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In order to study the rules of stress superposition effect and analyze the influence on the punching coal amount by borehole spacing, according to the general situation of Jiulishan Coal Mine and the actual situation of through-bed drilling construction, a solid mechanics model was established by using simulation software COMSOL. We mainly studied the stress superposition effect under different borehole spacings when multiple boreholes are arranged, and analyzed the actual situation of punching coal amount in II1 coal seam of Jiulishan Coal Mine. The results show that when the pre-peak area of stress concentration is superimposed, the stress value near the superimposed area increases with the decrease of hole spacing; when the post-peak area of stress concentration and the pressure relief area are superimposed, the stress values near the superimposed area decrease, but the stress values on both sides still increase; the number of boreholes can lead to a greater degree of superposition effect by affecting the number of coal disturbance, and the stress of the layout of three holes is circular distribution, and the degree of superposition effect will be weakened by increasing the force area; when drilling in the area of stress superposition, the punching coal amount of drilling is often large and instability may occur.

This study investigates the impact of warm-rolling and subsequent annealing on the microstructure and tensile properties of a dual-phase Al0.45CoCrFeNiTi0.25 high-entropy alloy (HEA) containing both face-centered cubic and body-centered cubic phases. The HEA underwent warm-rolling at temperatures of 450, 600, and 750 °C with a 50% reduction in thickness, followed by annealing at various temperatures. Higher warm-rolling temperatures facilitated the precipitation of B2 particles, significantly influencing the alloy's phase distribution. Throughout the experiments, no new phases emerged, and annealing maintained the alloy's original phase composition.Warm-rolling at 450 °C, followed by annealing at 1200 °C, led to substantial microstructural changes, including the formation of distinctive annealed twins. These microstructural changes enhanced ductility significantly, increasing elongation to 13.4% (a 538% improvement over the as-cast state) while maintaining a fracture strength of 983 MPa. Overall, this comprehensive analysis demonstrates that optimizing the warm-rolling and annealing parameters can significantly enhance the properties of dual-phase HEA.

This study investigated the microstructure and mechanical properties of GdxCoCrFeNiV0.4 alloys. Various techniques such as XRD, SEM, EBSD, and TEM were utilized, alongside hardness and compression tests at room temperature. The findings revealed that the high-entropy alloy without Gd element exhibited a single face-centered cubic (FCC) phase. Upon the introduction of Gd element, the phase composition shifted to FCC + hexagonal structure (HS) phases, and further addition of Gd resulted in the presence of FCC + HS + body-centered cubic (BCC) phases. Additionally, the inclusion of Gd element led to the precipitation of Gd-rich particles within the alloy. The Vickers hardness test results revealed a significant increase in alloy hardness as the Gd content rose, from 177.5 HV for Gd0 to 848.4 HV for Gd0.4. This suggests that the presence of the HS phase and BCC phase notably influences alloy hardness. Furthermore, compressive test outcomes demonstrated that the alloy's yield strength rose from 173.74 MPa for Gd0 to 1356.17 MPa for Gd0.3 with increasing Gd content. However, the excessive addition of Gd elements results in significant precipitation of V and Cr elements, leading to grain coarsening, adversely affecting its mechanical properties. The high strength of Gd-containing high-entropy alloys can be attributed to various strengthening mechanisms, such as solid solution strengthening, the presence of the HS phase, the precipitation of a small number of Gd-rich particles, and the grain refinement caused by the addition of Gd.

Abstract Background Stroke is a leading cause of death worldwide, with oxidative stress and calcium overload playing significant roles in the pathophysiology of the disease. Ozone, renowned for its potent antioxidant properties, is commonly employed as an adjuvant therapy in clinical settings. Nevertheless, it remains unclear whether ozone therapy on parthanatos in cerebral ischemia–reperfusion injury (CIRI). This study aims to investigate the impact of ozone therapy on reducing parthanatos during CIRI and to elucidate the underlying mechanism. Methods Hydrogen peroxide (H2O2) was utilized to mimic the generation of reactive oxygen species (ROS) in SH-SY5Y cell reperfusion injury in vitro, and an in vivo ischemic stroke model was established. Ozone saline was introduced for co-culture or intravenously administered to mice. Apoptosis and oxidative stress were assessed using flow cytometry and immunofluorescence. Western blotting was utilized to examine the expression of parthanatos signature proteins. The mechanism by which ozone inhibits parthanatos was elucidated through inhibiting PPARg or Nrf2 activity. Results The findings demonstrated that ozone mitigated H2O2-induced parthanatos by either upregulating nuclear factor erythroid 2-related factor 2 (Nrf2) or activating peroxisome proliferator-activated receptorg (PPARg). Furthermore, through the use of calcium chelators and ROS inhibitors, it was discovered that ROS directly induced parthanatos and facilitated intracellular calcium elevation. Notably, a malignant feedback loop between ROS and calcium was identified, further amplifying the induction of parthanatos. Ozone therapy exhibited its efficacy by increasing PPARg activity or enhancing the Nrf2 translation, thereby inhibiting ROS production induced by H2O2. Concurrently, our study demonstrated that ozone treatment markedly inhibited parthanatos in stroke-afflicted mice. Additionally, ozone therapy demonstrated significant neuroprotective effects on cortical neurons, effectively suppressing parthanatos. Conclusions These findings contribute valuable insights into the potential of ozone therapy as a therapeutic strategy for reducing parthanatos during CIRI, highlighting its impact on key molecular pathways associated with oxidative stress and calcium regulation.

Abstract Colorectal adenocarcinoma (COAD) is the most common subtype of colorectal cancer. Due to the imperfect prognosis of COAD, related prognostic factors and possible mechanisms need to be further investigated. During tumor development, mitochondria help tumor cells survive in a variety of ways, so that further screening of mitochondrial metabolism related targets has positive implications for COAD. We screened the mitochondrial metabolism-related genes (MMRG) associated with the COAD prognosis and explored the MMRG-related molecular subtype characteristics of by unsupervised consensus clustering analysis. Using ESTIMATE and ssGSEA algorithms, we evaluated the immunoinfiltration characteristic landscape of different molecular subtypes defined by MMRG. Combining the expression profiles of differentially expressed genes associated with the MMRG subgroup and the survival characteristics of COAD, we constructed an MMRG prognostic model using LASSO-univariate Cox analysis and successfully validated its impact on independently predicting risk stratification of COAD. The potential clinical value of the MMRG score was subsequently evaluated by subgroup immunoinfiltration characteristics and drug susceptibility prediction analysis. We also offer SEC11A as a new potential target for COAD by single-cell sequencing analysis. The effect of SEC11A on the proliferation, invasion abilities and mitochondrial dysfunction of COAD cells was confirmed through in vitro experiments. Our study provides new insights into the role of MMRG and new target for COAD potential intervention.

Abstract Background Hepatic epithelioid hemangioendothelioma (EHE) is an extremely rare tumour. The aim of this study was to investigate the long-term prognosis and its relationship with treatment modalities. Methods From March 2014 to June 2024, a total of 234 patients with histologically confirmed hepatic EHE were treated or followed up regularly by our team. The patients’ clinical data at the time of diagnosis and initial treatment modalities were retrospectively collected. Kaplan–Meier curves were constructed to determine overall survival (OS). To explore prognostic factors and treatment outcomes, univariable and multivariable Cox proportional hazard models were developed. Results A total of 228 patients were ultimately included. The median age of the cohort was 41 years. For all patients, the OS of 1-, 3- and 5-year were 96.2%, 87.9% and 84.9%, respectively. For patients who underwent liver transplantation (LT), the OS of 1- and 3-year were 62.5% and 25%, respectively. No difference was found in the OS between patients who received surgical therapy and those who did not (1-year: 100% vs. 96.9%; 3-year: 90.1% vs. 91.5%; 5-year: 87.2% vs. 88.2%; P = 0.891). In the multivariable analysis, age ≥ 60 years [HR (95% CI): 4.207 (1.266–13.973), P = 0.019], the size of the largest lesion > 10 cm [HR (95% CI): 12.140 (1.419–103.872), P = 0.023] and LT [HR (95% CI): 5.502 (1.343–22.536), P = 0.018] were poor prognostic factors. Conclusions Compared with nonsurgical therapy, surgical therapy has no advantage in terms of long-term survival. The role of LT in the management of hepatic EHE should be reevaluated. Age ≥ 60 years and the size of the largest lesion > 10 cm are poor prognostic factors.

