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Abstract Background Due to a special hemodynamic feature, pulmonary vascular disease in pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) has two stages: reversible and irreversible. So far, the mechanism involved in the transition from reversible to irreversible stage is elusive. Moreover, no recognized and reliable assessments to distinguish these two stages are available. Furthermore, we found that compared with control and reversible PAH, thrombospondin-4 (THBS4) was significantly upregulated in irreversible group by bioinformatic analysis. Hence, we further verify and investigate the expression and role of THBS4 in PAH-CHD. Methods We established the monocrotaline plus aorto-cava shunt-induced (MCT-AV) rat model. We measured the expression of THBS4 in lung tissues from MCT-AV rats. Double immunofluorescence staining of lung tissue for THBS4 and α-SMA (biomarker of smooth muscle cells) or vWF (biomarker of endothelial cells) to identify the location of THBS4 in the pulmonary artery. Primary pulmonary artery smooth muscle cells (PASMCs) were cultivated, identified, and used in this study. THBS4 was inhibited and overexpressed by siRNA and plasmid, respectively, to explore the effect of THBS4 on phenotype transformation, proliferation, apoptosis, and migration of PASMCs. The effect of THBS4 on pulmonary vascular remodeling was evaluated in vivo by adeno-associated virus which suppressed THBS4 expression. Circulating level of THBS4 in patients with PAH-CHD was measured by ELISA. Results THBS4 was upregulated in the lung tissues of MCT-AV rats, and was further upregulated in severe pulmonary vascular lesions. And THBS4 was expressed mainly in PASMCs. When THBS4 was inhibited, contractile markers α-SMA and MYH11 were upregulated, while the proliferative marker PCNA was decreased, the endothelial-mensenchymal transition marker N-cad was downregulated, proapototic marker BAX was increased. Additionally, proliferation and migration of PASMCs was inhibited and apoptosis was increased. Conversely, THBS4 overexpression resulted in opposite effects. And the impact of THBS4 on PASMCs was probably achieved through the regulation of the PI3K/AKT pathway. THBS4 suppression attenuated pulmonary vascular remodeling. Furthermore, compared with patients with simple congenital heart disease and mild PAH-CHD, the circulating level of THBS4 was higher in patients with severe PAH-CHD. Conclusions THBS4 is a promising biomarker to distinguish reversible from irreversible PAH-CHD before repairing the shunt. THBS4 is a potential treatment target in PAH-CHD, especially in irreversible stage.

IntroductionIn recent years, the frequency and intensity of anthropogenic wildfires have drastically increased, significantly altering terrestrial ecosystems worldwide. These fires not only devastate vegetative cover but also impact soil environments and microbial communities, affecting ecosystem structure and function. The extent to which fire severity, soil depth, and their interaction influence these effects remains unclear, particularly in Pinus tabulaeformis forests.MethodsThis study investigated the impact of wildfire intensity and soil stratification on soil physicochemical properties and microbial diversity within P. tabulaeformis forests in North China. Soil samples were collected from different fire severity zones (Control, Light, Moderate, High) and depths (topsoil: 0–10 cm; subsoil: 10–20 cm). Analyses included measurements of soil pH, organic carbon (SOC), total nitrogen (TN), and other nutrients. Microbial diversity was assessed using 16S rRNA gene sequencing.ResultsOur findings revealed significant variations in soil pH, SOC, TN, and other nutrients with fire severity and soil depth, profoundly affecting microbial community composition and diversity. Soil pH emerged as a critical determinant, closely linked to microbial α-diversity and community structure. We found that fire severity significantly altered soil pH (p = 0.001), pointing to noteworthy changes in acidity linked to varying severity levels. Topsoil microbial communities primarily differentiated between burned and unburned conditions, whereas subsoil layers showed more pronounced effects of fire severity on microbial structures. Analysis of bacterial phyla across different fire severity levels and soil depths revealed significant shifts in microbial communities. Proteobacteria consistently dominated across all conditions, indicating strong resilience, while Acidobacteriota and Actinobacteriota showed increased abundances in high-severity and light/moderate-severity areas, respectively. Verrucomicrobiota were more prevalent in control samples and decreased significantly in fire-impacted soils. Chloroflexi and Bacteroidota displayed increased abundance in moderate and high-severity areas, respectively. Correlation analyses illustrated significant relationships between soil environmental factors and dominant bacterial phyla. Soil organic carbon (SOC) showed positive correlations with total nitrogen (TN) and alkaline hydrolysable nitrogen (AN). Soil pH exhibited a negative correlation with multiple soil environmental factors. Soil pH and available phosphorus (AP) significantly influenced the abundance of the phylum Myxococcota. Soil water content (WC) significantly affected the abundances of Acidobacteriota and Actinobacteriota. Additionally, ammonium nitrogen (NH4+-N) and nitrate nitrogen (NO3−-N) jointly and significantly impacted the abundance of the phylum Chloroflexi.DiscussionThis study highlights the significant long-term effects of anthropogenic wildfires on soil microenvironment heterogeneity and bacterial community structure in P. tabulaeformis forests in North China, 6 years post-fire. Our findings demonstrate that fire severity significantly influences soil pH, which in turn affects soil nutrient dynamics and enhances microbial diversity. We observed notable shifts in the abundance of dominant bacterial phyla, emphasizing the critical role of soil pH and nutrient availability in shaping microbial communities. The results underscore the importance of soil stratification, as different soil layers showed varying responses to fire severity, highlighting the need for tailored management strategies. Future research should focus on long-term monitoring to further elucidate the temporal dynamics of soil microbial recovery and nutrient cycling following wildfires. Studies investigating the roles of specific microbial taxa in ecosystem resilience and their functional contributions under varying fire regimes will provide deeper insights. Additionally, exploring soil amendments and management practices aimed at optimizing pH and nutrient availability could enhance post-fire recovery processes, supporting sustainable ecosystem recovery and resilience.

