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Abstract Revealing key factors that modulate the regioselectivity in heterogeneous hydroformylation requires identifying and monitoring the dynamic evolution of the truly active center under real reaction conditions. However, unambiguous in situ characterizations are still lacking. Herein, we elaborately construct a series of Rh-POPs catalysts for propylene hydroformylation which exhibited tunable regioselectivity. Multi-technique approaches reveal the unique microenvironment of the diverse HRh(CO)(PPh3-frame)2 sites with distinct P-Rh-P bite angles ranging from 90° to 120° and 158° to 168°, respectively. In situ time-resolved XAFS, FT-IR, and quasi-in situ Solid-state NMR experiments combined with DFT calculations explain the dynamic evolution of the electronic and coordinate state of the distinct active sites induced by hemilabile PPh3-frame ligands and further disclose the regulatory mechanism of regioselectivity. These state-of-the-art techniques and multiscale analysis advance the understanding of how hemilabile coordination influences regioselectivity and will provide a new thought to modulate the regioselectivity in future industrial processes.

Abstract Ru single-atom catalysts have great potential to replace toxic mercuric chloride in acetylene hydrochlorination. However, long-term catalytic stability remains a grand challenge due to the aggregation of Ru atoms caused by over-chlorination. Herein, we synthesize an asymmetric Ru-In atomic pair with vinyl chloride monomer yield (>99.5%) and stability (>600 h) at a gas hourly space velocity of 180 h−1, far surpassing those of the Ru single-atom counterparts. A combination of experimental and theoretical techniques reveals that there is a strong d-p orbital interaction between Ru and In atoms, which not only enables the selective adsorption of acetylene and hydrogen chloride at different atomic sites but also optimizes the electron configuration of Ru. As a result, the intrinsic energy barrier for vinyl chloride generation is lowered, and the thermodynamics of the chlorination process at the Ru site is switched from exothermal to endothermal due to the change of orbital couplings. This work provides a strategy to prevent the deactivation and depletion of active Ru centers during acetylene hydrochlorination.

Abstract Background The Omicron variant broke out in China at the end of 2022, causing a considerable number of severe cases and even deaths. The study aimed to identify risk factors for death in patients hospitalized with SARS-CoV-2 Omicron infection and to establish a scoring system for predicting mortality. Methods 1817 patients were enrolled at eight hospitals in China from December 2022 to May 2023, including 815 patients in the training group and 1002 patients in the validation group. Forty-six clinical and laboratory features were screened using LASSO regression and multivariable logistic regression. Results In the training set, 730 patients were discharged and 85 patients died. In the validation set, 918 patients were discharged and 84 patients died. LASSO regression identified age, levels of interleukin (IL) -6, blood urea nitrogen (BUN), lactate dehydrogenase (LDH), and D-dimer; neutrophil count, neutrophil-to-lymphocyte ratio (NLR) as associated with mortality. Multivariable logistic regression analysis showed that older age, IL-6, BUN, LDH and D-dimer were significant independent risk factors. Based on these variables, a scoring system was developed with a sensitivity of 83.6% and a specificity of 83.5% in the training group, and a sensitivity of 79.8% and a sensitivity of 83.0% in the validation group. Conclusions A scoring system based on age, IL-6, BUN, LDH and D-dime can help clinicians identify patients with poor prognosis early.

Abstract Background AP2/ERF is a large family of plant transcription factor proteins that play essential roles in signal transduction, plant growth and development, and responses to various stresses. The AP2/ERF family has been identified and verified by functional analysis in various plants, but so far there has been no comprehensive study of these factors in Chinese prickly ash. Phylogenetic, motif, and functional analyses combined with transcriptome analysis of Chinese prickly ash fruits at different developmental stages (30, 60, and 90 days after anthesis) were conducted in this study. Results The analysis identified 146 ZbAP2/ERF genes that could be classified into 15 subgroups. The motif analysis revealed the presence of different motifs or elements in each group that may explain the functional differences between the groups. ZbERF13.2, ZbRAP2-12, and ZbERF2.1 showed high levels of expression in the early stages of fruit development. ZbRAP2-4, and ZbERF3.1 were significantly expressed at the fruit coloring stage (R2 and G2). ZbERF16 were significantly expressed at fruit ripening and expression level increased as the fruit continued to develop. Relative gene expression levels of 6 representative ZbAP2/ERFs assessed by RT-qPCR agreed with transcriptome analysis results. Conclusions These genes identified by screening can be used as candidate genes that affect fruit development. The results of the analysis can help guide future genetic improvement of Chinese prickly ash and enrich our understanding of AP2/ERF transcription factors and their regulatory functions in plants.

Abstract Translationally controlled tumor protein (TCTP), also known as histamine-releasing factor (HRF) or fortilin, is a highly conserved protein found in various species. To date, multiple studies have demonstrated the crucial role of TCTP in a wide range of cellular pathophysiological processes, including cell proliferation and survival, cell cycle regulation, cell death, as well as cell migration and movement, all of which are major pathogenic mechanisms of tumorigenesis and development. This review aims to provide an in-depth analysis of the functional role of TCTP in tumor initiation and progression, with a particular focus on cell proliferation, cell death, and cell migration. It will highlight the expression and pathological implications of TCTP in various tumor types, summarizing the current prevailing therapeutic strategies that target TCTP.

Objective To investigate the reasonable serological detection method by analyzing the characteristics of anti-K and anti-Wra from a patient who received treatment with daratumumab. Methods Unexpected antibody screening and identification were performed by saline method, polybrene, cardioagglutinin, dithiothreitol (DTT) treatment, trypsin treatment and papain treatment in the patient's plasma and acid elution solution. Heat elution test was detected after absorbing patient serum with K antigen negative red blood cells. The characteristics of antibodies were analyzed and their titer was continuously detected. Cross matching was performed after excluding interference of daratumumab. Results Anti-K and anti-Wra were detected in saline and polybrene in the patient's plasma. The patient's elution solution contained daratumumab. DTT or trypsin treatment excluded interference of daratumumab but papain treatment did not. DTT treatment destroyed K antigen and missed the detection of IgG antibodies in the Kell system. Trypsin treatment did not affect K antigen and can detect IgG antibodies of Kell system(anti-k)in the serum of the patient treated with daratumumab. Anti K was IgM and the titer was 4 by saline method and it decreased to no agglutination in room temperature after 39 days. Anti-Wra was IgG and the titer by polybrene method was 4, and it decreased to 1 after 39 days. After 76 days, neither anti-K nor anti-Wra could be detected. Transfusions of K and Wra antigen negative red blood cells were safe and effective. Conclusion DTT treatment can exclude interference of daratumumab, but attention should be paid to missed detection of anti-K. To avoid interference of daratumumab and identify unexpected antibody, multiple methods such as DTT treatment, polybrene and trypsin treatment in combination are recommended.