Abstract. Background:. Human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) can profoundly affect the mental health of the people living with HIV (PLWH), with higher rates of anxiety, depression, and sleep disturbances. The disparities in neuropsychological problems evaluated by physicians and self-assessed by patients are still unknown. Methods:. A total of 5000 PLWH and 500 physicians from 167 hospitals were enrolled in this cross-sectional study from September 2022 to February 2023. 4-Item Patient Health Questionnaire (PHQ-4) was used for the evaluation of depressive issues and anxiety issues by PLWH. Each physician assessed 10 PLWH under their care for the presence of depressive or anxiety issues. The primary outcomes of this study are the concordance rates on the depressive issues and anxiety issues evaluation between physicians and PLWH. The Cohen’s kappa test was used to assess the agreement between physicians and PLWH. Results:. The concordance rate for the evaluation of depressive issues is 73.84% (95% confidence interval [CI]: 72.60–75.04%), and it is significantly different from the expected rate of 80% (P

This article selected the monitoring data of the TJ-2 volumetric strain gauge at Yixian seismic station from 2020 to 2022, and analyzed the continuity, completeness, annual drift, and accuracy of the volumetric strain data during this period. By analyzing the impact of natural weather changes, instrument failures, and human interference on the monitoring data, the article discussed the observation and seismic reflection ability of the Yixian seismic station. The conclusion incledes: ① The TJ-2 volumetric strain gauge at Yixian seismic station operates well and has high monitoring data quality. ② Natural weather change (rainfall, atmospheric pressure) are the main interfering factors affecting the monitoring data of the TJ-2 volumetric strain gauge. ③ The TJ-2 volumetric strain gauge exhibits extremely significant co-seismic responses to earthquakes with global MS≥7.0 and domestic MS≥6.0. The larger the magnitude and closer the epicenter distance, the longer of the duration of the monitoring data curve’ s co-seismic response. Due to the early installation time of the TJ-2 volumetric strain gauge at Yixian seismic station, severe aging of the line, and disorderly installation of the station’s instrument circuits, circuit interference often occurs. Therefore, it is necessary to optimize the instrument’s power supply line to improve the quality of observation data.

In this paper，the typical site environmental events covered by 48 stations in 7 center stations of Hebei geophysical station network are reviewed, involving deformation, geoelectricity, geomagnetic and fluid disciplines. According to the number of recorded events and the number of affecting instrument sets, typical influential factors such as HVDC transmission, equipment leakage, water (oil) well spring pumping, and reservoir water level fluctuation are selected for analysis. The process of occurrence of the event is described in detail, its rules and reasons are found, and effective solutions are proposed to provide reference for anomaly verification, analysis and prediction.

Background: Metaplastic breast cancer (MBC) is a rare and highly aggressive histological subtype of breast cancer. There remains a significant lack of precise predictive models available for use in clinical practice. Methods: This study utilized patient data from the SEER database (2010–2018) for data analysis. We utilized prognostic factors to develop a novel machine learning model (CatBoost) for predicting patient survival rates. Simultaneously, our hospital's cohort of MBC patients was utilized to validate our model. We compared the benefits of radiotherapy among the three groups of patients. Results: The CatBoost model we developed exhibits high accuracy and correctness, making it the best-performing model for predicting survival outcomes in patients with MBC (1-year AUC = 0.833, 3-year AUC = 0.806; 5-year AUC = 0.810). Furthermore, the CatBoost model maintains strong performance in an external independent dataset, with AUC values of 0.937 for 1-year survival, 0.907 for 3-year survival, and 0.890 for 5-year survival, respectively. Radiotherapy is more suitable for patients undergoing breast-conserving surgery with M0 stage [group1: (OS:HR = 0.499, 95%CI 0.320–0.777 p

Abstract Muscle atrophy, characterized by the loss of muscle mass and function, is a hallmark of sarcopenia and cachexia, frequently associated with aging, malignant tumors, chronic heart failure, and malnutrition. Moreover, it poses significant challenges to human health, leading to increased frailty, reduced quality of life, and heightened mortality risks. Despite extensive research on sarcopenia and cachexia, consensus in their assessment remains elusive, with inconsistent conclusions regarding their molecular mechanisms. Muscle atrophy models are crucial tools for advancing research in this field. Currently, animal models of muscle atrophy used for clinical and basic scientific studies are induced through various methods, including aging, genetic editing, nutritional modification, exercise, chronic wasting diseases, and drug administration. Muscle atrophy models also include in vitro and small organism models. Despite their value, each of these models has certain limitations. This review focuses on the limitations and diverse applications of muscle atrophy models to understand sarcopenia and cachexia, and encourage their rational use in future research, therefore deepening the understanding of underlying pathophysiological mechanisms, and ultimately advancing the exploration of therapeutic strategies for sarcopenia and cachexia.

Summary: Tank-binding kinase 1 (TBK1) is a critical signal transducer in the nuclear factor κB (NF-κB) and interferon regulatory factor (IRF) pathways, essential for innate immunity. However, its negative regulation mechanisms remain unclear. This study demonstrates that TBK1 succinylation, regulated by desuccinylase SIRT5, inhibits lipopolysaccharide (LPS)/Toll-like receptor 4 (TLR4)-mediated NF-κB and IRF signaling activation. We identified three key succinylation sites on TBK1: K38, K154, and K692. In endotoxemia and sepsis models, reduced SIRT5 levels in macrophages increased TBK1 succinylation, inhibiting its binding to IRF3 and TRAF2 and suppressing the inflammatory response. In vivo, adoptive transfer of macrophages expressing the succinylation-resistant TBK1-2KR (K154/692R) mutant reversed the inflammatory cytokine suppression caused by SIRT5 deficiency, exacerbating sepsis-induced lung injury. These findings reveal a novel mechanism by which SIRT5 modulates TBK1 activity and macrophage-mediated inflammation during sepsis.

Abstract With development of blockchain technology, clouding computing and Internet of Things (IoT), blockchain and cloud of things (BCoT) has become development tendency. But the security has become the most development hinder of BCoT. Attack detection model is a crucial part of attack revelation mechanism for BCoT. As a consequence, attack detection model has received more concerned. Due to the great diversity and variation of network attacks aiming to BCoT, tradition attack detection models are not suitable for BCoT. In this paper, we propose a novel attack detection model for BCoT, denoted as cVAE-DML. The novel model is based on contrastive variational autoencoder (cVAE) and deep metric learning (DML). By training the cVAE, the proposed model generates private features for attack traffic information as well as shared features between attack traffic information and normal traffic information. Based on those generated features, the proposed model can generate representative new samples to balance the training dataset. At last, the decoder of cVAE is connected to the deep metric learning network to detect attack aiming to BCoT. The efficiency of cVAE-DML is verified using the CIC-IDS 2017 dataset and CSE-CIC-IDS 2018 dataset. The results show that cVAE-DML can improve attack detection efficiency even under the condition of unbalanced samples.

The destruction of cratons is one of the key research objects of geophysicists. According to China Earthquake Networks Center, small and medium-sized earthquakes have occurred more frequently in southern Hebei in recent years than before. In order to explore the reasons for the instability of the crustal structure in southern Hebei, in this paper the earthquakes are precisely located based on the P-wave arrival time data recorded by China Earthquake Networks Center, and the double difference tomography of the crustal velocity structure is performed by using the P-wave seismic phase data. It is found that the sources after fine location are mainly distributed in the crust depth of 5～15 km, mainly near the faults. In terms of velocity structure, the mean RMS value of seismic travel time residuals decreases from 0.81 s to 0.36 s, and the earthquakes are more likely to occur in the transition zone at the edge of the high-speed region. There is a low-speed anomaly zone at the junction of the crust and mantle in Handan and Xingtai. The Moho surface and upper mantle may be upwelling by hot flow materials such as magma, intruding into the crust and undergoing chemical reactions, leading to the thinning and damage of the lithosphere, resulting in an unstable crustal structure and creating favorable conditions for shallow earthquakes.

