishes spatial shape equations for the sliding mass. By integrating the shear resistance and sliding force of each row of microstrip columns onto the bottom surface of the strip corresponding to the main sliding surface, a novel 2D equivalent physical and mechanical parameters analysis method for the strips on the main sliding surface of 3D sliding masses is proposed. Subsequently, a comprehensive 3D stability calculation method for composite slopes is developed, and the quantitative relationship between the coordinated development distance and its 3D stability coefficients is examined. The analysis reveals that the failure mode of the composite slope is characterized by cutting-bedding sliding, with the arc serving as the side interface and the weak layer as the bottom interface, while the destabilization mechanism primarily involves shear failure. The spatial form equation of the sliding mass comprises an ellipsoid and weak plane equation. The analysis revealed that when the coordinated development distance is 1500 m, the error rate between the 3D stability calculation result and the 2D stability calculation result of the composite slope is less than 8%, thereby verifying the proposed analytical method of equivalent physical and mechanical parameters and the 3D stability calculation method for composite slopes. Furthermore, the 3D stability coefficient of the composite slope exhibits an exponential correlation with the coordinated development distance, with the coefficient gradually decreasing as the coordinated development distance increases. These findings provide a theoretical guideline for designing similar slope shape parameters and conducting stability analysis.

B4C–TiB2 is an advanced electrically conductive ceramic with excellent mechanical and electrical discharge machinable properties. It is challenging and rewarding to achieve highly conductive and hard B4C–TiB2 composites at a minimum content of conductive TiB2 that has inferior hardness but double specific gravity of the B4C matrix. A novel strategy was used to construct conductive networks in B4C‒15 vol% TiB2 composite ceramics with B4C, TiC, and amorphous B as raw materials by a two-step spark plasma sintering method. The influences of particle size matching between B4C and TiC on the conducting of the strategy and the microstructure were discussed based on the selective matrix grain growth mechanism. The mechanical and electrical properties were also systematically investigated. The B4C–15 vol% TiB2 composite ceramic prepared from 10.29 µm B4C and 0.05 µm TiC powders exhibited a perfect three-dimensional interconnected conductive network with a maximum electrical conductivity of 4.25×104 S/m, together with excellent mechanical properties including flexural strength, Vickers hardness, and fracture toughness of 691±58 MPa, 30.30±0.61 GPa, and 5.75±0.32 MPa·m1/2, respectively, while the composite obtained from 3.12 µm B4C and 0.8 µm TiC powders had the best mechanical properties including flexural strength, Vickers hardness, and fracture toughness of 827±35 MPa, 32.01±0.51 GPa, and 6.45±0.22 MPa·m1/2, together with a decent electrical conductivity of 0.65×104 S/m.

Abstract Aims Risk assessment for triple-vessel disease (TVD) remain challenging. Stress hyperglycemia represents the regulation of glucose metabolism in response to stress, and stress hyperglycemia ratio (SHR) is recently found to reflect true acute hyperglycemic status. This study aimed to evaluate the prognostic value of SHR and its role in risk stratification in TVD patients with acute coronary syndrome (ACS). Methods A total of 3812 TVD patients with ACS with available baseline SHR measurement were enrolled from two independent centers. The endpoint was cardiovascular mortality. Cox regression was used to evaluate the association between SHR and cardiovascular mortality. The SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) II (SSII) was used as the reference model in the model improvement analysis. Results During a median follow-up of 5.1 years, 219 (5.8%) TVD patients with ACS suffered cardiovascular mortality. TVD patients with ACS with high SHR had an increased risk of cardiovascular mortality after robust adjustment for confounding (high vs. median SHR: adjusted hazard ratio 1.809, 95% confidence interval 1.160–2.822, P = 0.009), which was fitted as a J-shaped pattern. The prognostic value of the SHR was found exclusively among patients with diabetes instead of those without diabetes. Moreover, addition of SHR improved the reclassification abilities of the SSII model for predicting cardiovascular mortality in TVD patients with ACS. Conclusions The high level of SHR is associated with the long-term risk of cardiovascular mortality in TVD patients with ACS, and is confirmed to have incremental prediction value beyond standard SSII. Assessment of SHR may help to improve the risk stratification strategy in TVD patients who are under acute stress.

Abstract The angiotensin-converting enzyme 2 (ACE2) is a primary cell surface viral binding receptor for SARS-CoV-2, so finding new regulatory molecules to modulate ACE2 expression levels is a promising strategy against COVID-19. In the current study, we utilized islet organoids derived from human embryonic stem cells (hESCs), animal models and COVID-19 patients to discover that fibroblast growth factor 7 (FGF7) enhances ACE2 expression within the islets, facilitating SARS-CoV-2 infection and resulting in impaired insulin secretion. Using hESC-derived islet organoids, we demonstrated that FGF7 interacts with FGF receptor 2 (FGFR2) and FGFR1 to upregulate ACE2 expression predominantly in β cells. This upregulation increases both insulin secretion and susceptibility of β cells to SARS-CoV-2 infection. Inhibiting FGFR counteracts the FGF7-induced ACE2 upregulation, subsequently reducing viral infection and replication in the islets. Furthermore, retrospective clinical data revealed that diabetic patients with severe COVID-19 symptoms exhibited elevated serum FGF7 levels compared to those with mild symptoms. Finally, animal experiments indicated that SARS-CoV-2 infection increased pancreatic FGF7 levels, resulting in a reduction of insulin concentrations in situ. Taken together, our research offers a potential regulatory strategy for ACE2 by controlling FGF7, thereby protecting islets from SARS-CoV-2 infection and preventing the progression of diabetes in the context of COVID-19.

Objective To ensure the smooth implementation of urban rail transit station entry/exit pipe jacking construction project, it is essential to study the impact of ground settlement and explore settlement control measures for its engineering through urban roads. Method With reference to the long-distance bus station entry/exit pipe jacking engineering on Jinan Rail Transit R2 Line , and based on the description of project geological conditions and key difficulties, a 3D numerical calculation model for large profile pipe jacking engineering through urban roads with dense underground pipelines is established. Land subsidence curves at different distances from the excavation face and settlement curves at different depths of the soil layer are obtained. A comparison is made between the simulated vertical displacement values of land monitoring points above the pipe central axis and the field-measured values changing with excavation distances. Corresponding construction optimization measures are proposed, and the optimization effects are analyzed and verified based on field-measured data. Result & Conclusion During the jacking process, as the distance from pipe central axis increases, the land subsidence gradually decreases. With increasing depth, the deep layer displacement of the soil layer gradually increases, and the settlement curve gradually transitions from ′stout and short′ to ′slender and tall′. Factors such as significant fluctuations in soil chamber pressure and frictional disturbance between the pipe and the stratum on-site lead to an outcome of the maximum simulated settlement, which is slightly less than the maximum field-measured settlement, posing certain discrepancy. By adopting measures such as controlling excavation speed and rational grouting for reducing friction, the subsequent construction settlement control effect is evident, with a maximum land subsidence of 18.18 mm, and the deformation is within construction allowable range.