In this study, a fixed-bed biofilm membrane bioreactor was used to assess denitrification and carbon removal performance, membrane fouling, composition, and the dynamics of microbial communities across 10 salinity levels. As salinity levels increased (from 0 to 30 g/L), the removal efficiency of total nitrogen and chemical oxygen demand decreased from 98 and 86% in Phase I to 25 and 45% in Phase X, respectively. Beyond a salinity level of 10 g/L, membrane fouling accelerated considerably. The analysis of fouling resistance distribution suggested that soluble microbial products (SMPs) were the primary cause of this phenomenon. The irregularity in microbial community succession reflected the varying adaptability of different bacteria to different salinity levels. The relative abundance of Sulfuritalea, Lentimircobium, Thauera, and Pseudomonas increased from 20.2 to 47.7% as the experiments progressed. Extracellular polymeric substances-related analysis suggested that Azospirillum plays a positive role in preserving the structural integrity of the biofilm carrier. The SMP-related analysis showed a positive correlation between Lentimircobium, Thauera, Pseudomonas, and the SMP content. These results suggested that these three bacterial genera significantly promoted the release of SMP under salt stress, which in turn led to severe membrane fouling. HIGHLIGHTS Fixed-bed biofilm membrane bioreactor maintains good performance at low-salinity levels.; Soluble microbial products are the major cause for fixed-bed biofilm membrane bioreactor membrane fouling.; Azospirillum has a positive effect on carrier biofilms.; Lentimicrobium, Pseudomonas, and Thauera are highly correlated with soluble microbial product concentration.;

Abstract Despite the successful application of immune checkpoint therapy, no response or recurrence is typical in lung cancer. Cancer stem cells (CSCs) have been identified as a crucial player in immunotherapy-related resistance. Ferroptosis, a form of cell death driven by iron-dependent lipid peroxidation, is highly regulated by cellular metabolism remolding and has been shown to have synergistic effects when combined with immunotherapy. Metabolic adaption of CSCs drives tumor resistance, yet the mechanisms of their ferroptosis defense in tumor immune evasion remain elusive. Here, through metabolomics, transcriptomics, a lung epithelial-specific Cpt1a-knockout mouse model, and clinical analysis, we demonstrate that CPT1A, a key rate-limiting enzyme of fatty acid oxidation, acts with L-carnitine, derived from tumor-associated macrophages to drive ferroptosis-resistance and CD8+ T cells inactivation in lung cancer. Mechanistically, CPT1A restrains ubiquitination and degradation of c-Myc, while c-Myc transcriptionally activates CPT1A expression. The CPT1A/c-Myc positive feedback loop further enhances the cellular antioxidant capacity by activating the NRF2/GPX4 system and reduces the amount of phospholipid polyunsaturated fatty acids through ACSL4 downregulating, thereby suppressing ferroptosis in CSCs. Significantly, targeting CPT1A enhances immune checkpoint blockade-induced anti-tumor immunity and tumoral ferroptosis in tumor-bearing mice. The results illustrate the potential of a mechanism-guided therapeutic strategy by targeting a metabolic vulnerability in the ferroptosis of CSCs to improve the efficacy of lung cancer immunotherapy.

Chylothorax is a serious postoperative complication of oesophageal cancer, and to date, there is no standardized and effective intraoperative diagnostic tool that can be used to identify the thoracic duct and determine the location of lymphatic fistulas. A 50-year-old patient with oesophageal squamous cell carcinoma developed chylothorax after thoracolaparoscopy combined with radical resection of oesophageal cancer. Twelve hours after surgery, 1200 mL of clear fluid was drained from the thoracic drainage tube, and a chyle test was sent. A thoracothoracic duct ligation procedure was performed on the first day after surgery. Although fluid accumulating in the posterior mediastinum was observed, the location of the lymphatic fistula could not be determined. During the surgery, indocyanine green (ICG) was injected into the bilateral inguinal lymph nodes, and a fluorescent lens was used to determine the location of the lymphatic fistula so the surgeon could ligate the thoracic duct. ICG fluorescence imaging technology can help surgeons effectively manage chylothorax after oesophageal cancer surgery. To our knowledge, this is the first report to describe the use of ICG fluorescence imaging technology to treat postoperative chylothorax in patients with oesophageal cancer in China.

Abstract The increasing prevalence of wearable devices has sparked a growing interest in real‐time health monitoring and physiological parameter tracking. This study focuses on the development of a cost‐effective sweat analysis device, utilizing microfluidic technology and selective electrochemical electrodes for non‐invasive monitoring of glucose and potassium ions. The device, through real‐time monitoring of glucose and potassium ion levels in sweat during physical activity, issues a warning signal when reaching experimentally set thresholds (K+ concentration at 7.5 mM, glucose concentrations at 60 μM and 120 μM). This alerts users to potential dehydration and hypoglycemic conditions. Through the integration of microfluidic devices and precise electrochemical analysis techniques, the device enables accurate and real‐time monitoring of glucose and potassium ions in sweat. This advancement in wearable technology holds significant potential for personalized health management and preventive care, promoting overall well‐being, and optimizing performance during physical activities.

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

Walnuts (Juglans regia L.), renowned for their nutritional potency, are a rich source of unsaturated fatty acids. Their regular intake plays a pivotal role in health maintenance and recuperation from a myriad of ailments. Fatty acyl-acyl carrier protein thioesterases, which orchestrate the hydrolysis of acyl-ACP thioester bonds, thereby yielding fatty acids of varying chain lengths, are instrumental in augmenting plant fatty acid content and modulating the balance between saturated and unsaturated fatty acids. Despite some investigative efforts into the synthesis and metabolic pathways of fatty acids in walnuts, our comprehension of Fat in walnuts remains rudimentary. This research undertook a comprehensive characterization of the JrFat family, predicated on the complete genome sequence of walnuts, leading to the identification of 8 JrFat genes and an exploration of their protein physicochemical properties. Utilizing Arabidopsis and soybean Fat genes as outgroups, JrFat genes can be categorized into 5 distinct subgroups, three of which encompass a pair of homologous gene pairs. These genes have demonstrated remarkable conservation throughout the evolutionary process, with highly analogous conserved base sequences. The promoter region of JrFats genes predominantly harbors light response and plant hormone response regulatory elements, with no discernible disparity in promoter elements among different JrFats. Predictive analyses indicate that JrFats proteins engage extensively with walnut fatty acid synthesis and metabolism-associated proteins. qRT-PCR analysis reveals an initial surge in the expression of JrFats during the development of walnut kernels, which either stabilizes or diminishes following the hard core period. Homologous gene pairs exhibit analogous expression patterns, and the expression trajectory of JrFats aligns with the dynamic accumulation of fatty acids in kernels. The expression of JrFatA2 exhibits a strong correlation with the content of Alpha-linolenic acid, while the expression of JrFatB2 is inversely correlated with the content of two saturated fatty acids. Collectively, these findings enrich our understanding of fatty acid synthesis and metabolism in walnuts and furnish gene resources for enhancing the content and ratio of fatty acids in walnuts.

Castor bean (Ricinus communis L.) is an important oil crop. However, the influence of transposable elements (TEs) on the dynamics of castor bean evolution awaits further investigation. This study explored the role of transposable elements in the genomes of wild castor bean accessions from Ethiopia (Rc039) and Kenya (WT05) as well as in the cultivated variety (Hale). The distribution and composition of repeat sequences in these three lineages exhibited relative consistency, collectively accounting for an average of 36.7% of the genomic sequences. Most TE families displayed consistent lengths and compositions across these lineages. The dynamics of TEs significantly differed from those of genes, showing a lower correlation between the two. Additionally, the distribution of TEs on chromosomes showed an inverse trend compared to genes. Furthermore, Hale may have originated from the ancestor of Rc039. The divergent evolutionary paths of TEs compared to genes indicate the crucial role of TEs in shaping castor bean genetics and evolution, providing insights into the fields of castor bean and plant genomics research.

This study investigates the effects of steel fiber shape (straight and hooked-end) and content (0, 0.5, 1.0, and 1.5 vol%) on rheological properties, printability, mechanical performance and microstructure of 3D printable steel fiber reinforced high strength concrete (3DP-SFHSC). The results indicate that the increase of fiber content improves the mechanical behaviors of 3DP-SFHSC, but the extrudability suffers from reduction when the fiber content exceeded 1.0 vol% due to the significant increase in yield stress. The addition of 1.5 vol% hooked-end fibers enhances the compressive strength of 3DP-SFHSC by 8%, 25.7%, and 40.4% in the X, Y, and Z directions, respectively. Additionally, it also improves the tensile strength in the X direction by 37.67%. The printed specimens exhibit weaker mechanical properties compared to the cast specimens. On the one hand, the lower fiber-matrix compactness resulting from the absence of vibration during printing leads to increased porosity and weak bonding between the steel fibers and matrix. On the other hand, the inconsistent movement between fibers and mortar matrix during extrusion process may also cause the formation of gaps around fibers. Straight fibers show pronounced enhancements in buildability, compressive strength and tensile strength compared to hooked-end fibers at the same fiber volume fraction. Straight fibers align easily during the extrusion process, contributing to a matrix with lower porosity and smaller average pore size.