Abstract Lysosome, the digestive organelle in eukaryotic cells, plays an important role in the degradation and recirculation of cellular products as well as in maintaining the stability of cellular metabolic microenvironment. Surface‐enhanced Raman scattering (SERS) is a molecular fingerprint technology with high detection sensitivity and photostability, suited for revealing various intracellular molecular information by inducing endocytosis of SERS‐active nanoparticles. However, it remains challenging to selectively extract the molecular information of specific organelles (e.g., lysosomes) from a high‐dimensional spectral set. Herein, we proposed a novel paradigm by combining label‐free SERS spectroscopy with confocal fluorescence imaging to investigate the digestion behavior of lysosomes in cells. The structural similarity algorithm was innovatively introduced and exhibited its effectiveness in screening out the wavenumbers in the SERS spectral set with high correlation with the metabolic behaviors of lysosomes. With comprehensive experiments on HeLa single cells, we captured the intracellular macromolecular digestion phenomenon and discovered the changing pattern of cellular SERS spectra after starvation‐induced autophagy, and analyzed the molecular information within the lysosomes in three‐dimensional space.

In the realm of real-time spaceborne synthetic aperture radar (SAR) imaging, the accurate and swift phase factors calculation (PFC) holds significant importance. This article introduces an innovative advanced RISC machines (ARM) field-programmable gate array (FPGA) hybrid acceleration technique designed to expedite the phase factor computation process of SAR imaging. By combing the strengths of ARM and FPGA, our approach achieves optimal performance. The proposed methodology strategically allocates the initial and intermediate calculations to ARM, while delegating the intricate exponential functions to FPGA. By incorporating a parallel four-channel coordinated rotation digital computer (CORDIC) structure and redundancy-based fault tolerant modules with error correction codes, the protection of soft errors is realized and the reliability is improved. By utilizing a modified three-tiered reconfigurable processing elements exchange network for fault tolerant CORDIC processors, the acceleration of computing time is realized and hardware overhead is reduced. A comprehensive prototype verification illustrates the method's efficacy for PFC in spaceborne SAR imaging. The evaluation of computational time and resource utilization unveils ARM's suitability for the initial two levels, while the complexities and precision of the third level warrant FPGA computing acceleration. Overall, this research advances a novel ARM-FPGA hybrid strategy that elevates phase factor computation in spaceborne SAR imaging, opening up avenues for efficient and dependable radar imaging applications.