Abstract Engineering atom-scale sites are crucial to the mitigation of polysulfide shuttle, promotion of sulfur redox, and regulation of lithium deposition in lithium–sulfur batteries. Herein, a homonuclear copper dual-atom catalyst with a proximal distance of 3.5 Å is developed for lithium–sulfur batteries, wherein two adjacent copper atoms are linked by a pair of symmetrical chlorine bridge bonds. Benefiting from the proximal copper atoms and their unique coordination, the copper dual-atom catalyst with the increased active interface concentration synchronously guide the evolutions of sulfur and lithium species. Such a delicate design breaks through the activity limitation of mononuclear metal center and represents a catalyst concept for lithium–sulfur battery realm. Therefore, a remarkable areal capacity of 7.8 mA h cm−2 is achieved under the scenario of sulfur content of 60 wt.%, mass loading of 7.7 mg cm−2 and electrolyte dosage of 4.8 μL mg−1.

Abstract Designing two-dimensional halide perovskites for high-performance optoelectronic applications requires deep understanding of the structure-property relationship that governs their excitonic behaviors. However, a design framework that considers both intra and interlayer structures modified by the A-site and spacer cations, respectively, has not been developed. Here, we use pressure to synergistically tune the intra and interlayer structures and uncover the structural modulations that result in improved optoelectronic performance. Under applied pressure, (BA)2(GA)Pb2I7 exhibits a 72-fold boost of photoluminescence and 10-fold increase of photoconductivity. Based on the observed structural change, we introduce a structural descriptor χ that describes both the intra and interlayer characteristics and establish a general quantitative relationship between χ and photoluminescence quantum yield: smaller χ correlates with minimized trapped excitons and more efficient emission from free excitons. Building on this principle, we design a perovskite (CMA)2(FA)Pb2I7 that exhibits a small χ and an impressive photoluminescence quantum yield of 59.3%.

Abstract Plasma proteins are considered the most informative source of biomarkers for disease diagnosis and monitoring. Mass spectrometry (MS)-based proteomics has been applied to identify biomarkers in plasma, but the complexity of the plasma proteome and the extremely large dynamic range of protein abundances in plasma make the clinical application of plasma proteomics highly challenging. We designed and synthesized zeolite-based nanoparticles to deplete high-abundance plasma proteins. The resulting novel plasma proteomic assay can measure approximately 3000 plasma proteins in a 45 min chromatographic gradient. Compared to those in neat and depleted plasma, the plasma proteins identified by our assay exhibited distinct biological profiles, as validated in several public datasets. A pilot investigation of the proteomic profile of a hepatocellular carcinoma (HCC) cohort identified 15 promising protein features, highlighting the diagnostic value of the plasma proteome in distinguishing individuals with and without HCC. Furthermore, this assay can be easily integrated with all current downstream protein profiling methods and potentially extended to other biofluids. In conclusion, we established a robust and efficient plasma proteomic assay with unprecedented identification depth, paving the way for the translation of plasma proteomics into clinical applications. Graphical Abstract

Background: Osteoarthritis (OA) is a degenerative joint disease characterized by the breakdown of joint cartilage and underlying bone. Macrophages are a type of white blood cell that plays a critical role in the immune system and can be found in various tissues, including joints. Research on the relationship between OA and macrophages is essential to understand the mechanisms underlying the development and progression of OA. Objective: This study was performed to analyze the functions of the IRF1-GCN5-SETD2-SMARCC1 axis in osteoarthritis (OA) development. Methods: A single-cell RNA sequencing (scRNA-seq) dataset, was subjected to a comprehensive analysis aiming to identify potential regulators implicated in the progression of osteoarthritis (OA). In order to investigate the role of IRF1 and SMARCC1, knockdown experiments were conducted in both OA-induced rats and interleukin (IL)-1β-stimulated chondrocytes, followed by the assessment of OA-like symptoms, secretion of inflammatory cytokines, and polarization of macrophages. Furthermore, the study delved into the identification of aberrant epigenetic modifications and functional enzymes responsible for the regulation of SMARCC1 by IRF1. To evaluate the clinical significance of the factors under scrutiny, a cohort comprising 13 patients diagnosed with OA and 7 fracture patients without OA was included in the analysis. Results: IRF1 was found to exert regulatory control over the expression of SMARCC1, thus playing a significant role in the development of osteoarthritis (OA). The knockdown of either IRF1 or SMARCC1 disrupted the pro-inflammatory effects induced by IL-1β in chondrocytes, leading to a mitigation of OA-like symptoms, including inflammatory infiltration, cartilage degradation, and tissue injury, in rat models. Additionally, this intervention resulted in a reduction in the predominance of M1 macrophages both in vitro and in vivo. Significant epigenetic modifications, such as abundant H3K27ac and H3K4me3 marks, were observed near the SMARCC1 promoter and 10 kb upstream region. These modifications were attributed to the recruitment of GCN5 and SETD2, which are functional enzymes responsible for these modifications. Remarkably, the overexpression of either GCN5 or SETD2 restored SMARCC1 expression in rat cartilages or chondrocytes, consequently exacerbating the OA-like symptoms. Conclusion: This research postulates that the transcriptional activity of SMARCC1 can be influenced by IRF1 through the recruitment of GCN5 and SETD2, consequently regulating the H3K27ac and H3K4me3 modifications in close proximity to the SMARCC1 promoter and 10 kb upstream region. These modifications, in turn, facilitate the M1 skewing of macrophages and contribute to the progression of osteoarthritis (OA). The Translational Potential of this Article: The study demonstrated that the regulation of SMARCC1 by IRF1 plays a crucial role in the development of OA. Knocking down either IRF1 or SMARCC1 disrupted the pro-inflammatory effects induced by IL-1β in chondrocytes, leading to a mitigation of OA-like symptoms in rat models. These symptoms included inflammatory infiltration, cartilage degradation, and tissue injury. These findings suggest that targeting the IRF1-SMARCC1 regulatory axis, as well as the associated epigenetic modifications, could potentially be a novel approach in the development of OA therapies, offering new opportunities for disease management and improved patient outcomes.

The Qixia Formation in the foothills of Longmen Mountain in the western Sichuan Basin is gaining attention for oil and gas exploration. However, exploration of the Qixia Formation in the middle Longmen Mountain is insufficient. Consequently, it is essential to understand its stratigraphic sedimentary characteristics for guiding natural gas exploration. This study focuses on the Beichuan Tongkou section, combines field measurements, thin-section observation and trace element analyses to investigate the sequence stratigraphy and sedimentary features of the Qixia Formation, thereby defining its sedimentary environment. Within the Beichuan Tongkou section, which spans from the Liangshan Formation to the Qixia Formation, researchers have identified two third-order and one fourth-order sequence boundaries, delineating one third-order sequence and two fourth-order sequences. The sedimentary facies found in this interval include shore-swamp, open platform, and platform edge environments, which are further classified into four subfacies including open sea, intertidal sea, intra-platform beach, and platform edge beach. Additionally, three microfacies are identified including intra-platform bioclastic beach, platform edge bioclastic beach, and platform edge sand debris and bioclastic beach. The Qi1 member and lower part of the Qi2 member is located on an open platform, while the upper-middle part of the Qi2 member is found at the platform edge. This setup defines a sedimentary model for a carbonate-rimmed platform in the Qixia Formation of the middle Longmen Mountain. During the sedimentary period of the Qixia Formation, a warm, humid, and oxygen-rich marine environment supported abundant ancient organisms. In the highstand system tract of the upper-middle part of the Qi2 member, the Sr/Ba ratio is lowest, while the MgO/CaO ratio is highest, indicating elevated ancient water temperatures and specific chemical compositions. The m value, reflective of paleosalinity, is notably high, suggesting a shallow, high-energy platform edge environment away from the mainland. Thick, high-energy platform edge sand debris and bioclastic beaches in this area promote the development of high-quality porous dolomite reservoirs of beach facies. The sedimentary facies and reservoir conditions of the Qi2 member in the middle Longmen Mountain are comparable to those in other sections, making it a promising target for oil and gas exploration within the Qixia Formation and a potential strategic replacement area for reservoir expansion.