ObjectivesWith the continuous development of larger scale and more complex ships, the number of finite element model elements required to model hull structures at the cabin structure level and above is increasing dramatically, resulting in collision, impact, contact and other large-scale non-linear mechanical problems which are difficult to solve. To this end, a simplified method for the deformation of two-way stiffened plate structures based on orthotropic equivalent theory is proposed in order to simplify the modeling of ship structures.MethodsFirst, the current well-established simplification method for the plane stress of one-way stiffened plates is extended to the more complex plane bending problem of two-way stiffened plates. The ratio of the total moment of inertia of stiffened plates to the moment of inertia of plates in the orthogonal direction is introduced to reflect the structural orthotropism. Next, the moment of inertia ratios are substituted into the equivalent constitutive equation for the plane bending of stiffened plates to achieve the transformation to physical orthotropism, thereby taking into account both the deformation resistance of the structure and the influence of the membrane forces generated by shifting the neutral surface at the mechanical level. Finally, finite element calculations are used to classify the deformation modes of the four-sided fixed stiffened plates according to different displacement distributions, and the actual results of the stiffened plates are analyzed in terms of error comparisons with the equivalent results of this method and the traditional method.ResultsThe result comparison shows that the proposed method can reduce the number of elements in two-way stiffened plates by up to 84%, and the equivalent errors in all three deformation modes can be controlled within 6%, which is much lower than those of the two traditional methods.ConclusionsWith high precision, a wide application range and greatly reduced calculation resources, the proposed method can provide a direct modeling and simulation calculation solution to address the nonlinear mechanical problems of large hull structures for practical engineering applications.

Sequestration of CO2 in the unmineable coal seams is not only one of the most ideal options for reducing greenhouse gas effects, but also the only way for the coal industry to reduce CO2 emissions and achieve low carbonization sustainable development. However, the key unresolved issues regarding the CO2 geo-sequestration in coal seams is: “how long does CO2 injected into a coal seam remain in the seam?”. In this regard, on the basis of clarifying the hysteresis law of CO2 desorption in coals, this paper reveals the mechanism of supercritical CO2 desorption hysteresis, establishes a quantitative model for the geological storage of CO2, and explores the use of desorption hysteresis to achieve a long-term safe storage of CO2 in coal seams. The study results shows that the degree of desorption hysteresis of supercritical CO2 in coal is greater than that of subcritical CO2, and a stable hysteresis characteristic similar to a “parallel line” in the supercritical phase is formed between the adsorption and desorption isotherm. The fundamental reason for the desorption hysteresis is that the micro and nano sized pores in coal form curved surfaces due to their hydrophilicity, which generate strong capillary pressure following the Laplace’s equation, absorb liquid water, truncate and fix the supercritical CO2 fluid, and ultimately form CO2 residual trapping. For example, the cylindrical inorganic pores with a diameter of 40–10 nm in coal can generate a capillary pressure of 7.30–29.12 MPa, which is sufficient to block supercritical CO2. Taking the desorption isotherm of Jiulishan coal as an example, using the quantitative model for the geological storage of CO2 established in this study, it has been estimated that the total trapping capacity of the No.21 coal seam at depths of 900–1 500 m is stable at 35–37 m3/t. Among them, the adsorption trapping capacity accounts for about 80%, residual trapping capacity accounts for about 15%, and structural trapping capacity only accounts for 5%. Desorption hysteresis suggests that some measures should be taken to increase the proportion of CO2 residual trapping in coal seams as much as possible, the reason is that the residual CO2 sealed by capillary blockage is safer and has no risk of leakage compared to the free and adsorbed CO2 sealed by surrounding rock. The physical parameters such as ash content, moisture content, pore size, and morphology of coal seams are the main factors affecting the residual trapping efficiency.

Abstract Background Trichinella spiralis (T. spiralis) is a parasitic helminth that causes a globally prevalent neglected zoonotic disease, and worms at different developmental stages (muscle larvae, adult worms, newborn larvae) induce immune attack at different infection sites, causing serious harm to host health. Several innate immune cells release extracellular traps (ETs) to entrap and kill most pathogens that invade the body. In response, some unicellular pathogens have evolved a strategy to escape capture by ETs through the secretion of nucleases, but few related studies have investigated multicellular helminths. Results In the present study, we observed that ETs from neutrophils capture adult worms of T. spiralis, while ETs from macrophages trap muscle larvae and newborn larvae, and ETs had a killing effect on parasites in vitro. To defend against this immune attack, T. spiralis secretes plancitoxin-1, a DNase II-like protein, to degrade ETs and escape capture, which is essential for the survival of T. spiralis in the host. Conclusions In summary, these findings demonstrate that T. spiralis escapes ET-mediated capture by secreting deoxyribonuclease as a potential conserved immune evasion mechanism, and plancitoxin-1 could be used as a potential vaccine candidate.

Abstract Internal solitary wave (ISW), as a typical marine dynamic process in the deep sea, widely exists in oceans and marginal seas worldwide. The interaction between ISW and the seafloor mainly occurs in the bottom boundary layer. For the seabed boundary layer of the deep sea, ISW is the most important dynamic process. This study analyzed the current status, hotspots, and frontiers of research on the interaction between ISW and the seafloor by CiteSpace. Focusing on the action of ISW on the seabed, such as transformation and reaction, a large amount of research work and results were systematically analyzed and summarized. On this basis, this study analyzed the wave–wave interaction and interaction between ISW and the bedform or slope of the seabed, which provided a new perspective for an in‐depth understanding of the interaction between ISW and the seafloor. Finally, the latest research results of the bottom boundary layer and marine engineering stability by ISW were introduced, and the unresolved problems in the current research work were summarized. This study provides a valuable reference for further research on the hazards of ISW to marine engineering geology.

IntroductionMucosal deficiency is one of the most challenging conditions in patients with acute severe ulcerative colitis (ASUC). Intravenous corticosteroids (CS) are the first-line treatment, with infliximab (IFX) used as a rescue therapy. However, the efficacy remains unsatisfactory. We investigated whether CS combined with IFX as first-line therapy would improve outcomes in patients with ASUC with mucosal deficiency.MethodsA retrospective study was performed at a tertiary inflammatory bowel disease center. The primary outcomes included clinical remission, endoscopic improvement, and endoscopic remission at week 14. The secondary outcomes included the colectomy rate within 90 days and durable clinical remission.ResultsA total of 43 patients with ASUC with mucosal deficiency were included in the analysis (25 in the CS combined with the IFX group and 18 in the CS sequential IFX group). At week 14, endoscopic improvement was observed in 21 of 25 patients (84.0%) receiving the CS combined with the IFX regimen, compared to 9 of 18 (50.0%) patients receiving the CS sequential IFX regimen (p = 0.017). Durable clinical remission rates were significantly higher in the combined group than in the sequential group (85.7% vs. 35.7%, p = 0.004). There was no statistically significant difference between the two groups in terms of clinical and endoscopic remission at week 14 or colectomy rate within 90 days. Multivariate analysis confirmed that the CS combined with the IFX regimen was an independent predictive factor for a higher endoscopic improvement rate at week 14 (odds ratio (OR) 8.428, 95%confidence interval (CI) 1.539–46.153, p = 0.014) and a higher durable clinical remission rate (OR 10.800, 95%CI 2.095–55.666, p = 0.004).ConclusionCS combined with IFX as first-line therapy may be an effective induction strategy in patients with ASUC with mucosal deficiency. Further large-scale, multicenter prospective studies are needed.

The seabed surface is an important boundary for ocean exploration and foundation for ocean engineering construction. Accurate acquisition of seabed sediment mechanical properties and environmental parameters is critical to the development of marine resources and marine engineering. In this study, by designing the Seabed Cone Penetration Test (CPT) and Sampling System, multiparameter in situ testing and low-disturbance sampling of 3,000-m deep-sea seabed sediments are performed. Accounting for the stable penetration speed of the probe rod is the basis for ensuring the accuracy of the static penetration test results. The system adopts electrohydraulic proportional position control and a fuzzy proportional integral derivative (PID) controller to precisely control the position of the piston of the hydraulic circuit, which can improve the accuracy of the cone test data and reduce the interference of the sampling tube with the original sediment during the sampling process. Moreover, electrohydraulic co-simulation of the hydraulic control system was conducted with the AMESim and Simulink software, and the position control and speed control effects of the system were verified. The entire system was tested on site in the Shenhu Sea area of the South China Sea. This test successfully obtained nine in situ parameters, including physical and chemical parameters, for sediments within a depth range of 2.66 m on the seabed surface at a depth of 1,820 m. This system accurately and efficiently reflects the property characteristics of seafloor sediments in an in situ environment and can be widely used in marine engineering geological investigations.