Abstract Bone morphogenetic protein (BMP) signaling plays a vital role in differentiation, organogenesis, and various cell processes. As a member of TGF‐β superfamily, the BMP initiation usually accompanies crosstalk with other signaling pathways and simultaneously activates some of them. It is quite challenging to solely initiate an individual pathway. In this study, an opsin‐free optical method to specifically activate BMP receptors (BMPR) and subsequent pSmad1/5/8 cascades by a single‐time scan of a tightly‐focused femtosecond laser in the near infrared range is reported. Via transient two‐photon excitation to intrinsic local flavins near the cell membrane, the photoactivation drives conformational changes of preformed BMPR complexes to enable their bonding and phosphorylation of the GS domain in BMPR‐I by BMPR‐II. The pSmad1/5/8 signaling is initiated by this method, while p38 and pSmad2 are rarely perturbed. Based on a microscopic system, primary adipose‐derived stem cells in an area of 420 × 420 µm2 are photoactivated by a single‐time laser scanning for 1.5 s and exhibit pSmad1/5/8 upregulation and osteoblastic differentiation after 21 days. Hence, an opsin‐free, specific, and noninvasive optical method to initiate BMP signaling, easily accomplished by a two‐photon microscope system is reported.

Atrial septal aneurysm (ASA) is defined as excursion of the atrial septum exceeding 10 mm beyond the atrial septum into the right or left atrium, or a combined total excursion of 15 mm on the right and left sides during the cardiac cycle. According to previous studies, 20–40% of patent foramen ovale (PFO) cases are accompanied by ASAs. ASA is associated with the presence of PFO, left atrial dysfunction, cryptogenic stroke, migraine, and arterial embolism, thus making closure of PFO in patients with concomitant ASA necessary but challenging. The anatomy of ASAs associated with PFO has crucial effects on complications after the closure procedure; therefore, several factors must be considered. Herein, we review the clinical implications of concomitant PFO and ASA; discuss the complications occurring after the closure procedure; and provide practical guidance for the closure of concomitant PFO and ASA.

The direct copolymerization of ethylene with polar monomers to produce functional polyolefins continues to be highly appealing due to its simple operation process and controllable product microstructure. Low-cost nickel catalysts have been extensively utilized in academia for the synthesis of polar polyethylenes. However, the development of high-temperature copolymerization catalysts suitable for industrial production conditions remains a significant challenge. Classified by the resultant copolymers, this review provides a comprehensive summary of the research progress in nickel complex catalyzed ethylene-polar monomer copolymerization at elevated temperatures in the past five years. The polymerization results of ethylene–methyl acrylate copolymers, ethylene-tert–butyl acrylate copolymers, ethylene–other fundamental polar monomer copolymers, and ethylene–special polar monomer copolymers are thoroughly summarized. The involved nickel catalysts include the phosphine-phenolate type, bisphosphine-monoxide type, phosphine-carbonyl type, phosphine-benzenamine type, and the phosphine-enolate type. The effective modulation of catalytic activity, molecular weight, molecular weight distribution, melting point, and polar monomer incorporation ratio by these catalysts is concluded and discussed. It reveals that the optimization of the catalyst system is mainly achieved through the methods of catalyst structure rational design, extra additive introduction, and single-site catalyst heterogenization. As a result, some outstanding catalysts are capable of producing polar polyethylenes that closely resemble commercial products. To achieve industrialization, it is essential to further emphasize the fundamental science of high-temperature copolymerization systems and the application performance of resultant polar polyethylenes.

Most research conducted so far has primarily focused on pile-supported gravel embankments. The ability of solidified soil used as an embankment filling material has been verified, and a clear view on the performance of solidified soil embankments on piled foundations is rather limited. The three-dimensional unit cell models of pile-supported embankments are conducted to investigate the performance of solidified soil embankments in comparison to gravel embankments under static and dynamic loads. Then, a systematic parametric analysis is performed to investigate the effects of various factors, including the cohesion and friction of solidified soil, the velocity and wheel load of vehicles, the pile spacing, the height of embankments. The results show that, compared with the results of gravel embankments, the heights of the outer soil arch plane in solidified soil embankments reduces under static and dynamic loads, and the piles bear more load. In addition, the total settlements of solidified soil embankments decrease with increasing cohesions, and there is an economical cohesion of 25 kPa. The vehicle wheel load, pile spacing, and the height of embankment significantly influence the load transfer mechanism and total settlement of solidified soil embankment, while the friction angles and velocities have little effect on the total settlements and vertical stress. The relationship between the soil arch height and various parameters in solidified soil embankments is established by multiple regression analysis. This investigation highlights the advantage of solidified soil in reducing total settlement and provides an insightful understanding of the load transfer mechanism of solidified soil embankment on piled foundation.