In recent years, fractional slot concentrated winding permanent magnet synchronous motors (FSCW PMSMs) have become a hotspot in the research field. Due to the unique inductance characteristics of the FSCW PMSM, a fast and accurate calculation of the d/q-axis inductance and saliency ratio is necessary. In this paper, a method is proposed to calculate the d/q-axis reactance of the FSCW SPMSM, which constructs the equivalent magnetic circuit model of the d/q-axis armature reaction flux separately, and the saliency ratio characteristics of the FSCW SPMSM were demonstrated. In addition, to meet the high requirements of the modern industries, especially in servo systems, accurate consideration of the effect of stator resistance on torque and electromagnetic performance is important and more applicable. According to the relationship between the vector parameter, the explicit expression of the d/q-axis currents that consider the stator resistance is obtained, and the prediction of load angle at maximum electromagnetic torque is achieved. Then, combined with the finite element method, the influence mechanism of stator resistance on the motor steady-state performance is revealed. Finally, the experimental data are compared with the calculation data, and the correctness of the models and analysis was verified.

Abstract Recently, numerous measures have been proposed for quantifying the quantumness of a given system, and the existence of intrinsic connections among quantum resource measures has been proven. Here, we study the unified relationship between duality, first-order coherence, three-setting linear steering inequality, and maximum average fidelity between two masses due to gravity. Under gravitational inducement, an equivalent relationship was identified between the first-order coherence and duality. The coherence of a system can be controlled by adjusting arm lengths and the distance between the arms of an interferometer. In most cases, the first-order coherence of a system cannot be maximised. Furthermore, a trade-off relationship between gravitationally induced duality and steering violations was derived. We can adjust the arm length and distance between the arms of the interferometer such that the steering violation reaches its maximum at phase $$\pi $$ π . The results show that the value of the steering violation is always greater than 1; that is, the state of the system is steerable. In addition, we explored the intrinsic relationship between duality and the maximal average fidelity due to gravity. In most cases, the maximum average fidelity of the system is greater than 2/3, indicating that the state is useful for quantum teleportation. These results are important for investigating the intrinsic relationships among various quantum resources within the framework of gravity.

Abstract Tai Chi serves as an effective exercise modality for enhancing autonomic regulation. However, a majority of existing studies have employed the single routine (SR) protocol as the basis for health interventions. The extent to which the gong routine application (GRA) protocol achieves similar levels of exercise load stimulation as traditional single practice routines remains uncertain. Therefore, this study the distinct characteristics of autonomic load stimulation in these different protocols, thus providing a biological foundation to support the development of Tai Chi health promotion intervention programs. we recruited a cohort of forty-five university students to participate in the 15 min GRA protocol and SR protocol. We collected heart rate and heart rate variability indicators during periods of rest, GRA protocol, and SR protocol utilizing the Polar Scale. Additionally, we assessed the mental state of the participants using the BFS State of Mind Scale. In summary, the autonomic load is lower in the GRA protocol compared to the SR protocol, with lower sympathetic activity but higher parasympathetic activity in the former. Results are specific to college students, additional research is necessary to extend support for frail older adults. It is advised to incorporate GRA protocol alongside SR protocol in Tai Chi instruction. This approach is likely to enhance Tai Chi skills and yield greater health benefits.

Abstract Extensive investigations on the moiré magic angle in twisted bilayer graphene have unlocked the emerging field—twistronics. Recently, its optics analogue, namely opto-twistronics, further expands the potential universal applicability of twistronics. However, since heat diffusion neither possesses the dispersion like photons nor carries the band structure as electrons, the real magic angle in electrons or photons is ill-defined for heat diffusion, making it elusive to understand or design any thermal analogue of magic angle. Here, we introduce and experimentally validate the twisted thermotics in a twisted diffusion system by judiciously tailoring thermal coupling, in which twisting an analog thermal magic angle would result in the function switching from cloaking to concentration. Our work provides insights for the tunable heat diffusion control, and opens up an unexpected branch for twistronics -- twisted thermotics, paving the way towards field manipulation in twisted configurations including but not limited to fluids.

Abstract Background In the past decade, single nucleotide variants (SNVs) have been identified as having a significant relationship with the development and treatment of diseases. Among them, prioritizing missense variants for further functional impact investigation is an essential challenge in the study of common disease and cancer. Although several computational methods have been developed to predict the functional impacts of variants, the predictive ability of these methods is still insufficient in the Mendelian and cancer missense variants. Results We present a novel prediction method called the disease-related variant annotation (DVA) method that predicts the effect of missense variants based on a comprehensive feature set of variants, notably, the allele frequency and protein–protein interaction network feature based on graph embedding. Benchmarked against datasets of single nucleotide missense variants, the DVA method outperforms the state-of-the-art methods by up to 0.473 in the area under receiver operating characteristic curve. The results demonstrate that the proposed method can accurately predict the functional impact of single nucleotide missense variants and substantially outperforms existing methods. Conclusions DVA is an effective framework for identifying the functional impact of disease missense variants based on a comprehensive feature set. Based on different datasets, DVA shows its generalization ability and robustness, and it also provides innovative ideas for the study of the functional mechanism and impact of SNVs.

Background: Intravenous immune checkpoint inhibitors (ICIs) have shown efficacy in treating locally advanced rectal cancer (LARC), but concerns about systemic toxicity persist. This study developed a unique approach termed chemo-immuno-embolization with transcatheter rectal arterial intervention (CIETAI), aiming to enhance the anti-tumor response while minimizing systemic toxicity. Method: This is a prospective, single-arm, phase II clinical trial conducted in Daping hospital. Patients with previously untreated stage II/III LARC underwent preoperative CIETAI combined with PD-1 inhibitor tislelizumab plus oxaliplatin, followed by standard concomitant chemoradiotherapy (capecitabine and 50.4 Gy radiation). Intravenous tislelizumab was administered for an additional two cycles. Results: Between January 2023 and December 2023, a total of 38 patients were enrolled. As the primary endpoint, 17 (44.74 %) patients achieved pathological complete response (TRG0), with a major pathologic response (MPR) rate of 65.79 %. The anal preservation rate was 84.21 % (32/38), and importantly, 15 of 21 patients with low rectal cancer achieved organ preservation with functional maintenance. Eight patients experienced grade 3–4 adverse events (AEs). All immune-related AEs were grade 1–2, with the most common being endocrine toxicity (5/6, 83.33 %). No grade 5 AEs occurred. Conclusion: This study provides preliminary evidence supporting the safety and efficacy of intraarterial tislelizumab delivery in the neoadjuvant setting for LARC. These promising results encourage further exploration in larger cohorts to validate the clinical impact of this novel CIETAI strategy. Trial registration: ClinicalTrials.gov Identifier: NCT05957016.