Study DesignRetrospective radiological analysis.ObjectiveThe aim of this study is to evaluate the distribution of bone mineral density (BMD) in lumbar vertebrae using the Hounsfield unit (HU) measurement method and investigate the clinical implications of HU values for assessing lumbar vertebrae BMD.MethodTwo hundred and ninety-six patients were retrospectively reviewed and divided into six groups according to age: Group 1(20–29 years old), Group 2 (30–39 years old), Group 3 (40–49 years old), Group 4 (50–59 years old), Group 5 (60–69 years old), Group 6 (70–79 years old). Six different locations from each vertebra of L1-L5 were selected as regions of interest: the anterior, middle and posterior parts of the upper and lower slices of the vertebrae. HU values were measured for the six regions of interest, followed by statistical analysis.ResultsThe HU values of vertebrae showed a decreasing trend from young patients to elderly patients in Group 1 to Group 5. There was no significant difference in HU values among different vertebrae in the same age group. In all age groups, the HU values of the anterior and posterior part of the vertebral body were significantly different from L1 to L3, with the anterior part of the vertebral body having lower HU values than the posterior part. The HU values of the anterior and posterior part of the vertebral body of L4 and L5 were statistically significant only in Group 5 and Group 6, and the HU values of the anterior part of the vertebral body were lower than those of the posterior part. The HU values of posterior part of L4 and L5 in Group6 were higher than those in Group5.ConclusionBone mineral density in the lumbar vertebrae is not uniformly distributed, potentially attributed to varying stress stimuli. The assessment of local HU values in the lumbar spine is of significant importance for surgical treatment.

Abstract A wide variety of bridge barriers are used on highways. The bearing capacities of different types of deck slabs are measured in this study by applying the yield line theory to determine the worst-case scenario. An improved configuration for the worst-case barrier base and deck slab is developed, namely the universal double-beam assembled bridge barrier, which can enhance the safety performance of exiting concrete-base bridge barriers. According to the simulated impact test results, the new barrier meets SS-level requirements in terms of containment, redirective, and buffering performance as specified in the Standard for Safety Performance Evaluation of Highway Barriers (JTG B05-01-2013). The barrier structure’s compatibility with various bases is also analyzed. SS-level impact tests are conducted on real vehicles, including cars, buss, and trucks. The results show that the safety performance of the new barrier configuration reaches SS-level, and the barrier is universally compatible with concrete bases with a height of 63 cm and above.

The scattering properties of targets in polarimetric synthetic aperture radar (PolSAR) images are directly influenced by the targets' orientations, as the scattering properties from the same target with different orientations can be very different. This interpretation diversity caused by the target orientations is one of the primary technical bottlenecks in PolSAR image interpretation. In this article, a 3-D convolutional vision transformer (3-D-Conv-ViT) is proposed to describe the relationship between polarimetric coherent matrices with different polarization orientation angles (POAs) for PolSAR image classification and change detection. First, 3-D convolutional neural networks are used to capture the high-level feature representations of the polarimetric coherent matrix sequence. Second, a new Rotation-3-D-ViT block is proposed to learn the local and global representations of the high-level feature maps. The self-attention mechanism in the ViT can express the regularity of polarimetric coherent matrices with different POAs and improve the PolSAR image interpretation performance. Third, combined with different classifiers, the proposed 3-D-Conv-ViT can be applied to both PolSAR image classification and change detection. Experiments on real PolSAR image datasets demonstrate that the proposed method can overcome the problem of the interpretation ambiguity caused by the target orientation. The classification accuracies of the proposed method can reach 94.01%–99.48%, and the change detection accuracies can reach 93.84%–96.86%.

Multimodal Sentiment Analysis (MSA) is gaining attention, but faces two main challenges: efficient extraction of cross-modal features without redundancy and removing spurious correlations between sentiment labels and multimodal features. In this paper, we propose a novel multimodal learning debiasing model, named Bilateral Cross-modal Debias Multimodal sentiment analysis Model (BCD-MM), to address these issues. Specifically, BCD-MM ultimately enhances the generalisation of the model to out-of-distribution (OOD) situations by improving the ability of cross-modal low-redundancy feature extraction and reducing the reliance on non-causal correlations. First, BCD-MM utilizes an attention score-based method to preserve critical information and eliminate redundancy within modalities. It also employs a gated crossmodal attention mechanism to filter inconsistencies through modal interaction, thereby enhancing the extraction of cross-modal specific features. Second, BCD-MM incorporates a debiasing approach with double bias extraction, using a Tanh-based Mean Absolute Error (TMAE) loss function and inverse probability weighting to mitigate spurious correlations. Finally, extensive testing on three public datasets (MOSI, MOSEI, and SIMS) and two OOD datasets (OOD MOSI and OOD MOSEI) demonstrates our model’s effectiveness in both MSA and debiasing tasks.

Plant functional traits are indicative of plant responses to environmental changes, influencing ecosystem functions. Leaves, as a key focus in studying plant functional traits, present an area where the impact of nitrogen deposition and altered rainfall patterns on functional diversity remains ambiguous. To elucidate plant response mechanisms to environmental factors, we employed a canopy-based platform to add nitrogen, water, and their combination. We assessed the functional traits and community-weighted mean of the leaves of three dominant trees and three dominant shrubs. The results showed that nitrogen addition to the canopy significantly increased the leaf dry matter content of the Celtis sinensis Pers, but markedly decreased the specific leaf area of the Liquidambar formosana Hance. The nitrogen-water interaction did not notably affect the specific leaf area and equivalent water thickness of leaves. Canopy addition of nitrogen, water, and their combined interaction substantially lowered leaf nitrogen content and markedly increased leaf C/N. The structural equation model demonstrated a significant negative correlation between leaf dry matter content, equivalent water thickness, and leaf nitrogen content, as well as between equivalent water thickness and leaf phosphorus content. Our results provide evidence for the adaptation of plants to the environment and different strategies for resource and energy utilization.

The 1/6g environment simulation system is essential in scientific research, exploration, and future space development. The system is technically demanding and must accurately simulate a low-gravity environment while ensuring the reliability and precision of the experiment, which involves complex machinery and control systems that are technically challenging. This paper proposes a new simulation experiment method that combines the traditional hanging low-gravity simulation method and magnetic levitation technology.Realization of the design of the magnetic levitation suspended low gravity simulation system. The magnetically levitated overhead crane, which counteracts 5/6 of the lunar rover’s gravity, is the most important component of the entire test system. The article first designs the principle scheme of the magnetically levitated hanging active following a low gravity simulation system, which reduces the influence of the bulky wheel slip structure of the existing equipment on the experiment and improves the system’s anti-interference ability. Secondly, the article establishes the dynamics model of the magnetic suspension crane tracking system, analyzes and derives the relationship between the force, the magnetic suspension air gap and the voltage, and lays a theoretical foundation for the smooth operation of the precise control system. Finally, based on the cross-coupling control strategy, the magnetic suspension crane following control system is designed and the cross-coupling control system model is established.