Maximum Dry Density (MDD) and Optimum Moisture Content (OMC) are two important parameters of soil filling, which affect the soil stability and bearing capacity, and thus the reliability and durability of facilities such as highways and bridges. Therefore, it is important to make reasonable predictions of OMC and MDD. Four machine learning algorithms, namely, Support Vector Machine (SVM), Artificial Neural Network (ANN), Random Forest (RF), and Extreme Gradient Boosting Tree (XGBoost), are adopted in this paper to establish MDD and OMC prediction models. After training and testing, the best models of the four algorithms are compared. The results show that, as an ensemble learning algorithm, XGBoost is the best model for predicting MDD and OMC, with an R2 of 0.9234 for OMC, and an R2 of 0.9098 for MDD. Finally, the feature importance analysis concludes that the plastic limit (PL) and the liquid limit (LL) are the two features that affect OMC and MDD the most. The prediction of soil compaction parameters using machine learning models, especially ensemble learning, can significantly reduce the amount of laboratory work and improve the efficiency of optimizing design for soil resource utilization in engineering construction.

This study aims to optimize the sustainable utilization of excavated soil by incorporating it exclusively as a fine aggregate and cement in the formulation of soil-based controlled low-strength materials. The polycarboxylate superplasticizer was introduced to enhance flowability. Various factors, including the cement contents, initial water contents, and curing time, were systematically analyzed for their effects on the fresh properties, mechanical parameters, transverse relaxation time distribution, pore size distribution, porosity, and corrosivity of soil-based controlled low-strength materials. The results indicate that polycarboxylate superplasticizer effectively dispersed clay minerals and cement particles, enhancing the flowability. The unconfined compressive strength increased with the rising cement content and decreased with the increasing initial water content. Additionally, the transverse relaxation time distribution curves of the soil-based controlled low-strength materials exhibited two peaks. These curves shifted to smaller transverse relaxation time values with the increasing cement content, while gradually shifting to larger transverse relaxation time values with the increasing initial water content. An increase in the cement content resulted in higher volume percentages of small and mesopores, while extra-large pores and macropores decreased. The addition of the polycarboxylate superplasticizer had minimal impact on the pore volume percentage distribution. Furthermore, porosity experienced a decline with the rise in the cement content and curing time, in contrast to a notable increase with a higher initial water content. This investigation provides valuable insights into the engineering properties and microstructural characteristics of soil-based controlled low-strength materials, offering a foundation for sustainable waste management practices in geotechnical applications.

The calculation of the factor of safety (FOS) is an important means of slope evaluation. This paper proposed an improved double strength reduction method (DRM) to analyze the safety of layered slopes. The physical properties of different soil layers of the slopes are different, so the single coefficient strength reduction method (SRM) is not enough to reflect the actual critical state of the slopes. Considering that the water content of the soil in the natural state is the main factor for the strength of the soil, the attenuation law of shear strength of clayey soil changing with water content is fitted. This paper also establishes the functional relationship between different reduction coefficients. Then, a USDFLD subroutine is programmed using the secondary development function of finite element software. Controlling the relationship between field variables and calculation time realizes double strength reduction applicable to the layered slope. Finally, by comparing the calculation results of different examples, it is proved that the stress and displacement distribution of the critical slope state obtained by the improved method is more realistic, and the calculated safety factor is more reliable. The newly proposed method considers the difference of intensity attenuation between different soil layers under natural conditions and avoids the disadvantage of the strength reduction method with uniform parameters, which provides a new idea and method for stability analysis of layered and complex slopes. [ABSTRACT FROM AUTHOR]