Sea urchins produced by aquaculture could enhance declining wild populations and provide a sufficient roe product to satisfy increasing market demand. This study reports a method for large-scale rearing of the edible tropical sea urchin Salmacis sphaeroides, from induction of larval metamorphosis and settlement, to juvenile rearing and grow-out. Larvae were reared in 500-L hatchery tanks, on a diet of the microalga Chaetoceros muelleri at concentrations ranging from 2500 to 24,000 cells mL−1, with daily water renewal of one-third to two-thirds of the volume depending on their developmental stage. The larvae breeding protocol proved suitable for this species, and competent larvae occurred at 12 days post-fertilization. To induce metamorphosis, we tested exposure to potassium chloride (KCl) at different concentrations (0, 25, 50, 100, 200, and 400 mmol L−1) and for different durations (5, 10, and 20 min). Exposure to 200 mmol L−1 KCl for 5 min resulted in the highest proportion of metamorphosed individuals (41.67 ± 2.89 %). Using this method, the densities of juveniles attaching to settlement plates (232.50 ± 41.23 ind. per plate; settlement percentage ca. 3.88 ± 0.69 %) were approximately twice as high as those of the controls (105.75 ± 15.52 ind. per plate; settlement percentage ca. 1.76 ± 0.26 %). Next, two batches of juveniles were grown out in sea cages. In the first batch (deployed for ca. 4 months), the absolute growth rate of the test diameter (AGRD) was 12.79 ± 0.98 mm month−1 from May to September; in the second batch (deployed for 6 months), the AGRD was 5.68 ± 0.90 mm month−1 from October to May of the following year. Survival of the juvenile S. sphaeroides in the sea cages was high (86.56 %–100 %). Finally, the S. sphaeroides cultivated in the second batch were harvested (at a mean test diameter of 71.24 ± 1.45 mm, and wet weight of 101.24 ± 1.91 g) on May 28 of the second year; all animals had matured and could be successfully utilized as broodstock. The fatty acid composition of the gonads was then compared between cultivated and wild-collected adult S. sphaeroides. The proportion of polyunsaturated fatty acids in the cultivated sea urchins (16.59 ± 0.67 %) exceeded that in wild-collected individuals (13.13 ± 0.42 %). From these experiments we conclude that S. sphaeroides is a sea urchin species with excellent potential for aquaculture; the present methods and data will provide helpful information for their mass production in South China.

Plastic waste has caused a global environmental crisis. Biocatalytic depolymerization mediated by enzymes has emerged as an efficient and sustainable alternative for plastic treatment and recycling. However, it is challenging and time-consuming to discover novel plastic-degrading enzymes using conventional cultivation-based or omics methods. There is a growing interest in developing effective computational methods to identify new enzymes with desirable plastic degradation functionalities by exploring the ever-increasing databases of protein sequences. In this study, we designed an innovative machine learning-based framework, named PEZy-Miner, to mine for enzymes with high potential in degrading plastics of interest. Two datasets integrating information from experimentally verified enzymes and homologs with unknown plastic-degrading activity were created respectively, covering eleven types of plastic substrates. Protein language models and binary classification models were developed to predict enzymatic degradation of plastics along with confidence and uncertainty estimation. PEZy-Miner exhibited high prediction accuracy and stability when validated on experimentally verified enzymes. Furthermore, by masking the experimentally verified enzymes and blending them into homolog dataset, PEZy-Miner effectively concentrated the experimentally verified entries by 14∼30 times while shortlisting promising plastic-degrading enzyme candidates. We applied PEZy-Miner to 0.1 million putative sequences, out of which 27 new sequences were identified with high confidence. This study provided a new computational tool for mining and recommending promising new plastic-degrading enzymes.

ABSTRACTThe Vertical Takeoff and Landing Aircraft (VTOL) is capable of both low-speed hovering and high-speed flight. This paper proposes an autonomous motion planning and anti-wind disturbance control algorithm for the VTOL, implemented spatial and temporal joint motion planning for VTOL, under the limitation of maximum flight speed of the aircraft, VTOL can achieve fully autonomous flight in complex environments, which can realize the autonomous flight of a single aircraft in a complex and dense environment, achieve real-time perception and avoidance of static and dynamic obstacles. The information generated by motion planning includes the position, velocity, and acceleration information of the aircraft, and proposes a wind disturbance estimation and active control strategy in a wind disturbance environment, accurate estimation of wind disturbance is achieved through a state observer, and the wind disturbance was suppressed through nonlinear error feedback control law, implemented wind disturbance estimation and suppression for aircraft in wind disturbance environments, and achieved complete autonomous motion planning and trajectory tracking of VTOL in a complex and wind disturbance environment. Our work can provide a basis for the collaborative control of multiple UAVs.

Antifibrotic drug screening requires evaluating the inhibitory effects of drug candidates on fibrotic cells while minimizing any adverse effects on normal cells. It is challenging to create organ-specific vascularized organoids that accurately model fibrotic and normal tissues for drug screening. Our previous studies have established methods for culturing primary microvessels and epithelial cells from adult tissues. In this proof-of-concept study, we used rats as a model organism to create a two-dimensional vascularized liver organoid model that comprised primary microvessels, epithelia, and stellate cells from adult livers. To provide appropriate substrates for cell culture, we engineered ECMs with defined stiffness to mimic the different stages of fibrotic tissues and normal tissues. We examined the effects of two TGFβ signaling inhibitors, A83-01 and pirfenidone, on the vascularized liver organoids on the stiff and soft ECMs. We found that A83-01 inhibited fibrotic markers while promoting epithelial genes of hepatocytes and cholangiocytes. However, it inhibited microvascular genes on soft ECM, indicating a detrimental effect on normal tissues. Furthermore, A83-01 significantly promoted the expression of markers of stem cells and cancers, increasing the potential risk of it being a carcinogen. In contrast, pirfenidone, an FDA-approved compound for antifibrotic treatments, did not significantly affect all the genes examined on soft ECM. Although pirfenidone had minor effects on most genes, it did reduce the expression of collagens, the major components of fibrotic tissues. These results explain why pirfenidone can slow fibrosis progression with minor side effects in clinical trials. In conclusion, our study presents a method for creating vascularized liver organoids that can accurately mimic fibrotic and normal tissues for drug screening. Our findings provide valuable insights into the potential risks and benefits of using A83-01 and pirfenidone as antifibrotic drugs. This method can be applied to other organs to create organ-specific vascularized organoids for drug development.

Abstract Establishing an advanced ecosystem incorporating freshwater harvesting, plastic utilization, and clean fuel acquisition is profoundly significant. However, low‐efficiency evaporation, single energy utilization, and catalyst leakage severely hinder sustainable development. Herein, a nanofiber‐based mortise‐and‐tenon structural Janus aerogel (MTSJA) is strategically designed in the first attempt and supports Z‐scheme catalysts. By harnessing of the upper hydrophilic layer with hydrophilic channels embedding into the hydrophobic bottom layer to achieve tailoring bottom wettability states. MTSJA is capable of a fully‐floating function for lower heat loss, water supply, and high‐efficiency solar‐to‐vapor conversion. Benefiting from the ultrasonic cavitation effect and high sensitivity of materials to mechanical forces, this is also the first demonstration of synergistic solar and ultrasound fields to power simultaneous evaporation desalination and waste plastics as reusable substrates generating fuel energy. The system enables persistent desalination with an exceptional evaporation rate of 3.1 kg m−2 h−1 and 82.3% efficiency (21 wt.% NaCl solution and 1 sun), and realizes H2, CO, and CH4 yields with 16.1, 9.5, and 3 µmol h−1 g−1, respectively. This strategy holds great potential for desalination and plastics value‐added transformation toward clean energy and carbon neutrality.