In spaces with any dimension, a class of logarithmic wave equations with Balakrishnan-Taylor damping, nonlinear weak damping and strong linear damping was considered $ {u_{tt}} - M(t)\Delta u + \left( {g * \Delta u} \right)(t) + h({u_t}){u_t} - \Delta {u_t} + f(u) + u = u\ln {\left| u \right|^k} $ with Dirichlet boundary condition. Under a set of specified assumptions, we established the existence of global weak solutions and elucidated the decay rate of the energy function for particular initial data. This contribution extended and surpassed prior investigations, as documented by A. Peyravi (2020), which omitted the consideration of Balakrishnan-Taylor damping and strong linear damping while being confined to three spatial dimensions. Our findings underscored the pivotal role of these overlooked damping factors. Furthermore, our demonstration underscored that Balakrishnan-Taylor damping, weak damping and strong damping collectively induced an exponential decay, although the precise nature of this decay was contingent upon the differentiable function associated with the memory damping term $ {\zeta (t)} $. Consequently, the absence of the damping term in reference by A. Peyravi (2020) was unequivocally shown not to augment the decay rate. This insight enhanced our understanding of the nuanced dynamics involved and contributed to the refinement of existing models.

In recent years, change detection (CD) of optical remote sensing images has made remarkable progress through using deep learning. However, current CD deep learning methods are usually improved from the semantic segmentation models, and focus on enhancing the separability of changed and unchanged features. They ignore the essential characteristics of CD, i.e., different land cover changes exhibit different change magnitudes, resulting in limited accuracy and serious false alarms. To address this limitation, in this article, a category context learning-based difference refinement network (CLDRNet) based on our previous work is proposed. Considering the semantic content differences of heterogeneous land covers, a category context learning module is designed, which introduces a clustering learning procedure to generate an overall representation for each category, guiding the category context modeling. The clustering learning process is differentiable and can be integrated into the end-to-end trainable CD network, so it considers the semantic content differences from the CD perspective, thereby improving the CD performance. In addition, to address the magnitude differences of different land cover changes, a two-stage CD strategy is introduced. The two stages correspond to difference map learning and difference map refinement, aiming at ensuring high detection rates and revising false alarms, respectively. Finally, experimental results on three CD datasets verify the effectiveness of our CLDRNet in both visual and quantitative analysis.

Argatroban is a synthetic thrombin inhibitor approved by U.S. Food and Drug Administration for the treatment of thrombosis. However, whether it plays a role in the repair of spinal cord injury is unknown. In this study, we established a rat model of T10 moderate spinal cord injury using an NYU Impactor Moder III and performed intraperitoneal injection of argatroban for 3 consecutive days. Our results showed that argatroban effectively promoted neurological function recovery after spinal cord injury and decreased thrombin expression and activity in the local injured spinal cord. RNA sequencing transcriptomic analysis revealed that the differentially expressed genes in the argatroban-treated group were enriched in the JAK2/STAT3 pathway, which is involved in astrogliosis and glial scar formation. Western blotting and immunofluorescence results showed that argatroban downregulated the expression of the thrombin receptor PAR1 in the injured spinal cord and the JAK2/STAT3 signal pathway. Argatroban also inhibited the activation and proliferation of astrocytes and reduced glial scar formation in the spinal cord. Taken together, these findings suggest that argatroban may inhibit astrogliosis by inhibiting the thrombin-mediated PAR1/JAK2/STAT3 signal pathway, thereby promoting the recovery of neurological function after spinal cord injury.

The enhanced Coulomb interaction in two dimensions leads to not only tightly bound excitons but also many-particle excitonic complexes: excitons interacting with other quasiparticles, which results in improved and even new exciton properties with better controls. Here, we summarize studies of excitonic complexes in monolayer transition metal dichalcogenides and their moiré heterojunctions, envisioning how to utilize them for exploring quantum many-body physics.

Abstract Background Hypoxic pulmonary hypertension (HPH) is a common type of pulmonary hypertension and characterized by pulmonary vascular remodeling and constriction. A large number of studies have shown that pulmonary vascular endothelial cells (PVECs) dysfunction plays an important role in the initiation and development stages of HPH, but the mechanism of PVECs dysfunction after hypoxia remains unclear. In this study, we explored the exact mechanism of PVECs dysfunction after hypoxia. Methods In vitro, we used primary cultured PVECs hypoxia model to mimic HPH injury. We detected the expressions of mitochondrial biogenesis markers, mitochondrial transcription factor A (TFAM) level inside mitochondria, mitochondrial quantity and function, and the components expressions of translocase of outer mitochondrial membrane (TOM) at 24 h after hypoxia. To explore the effects of Tom70 on mitochondrial biogenesis and functions of PVECs after hypoxia, Tom70 overexpression adenovirus was constructed, and the expressions of mitochondrial biogenesis markers, TFAM level inside mitochondria, mitochondrial quantity and function, and the functions of PVECs were detected. And in vivo, we used cre-dependent overexpression adenovirus of Tom70 in the Cdh5-CreERT2 mouse model of HPH to verify the role of upregulating PVECs Tom70 in improving HPH. Results Hypoxia obviously increased the expressions of mitochondrial biogenesis markers for PGC-1α, NRF-1 and TFAM, but reduced the content of TFAM in mitochondria and the quantity and functions of mitochondria. In addition, only Tom70 expression among the TOM components was significantly decreased after hypoxia, and up-regulation of Tom70 significantly increased the content of TFAM in mitochondria of PVECs by transporting TFAM into mitochondria after hypoxia, enhanced the quantity and functions of mitochondria, improved the functions of PVECs, and ultimately alleviated HPH. Conclusion The findings of present study demonstrated that hypoxia induced the decreased expression of Tom70 in PVECs, reduced the mitochondrial biogenesis-associated TFAM protein transporting into mitochondria, inhibited mitochondrial biogenesis, caused PVECs injury, and prompted the formation of HPH. However, up-regulation of Tom70 abolished the hypoxia-induced injurious effects on PVECs and alleviated HPH.

In recent years, RS and GIS technologies have played an increasingly important role in various aspects of rainfall induced landslide research. In order to systematically understand their application situation, this paper extensively used various visualization analysis technologies for in-depth analysis of 1,161 documents collected by the WOS data platform in the past 27 years by combining quantitative and qualitative methods. Then, this article focuses on sub domain analysis from four aspects: landslide detection and monitoring, prediction models, sensitivity mapping, and risk assessment. The study found that the number of literature in this field has steadily increased and is expected to continue to rise. This literature review has attracted widespread attention from the academic community, but it is challenging to meet research needs. Frequent and effective cooperation between countries, institutions, and authors is very beneficial for promoting progress in this field. The future development direction is a new intelligent hybrid model that integrates multiple research methods. This study can provide researchers in this field with the core research force, hot topic evolution, and future development trends of future rainfall-induced landslides and contribute to landslide prevention and control decision-making and achieving the United Nations’sustainable development goals.

Randomized clinical trials (RCTs) of PCSK9 monoclonal antibody(mAb) specifically for Chinese patients have been limited. This multi-center RCT is to clarify the efficacy and safety of a novel mAb, Ebronucimab, in Chinese patients. Patients diagnosed with primary hypercholesterolemia, including Heterozygous Familial Hypercholesterolemia, or mixed dyslipidemia, were categorized by ASCVD risk and randomly assigned at a ratio of 2:1:2:1 to receive Ebronucimab 450 mg or matching placebo every 4 weeks (Q4W), or Ebronucimab 150 mg or matching placebo every 2 weeks (Q2W). The primary outcome was the percentage change of LDL-C from baseline to week 12 for all groups. The least squares mean reduction difference (95 %CI) in LDL-C from baseline to week 12 of Ebronucimab 450 mg Q4W and Ebronucimab 150 mg Q2W groups versus the placebo group was −59.13 (-64.103, −54.153) (Adjusted p

To promote the application of nanorefrigerant in Organic Rankine Cycle and Integrated Energy System a reliable model with simple structure and favorable accuracy for predicting the flow boiling heat transfer coefficient (HTC) of nanorefrigerant is essential. In this work, four intelligence models—the radial basis function (RBF), multilayer perceptron (MLP), least squares support vector machine (LSSVM), and adaptive neuro fuzzy inference system (ANFIS)—were developed to predict the flow boiling heat transfer coefficient using nanorefrigerants, based on 765 experimental samples. The performances of these artificial intelligence models were comprehensively evaluated through accuracy analysis, variation trend analysis, and sensitivity analysis. Results indicated that the comprehensive performance of the RBF model was superior than those of other intelligence models and the existing empirical models. The RBF model accurately captured the variation trend of the output as the input variables were varied. Meanwhile, the impact degrees of all input variables in decreasing order were nanoparticle concentration (φ), mass flux (G), thermal conductivity of nanoparticle (kp), and vapor quality (x).