Ports are of great significance in processing cargo containers and facilitating global marine logistics. Nevertheless, the susceptibility of the container shipping network for hazardous cargo is likely to intensify in the event of a significant disruption at a major port, such as adverse weather conditions, inadequate management practices, or unforeseen catastrophes. Such situations require the deployment of port protection emergency response and prevention in advance. This study proposes a digital twin (DT) model that employs extensive and trajectory data within containers to comprehensively analyze the occurrence of hazardous cargo failures within the port storage process. The virtual models of physical entities in the port are created through a data-driven approach, and the behavior of these entities in a port environment with big data is then simulated. A combination of a convolutional neural network (CNN) and a long short-term memory (LSTM) algorithm is employed to provide predictions for the service layer of the DT system. The predicted correlation coefficients of temperature and humidity in the container reach 0.9855 and 0.9181, respectively. The developed system driven by DT models integrated with a CNN and the LSTM algorithm can more effectively assist the safety manager in achieving prevention in port operations. This study enables marine authorities and decision-makers to optimize emergency procedures, thereby reducing the probability of accidents in port operations and logistics.

Introduction: Neuroinflammation and autophagy are implicated in stress-related major depressive disorder (MDD), but the underlying molecular mechanisms remain largely unknown. Objectives: Here, we identified that MDD regulated by HMGB1/STAT3/p65 axis mediated microglial activation and autophagy for the first time. Further investigations were performed to uncover the effects of this axis on MDD in vivo and in vitro. Methods: Bioinformatics analyses were used to re-analysis the transcriptome data from the dorsolateral prefrontal cortex (dlPFC) of post-mortem male MDD patients. The expression level of HMGB1 and its correlation with depression symptoms were explored in MDD clinical patients and chronic social defeat stress (CSDS)-induced depression model mice. Specific adeno-associated virus and recombinant (r)HMGB1 injection into the medial PFC (mPFC) of mice, and pharmacological inhibitors with rHMGB1 in two microglial cell lines exposed to lipopolysaccharide were used to analyze the effects of HMGB1/STAT3/p65 axis on MDD. Results: The differential expression of genes from MDD patients implicated in microglial activation and autophagy regulated by HMGB1/STAT3/p65 axis. Serum HMGB1 level was elevated in MDD patients and positively correlated with symptom severity. CSDS not only induced depression-like states in mice, but also enhanced microglial reactivity, autophagy as well as activation of the HMGB1/STAT3/p65 axis in mPFC. The expression level of HMGB1 was mainly increased in the microglial cells of CSDS-susceptible mice, which also correlated with depressive-like behaviors. Specific HMGB1 knockdown produced a depression-resilient phenotype and suppressed the associated microglial activation and autophagy effects of CSDS-induced. The effects induced by CSDS were mimicked by exogenous administration of rHMGB1 or specific overexpression of HMGB1, while blocked by STAT3 inhibitor or p65 knockdown. In vitro, inhibition of HMGB1/STAT3/p65 axis prevented lipopolysaccharide-induced microglial activation and autophagy, while rHMGB1 reversed these changes. Conclusion: Our study established the role of microglial HMGB1/STAT3/p65 axis in mPFC in mediating microglial activation and autophagy in MDD.

Abstract Damage to the ribosome or an imbalance in protein biosynthesis can lead to some human diseases, such as diabetic retinopathy (DR) and other eye diseases. Here, we reported that the kri1l gene was responsible for retinal development. The kri1l gene encodes an essential component of the rRNA small subunit processome. The retinal structure was disrupted in kri1l mutants, which resulted in small eyes. The boundaries of each layer of cells in the retina were blurred, and each layer of cells was narrowed and decreased. The photoreceptor cells and Müller glia cells almost disappeared in kri1l mutants. The lack of photoreceptor cells caused a fear of light response. The development of the retina started without abnormalities, and the abnormalities began two days after fertilization. In the kri1l mutant, retinal cell differentiation was defective, resulting in the disappearance of cone cells and Müller cells. The proliferation of retinal cells was increased, while apoptosis was also enhanced in kri1l mutants. γ-H2AX upregulation indicated the accumulation of DNA damage, which resulted in cell cycle arrest and apoptosis. The kri1l mutation reduced the expression of some opsin genes and key retinal genes, which are also essential for retinal development.

Abstract Background Beyond their crucial role in hemostasis, platelets possess the ability to regulate inflammation and combat infections through various mechanisms. Stringent control of macrophage activation is essential during innate immune responses in sepsis. Macrophages are considered crucial phagocytic cells that aid in the elimination of pathogens. Platelet interactions with monocytes-macrophages are known to be significant in the response against bacterial infections, but the primary mediator driving these interactions remains unclear. EGFR plays critical role in the regulation of inflammation and infection through various mechanisms. Results The overexpression of platelets by thrombopoietin (TPO) leads to the sequestration of both pro-inflammatory (IL-6/IL-1) and anti-inflammatory (IL-10) cytokines in the organ tissue of septic mice. Epidermal growth factor receptor (EGFR) is critical for platelet activation in sepsis. EGFR-licensed platelets enhance macrophage immune function, including the production of reactive oxygen species (ROS) and the clearance of bacteria. Platelet EGFR also induces M1 macrophage polarization by increasing the expression of inducible nitric oxide synthase (iNOS) and CD64. Conclusion EGFR can activate platelet immune function. Moreover, activated platelets efficiently regulate bacterial phagocytosis and pro-inflammatory function of macrophages through an EGFR-dependent pathway.

Abstract Background Esophageal squamous cell carcinoma (ESCC) is the main subtype of esophageal cancer. Current therapeutic effect is far from satisfaction. Hence, identifying susceptible genes and potential targets is necessary for therapy of ESCC patients. Methods Plant homeodomain (PHD)-finger domain protein 5 A (PHF5A) expression in ESCC tissues was examined by immunohistochemistry. RNA interference was used for in vitro loss-of-function experiments. In vivo assay was performed using xenograft mice model by subcutaneous injection. Besides, microarray assay and co-immunoprecipitation experiments were used to study the potential downstream molecules of PHF5A in ESCC. The molecular mechanism between PHF5A and vascular endothelial growth factor A (VEGFA) was explored by a series of ubiquitination related assays. Results We found that PHF5A was highly expressed in ESCC tissues compared to normal tissues and that was correlated with poor prognosis of ESCC. Loss-of-function experiments revealed that PHF5A silence remarkably inhibited cell proliferation, migration, and induced apoptosis as well as cell cycle arrest. Consistently, in vivo assay demonstrated that PHF5A deficiency was able to attenuate tumor growth. Furthermore, molecular studies showed that PHF5A silencing promoted VEGFA ubiquitination by interacting with MDM2, thereby regulating VEGFA protein expression. Subsequently, in rescue experiments, our data suggested that ESCC cell viability and migration promoted by PHF5A were dependent on intact VEGFA. Finally, PI3K/AKT signaling rescue was able to alleviate shPHF5A-mediated cell apoptosis and cell cycle arrest. Conclusion PHF5A is a tumor promoter in ESCC, which is dependent on VEGFA and PI3K/AKT signaling. PHF5A might serve as a potential therapeutic target for ESCC treatment.

Gassy soil is prevalent in coastal regions, and the presence of gas bubbles can significantly alter the mechanical properties of soil, potentially leading to various marine engineering geological hazards. In this study, a series of triaxial tests were conducted on fine-grained gassy soils under different consolidation pressures (pc’), stress paths, and initial pore water pressures (uw0). These tests were also used to verify the applicability of a newly proposed constitutive model. According to the test results, the response to excess pore pressure and the stress–strain relationship of fine-grained gassy soils strongly depend on the initial pore water pressure (uw0), with the degree of variation being influenced by the consolidation pressure (pc’) and stress path. As uw0 decreases, the undrained shear strength (cu) of fine-grained gassy soils gradually increases, and this is lower under the reduced triaxial compression (RTC) path compared to the conventional triaxial compression (CTC) path, which can be attributed to the destruction of the pore structure due to an increase in gas volume. The newly proposed model accurately predicts the pore pressure and stress–strain relationship of fine-grained gassy soils at low consolidation pressures (pc’), but it falls short in predicting the mechanical behavior during shear progression under high pc’ or the RTC path. Although the model effectively predicts the excess pore pressure and deviator stress at the shear failure point (axial strain = 15%), further improvement is still required.