Urban green infrastructure (UGI) is pivotal in reconciling biodiversity conservation with sustainable urban development through adaptive management approaches. This paper introduces a comprehensive conceptual framework integrating ecological principles, urban planning strategies, and adaptive management methodologies to nurture resilient and biodiverse urban landscapes. The essence of UGI lies in its capacity to bolster ecological connectivity, restore ecosystem functions, and provide habitats for diverse flora and fauna within urban settings. Fundamental principles governing UGI design underscore its multifunctionality, connectivity, diversity, and accessibility, emphasizing the importance of adaptive management marked by its iterative and participatory nature. Despite challenges posed by urbanization, such as habitat loss, pollution, and climate change, UGI interventions offer promising avenues for enhancing habitat quality, connectivity, and ecosystem resilience. Global case studies demonstrate the effectiveness of UGI in biodiversity conservation, leveraging initiatives like green roofs, urban forests, and community gardens. UGI significantly contributes to sustainable urban development by offering diverse ecosystem services across various domains. Adaptive management is critical for effective UGI planning and implementation, ensuring flexibility amidst evolving environmental conditions. However, UGI encounters hurdles, including funding constraints, institutional fragmentation, and equity issues. Addressing these challenges necessitates innovative financing mechanisms, community involvement, and policy innovations. UGI presents a transformative pathway towards fostering resilient, biodiverse, and sustainable urban landscapes, imperative for cities to thrive in the 21st century.

The uncertainty principle is deemed as one of cornerstones in quantum mechanics, and exploring its lower limit of uncertainty will be helpful to understand the principle's nature. In this study, we propose a generalized entropic uncertainty relation for arbitrary multiple-observable in multipartite system, and further derive a tighter lower bound by considering Holevo quality and mutual information. Importantly, we detailedly discuss the proposed uncertainty relations and quantum coherence in the context of Schwarzschild space-time. It is interesting to find that Hawking radiation will damage the coherence of the physically accessible region and increase the uncertainty. Furthermore, we argue that the properties of the uncertainty in Schwarzschild space-time can be explained from the systems' purity and the information redistribution of the different regions. Therefore, it is believed that our findings provide the generalized entropic uncertainty relations in multipartite systems, which may facilitate us deeper understanding of quantumness and information paradox of the black holes.

Study region: The Huai River Basin, China. Study focus: This study chooses the daily flow data of Huai River and its tributaries, Shi River and Hong River during 1959–2016. The co-occurrence of floods in different tributaries of the catchment is assessed by analyzing the flood peak and flood timing at three different gauging stations located in the river network. What’s more, the parameters(estimated from the 30-year scale time windows) of the marginal and joint distributions are assumed stationary and nonstationary respectively to explore how the trend of coincidence probability(CP) is effected by them. New hydrological insights for the region: The results show that, over the period analyzed, the most probable time of flood co-occurrence over the gauge stations in the study area tends to move backwards from 10 July to about 20 July. The probability of flood co-occurrence at the Bantai and Jiangjiaji gauging stations, which singularly experience an increase in flood peak, increases from 9.25×10−9(the 1st window) to 1.17×10−5(the 25th window) when the return period of flood is 20 year, while in the same condition, the CP of Bantai and Wangjiaba decreased from 6.16×10−6 to 2.48×10−7.

Ongoing inflammation in the heart is positively correlated with adverse remodeling, characterized by elevated levels of cytokines that stimulate activation of cardiac fibroblasts. It was found that CaMKIIδ response to Ang II or TAC triggers the accumulation of ROS in cardiomyocytes, which subsequently stimulates NF-κB/NLRP3 and leads to an increase in IL-6, IL-1β, and IL-18. This is an important causative factor in the occurrence of adverse remodeling in heart failure. Sweroside is a biologically active natural iridoids extracted from Lonicerae Japonicae Flos. It shows potent anti-inflammatory and antioxidant activity in various cardiovascular diseases. In this study, we found that sweroside inhibited ROS-mediated NF-κB/NLRP3 in Ang II-treated cardiomyocytes by directly binding to CaMKIIδ. Knockdown of CaMKⅡδ abrogated the effect of sweroside regulation on NF-κB/NLRP3 in cardiomyocytes. AAV-CaMKⅡδ induced high expression of CaMKⅡδ in the myocardium of TAC/Ang II-mice, and the inhibitory effect of sweroside on TAC/Ang Ⅱ-induced elevation of NF-κB/NLRP3 was impeded. Sweroside showed significant inhibitory effects on CaMKIIδ/NF-κB/NLRP3 in cardiomyocytes from TAC/Ang Ⅱ-induced mice. This would be able to mitigate the adverse events of myocardial remodeling and contractile dysfunction at 8 weeks after the onset of the inflammatory response. Taken together, our findings have revealed the direct protein targets and molecular mechanisms by which sweroside improves heart failure, thereby supporting the further development of sweroside as a therapeutic agent for heart failure.

Like other tropical and subtropical regions, influenza viruses can circulate year-round in Hong Kong. However, during the COVID-19 pandemic, there was a significant decrease in influenza activity. The objective of this study was to retrospectively forecast influenza activity during the year 2020 and assess the impact of COVID-19 public health social measures (PHSMs) on influenza activity and hospital admissions in Hong Kong. Using weekly surveillance data on influenza virus activity in Hong Kong from 2010 to 2019, we developed a statistical modeling framework to forecast influenza virus activity and associated hospital admissions. We conducted short-term forecasts (1-4 weeks ahead) and medium-term forecasts (1-13 weeks ahead) for the year 2020, assuming no PHSMs were implemented against COVID-19. We estimated the reduction in transmissibility, peak magnitude, attack rates, and influenza-associated hospitalization rate resulting from these PHSMs. For short-term forecasts, mean ambient ozone concentration and school holidays were found to contribute to better prediction performance, while absolute humidity and ozone concentration improved the accuracy of medium-term forecasts. We observed a maximum reduction of 44.6% (95% CI: 38.6% - 51.9%) in transmissibility, 75.5% (95% CI: 73.0% - 77.6%) in attack rate, 41.5% (95% CI: 13.9% - 55.7%) in peak magnitude, and 63.1% (95% CI: 59.3% - 66.3%) in cumulative influenza-associated hospitalizations during the winter-spring period of the 2019/2020 season in Hong Kong. The implementation of PHSMs to control COVID-19 had a substantial impact on influenza transmission and associated burden in Hong Kong. Incorporating information on factors influencing influenza transmission improved the accuracy of our predictions.