Oxidative stress and iron accumulation-induced ferroptosis occurs in injured vascular cells and can promote thrombogenesis. Transferrin receptor 1 (encoded by the TFRC gene) is an initial element involved in iron transport and ferroptosis and is highly expressed in injured vascular tissues, but its role in thrombosis has not been determined. To explore the potential mechanism and therapeutic effect of TFRC on thrombogenesis, a DVT model of femoral veins (FVs) was established in rats, and weighted correlation network analysis (WGCNA) was used to identify TFRC as a hub protein that is associated with thrombus formation. TFRC was knocked down by adeno-associated virus (AAV) or lentivirus transduction in FVs or human umbilical vein endothelial cells (HUVECs), respectively. Thrombus characteristics and ferroptosis biomarkers were evaluated. Colocalization analysis, molecular docking and coimmunoprecipitation (co-IP) were used to evaluate protein interactions. Tissue-specific TFRC knockdown alleviated iron overload and redox stress, thereby preventing ferroptosis in injured FVs. Loss of TFRC in injured veins could alleviate thrombogenesis, reduce thrombus size and attenuate hypercoagulability. The protein level of thrombospondin-1 (THBS1) was increased in DVT tissues, and silencing TFRC decreased the protein level of THBS1. In vitro experiments further showed that TFRC and THBS1 were sensitive to erastin-induced ferroptosis and that TFRC knockdown reversed this effect. TFRC can interact with THBS1 in the domain spanning from TSR1-2 to TSR1-3 of THBS1. Amino acid sites, including GLN320 of TFRC and ASP502 of THBS1, could be potential pharmacological targets. Erastin induced ferroptosis affected extracellular THBS1 levels and weakened the interaction between TFRC and THBS1 both in vivo and in vitro, and promoted the interaction between THBS1 and CD47. This study revealed a linked relationship between venous ferroptosis and coagulation cascades. Controlling TFRC and ferroptosis in endothelial cells can be an efficient approach for preventing and treating thrombogenesis.

The selection of targets with specific masses, including molecules, atoms, and clusters, has broad applications in spectrometry. As an ion mass-gate with a very high resolution, Bradbury–Nielsen Gates (BNGs) are widely used in the study of size-dependent effects of clusters. Here, wepresent a simple and low-cost method for fabricating high resolution BNGs using a printed circuit board and a 3D printed wire winding and transfer tool. It can produce a pitch of 400 µm with 25 µm diameter tungsten wires. The test results indicate that its resolution reaches more than 1500 when it couples with a homemade ultrafast voltage switch.

Consuming foods with excess sulfonamide residues threatens human health, underscoring the importance of their detection in food. This study presents an innovative one-pot derivatization/magnetic solid-phase extraction (OPD/MSPE) method for sulfonamides analysis. This approach integrates the derivatization and extraction steps into a single process. The sample solution, along with the derivatization reagent fluorescamine and the sorbent magnetic hydroxyl multi-walled carbon nanotubes, is mixed and vortexed for 3 min. This procedure simultaneously conducts derivatization and extraction, with easy phase separation using an external magnet. This streamlined sample preparation method is completed in only 5 min and, when combined with liquid chromatography-fluorescence detection (LC-FLD), demonstrates excellent linearity (R2 > 0.99) and satisfactory detection limits (0.004–0.04 ng/g) for the quantification of nine sulfonamides in honey samples. The proposed OPD/MSPE-LC-FLD method is distinguished by its simplicity, rapidity, high sensitivity, and specificity, making it an outstanding advancement in the field of food safety analysis.

Abstract In this study, H∞ loop shaping is designed for single‐phase pulse width modulation (PWM) rectifier under current sensor gain faults. Pre‐compensator is used to obtain the desired loop shape at all frequencies and robust stabilization through the normalized coprime factorization. The mathematical model for the rectifier is developed to obtain the nominal plant transfer function, and two algebraic Riccati equations are used to solve the designed controller and obtain the loop shaping controller by combining the designed controller with the weights. ν‐gap metric is adopted to measure the magnitude of the current sensor gain fault that can be stabilized by the controller. The proposed controller is compared with H∞‐mixed sensitivity (H∞‐MS) controller. The robustness capability and dynamic performance is investigated and, hardware‐in‐loop experimental results show excellent balance between robustness and performance in the presence of current sensor gain faults.

Abstract Background Lipid metabolism has a crucial role in neural repair in neurodegenerative diseases. We recently revealed that lipogenesis-mediated interleukin-33 (IL-33) upregulation lead to blood–brain barrier (BBB) repair after ischemic stroke. However, manipulating the key enzyme fatty acid synthase (FASN) to enhance lipogenesis was very challenging. Glyceryl triacetate (GTA) was used as a donor of acetate and precursor of acetyl coenzyme A, the key substrate for de novo lipogenesis catalyzed by FASN. Therefore, we hypothesized that GTA would promote lipogenesis the peri-infarct after ischemic stroke and contribute to the BBB repair through IL-33. Methods Middle cerebral artery occlusion (MCAO) was performed on C57BL mice and GTA was gavage administrated (4 g/kg) on day 2 and 4 after MCAO. Lipogenesis was evaluated by assessment of the protein level of FASN, lipid droplets, and fatty acid products through liquid chromatography-mass spectrometry in the peri-infarct area on day 3 after MCAO, respectively. BBB permeability was determined by extravasation of Evans blue, IgG and dextran, and levels of tight junction proteins in the peri-infarct area on day 7 after MCAO, respectively. Infarct size and neurological defects were assessed on day 7 after MCAO. Brain atrophy on day 30 and long-term sensorimotor abilities after MCAO were analyzed as well. The inhibitor of FASN, C75 and the virus-delivered FASN shRNA were used to evaluate the role of FASN-driven lipogenesis in GTA-improved BBB repair. Finally, the therapeutic potential of recombinant IL-33 on BBB repair and neurological recovery was evaluated. Results We found that treatment with GTA increased the lipogenesis as evidenced by lipid droplets level and lauric acid content, but not the FASN protein level. Treatment with GTA increased the IL-33 level in the peri-infarct area and decreased the BBB permeability after MCAO. However, infarct size and neurological defect score were unchanged on day 7 after MCAO, while the long-term recovery of sensorimotor function and brain atrophy were improved by GTA. Inhibition of lipogenesis using C75 or FASN shRNA reversed the beneficial effect of GTA. Finally, exogenous IL-33 improved BBB repair and long-term functional recovery after stroke. Conclusion Collectively, we concluded that treatment with GTA improved the BBB repair and functional recovery after ischemic stroke, probably by the enhancement of lipogenesis and IL-33 expression. Graphical Abstract

Recent advancements in network and multimedia technologies have facilitated the distribution and sharing of digital videos over the Internet. These long videos contain very complex contents. Additionally, it is very challenging to use as few frames as possible to cover the video contents without missing too much information. There are at least two ways to describe these complex videos contents with minimal frames: the keyframes extracted from the video or the video summary. The former lays stress on covering the whole video contents as much as possible. The latter emphasizes covering the video contents of interest. As a consequence, keyframes are widely used in many areas such as video segmentation and object tracking. In this paper, we propose a keyframe extraction method based on multiple features via a novel combinatorial optimization algorithm. The key frame extraction is modeled as a combinatorial optimization problem. A fast dynamic programming algorithm based on a forward non-overlapping transfer matrix in polynomial time and a 0-1 integer linear programming algorithm based on an overlapping matrix is proposed to solve our maximization problem. In order to quantitatively evaluate our approach, a long video dataset named 'Animal world' is self-constructed, and the segmentation evaluation criterions are introduced. A good result is achieved on 'Animal world' dataset and a public available Keyframe-Sydney KFSYD dataset [1].