Despite identifying genes regulating the coat colour in Western pig breeds, the genetic basis of the coat colour in Chinese indigenous pigs is still not understood due to the diversity of indigenous breeds and their genetic differences from exotic pigs. In this study, 215 Wuzhishan pigs with three coat colour patterns (white, black, and black-back/white-belly) were used to conduct a genome-wide association analysis. We found that genes responsible for the coat colour in the Wuzhishan breed are located on chromosome 8. Ninety-seven genome-wide significant SNPs are related to the animal’s coat colour. Using a haplotype-sharing analysis, we narrowed the potential candidate region to a 10.1 Mb interval encompassing only one gene, RAPGEF2, which participates in the regulation of melanogenesis. Two additional candidate genes, PDGFRA and KIT, are located within 1 Mb of the genome-wide significant SNPs. Gene ontology analysis and literature mining suggest that these candidate genes are associated with the animal’s coat colour. mRNA expression results revealed that RAPGEF2 and PDGFRA had significantly higher expressions in black pigs than in white pigs and higher expressions in black skin than in white skin from the same black-back/white-belly pigs. These results suggest that RAPGEF2 and PDGFRA are potential candidate genes regulating the coat colour in Wuzhishan pigs. Interestingly, mutations of KIT (a gene duplication and a G to A substitution at the splicing site in intron 17) were detected in white Wuzhishan pigs but not in black-back/white-belly or black pigs, suggesting a close genetic relationship between white Wuzhishan pigs and Western white pig breeds. In summary, these results indicate that the expression of RAPGEF2 and PDGFRA may cause the coat colour variation by influencing the deposition of melanin, while the mutation of KIT causes the white coat colour. Our results may provide a theoretical basis for the breeding of white coat colour Wuzhishan pigs, and shed light on the complex genetic background of coat colour variations in indigenous Chinese pig breeds.

Abstract As a practical reflection of the opportunity window of Madden‐Julian Oscillation (MJO), there are intermittent periods of relatively high forecasting skills, namely the forecast skill windows. Robust forecast skill windows are identified based on the subseasonal‐seasonal reforecast database, during which the majority of models show high forecast skills. A total of 15 MJO forecast skill windows during 1993–2020 have been identified. Most of the forecast skill windows are closely associated with active MJO events with high amplitude. Whether a high‐skill forecast window appears significantly depends on the magnitude of MJO intensity during the same period. The maintenance of active strong MJO events is potentially related with the warmer surface sea temperature anomalies in the western Pacific. Further research into such processes may unveil the MJO development mechanism and improve the MJO forecast skill.

Green hydrogen is an important future energy source, which offers a vast potential to implement the decarbonization of the marine sector and advance broad shift to clean-energy alternatives globally. There are various advantages of offshore floating photovoltaics (FPVs) technology for hydrogen production; however, hydrogen storage in FPVs-based hydrogen production system faces several challenges. It is found that the major barrier concerning the system under investigation is related to safety. The current study aims to present an applicable offshore FPVs-based hydrogen production system, which involves both the FPV section and the hydrogen production section based on a project in China. A numerical 3D model is performed to investigate the characteristics of accidental damage through potential hydrogen storage device failure during system operation. The hydrogen release process of an FPVs-based hydrogen production system is presented with different offshore wind conditions, and the parameters for understanding the motion state and hydrogen release mode of hydrogen are also analyzed. The study further explores the dynamic development of hydrogen dispersion from a hydrogen production platform, including a momentum-dominated region, a horizontal spreading region, and a vertical buoyancy region. In addition, the influence of hydrogen explosive flame on thermal damage evaluation is illustrated, and thermal hazards under different offshore wind conditions are also discussed. The current study contributes to a better understanding of failure analysis of the FPVs–hydrogen production system and elaborates on damage evolution of hydrogen storage integrated with the system. The study also concentrates on marine environmental synergistic limits considering thermally damaged mechanical properties.

Clonorchis sinensis is a significant zoonotic food-borne parasite that causes a range of hepatobiliary diseases, which in severe cases can even lead to cholangiocarcinoma. To explore new diagnostic and treatment strategies, the dynamic RNA regulatory processes across different developmental stages of C. sinensis were analyzed by using whole-transcriptome sequencing. The chromosomal-level genome of C. sinensis was used for sequence alignment and annotation. In this study, we identified a total of 59,103 RNAs in the whole genome, including 2,384 miRNAs, 25,459 mRNAs, 27,564 lncRNAs and 3,696 circRNAs. Differential expression analysis identified 6,556 differentially expressed mRNAs, 2,231 lncRNAs, 877 miRNAs and 20 circRNAs at different developmental stages. Functional enrichment analysis highlighted the critical role of microtubule-related biological processes in the growth and development of C. sinensis. And coexpression analysis revealed 97 lncRNAs and 85 circRNAs that were coexpressed with 42 differentially expressed mRNAs that associated with microtubules at different developmental stages of C. sinensis. The expression of the microtubule-related genes dynein light chain 2 (DLC2) and dynein light chain 4 (DLC4) increased with C. sinensis development, and DLC2/4 could be inhibited by albendazole. Finally, by constructing competing endogenous RNA (ceRNA) networks, the lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA regulatory relationships were constructed, and the ceRNA networks of MSTRG.14258.5-novel_miR_2287-newGene_28215 and MSTRG.14258.5-novel_miR_2216-CSKR_109340 were verified. This study suggests, through whole transcriptome sequencing, that the context of microtubule regulation may play an essential role in the development and growth of C. sinensis.

Introduction: Motoric cognitive risk syndrome (MCR), characterized by subjective cognitive complaints and slow gait in older populations, is associated with sleep duration. However, the association between MCR and daytime nap duration has not been thoroughly explored. Methods: Baseline data from the China Health and Retirement Longitudinal Study (CHARLS) were used in this study. MCR was defined as the coexistence of subjective cognitive complaints and objective slow gait speed without a history of dementia or mobility disability. Daytime nap duration was categorized into four groups: no napping, short napping (

The leakage from submarine gas pipelines presents a significant threat to marine ecological environments. Bubble plumes can be formed when gas escapes, which can give rise to the distinctive fountain phenomenon by interacting with the water surface. It is imperative to understand the factors that influence the physical dimensions and temporal characteristics of the resulting fountain to elucidate the formation mechanism of this phenomenon. Gas leakage experiments under various conditions are conducted to investigate the dynamic characteristics of the fountain in the study. The findings reveal the following: The initial kinetic energy of the escaping gas varies significantly under different leakage scenarios, resulting in the positive correlation between the maximum fountain height and width, as well as the leakage pressure and diameter of the leakage hole. Then, the analysis of dimensional indicates that the dynamic equilibrium of the bubbles is intricately tied to both the Froude number (Fr) and Reynolds number (Re). Notably, the effect of leakage pressure on Fr and Re follows similar patterns. However, the trends of Fr and Re values across varying leak hole diameters are opposite. At last, the frequency analysis of the time series data related to the fountain height demonstrates that higher leakage pressure and larger leak hole diameters result in an increase in both the main frequency and bandwidth. The research results offer valuable insights for evaluating the impact of gas leakage intensity on the marine environment by analyzing the size parameters of fountain.