Abstract Grayscale digital light processing (DLP) printing is a simple yet effective way to realize the variation of material properties by tuning the grayscale value. However, there is a lack of available design methods for grayscale DLP 3D‐printed structures due to the complexities arising from the voxel‐level grayscale distribution, nonlinear material properties, and intricate structures. Inspired by the dexterous motions of natural organisms, a design and fabrication framework for grayscale DLP‐printed soft robots is developed by combining a grayscale‐dependent hyperelastic constitutive model and a voxel‐based finite‐element model. The constitutive model establishes the relationship between the projected grayscale value and the nonlinear mechanical properties, while the voxel‐based finite‐element model enables fast and efficient calculation of the mechanical performances with arbitrarily distributed material properties. A multiphysics modeling and experimental method is developed to validate the homogenization assumption of the degree of conversion (DoC) variation in a single voxel. The design framework is used to design structures with reduced stress concentration and programmable multimodal motions. This work paves the way for integrated design and fabrication of functional structures using grayscale DLP 3D printing.

Abstract Low‐temperature zinc batteries (LT‐ZIBs) based on aqueous electrolytes show great promise for practical applications owing to their natural resource abundance and low cost. However, they suffer from sluggish kinetics with elevated energy barriers due to the dissociation of bulky Zn(H2O)62+ solvation structure and free Zn2+ diffusion, resulting in unsatisfactory lifespan and performance. Herein, dissimilar to solvation shell tuning or layer spacing enlargement engineering, delocalized electrons in cathode through constructing intrinsic defect engineering is proposed to achieve a rapid electrocatalytic desolvation to obtain free Zn2+ for insertion/extraction. As revealed by density functional theory calculations and interfacial spectroscopic characterizations, the intrinsic delocalized electron distribution propels the Zn(H2O)62+ dissociation, forming a reversible interphase and facilitating Zn2+ diffusion across the electrolyte/cathode interface. The as‐fabricated oxygen defect‐rich V2O5 on hierarchical porous carbon (ODVO@HPC) electrode exhibits high capacity robustness from 25 to −20°C. Operating at −20°C, the ODVO@HPC delivers 191 mAh g−1 at 50 A g−1 and lasts for 50 000 cycles at 10 A g−1, significantly enhancing the power density and lifespan under low‐temperature environments in comparison to previous reports. Even with areal mass loading of ~13 mg cm−2, both coin cells and pouch batteries maintain excellent stability and areal capacities, realizing practical high‐performance LT‐ZIBs.

Understanding the complex influencing factors of soil erosion is critical for maintaining regional ecological security. The revised wind erosion equation (RWEQ) and partial least squares regression (PLSR) model were used to reveal the primary factors affecting soil erosion. Based on the results of the RWEQ model, the wind erosion area was 8,439.3 km2 in 2018, accounting for 54.3% of the total planning area, and mild erosion, moderate erosion, intense erosion, very intense erosion, and fierce erosion accounted for 18.22%, 11.43%, 11.78%, 10.16%, and 2.74% of the total planning area, respectively. Based on the results of the PLSR model, the results indicate that the proportion of mining land, meteorological indicators, and mean square deviation of slope difference were positively correlated with the soil erosion area, intensity, and severity, respectively. The proportion of grassland and forest land was negatively correlated with the soil erosion area, intensity, and severity. The mean square deviation of slope difference, the mean square deviation of difference in elevation, and the proportion of urban land use contributed the most to the soil erosion severity index, with variable importance in projection (VIP) scores of 1.55, 1.44 and 1.43, respectively. The mean square deviation of slope difference, the proportion of urban land, and the mean square deviation of difference in elevation contributed the most to the soil erosion area, with VIP scores of 1.53, 1.26 and 1.24, respectively. The results provide new insights into wind erosion and the influences of weather conditions and human influences, which can guide regional soil and water conservation planning in wind erosion regions.

Nerve injuries significantly impact the quality of life for patients, with severe cases posing life-threatening risks. A comprehensive understanding of the pathophysiological mechanisms underlying nerve injury is crucial to the development of effective strategies to promote nerve regeneration. Circular RNAs (circRNAs), a recently characterized class of RNAs distinguished by their covalently closed-loop structures, have been shown to play an important role in various biological processes. Numerous studies have highlighted the pivotal role of circRNAs in nerve regeneration, identifying them as potential therapeutic targets. This review aims to succinctly outline the latest advances in the role of circRNAs related to nerve injury repair and the underlying mechanisms, including peripheral nerve injury, traumatic brain injury, spinal cord injury, and neuropathic pain. Finally, we discuss the potential applications of circRNAs in drug development and consider the potential directions for future research in this field to provide insights into circRNAs in nerve injury repair.

Abstract Elasticity, featured by a recoverable strain, refers to the ability that materials can return to their original shapes after deformation. Typically, the elastic strains of most metals are well‐known 0.2%. In shape memory alloys and high entropy alloys, the elastic strains can be several percent, as called superelasticity, which are all triggered by external stresses. A superelasticity induced by magnetic field, termed as magneto‐superelasticity, is extremely important for contactless work of materials and for developing brand‐new large stroke actuators and high efficiency energy transducers. In magnetic shape memory alloys, the twin boundary motion driven by magnetic field can output a strain of several percent. However, this strain is unrecoverable when removing the magnetic field and hence it is not magneto‐superelasticity. Here, a giant magneto‐superelasticity of 5% in a Ni34Co8Cu8Mn36Ga14 single crystal is reported by introducing arrays of ordered dislocations to form preferentially oriented martensitic variants during the magnetically induced reverse martensitic transformation. This work provides an opportunity to achieve high performance in functional materials by defect engineering.

The study aimed to test the hypothesis that biochar's unique properties, such as its microporous structure, can enhance concrete's resilience to high temperatures. Despite expectations of reduced crack formation and enhanced fire resistance, the experimental results revealed a limited impact on concrete's fire behaviour. The investigation involved the use of two biochar types, fine and coarse biochar as replacements for cement and aggregates, respectively. Fine biochar exhibited higher water absorption and Young's modulus than coarse biochar, but both resisted ignition at 35 kW/m2 radiative heat flux and had peak heat release rates below 40 kW/m2. Incorporating these biochars at varying weight percentages (10, 15, and 20 wt.%) into concrete led to a gradual decline in compressive and tensile strength due to reduced binding ability with increased biochar content. Exposure to 1000 °C compromised mechanical properties across all the samples. However, the biochar concrete maintained compressive strength (compared to the control) with up to 20 wt.% biochar as a fine aggregate substitute after exposure to 600 °C, and as a cement replacement after exposure to 200 °C. This substitution also yielded a significant reduction in CO2 emissions (50 % reduction as the biochar loading amount doubled) from concrete manufacturing, showcasing biochar's potential for sustainable construction practices. Despite not fully supporting the initial hypothesis, the study demonstrated biochar's viability in reducing carbon footprint while maintaining concrete strength under certain fire conditions.