The semantic matching problem detects whether the candidate text is related to a specific input text. Basic text matching adopts the method of statistical vocabulary information without considering semantic relevance. Methods based on Convolutional neural networks (CNN) and Recurrent networks (RNN) provide a more optimized structure that can merge the information in the entire sentence into a single sentence-level representation. However, these representations are often not suitable for sentence interactive learning. We design a multi-dimensional semantic interactive learning model based on the mechanism of multiple written heads in the transformer architecture, which not only considers the correlation and position information between different word levels but also further maps the representation of the sentence to the interactive three-dimensional space, so as to solve the problem and the answer can select the best word-level matching pair, respectively. Experimentally, the algorithm in this paper was tested on Yahoo! and StackEx open-domain datasets. The results show that the performance of the method proposed in this paper is superior to the previous CNN/RNN and BERT-based methods.

Abstract Biophysically detailed multi-compartment models are powerful tools to explore computational principles of the brain and also serve as a theoretical framework to generate algorithms for artificial intelligence (AI) systems. However, the expensive computational cost severely limits the applications in both the neuroscience and AI fields. The major bottleneck during simulating detailed compartment models is the ability of a simulator to solve large systems of linear equations. Here, we present a novel Dendritic Hierarchical Scheduling (DHS) method to markedly accelerate such a process. We theoretically prove that the DHS implementation is computationally optimal and accurate. This GPU-based method performs with 2-3 orders of magnitude higher speed than that of the classic serial Hines method in the conventional CPU platform. We build a DeepDendrite framework, which integrates the DHS method and the GPU computing engine of the NEURON simulator and demonstrate applications of DeepDendrite in neuroscience tasks. We investigate how spatial patterns of spine inputs affect neuronal excitability in a detailed human pyramidal neuron model with 25,000 spines. Furthermore, we provide a brief discussion on the potential of DeepDendrite for AI, specifically highlighting its ability to enable the efficient training of biophysically detailed models in typical image classification tasks.

The detection of pathogens in medical wastewater is crucial due to the high content of pathogenic microorganisms that pose significant risks to public health and the environment. Medical wastewater, which includes waste from infectious disease and tuberculosis facilities, as well as comprehensive medical institutions, contains a variety of pathogens such as bacteria, viruses, fungi, and parasites. Traditional detection methods like nucleic acid detection and immunological assays, while effective, are often time-consuming, expensive, and not suitable for rapid detection in underdeveloped areas. Electrochemical biosensors offer a promising alternative with advantages including simplicity, rapid response, portability, and low cost. This paper reviews the sources of pathogens in medical wastewater, highlighting specific bacteria (e.g., E. coli, Salmonella, Staphylococcus aureus), viruses (e.g., enterovirus, respiratory viruses, hepatitis virus), parasites, and fungi. It also discusses various electrochemical biosensing techniques such as voltammetry, conductometry, impedance, photoelectrochemical, and electrochemiluminescent biosensors. These technologies facilitate the rapid, sensitive, and specific detection of pathogens, thereby supporting public health and environmental safety. Future research may should pay more attention on enhancing sensor sensitivity and specificity, developing portable and cost-effective devices, and innovating detection methods for diverse pathogens to improve public health protection and environmental monitoring.

Abstract Background Psoriasis is an immune‐mediated chronic inflammatory skin disease, in which T helper 17 (Th17) cells and its effective cytokine interleukin (IL)‐17A play a pivotal pathogenic role. High mobility group box 1 (HMGB1) is an important proinflammatory cytokine, which has been confirmed to be highly expressed in the peripheral circulation and epidermis tissues of psoriasis patients. The regulatory effect of HMGB1 on IL‐17A expression and function has been reported in some inflammatory and autoimmune diseases by the HMGB1‐Toll‐like receptor 4 (TLR4)‐interleukin (IL)‐23‐IL‐17A pathway. While, in the pathological environment of psoriasis, whether HMGB1 can exert the regulatory effect on IL‐17A is not clear. Objective We aimed to evaluate the role of HMGB1‐TLR4‐IL‐23‐IL‐17A pathway in the pathogenesis of psoriasis and explore the possible regulatory mechanism of HMGB1 on Th17 cell differentiation. Methods Serum levels of HMGB1, TLR4, IL‐23, and IL‐17A were quantified in 50 patients with moderate‐to‐severe plaque psoriasis and 30 healthy controls. Peripheral blood mononuclear cells were acquired from 10 severe psoriasis patients and administrated by different concentrations of recombinant‐HMGB1 (rHMGB1) to detect the Th17 cell percentage, mRNA and protein levels of TLR4, IL‐23, IL‐17A and retinoid‐related orphan receptor γt (RORγt). Results The serum levels of HMGB1, TLR4, IL‐23, and IL‐17A in psoriasis patients were significantly higher than healthy controls, especially in severe patients, and positively correlated with the severity index. There were also positive correlations between every two detected indicators of HMGB1, TLR4, IL‐23, and IL‐17A. In vitro study, rHMGB1 can promote the elevated expression of Th17 cell percentage as well as TLR4, IL‐23, IL‐17A, and RORγt in a dose‐dependent manner. Conclusion HMGB1 can contribute to the pathogenesis of psoriasis by regulating Th17 cell differentiation through HMGB1‐TLR4‐IL‐23‐RORγt pathway, then promotes IL‐17A production and aggravates inflammation process. Targeting HMGB1 may be a possible potential candidate for the immunotherapy of psoriasis.

IntroductionSenecavirus A (SVA) is a highly contagious virus that causes vesicular disease in pigs. At present, laboratory detection methods, such as virus isolation and polymerase chain reaction (PCR), required precision instruments and qualified personnel, making them unsuitable for point-of-care tests (POCT). Fortunately, the emergence of CRISPR/Cas system has provided new opportunities for fast and efficient pathogen detection.MethodsThis study successfully developed a precise and sensitive detection platform for diagnosing SVA by combining the CRISPR system with recombinase polymerase amplification (RPA). ResultsThe minimum detection limit of the assay was 10 copies of the SVA genome. Meanwhile, the assay demonstrated high specificity. To validate the effectiveness of this system, we tested 85 swine clinical samples and found that the fluorescence method had a 100% coincidence rate compared to RT-qPCR. DiscussionOverall, the RPA-CRISPR/Cas12a assay established in our study is a highly effective method for detecting SVA and holds great potential for practical applications in the resource-limited settings.