BackgroundIn 2022, the European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Association for the Study of Obesity (EASO) launched a consensus on the diagnostic methods for sarcopenic obesity (SO). The study aimed to identify the prevalence and diagnostic agreement of SO using different diagnostic methods in a cohort of subjects from West China aged at least 50 years old.MethodsA large multi-ethnic sample of 4,155 participants from the West China Health and Aging Trend (WCHAT) study was analyzed. SO was defined according to the newly published consensus of the ESPEN/EASO. Furthermore, SO was diagnosed as a combination of sarcopenia and obesity. The criteria established by the Asian Working Group for Sarcopenia 2019 (AWGS2019) were used to define sarcopenia. Obesity was defined by four widely used indicators: percent of body fat (PBF), visceral fat area (VFA), waist circumference (WC), and body mass index (BMI). Cohen’s kappa was used to analyze the diagnostic agreement of the above five diagnostic methods.ResultsA total of 4,155 participants were part of the study, including 1,499 men (63.76 ± 8.23 years) and 2,656 women (61.61 ± 8.20 years). The prevalence of SO was 0.63–7.22% with different diagnostic methods. The diagnosis agreement of five diagnostic methods was poor-to-good (κ: 0.06–0.67). The consensus by the ESPEN/EASO had the poorest agreement with other methods (κ: 0.06–0.32). AWGS+VFA had the best agreement with AWGS+WC (κ = 0.67), and consensus by the ESPEN/EASO had the best agreement with AWGS+ PBF (κ = 0.32).ConclusionThe prevalence and diagnostic agreement of SO varies considerably between different diagnostic methods. AWGS+WC has the highest diagnostic rate in the diagnosis of SO, whereas AWGS+BMI has the lowest. AWGS+VFA has a relatively good diagnostic agreement with other diagnostic methods, while the consensus of the ESPEN/EASO has a poor diagnostic agreement. AWGS+PBF may be suitable for the alternative diagnosis of the 2022 ESPEN/EASO.

ABSTRACT Hyperactivation of pro-inflammatory type 1 cytokines (e.g., tumor necrosis factor alpha [TNF-α] and interferon gamma [IFN-γ]) mirrors the inflammation of coronavirus disease 2019. Helminths could alleviate excessive immune responses. Here, helminth Trichinella spiralis (Ts) infection was shown to protect against TNF-α- and IFN-γ-induced shock. Mechanistically, Ts-induced protection was interleukin-9 (IL-9) dependent but not IL-4Rα. Recombinant IL-9 treatment not only improved the survival of wild-type mice with TNF-α- and IFN-γ-induced shock but also that of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected K18-human angiotensin-converting enzyme 2 (hACE2) mice, emphasizing the significance of IL-9 in alleviating cytokine storm syndromes during SARS-CoV-2 infection. Interestingly, Ts excretory/secretory (TsES)-induced protection was also observed in SARS-CoV-2 infection, indicating that identifying anti-inflammatory molecules from TsES could be a novel way to mitigate adverse pathological inflammation during pathogen infection.IMPORTANCESevere coronavirus disease 2019 (COVID-19) is linked to cytokine storm triggered by type 1 pro-inflammatory immune responses. TNF-α and IFN-γ shock mirrors cytokine storm syndromes, including COVID-19. Helminths (e.g., Trichinella spiralis, Ts) can potently activate anti-inflammatory type 2 immune response. Here, we found that helminth Ts-induced protection against TNF-α and IFN-γ shock was IL-9 dependent. Treatment with recombinant IL-9 could protect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in K18-hACE2 mice. Helminth Ts excretory/secretory (TsES) products also ameliorated SARS-CoV-2 infection-related cytokine storm. In conclusion, our study emphasizes the significance of IL-9 in protecting from cytokine storm syndromes associated with SARS-CoV-2 infection. Anti-inflammatory molecules from TsES could be a new source to mitigate adverse pathological inflammation associated with infections, including COVID-19.

Purpose: This study aimed to analyze the current medication treatment status for women with osteoporosis (OP) based on real-world prescription data from 2016 to 2021 in Chinese nine cities' tertiary Grade A hospital and systematically describe the medication treatment patterns in women with OP. Methods: Prescription information for female OP patients in nine cities (Beijing, Shanghai, Guangzhou, Hangzhou, Tianjin, Zhengzhou, Chengdu, Shenyang, Harbin) was extracted from the Hospital Prescription Analysis Collaboration Project Database of the Hospital Pharmacy Professional Committee of the Chinese Pharmaceutical Association. Statistical analysis was conducted to evaluate demographic characteristics and medication treatment patterns. Results: A total of 669,505 prescriptions for medication treatment of female OP patients were included in this study. The majority of patients were aged 60 to 99 years (69.79 %) followed by 50 to 59 years (18.81 %) and 40 to 49 years (6.69 %). Geographically, the highest concentration of patients was in North China (Beijing, Tianjin) (43.05 %) followed by East China (Shanghai, Hangzhou) (31.43 %). The top three prescribed medications were active vitamin D and its analogs (40.78 %), calcium supplements (32.51 %), and bisphosphonates (18.75 %). The prescription frequency of menopausal hormone therapy (MHT) was 0.31 %. The proportion of female OP patients receiving monotherapy and two drug combinations therapy is equivalent (about 37 %). Conclusion: The diagnosis and treatment of female OP patients in China showed regional variations. The most commonly prescribed medications for this population were calcitriol, calcium carbonate with vitamin D3, and alendronate sodium with vitamin D3. The use of MHT was relatively limited.

Background. Managing hepatocellular carcinoma (HCC) presents significant clinical challenges, often necessitating orthotopic liver transplantation (OLT). To mitigate the risk of iatrogenic metastasis during OLT and reduce posttransplantation recurrence (PTR), we introduced the “no-touch” left (NTL) approach for recipient hepatectomy in OLT. Methods. In this retrospective cohort study, our aim was to compare the safety and PTR rates in patients undergoing OLT via either the NTL technique or the conventional approach for recipient hepatectomy. We included 106 patients who met the Hangzhou criteria and exhibited a high tumor burden in the right lobe, with 50 patients assigned to the NTL group and 56 to the conventional group. The primary endpoint was the 1-y PTR rate, whereas secondary endpoints encompassed the safety of the NTL approach, PTR rates at 2 and 5 y, and overall survival. Results. Baseline demographics and clinical characteristics showed no significant differences between the groups. The NTL approach exhibited major surgical outcomes similar to those of the conventional approach. The cumulative PTR rates at 1, 2, and 5 y were 14.0% in the NTL group, compared with 24.5%, 35.8%, and 35.8% in the conventional group (P = 0.013). Cumulative overall survival rates at 1, 2, and 5 y were 94.0%, 91.9%, and 89.7% in the NTL group and 88.7%, 75.5%, and 72.5% in the conventional group (P = 0.03). Conclusions. This innovative surgical technique enhances safety and significantly reduces the risk of PTR, leading to improved long-term survival. Further prospective studies with larger cohorts and longer follow-up periods are needed to validate our findings and establish the NTL approach as a standard practice in OLT.

Abstract Background Nowadays, there is a lack of effective intraoperative treatment for thoracolumbar fascia injury (TFI) of osteoporotic vertebral compression fractures (OVCFs), which may lead to postoperative residual pain. We aimed to evaluate the clinical effects of cocktail injection on the TFI during percutaneous vertebroplasty (PVP) for OVCFs. Methods A retrospective study of OVCFs with TFI underwent PVP with cocktail injection (Cocktail group, 58 cases) or PVP (Routine group, 64 cases) was conducted. The surgical outcomes, visual analog scale (VAS) score, oswestry disability index (ODI), incidence of residual pain at 1 day and 7 days postoperatively, the rate and duration of taking painkillers during 7 days postoperatively after PVP were compared between them. Results No differences in baseline data, volume of bone cement injected and bone cement leakage were observed between the two groups, while the operation time of the routine group (44.3 ± 7.8 min) was less than that (47.5 ± 9.1 min) of the cocktail group (P

Abstract Trichinella spiralis (T. spiralis) is a zoonotic parasitic nematode with a unique life cycle, as all developmental stages are contained within a single host. Excretory-secretory (ES) proteins are the main targets of the interactions between T. spiralis and the host at different stages of development and are essential for parasite survival. However, the ES protein profiles of T. spiralis at different developmental stages have not been characterized. The proteomes of ES proteins from different developmental stages, namely, muscle larvae (ML), intestinal infective larvae (IIL), preadult (PA) 6 h, PA 30 h, adult (Ad) 3 days post-infection (dpi) and Ad 6 dpi, were characterized via label-free mass spectrometry analysis in combination with bioinformatics. A total of 1217 proteins were identified from 9341 unique peptides in all developmental stages, 590 of which were quantified and differentially expressed. GO classification and KEGG pathway analysis revealed that these proteins were important for the growth of the larvae and involved in energy metabolism. Moreover, the heat shock cognate 71 kDa protein was the centre of protein interactions at different developmental stages. The results of this study provide comprehensive proteomic data on ES proteins and reveal that these ES proteins were differentially expressed at different developmental stages. Differential proteins are associated with parasite survival and the host immune response and may be potential early diagnostic antigen or antiparasitic vaccine candidates.