Background: The purpose of this study was to examine the relationship between sleep duration and risk of sarcopenia in in general U.S. population. Methods: Utilizing publicly available data from the National Health and Nutrition Examination Survey spanning from 2011 to 2014, we explored the association between sleep duration and prevalence of sarcopenia. To investigate their relationship, we conducted weighted multivariate logistic regression analysis, restricted cubic splines (RCS) curve, and subgroup analysis. Results: The study included 8,200 individuals, among whom 99 (0.9 %) had sarcopenia. The RCS curve revealed a U-shaped association of sarcopenia with sleep duration (P for nonlinearity = 0.020), showing that the risk of sarcopenia decreases with increasing sleep duration, reaching the lowest risk around 6.67 h. After controlling for underlying cofounders, compared to individuals with sleep duration 9 h group. The U-shaped association between sleep time and prevalence of sarcopenia also was observed in the subjects who aged

In response to the rail head line defect in the production process of hundred-meter rails, through inspection and analysis of rail tracks with line defects, theoretical calculations of rolling deformation, and on-site industrial trials, it is clarified that the rail head line defect is caused by defects such as cracks in the ingot corners, slab furnace marks, and scratches during rolling. Correspondingly, effective measures to reduce the occurrence of rail head line defects are proposed for each of the three defect causes.

IntroductionPrevious studies have demonstrated that frailty is associated with depressive symptoms among older people and significantly increase the risk of difficulty in activities of daily living (ADL). However, uncertainties remain regarding the mechanisms behind such relationship. The aim of this study was to investigate the mediating effect of ADL in the relationship between frailty and depressive symptoms among older adults in China, and to explore to what extend sleep duration moderated the association between ADL and depressive symptoms.MethodsIn this study, we carried out cross-sectional descriptive analysis and 1,429 participants were included in the analysis. A survey was conducted using questionnaires and instruments measuring frailty, depressive symptoms, ADL and sleep duration. Bootstrap analyses served to explore the impact of ADL in mediating frailty and depressed symptoms, as well as the effect of sleep duration in moderating ADL and depressive symptoms.ResultsCompared to the robust group, the mediating effects of ADL between frailty and depressive symptoms were significant in the prefrail group and the frail group. The interaction term between sleep duration and ADL was significantly presented in the regression on depressive symptoms. Specifically, the Johnson–Neyman technique determined a range from 8.31 to 10.19 h for sleep duration, within which the detrimental effect of frailty on depressive symptoms was offset.ConclusionSleep duration moderated the indirect effect of ADL on the association between frailty and depressive symptoms. This provides support for unraveling the underlying mechanism of the association between frailty and depressive symptoms. Encouraging older adults to enhance ADL and obtain appropriate sleep duration might improve depressive symptoms for older adults with frailty and prefrailty.

Plant-derived extracellular vesicles (PDEV) constitute nanoscale entities comprising lipids, proteins, nucleic acids and various components enveloped by the lipid bilayers of plant cells. These vesicles play a crucial role in facilitating substance and information transfer not only between plant cells but also across different species. Owing to its safety, stability, and the abundance of raw materials, this substance has found extensive utilization in recent years within research endeavors aimed at treating various diseases. This article provides an overview of the pathways and biological characteristics of PDEV, along with the prevalent methods employed for its isolation, purification, and storage. Furthermore, we comprehensively outline the therapeutic implications of diverse sources of PDEV in musculoskeletal system disorders. Additionally, we explore the utilization of PDEV as platforms for engineering drug carriers, aiming to delve deeper into the significance and potential contributions of PDEV in the realm of the musculoskeletal system.

The global prevalence of nonalcoholic fatty liver disease (NAFLD) has reached 30 %, with an annual increase. The incidence of NAFLD-induced cirrhosis is rapidly rising and has become the leading indicator for liver transplantation in the US. However, there are currently no US Food and Drug Administration-approved drugs for NAFLD. Increasing evidence underscores the close association between NAFLD and bile acid metabolism disorder, highlighting the feasibility of targeting the bile acid signaling pathway for NAFLD treatment. The farnesoid X receptor (FXR) is an endogenous receptor for bile acids that exhibits favorable effects in ameliorating the metabolic imbalance of bile acids, lipid disorders, and disruption of intestinal homeostasis, all of which are key characteristics of NAFLD, making FXR a promising therapeutic target for NAFLD. The present review provides a comprehensive overview of the diverse mechanisms through which FXR improves NAFLD, with particular emphasis on its involvement in regulating bile acid homeostasis and the recent advancements in drug development targeting FXR for NAFLD treatment.

The degeneration of intervertebral discs is strongly associated with the occurrence of pyroptosis in nucleus pulposus (NP) cells. This pyroptosis is characterized by abnormal metabolism of fatty acids in the degenerative pathological state, which is further exacerbated by the inflammatory microenvironment and degradation of the extracellular matrix. In order to address this issue, we have developed a fibrin hydrogel complex (FG@PEV). This intricate formulation amalgamates the beneficial attributes of platelet extravasation vesicles, contributing to tissue repair and regeneration. Furthermore, this complex showcases exceptional stability, gradual-release capabilities, and a high degree of biocompatibility. In order to substantiate the biological significance of FG@PEV in intervertebral disc degeneration (IVDD), we conducted a comprehensive investigation into its potential mechanism of action through the integration of RNA-seq sequencing and metabolomics analysis. Furthermore, these findings were subsequently validated through experimentation in both in vivo and in vitro models. The experimental results revealed that the FG@PEV intervention possesses the capability to reshape the inflammatory microenvironment within the disc. It also addresses the irregularities in fatty acid metabolism of nucleus pulposus cells, consequently hindering cellular pyroptosis and slowing down disc degeneration through the regulation of extracellular matrix synthesis and degradation. As a result, this injectable gel system represents a promising and innovative therapeutic approach for mitigating disc degeneration.

Objective: To report a patient of pseudoaneurysm of carotid artery caused by brucellosis infection and improve the recognition, diagnosis and treatment of this disease. Methods: The etiology, clinical data and treatment of false aneurysm were reviewed A 75-year-old man with a high probability of pseudoaneurysm of the left common carotid artery was found by enhanced CT. Open surgery was performed. Bacterial culture return was Brucella. After regular oral drug treatment, the patient recovered well. Results: The patient recovered well after surgery and took oral medication regularly for 3 months without recurrence. Conclusion: Pseudoaneurysms of the carotid artery caused by brucella infection are very rare, and correct diagnosis and open surgery combined with drug therapy are the best choices.

To study the variation rule of workpiece temperature concerning machining parameters in the cylindrical transverse grinding process of gear steel, 18CrNiMo7-6 gear steel was selected as the workpiece material, and a CBN grinding wheel was used as the grinding tool. An infrared thermal imaging instrument was used to detect the temperature during the grinding process. A calibration scheme of thermal emissivity value, incorporating an additional air curtain device, was proposed. The high-speed airflow generated by the air curtain was used to slow down the entry of external air into the heating furnace, preventing the oxidation of samples during calibration, thus ensuring the accuracy of the emissivity value calibrated under high-temperature conditions. Based on the test results, the influence of workpiece speed \begin{document}${v_{\text{w}}}$\end{document}, workpiece grinding depth per revolution \begin{document}${f_{\text{a}}}$\end{document}, grinding wheel grain size \begin{document}${d_{\text{g}}}$\end{document}, grinding wheel diameter \begin{document}${d_{\text{s}}}$\end{document} and grinding width \begin{document}$b$\end{document} on the temperature was analyzed. The workpiece grinding depth per revolution \begin{document}${f_{\text{a}}}$\end{document} was identified as the most significant factor affecting the temperature change. The empirical formula between grinding temperature and aforementioned test parameters was obtained by fitting, with an error of 9.27%. The test measurement results of grinding temperature were compared with those derived from the theory of a moving heat source, Rayleigh distribution model and dry grinding heat distribution ratio model, resulting in a deviation of 8.51%.