Background: Nitrogen (N) deposition affects forest stoichiometric flexibility through changing soil nutrient availability to influence plant uptake. However, the effect of N deposition on the flexibility of carbon (C), N, and phosphorus (P) in forest plant-soil-microbe systems remains unclear. Methods: We conducted a meta-analysis based on 751 pairs of observations to evaluate the responses of plant, soil and microbial biomass C, N and P nutrients and stoichiometry to N addition in different N intensity (0–50, 50–100, >100 ​kg⋅ha−1⋅year−1 of N), duration (0–5, >5 year), method (understory, canopy), and matter (ammonium N, nitrate N, organic N, mixed N). Results: N addition significantly increased plant N:P (leaf: 14.98%, root: 13.29%), plant C:P (leaf: 6.8%, root: 25.44%), soil N:P (13.94%), soil C:P (10.86%), microbial biomass N:P (23.58%), microbial biomass C:P (12.62%), but reduced plant C:N (leaf: 6.49%, root: 9.02%). Furthermore, plant C:N:P stoichiometry changed significantly under short-term N inputs, while soil and microorganisms changed drastically under high N addition. Canopy N addition primarily affected plant C:N:P stoichiometry through altering plant N content, while understory N inputs altered more by influencing soil C and P content. Organic N significantly influenced plant and soil C:N and C:P, while ammonia N changed plant N:P. Plant C:P and soil C:N were strongly correlated with mean annual precipitation (MAT), and the C:N:P stoichiometric flexibility in soil and plant under N addition connected with soil depth. Besides, N addition decoupled the correlations between soil microorganisms and the plant. Conclusions: N addition significantly increased the C:P and N:P in soil, plant, and microbial biomass, reducing plant C:N, and aggravated forest P limitations. Significantly, these impacts were contingent on climate types, soil layers, and N input forms. The findings enhance our comprehension of the plant-soil system nutrient cycling mechanisms in forest ecosystems and plant strategy responses to N deposition.

Background: Wendan Decoction (WDD) is a six-herb Chinese medicine recipe that was first mentioned in about 652 AD. It is frequently used to treat hyperlipidemic patients’ clinical complaints. According to reports, oxidative stress has a significant role in hyperlipidemia.Purpose: There has not yet been a thorough pharmacokinetic-pharmacodynamic (PK-PD) examination of the clinical efficacy of WDD in the context of hyperlipemia-related oxidative stress. Therefore, the goal of this research is to explore the antioxidant essence of WDD by developing a PK-PD model, ordering to assure its implication in treating hyperlipidemia in medical practice.Methods: The model rats of foodborne hyperlipidemia were established by feeding with high-fat feed, and the lipid-lowering effect of WDD was explored. The plasma drug concentration of rats at different doses were measured by UPL-MS/MS technology, and PK parameters were calculated using Phoenix WinNonlin 8.1 software. The level of lipid peroxide (LPO) in plasma at different time points was measured by enzyme labeling instrument. Finally, the PK-PD model was established by using Phoenix WinNonlin 8.1 software, to explore the lipid-lowering effect of WDD and the relation between the dynamic changes of chemical components and antioxidant effect.Results: The findings suggested that, WDD can reduce the levels of triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) in plasma, and high-density lipoprotein cholesterol (HDL-C) was related to the dosage. Between the peak drug levels and the WDD’s maximal therapeutic response, there existed a hysteresis. WDD’s effect-concentration curves displayed a counterclockwise delaying loop. Alternatively, among the ten components of WDD, hesperetin, quercetin, naringenin and tangeretin might exert more significant effects in regulating the LPO levels in hyperlipidemic rats.Conclusion: This study can be helpful for other investigators to study the lipid-lowering effect of WDD.

Pavements are critical components of highway assets, but accurately estimating their value can be challenging due to the lack of connection between valuation and long-term service performance degradation. To address this issue, the replacement cost and condition-based valuation methods were introduced using the Yunnan province highway in China as an example, which divided pavement into four performance states based on service stages. The rationality of maintenance decisions and the impact of preventive maintenance investment on life cycle assessments were also considered. The results indicate that there are issues of irrational allocation of maintenance funds of the highway in Yunnan province, and a higher proportion of preventive maintenance investment is required. Moreover, it is recommended to balance the maintenance funds for bridge and tunnel engineering in the following year, focusing on bridge engineering with a rapid decline in the newness rate. The implementation of preventive maintenance has a positive correlation with the replacement cost and newness rate of the road sections. Through comparison, it was found that the road surface renewal rate in 2019 was lower than that in 2018, and some highway management departments in certain regions need to adjust their preventive maintenance strategies. Overall, the condition-based pavement asset valuation method comprehensively considers each stage of pavement operation and can serve as an effective tool for evaluating pavement asset depreciation. This research finding can promote the sustainable development of road infrastructure.

Objectives: Circ_003686 is a novel_circRNA with abnormally low expression found in the samples of multiple myeloma bone disease (MBD) patients. The current research intended to investigate the effects of novel_circ_003686 in osteogenesis-induced differentiation of bone marrow mesenchymal stem cells (BMSCs) in MBD. Methods: BMSCs were extracted from MBD patients and normal participants, the pcDNA3.1 encoding the circ_003686 (ov-circ_003686), miR-142-5p-mimic/inhibitor and siRNA oligonucleotides targeting insulin like growth factor 1 (IGF1, si-IGF1) were applied to intervene circ_003686, miR-142-5p and IGF1 levels, respectively. Results: Results showed that ov-circ_003686 could mediate the osteogenesis-induced differentiation of MBD-BMSC, and luciferase assay and RIP experiments confirmed that circ_003686 could bind to miR-142-5p. MiR-142-5p-inhibitor helped osteogenesis-induced differentiation, while miR-142-5p-mimic inhibited osteogenesis-induced differentiation and reversed the promoting effect of ov-circ_003686, suggesting that circ_003686/miR-142-5p axis participated in osteogenesis-induced differentiation of MBD-BMSC. In addition, miR-142-5p binds to the target gene IGF1 and negatively adjust its expression. Si-IGF1 significantly inhibited the osteogenesis-induced differentiation and reversed the promotion effects of miR-142-5p-inhibitor and ov-circ_003686. Moreover, circ_003686/miR-142-5p/IGF1 axis meaningfully regulates protein expressions in the PI3K/AKT pathway. Conclusion: In conclusion, this research confirmed that circ_003686 regulated the osteogenesis-induced differentiation of MBD-BMSC by sponging miR-142-5p and mediating IGF1, and the PI3K/AKT pathway may also be involved.

Sepsis is a clinical syndrome characterized by a dysregulated host response to infection, leading to life-threatening organ dysfunction. It is a high-fatality condition associated with a complex interplay of immune and inflammatory responses that can cause severe harm to vital organs. Sepsis-induced myocardial injury (SIMI), as a severe complication of sepsis, significantly affects the prognosis of septic patients and shortens their survival time. For the sake of better administrating hospitalized patients with sepsis, it is necessary to understand the specific mechanisms of SIMI. To date, multiple studies have shown that programmed cell death (PCD) may play an essential role in myocardial injury in sepsis, offering new strategies and insights for the therapeutic aspects of SIMI. This review aims to elucidate the role of cardiomyocyte’s programmed death in the pathophysiological mechanisms of SIMI, with a particular focus on the classical pathways, key molecules, and signaling transduction of PCD. It will explore the role of the cross-interaction between different patterns of PCD in SIMI, providing a new theoretical basis for multi-target treatments for SIMI.

At aquifer-sea interfaces, submarine groundwater discharge (SGD) and related chemical loads are closely related to groundwater environment in the intertidal zone of coastal aquifers. Although unstable salinity distribution in the intertidal zone associated with salt-fingering flow has been known as a natural phenomenon for some coastal aquifers, a quantitative understanding of groundwater dynamics in the intertidal zone during salt-fingering flow is still lacking. This study investigated the movement features of salt fingers and the response laws of freshwater discharge zone (FDZ) in the intertidal zone, considering the fixed and seasonal inland conditions. The results revealed that during salt-fingering flow, the finger was repeatedly generated and detached from the intertidal zone. Horizontally, the finger moved toward the sea, and the finger speed first increased at the development stage, then remained unchanged at the separation stage, and finally decreased at the mergence stage. The movement speed of salt fingers was closely related to ambient freshwater flow in the FDZ. In the vertical direction, the finger first permeated downward with a decreasing speed, and then the upward discharge of fresh groundwater in the FDZ region with an increased flow velocity pushed the finger upwards with an increasing speed. In contrast to the results in a stable intertidal regime, the width of FDZ at the aquifer-sea interface fluctuated over time, and the variation trends possessed a well agreement with the flux of fresh groundwater discharge. This suggested that the width of FDZ at the aquifer-sea interface can be used as an indicator of fresh groundwater discharge, even in an unstable regime, to provide a basis for field monitoring. The intensity of salt-fingering flow varied over time under the condition of seasonal freshwater inflow. The mean duration of salt fingers decreased slightly with the increase of seasonal freshwater periods due to a decrease in the interface perturbation for the intertidal environment. These findings lay the foundation for gaining a better understanding of the potential implications of salt-fingering flow on SGD and related solute transports.