Abstract Atherosclerosis is one of the leading causes of death worldwide. miR-26 is a potential biomarker of atherosclerosis. Standardized diagnostic tests for miR-26 (MIR26-DX) have been developed, but the fastest progress has been in predicting the efficacy of IFN-α therapy for hepatocellular carcinoma (HCC, phase 3). MiR-26 slows atherosclerosis development by suppressing ACC1/2, ACLY, ACSL3/4, ALDH3A2, ALPL, BMP2, CD36, COL1A1, CPT1A, CTGF, DGAT2, EHHADH, FAS, FBP1, GATA4, GSK3β, G6PC, Gys2, HMGA1, HMGB1, LDLR, LIPC, IL-1β, IL-6, JAG2, KCNJ2, MALT1, β-MHC, NF-κB, PCK1, PLCβ1, PYGL, RUNX2, SCD1, SMAD1/4/5/7, SREBF1, TAB3, TAK1, TCF7L2, and TNF-α expression. Many agents targeting these genes, such as the ACC1/2 inhibitors GS-0976, PF-05221304, and MK-4074; the DGAT2 inhibitors IONIS-DGAT2Rx, PF-06427878, PF-0685571, and PF-07202954; the COL1A1 inhibitor HT-100; the stimulants 68Ga-CBP8 and RCT-01; the CPT1A inhibitors etomoxir, perhexiline, and teglicar; the FBP1 inhibitors CS-917 and MB07803; and the SMAD7 inhibitor mongersen, have been investigated in clinical trials. Interestingly, miR-26 better reduced intima-media thickness (IMT) than PCSK9 or CT-1 knockout. Many PCSK9 inhibitors, including alirocumab, evolocumab, inclisiran, AZD8233, Civi-007, MK-0616, and LIB003, have been investigated in clinical trials. Recombinant CT-1 was also investigated in clinical trials. Therefore, miR-26 is a promising target for agent development. miR-26 promotes foam cell formation by reducing ABCA1 and ARL4C expression. Multiple materials can be used to deliver miR-26, but it is unclear which material is most suitable for mass production and clinical applications. This review focuses on the potential use of miR-26 in treating atherosclerosis to support the development of agents targeting it.

Accurate posture detection is the foundation for analyzing animal behavior, which can promote animal welfare. With the development of computer vision, such technology has been widely used in analyzing animal behavior without physical contact. However, computer vision technology for pig posture detection often suffers from problems of missed or false detection due to complex scenarios. To solve the problem, this study proposed a novel object detection model YOLOv5DA, which was based on YOLOv5s and designed for pig posture detection from 2D camera video. Firstly, we established the annotated dataset (7220 images) including the training set (5776 images), validation set (722 images), and test set (722 images). Secondly, an object detection model YOLOv5DA based on YOLOv5s was proposed to recognize pig postures (standing, prone lying, and side lying), which incorporated Mosaic9 data augmentation, deformable convolution, and adaptive spatial feature fusion. The comparative and ablation experiments were conducted to verify the model’s effectiveness and reliability. Finally, we used YOLOv5DA to detect the posture distribution of pigs. The results revealed that the standing posture was more frequent in the morning and afternoon and the side-lying posture was most common at noon. This observation demonstrated that the posture of pigs is influenced by temperature variations. The study demonstrated that YOLOv5DA could accurately identify three postures of standing, prone lying, and side lying with an average precision (AP) of 99.4%, 99.1%, and 99.1%, respectively. Compared with YOLOv5s, YOLOv5DA could effectively handle occlusion while increasing the mean precision (mAP) by 1.7%. Overall, our work provided a highly accurate, effective, low-cost, and non-contact strategy of posture detection in grouped pigs, which can be used to monitor pig behavior and assist in the early prevention of disease.

Early and highly precise detection is essential for delaying the progression of coronary artery disease (CAD). Previous methods primarily based on single-modal data inherently lack sufficient information that compromises detection precision. This paper proposes a novel multi-modal learning method aimed to enhance CAD detection by integrating ECG, PCG, and coupling signals. A novel coupling signal is initially generated by operating the deconvolution of ECG and PCG. Then, various entropy features are extracted from ECG, PCG, and its coupling signals, as well as recurrence deep features also encoded by integrating recurrence plots and a parallel-input 2-D CNN. After feature reduction and selection, final classification is performed by combining optimal multi-modal features and support vector machine. This method was validated on simultaneously recorded standard lead-II ECG and PCG signals from 199 subjects. The experimental results demonstrate that the proposed multi-modal method by integrating all signals achieved a notable enhancement in detection performance with best accuracy of 95.96%, notably outperforming results of single-modal and joint analysis with accuracies of 80.41%, 86.51%, 91.44%, and 90.42% using ECG, PCG, coupling signal, and joint ECG and PCG, respectively. This indicates that our multi-modal method provides more sufficient information for CAD detection, with the coupling information playing an important role in classification.

Currently, the primary method for controlling red tides in the ocean involves spraying water solutions with special chemicals as solutes. High-pressure spraying results in the formation of typical jet structures. In this study, numerical simulation methods are employed to investigate the velocity variations, turbulent characteristics, and gas content distribution of jet flow fields under different initial jet flow pressures, cone angles, and nozzle diameters. Based on practical application scenarios, cluster analysis is used to explore the similarities and differences in jet equivalent diameters under different parameter conditions. The research findings indicate the following. (1) The difference of jet velocity distribution at the far field exit will be enlarged with the increase in the nozzle cone angle. When the nozzle cone angle is 4 mm, the velocity uniformity at the outlet is the best. (2) The TKE of the flow field has no consistent change law along the central axis. At the jet exit, the TKE shows an obvious multi-peak structure. (3) The gas content demonstrates a typical “double-valley” feature at the jet outlet cross-section. Increasing the initial pressure leads to a decrease in the gas content within the jet due to reduced entrainment, while the entrainment range remains largely constant. (4) Cluster analysis reveals that the similarity of jet flow width when it reaches the water surface is minimal compared to other operating conditions when the initial pressure is 0.36 MPa, the cone angle is 115°, and the nozzle diameter is 2 mm. All conditions can be categorized into two or three groups to ensure jet effectiveness. The study results provide scientific guidance for selecting spray devices for controlling red tides in the ocean.

LoRa (long range) is a communication technology that employs chirp spread spectrum modulation. Among various low-power wide area network (LPWAN) technologies, LoRa offers unique advantages, including low power consumption, long transmission distance, strong anti-interference capability, and high network capacity. Addressing the issue of power-constrained end devices in IoT application scenarios, this paper proposes an adaptive data rate (ADR) algorithm for LoRa networks designed for power-constrained end devices (EDs). The algorithm evaluates the uplink communication link state between the EDs and the gateway (GW) by using a combined weighting method to comprehensively assess the signal-to-noise ratio (SNR), received signal strength indication (RSSI), and packet reception rate (PRR), and calculates a list of transmission power and data rates that ensure stable and reliable communication between the EDs and the GW. By using ED power consumption models, network throughput models, and ED latency models to evaluate network performance, the Zebra optimization algorithm is employed to find the optimal data rate for each ED under power-constrained conditions while maximizing network performance. Test results show that, in a single ED scenario, the average PRR achieved by the proposed ADR algorithm for power-constrained EDs in LoRa networks is 14% higher than that of the standard LoRaWAN ADR algorithm. In a multi-ED link scenario (50 end devices), the proposed method reduces the average power consumption of EDs by 10% compared to LoRaWAN ADR, achieves a network throughput of 6683 bps, and an average latency of 2.10 s, demonstrating superior performance overall. The proposed method shows unique advantages in LoRa networks with power-constrained EDs and a large number of EDs, as it not only reduces the average power consumption of the EDs but also optimizes network throughput and average latency.

With the growth of the population and the development of modern industry and the economy, the problem of heavy metal pollution in cultivated soil has become increasingly prominent. Moreover, heavy metal poses a serious threat to plant growth due to its characteristics of difficult degradation, high mobility, easy enrichment, and potential toxicity and has become a social topic. Melatonin is a new type of plant hormone widely present in animals, plants, fungi, and bacteria, and its biological role has begun investigated in the last dozen years. Facing heavy metal stress, melatonin can play a pleiotropic role in the physiological processes of plants, such as stress resistance and growth regulation, mitigate the damage caused by stress on plants, and provide a new research idea for alleviating heavy metal stress in plants. From the aspects of the plant phenotype, physiology, element absorption, and molecular structure, this paper, therefore, mainly reviews the effects of melatonin on plants subjected to heavy metal stress and the mechanism of melatonin alleviating heavy metal stress and then puts forward future research directions. This information may be of great significance to the normal growth of crops under heavy metal stress and will provide an important theoretical basis for the genetic improvement of crop resistance in the future.