Objective Utilizing a specially engineered miR-144-GFP-H1 human embryonic stem cell (hESC) reporter line, this study leverages GFP fluorescence as an indicator of miR-144 expression to gauge the progression of erythropoiesis. The investigation is aimed at elucidating the potential roles of lncRNAs within the erythropoietic framework and conducting an initial assessment of their functional impact. Methods The miR-144/451-GFP-H1 cell line (hereafter referred to as 144-H1) was utilized for in vitro erythrocyte induction culture. The subpopulations of cells entering the erythropoiesis stage were characterized by the surface molecules CD71 and GPA. The GFP reporter gene of miR-144 served as a critical determinant to distinguish between GFP-positive cells (with a high propensity for erythropoiesis) and GFP-negative cells (with a low propensity for erythropoiesis). Transcriptome sequencing was performed on both groups to identify differentially expressed long non-coding RNAs (lncRNAs). LncRNA entries with potential for validation were selected for preliminary functional verification. The CRISPR/Cas9 gene editing technique was employed to design functional interference strategies for the targeted lncRNAs, obtaining 144-H1 cell lines with knocked-out function of the specific lncRNAs. These knockout cell lines, along with non-knockout 144-H1 cell lines, were used for parallel erythrocyte induction culture to identify differential nodes. This approach preliminarily verified their impact on erythropoiesis in an in vitro development model. Results 1)The constructed 144-H1 cell line was capable of expressing GFP fluorescence upon entering the stage of in vitro erythrocyte induction, indicating the activation of miR-144/451. 2)Within the CD71, GPA double-positive group, significant differences in lncRNA expression were observed between the GFP-positive and GFP-negative subpopulations. 3) Gene editing strategies involving the deletion of sequence segments capable of effectively interfering with the function of multiple lncRNA entries were designed and verified for successful editing. In the knockout cell lines, parts of the lncRNA sequences were directly deleted. 4)In parallel validation experiments of erythrocyte induction culture, cell lines with LINC01569 knocked out exhibited significant differences in flow cytometric subpopulations and cell proliferation capabilities compared to the non-knockout cell lines: ①The knockout cell lines showed sustained high expression of GFP fluorescence. ②The proportion of the CD71-GPA double-positive group in the knockout cell lines continuously decreased during erythrocyte maturation. ③No significant expression of hemoglobin was observed in the knockout cell lines, lacking the characteristic red color. ④The cell proliferation capability of the knockout cell lines was significantly lower than that of the non-knockout cell lines (P

Abstract How does the human brain construct cognitive maps for decision-making and inference? Here, we conduct an fMRI study on a navigation task in multidimensional abstract spaces. Using a deep neural network model, we assess learning levels and categorized paths into exploration and exploitation stages. Univariate analyses show higher activation in the bilateral hippocampus and lateral prefrontal cortex during exploration, positively associated with learning level and response accuracy. Conversely, the bilateral orbitofrontal cortex (OFC) and retrosplenial cortex show higher activation during exploitation, negatively associated with learning level and response accuracy. Representational similarity analysis show that the hippocampus, entorhinal cortex, and OFC more accurately represent destinations in exploitation than exploration stages. These findings highlight the collaboration between the medial temporal lobe and prefrontal cortex in learning abstract space structures. The hippocampus may be involved in spatial memory formation and representation, while the OFC integrates sensory information for decision-making in multidimensional abstract spaces.

There is limited research on robotic systems designed for Endoscopic Retrograde Cholangiopancreatography (ERCP) procedures using a side-view duodenoscope. The unique structure of the duodenoscope presents challenges to safely and precisely control the distal end pose. Control methods applied can reduce potential medical risks. We have redesigned the control section of the duodenoscope to facilitate its manipulation by a robotic system. An orthogonal compensator is employed to rectify the motion planes to standard planes. A hysteresis compensator based on the Prandtl-Ishlinskii model enables precise control of the distal pose of the duodenoscope. Furthermore, we utilize a contact force prediction model to prevent excessive contact force at the distal end. The performance of the modified duodenoscope is comparable to that of the standard duodenoscope. Following orthogonal compensation, the deviation angles of the motion planes is reduced by 32% to 98%. Post-hysteresis compensation, the root mean square error (RMSE) of the output angle of the distal end is decreased from 8.347° to 4.826°. The accuracy of distal end contact force prediction was approximately ±25% under conditions of high contact force. In conclusion, the modification and control strategy we proposed can achieve relatively safe and precise control of bending section, laying the foundation for the subsequent roboticization of duodenoscope systems for ERCP procedures.

Vortex beams carrying orbital angular momentum (OAM) provide a new degree of freedom for light waves in addition to the traditional degrees of freedom, such as intensity, phase, frequency, time, and polarization. Due to the theoretically unlimited orthogonal states, the physical dimension of OAM is capable of addressing the problem of low information capacity. With the advancement of the OAM optical communication technology, OAM router devices (OAM-RDs) have played a key role in significantly improving the flexibility and practicability of communication systems. In this review, major breakthroughs in the OAM-RDs are summarized, and the latest technological standing is examined. Additionally, a detailed account of the recent works published on techniques related to the OAM-RDs has been categorized into five areas: channel multicasting, channel switching, channel filtering, channel hopping, and channel adding/extracting. Meanwhile, the principles, research methods, advantages, and disadvantages are discussed and summarized in depth while analyzing the future development trends and prospects of the OAM-RDs.