Abstract Objective Unilateral biportal endoscopy (UBE)is a minimally invasive spine surgery with reduced traumatization of the posterior lumbar ligament and muscular structures. This study reports contralateral translaminar approach with UBE for highly down-migrated lumbar disc herniation (LDH). Methods Data of 32 patients with highly down-migrated LDH treated using UBE at our center from January 2020 to July 2022 were retrospectively analyzed. The operation time and perioperative complications were recorded, and the visual analog scale (VAS) of pain was recorded to evaluate the degree of lower back and extremity pain. The Oswestry disability index (ODI) was used to evaluate lumbar spine function. The modified MacNab score was used to evaluate clinical efficacy. Results All patients successfully underwent the operation, with a time range from 47 to 65 min and an average operation time of 56.09 ± 5.11 min. Overall, 17 and 15 were males and females, respectively, with ages ranging from 34 to 72 years and an average age of 56 ± 7.89 years. The postoperative follow-up period was 12–18 months, with an average of 14.9 ± 2.3 months. The postoperative lower back VAS pain score and ODI were statistically significant compared with preoperatively (P

Abstract Background The mediator complex subunits (MED) constitutes a multiprotein complex, with each subunit intricately involved in crucial aspects of plant growth, development, and responses to stress. Nevertheless, scant reports pertain to the VunMED gene within the context of asparagus bean (Vigna unguiculata ssp. sesquipedialis). Establishing the identification and exploring the responsiveness of VunMED to cold stress forms a robust foundation for the cultivation of cold-tolerant asparagus bean cultivars. Results Within this study, a comprehensive genome-wide identification of VunMED genes was executed in the asparagus bean cultivar 'Ningjiang3', resulting in the discovery of 36 distinct VunMED genes. A phylogenetic analysis encompassing 232 MED genes from diverse species, including Arabidopsis, tomatoes, soybeans, mung beans, cowpeas, and asparagus beans, underscored the highly conserved nature of MED gene sequences. Throughout evolutionary processes, each VunMED gene underwent purification and neutral selection, with the exception of VunMED19a. Notably, VunMED9/10b/12/13/17/23 exhibited structural variations discernible across four cowpea species. Divergent patterns of temporal and spatial expression were evident among VunMED genes, with a prominent role attributed to most genes during early fruit development. Additionally, an analysis of promoter cis-acting elements was performed, followed by qRT-PCR assessments on roots, stems, and leaves to gauge relative expression after exposure to cold stress and subsequent recovery. Both treatments induced transcriptional alterations in VunMED genes, with particularly pronounced effects observed in root-based genes following cold stress. Elucidating the interrelationships between subunits involved a preliminary understanding facilitated by correlation and principal component analyses. Conclusions This study elucidates the pivotal contribution of VunMED genes to the growth, development, and response to cold stress in asparagus beans. Furthermore, it offers a valuable point of reference regarding the individual roles of MED subunits.

Abstract Disulfidptosis a new cell death mode, which can cause the death of Hepatocellular Carcinoma (HCC) cells. However, the significance of disulfidptosis-related Long non-coding RNAs (DRLs) in the prognosis and immunotherapy of HCC remains unclear. Based on The Cancer Genome Atlas (TCGA) database, we used Least Absolute Shrinkage and Selection Operator (LASSO) and Cox regression model to construct DRL Prognostic Signature (DRLPS)-based risk scores and performed Gene Expression Omnibus outside validation. Survival analysis was performed and a nomogram was constructed. Moreover, we performed functional enrichment annotation, immune infiltration and drug sensitivity analyses. Five DRLs (AL590705.3, AC072054.1, AC069307.1, AC107959.3 and ZNF232-AS1) were identified to construct prognostic signature. DRLPS-based risk scores exhibited better predictive efficacy of survival than conventional clinical features. The nomogram showed high congruence between the predicted survival and observed survival. Gene set were mainly enriched in cell proliferation, differentiation and growth function related pathways. Immune cell infiltration in the low-risk group was significantly higher than that in the high-risk group. Additionally, the high-risk group exhibited higher sensitivity to Afatinib, Fulvestrant, Gefitinib, Osimertinib, Sapitinib, and Taselisib. In conclusion, our study highlighted the potential utility of the constructed DRLPS in the prognosis prediction of HCC patients, which demonstrated promising clinical application value.

Abstract Background Isoorientin (ISO) is a glycosylated flavonoid with antitumor, anti-inflammatory, and antioxidant properties. However, its effects on bone metabolism remain largely unknown. Methods In this study, we aimed to investigate the effects of ISO on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation in vitro and bone loss in post-ovariectomy (OVX) rats, as well as to elucidate the underlying mechanism. First, network pharmacology analysis indicated that MAPK1 and AKT1 may be potential therapeutic targets of ISO and that ISO has potential regulatory effects on the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathways, as well as oxidative stress. ISO was added to RAW264.7 cells stimulated by RANKL, and its effects on osteoclast differentiation were evaluated using tartrate‐resistant acid phosphatase (TRAP) staining, TRAP activity measurement, and F-actin ring analysis. Reactive oxygen species (ROS) production in osteoclasts was detected using a ROS assay kit. The effects of ISO on RANKL-triggered molecular cascade response were further investigated by Western blotting, quantitative real-time polymerase chain reaction, and immunofluorescence staining. In addition, the therapeutic effects of ISO were evaluated in vivo. Results ISO inhibited osteoclastogenesis in a time- and concentration-dependent manner. Mechanistically, ISO downregulated the expression of the main transcription factor for osteoclast differentiation by inhibiting MAPK and PI3K/AKT1 signaling pathways. Moreover, ISO exhibited protective effects in OVX-induced bone loss rats. This was consistent with the results derived from network pharmacology. Conclusion Our findings suggest a potential therapeutic utility of ISO in the management of osteoclast-associated bone diseases, including osteoporosis.

Doubled haploid (DH) technology is an important tool in crop breeding because it can significantly accelerate the breeding process. ZmPLA1/MATL/NLD and ZmDMP are two key genes controlling haploid induction (HI) in maize, exhibiting a synergistic effect. However, it is unknown whether knock out of ZmDMP orthologs can stimulate HI in rice. In this study, a ZmPLA1 ortholog (OsPLA1) and two ZmDMP orthologs (OsDMP3 and OsDMP6) were identified in rice. All three genes encode plasma membrane-localized proteins and were highly expressed in mature anthers. Knockout of OsPLA1 in both Minghui 63 and Nipponbare resulted in reduced seed setting rate (SSR) and caused HI. The osdmp3, osdmp6 and the double mutant failed to trigger HI independently, nor increased the haploid induction rate (HIR) when combined with ospla1. Repeated pollinations operations of QX654A with the ospla1 mutant significantly improve SSR, while reducing HIR. RNA-seq profiling of mature ospla1 mutant anthers indicated that a large number of differentially expressed genes (DEGs) were enriched in redox homeostasis and lipid metabolic GO terms, plant hormone signal transduction, and MAPK signaling pathways. These findings provide important insights towards construction of an efficient DH breeding technology and study of the molecular mechanism of HI in rice.