Abstract Background Several studies have reported the roles of Trichinella spiralis extracellular vesicles in immune regulation and pathogen diagnosis. Currently, the T. spiralis muscle larvae excretory/secretory product (Ts-ML-ES) is the antigen recommended by the International Commission on Trichinellosis (ICT) for serological diagnosis of trichinellosis. However, it can only be used to detect middle and late stages of infections, and cross-reactions with other parasite detections occur. Therefore, there is a need to identify antigens for specific detection of early stage trichinellosis. Methods Extracellular vesicles of T. spiralis muscle larvae (Ts-ML-EVs) were isolated by ultracentrifugation and characterized by transmission electron microscopy, nanoparticle tracking analysis, flow cytometry and western blot. Ts-ML-EVs protein profiles were analyzed by LC-MS/MS proteomics for identification of potential antigens (Ts-TTPA). Ts-TTPA were cloned into pMAL-c5X vector and expressed as recombinant proteins for evaluation of potential as detected antigens by western blot and ELISA. Results Isolated Ts-ML-EVs were round or elliptic (with diameters between 110.1 and 307.6 nm), showing a bilayer membrane structure. The specific surface markers on the Ts-ML-EVs were CD81, CD63, enolase and the 14-3-3 protein. A total of 53 proteins were identified by LC-MS/MS, including a variety of molecules that have been reported as potential detection and vaccine candidates. The cDNA of Ts-TTPA selected in this study has a total length of 1152 bp, encoding 384 amino acids with a molecular weight of 44.19 kDa. It contains a trypsin domain and can be recognized by anti-His antibody. It reacted with swine sera infected with 10,000 T. spiralis at 15, 25, 35 and 60 days post-infection (dpi). At 10 μg/ml, this antigen could detect T. spiralis antibodies from the swine sera at 13 dpi. There were no cross-reactions with the swine sera infected with other parasites including Clonorchis sinensis, Toxoplasma gondii, Taenia suis, Ascaris suis and Trichuris suis. Conclusions This study identifies potential early stage detection antigens and more thoroughly characterizes a serine protease domain-containing protein. Extracellular vesicle proteins may be explored as effective antigens for the early stage detection of trichinellosis. Graphical Abstract

Abstract Upon encountering exogenous pathogens, polymorphonucleocytes (PMNs) engage in various processes to destroy them, including releasing neutrophil extracellular traps (NETs) that trap pathogens and induce phagocytosis and cytokine production. Parasites have unique strategies with which to evade the host's immune response. However, the strategy employed by Trichinella spiralis in response to the reaction of PMNs has yet to be elucidated. This study explored the effect of excretory/secretory products (ESP) on three major functions: NETs, phagocytosis, and cytokine production. Specifically, PMNs were pre-treated with the ESP of 3-day-old adults and then stimulated with phorbol 12-myristate 13-acetate (PMA). We found that in PMNs pretreated with ESP, PMA-induced NET generation was suppressed by ESP. ROS production is a hallmark of PMA-induced NETosis. The LDH assay results showed that ESP inhibits NETs by suppressing ROS rather than promoting PMN death. Furthermore, ESP enhanced Escherichia coli engulfment by PMNs, improving overall phagocytic function. Finally, cytokine analysis revealed an increase in pro-inflammatory cytokine IL-1β, and other cytokines (IL-10, TNF-α), while IL-4 displayed a significant reduction. In conclusion, this study has unraveled T. spiralis' evasion and regulation mechanisms against innate immune cells, providing insights into parasite strategies to manipulate host immunity, potentially informing new treatments for NET-related autoimmune diseases. Graphical Abstract

Abstract Background The gut microbiome and fecal metabolites have been found to influence sarcopenia, but whether there are potential bacteria that can alleviate sarcopenia has been under‐investigated, and the molecular mechanism remains unclear. Methods To investigate the relationships between the gut microbiome, fecal metabolites and sarcopenia, subjects were selected from observational multi‐ethnic study conducted in Western China. Sarcopenia was diagnosed according to the criteria of the Asian Working Group for Sarcopenia 2014. The gut microbiome was profiled by shotgun metagenomic sequencing. Untargeted metabolomic analysis was performed to analyse the differences in fecal metabolites. We investigated bacterium with the greatest relative abundance difference between healthy individuals and sarcopenia patients, and the differences in metabolites associated with the bacteria, to verify its effects on muscle mass and function in a mouse model. Results The study included 283 participants (68.90% females, mean age: 66.66 years old) with and without sarcopenia (141 and 142 participants, respectively) and from the Han (98 participants), Zang (88 participants) and Qiang (97 participants) ethnic groups. This showed an overall reduction (15.03% vs. 20.77%, P = 0.01) of Prevotella copri between the sarcopenia and non‐sarcopenia subjects across the three ethnic groups. Functional characterization of the differential bacteria showed enrichment (odds ratio = 15.97, P = 0.0068) in branched chain amino acid (BCAA) metabolism in non‐sarcopenia group. A total of 13 BCAA and their derivatives have relatively low levels in sarcopenia. In the in vivo experiment, we found that the blood BCAA level was higher in the mice gavaged with live P. copri (LPC) (P

The floating structure of floating photovoltaic can be attached by aquatic organisms, resulting in changes in the draft depth of the floating body, which can affect the resistance characteristics of the floating body at different water velocities. The analysis for the characteristics of flow field is the key to revealing the change law of resistance under different conditions. The k-ϵ turbulence model which has been verified by water channel experiment is used to research the influence of draft depths, velocities and number of floating bodies for the drag in the paper. The research results show that the draft depth has more influence on the drag of the single floating body than on the velocity of water flow. The main reason is that the separation of the boundary layer produces a larger separation bubble, which increases the pressure difference between the front and back surfaces of the floating body, leading to a larger entrainment range and reflux velocity in the wake. The high flow velocity will enlarge the influence of the draft depth on the drag. The shielding effect of the tandem floating bodies is reflected in the non-uniform fluctuation of velocity and pressure along the flow direction, which affects the wake development of the tandem floating bodies, resulting in the typical spatial characteristics of resistance at different positions. The increase of the number of tandem floating bodies will further expand the difference of flow field, which can affect the resistance distribution law. The research results can provide theoretical support for the stability design of floating photovoltaic.

Clonorchis sinensis is one of the most important fish-borne zoonotic parasitic worms in humans, and is distributed in several countries with more than 15 million people infected globally. However, the lack of a point-of-care testing (POCT) method is still the critical barrier to effectively prevent clonorchiasis. With the application of novel fluorescent nanomaterials, the development of on-site testing methods with high signal enhancement can provide a simple, precise and inexpensive tool for disease detection. In this study, Eu-(III) nanoparticles (EuNPs) were used as indicative probes, combined with C. sinensis tandem repeat sequence 1 (CSTR1) antigen to capture specific antibodies. Afterward, the complex binds to mouse anti-human IgG immobilized on the test line (T-line) producing a fluorescent signal under UV light. The EuNPs-fluorescent immunoassay (EuNPs-FIA) was successfully constructed, allowing sample detection within 10 min. It enabled both qualitative determination with the naked eye under UV light and quantitative detection by scanning the fluorescence intensity on the test line and control line (C-line). A total of 133 clinical human sera (74 negative, 59 clonorchiasis, confirmed by conventional Kato-Katz (KK) methods and PCR via testing fecal samples corresponding to each serum sample) were used in this study. For qualitative analysis, the cut-off value of fluorescence for positive serum was 31.57 by testing 74 known negative human samples. The assay had no cross-reaction with other 9 parasite-infected sera, and could recognize the mixed infection sera of C. sinensis and other parasites. The sensitivity and specificity of EuNPs-FIA were both 100% compared with KK smear method. Taking advantage of its high precision and user-friendly procedure, the established EuNPs-FIA provides a powerful tool for the diagnosis and epidemiological survey of clonorchiasis.