In this work, a three-dimensional porous carbon structure was constructed in situ by connecting carbon polyhedrons with graphitic nanosheets. The rich pores, high nitrogen doping content, and abundant defects formed on the surface provided multiple antennas to absorb electromagnetic waves. The optimized reflection loss of the material was as low as −41.65 dB with an effective absorption band of 5.84 GHz, which covered the entire Ku band. A mechanistic investigation based on density functional theory calculations and electrochemical analysis shows that the dipole loss and conduction loss were mainly caused by pyrrolic nitrogen and the higher electron mobility in the prepared materials. The conduction loss and polarization loss synergistically improve the absorption performance of nanosheet-linked porous carbon (NLPC). Furthermore, the potential practical application performance of the material, which was evaluated by computer simulation technology (CST), showed that all simulated RCS values were lower than 20 dBm2. Thus, this work provides new insights and methods to understand the microwave absorption properties of carbon materials.

However, its underlying mechanism remains largely undetermined. In this work, we examined the impacts of the continuous application of pig manure fertiliser for 10 years on wheat yield in the calcaric fluvisol soil with a texture of sandy loam, and the relationship between soil microbial community composition and soil properties was also analysed. The wheat yield, yield components and wheat biomass were analysed by collected aboveground part. Soil nutrient, enzymatic activity and microorganism compositions were analysed by collected soil samples at the filling stage. The results showed that long-term application of pig manure fertiliser could remarkably increase wheat yield by improving soil nutrient availability, enzyme activities, and microbial composition. Moreover, soil pH, nitrogen content, dehydrogenase and urease were closely related to the soil microbial diversity. In conclusions, the long-term application of pig manure in combination with term mineral fertiliser could optimise microbial community composition by regulating the interaction between microbial species and enhancing soil enzyme activity and soil fertility, leading to increased wheat yield.

Abstract Transition metal dichalcogenide (TMDC) moiré superlattices, owing to the moiré flatbands and strong correlation, can host periodic electron crystals and fascinating correlated physics. The TMDC heterojunctions in the type-II alignment also enable long-lived interlayer excitons that are promising for correlated bosonic states, while the interaction is dictated by the asymmetry of the heterojunction. Here we demonstrate a new excitonic state, quadrupolar exciton, in a symmetric WSe2-WS2-WSe2 trilayer moiré superlattice. The quadrupolar excitons exhibit a quadratic dependence on the electric field, distinctively different from the linear Stark shift of the dipolar excitons in heterobilayers. This quadrupolar exciton stems from the hybridization of WSe2 valence moiré flatbands. The same mechanism also gives rise to an interlayer Mott insulator state, in which the two WSe2 layers share one hole laterally confined in one moiré unit cell. In contrast, the hole occupation probability in each layer can be continuously tuned via an out-of-plane electric field, reaching 100% in the top or bottom WSe2 under a large electric field, accompanying the transition from quadrupolar excitons to dipolar excitons. Our work demonstrates a trilayer moiré system as a new exciting playground for realizing novel correlated states and engineering quantum phase transitions.

Abstract Background Tyrosine kinase inhibitors (TKIs) that specifically target mutational points in the EGFR gene have significantly reduced suffering and provided greater relief to patients with lung adenocarcinoma (LUAD). The third-generation EGFR-TKI, Osimertinib, has been successfully employed in clinical treatments to overcome resistance to both original and acquired T790M and L858R mutational points. Nevertheless, the issue of treatment failure response has emerged as an insurmountable problem. Methods By employing a combination of multiple and integrated approaches, we successfully identified a distinct population within the tumor group that plays a significant role in carcinogenesis, resistance, and recurrence. Our research suggests that addressing TKI resistance may involve targeting the renewal and repopulation of stem-like cells. To investigate the underlying mechanisms, we conducted RNA Microarray and m6A Epi-Transcriptomic Microarray analyses, followed by assessment of transcription factors. Additionally, we specifically designed a tag to detect the polypeptide circRNA-AA, and its expression was confirmed through m6A regulations. Results We initially identified unique molecular signatures present in cancer stem cells that contributed to poor therapeutic responses. Activation of the alternative Wnt pathway was found to sustain the renewal and resistant status of these cells. Through bioinformatics analysis and array studies, we observed a significant decrease in the expression of circFBXW7 in Osimertinib-resistant cell lines. Notably, the abnormal expression pattern of circFBXW7 determined the cellular response to Osimertinib. Functional investigations revealed that circFBXW7 inhibits the renewal of cancer stem cells and resensitizes both resistant LUAD cells and stem cells to Osimertinib. In terms of the underlying mechanism, we discovered that circFBXW7 can be translated into short polypeptides known as circFBXW7-185AA. These polypeptides interact with β-catenin in an m6A-dependent manner. This interaction leads to reduced stability of β-catenin by inducing subsequent ubiquitination, thereby suppressing the activation of canonical Wnt signaling. Additionally, we predicted that the m6A reader, YTHDF3, shares common binding sites with hsa-Let-7d-5p. Enforced expression of Let-7d post-transcriptionally decreases the levels of YTHDF3. The repression of Let-7d by Wnt signaling releases the stimulation of m6A modification by YTHDF3, promoting the translation of circFBXW7-185AA. This creates a positive feedback loop contributing to the cascade of cancer initiation and promotion. Conclusions Our bench study, in vivo experiments, and clinical validation have unequivocally shown that circFBXW7 effectively inhibits the abilities of LUAD stem cells and reverses resistance to TKIs by modulating Wnt pathway functions through the action of circFBXW7-185AA on β-catenin ubiquitination and inhibition. The regulatory role of circRNA in Osimertinib treatment has been rarely reported, and our findings reveal that this process operates under the influence of m6A modification. These results highlight the tremendous potential of this approach in enhancing therapeutic strategies and overcoming resistance to multiple TKI treatments.

Aiming at the problem of difficult detection of sedentarius ciliates, unclear pollution sources and difficult identification of species in the cold-water fish farming, the major parasitic species of the parasites and the infective factors were investigated and analyzed. Samples of cold-water fish and water were collected in different seasons in Hebei Province. Firstly, the sedentarius ciliates on the fish body and in the water environment were initially identified by using morphology. Secondly, a PCR method was established for molecular level identification and phylogenetic analysis. Finally, the reasons for cold-water fish infecting the parasite were analyzed. Morphological identification reveals that the mainly parasitic species of sedentarius ciliates were Epistylis sp. and Vorticella sp.; A PCR method to test the parasites is successfully established. The results of sequences alignment and phylogenetic analysis verify the correctness of morphological test. The established PCR method is used to detect the prevalence of sessile ciliates in the water environment, which is as high as 94.38%, and the infection rate of the fish is up to 100% with no seasonal difference. The parasites in water may be one of the reasons for the long-term infection of the fish. The findings provide a scientific basis for predicting, preventing and treating cold-water fish diseases, as well as serving as a reference for disease prevention and control in the sustainable development of the cold-water fish farming industry.