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Abstract As the capacity of medium or large hydroelectric generators increases, conventional grounding methods face challenges in effectively limiting single‐phase to earth fault current and neutral displacement voltage within acceptable range. Excessive fault current and neutral displacement voltage pose threats to the stability and safety of power generation and transmission systems. Inherent design deficiencies in conventional grounding methods lead to failures in meeting fault current and voltage requirements. To address this, this paper proposes a novel grounding method utilizing high impedance to restrict excessive fault current and neutral displacement voltage. The method minimizes both fault current and neutral displacement voltage by optimally selecting device parameters through minimal iterative trials. Additionally, a novel indicator is introduced to evaluate the effectiveness of grounding method by monitoring changes in neutral displacement voltage. The method is tested through theoretical calculation and field experiments, successfully implemented in large‐size hydroelectric generator.

Abstract In their letter-to-the-editor entitled “Letter to the Editor: Incidence rate of occult lymph node metastasis in clinical T1 − 2N0M0 small cell lung cancer patients and radiomic prediction based on contrast-enhanced CT imaging: a multicenter study”, Prof. Chen et al. provided insightful comments and suggestions on our original study. We appreciate the authors’ feedback and have conducted a preliminary exploration of the predictive value of serum tumor markers (TMs) for occult lymph node metastasis (OLM) in clinical T1 − 2N0M0 (cT1 − 2N0M0) small cell lung cancer (SCLC) patients. The results indicate that neuron-specific enolase (NSE), carbohydrate antigen 125 (CA125), and squamous cell carcinoma antigen (SCC) have potential predictive value for detecting OLM in cT1 − 2N0M0 SCLC patients. Additionally, further exploration and confirmation through prospective, large-scale studies with robust external validation are needed.

Abstract Background Multiple epiphyseal dysplasia-4 (MED-4, MIM 226900) is a rare autosomal recessive disease characterized by disproportionate height and early onset osteoarthritis of the lower limbs. MED-4 is caused by homozygous or compound heterozygous pathogenic variants in the SLC26A2 gene. However, the underlying pathogenic mechanisms in chondrocytes remains unknown. This study aimed to identify the pathogenic variants within a MED-4 family and explore the molecular etiology of this condition in human primary chondrocyte cells. Methods Clinical data were recorded and peripheral blood samples were collected for analysis. Whole exome sequencing (WES) and bioinformatic analyses were performed to determine causative variants. Wild-type SLC26A2 and corresponding mutant expression plasmids were constructed and transfected into human primary chondrocytes. The expression and subcellular distribution of SLC26A2 protein in chondrocytes were detected by immunoblotting and immunofluorescence. Effects of these variants on chondrocytes viability and apoptosis were measured by Cell Counting Kit-8 (CCK-8) assay. Expression of genes related to cartilage homeostasis was subsequently analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Results We identified two compound heterozygous variants c.1020_1022delTGT(p.Val341del) and c.1262 T > C(p.Ile421Thr) in the SLC26A2 gene in the patients. Mutant SLC26A2Val341del and SLC26A2Ile421Thr proteins were distributed in relatively few cells and were observed only within the nucleus. The viability of chondrocytes with the SLC26A2 variant group was similar to the wild-type (WT) group. However, the protein expressions of SLC26A2Val341del and SLC26A2Ile421Thr were decreased compared with SLC26A2WT. Expression levels of matrix metallopeptidase 13 (MMP13), α-1 chain of type X collagen (COL10A1), and Runt-related transcription factor 2 (RUNX2) were significantly decreased in the variant group. However, aggrecan (ACAN) expression was higher in the variant group than the WT group. Conclusions Overall, our data demonstrate that the variants p.Val341del and p.Ile421Thr in SLC26A2 cause MED-4 and that these two variants promote chondrocyte proliferation while inhibiting chondrocyte differentiation.

Future industries are crucial in shaping new productive forces, and their development highly depends on innovation breakthroughs in disruptive technologies. However, the current basic research and technological innovation capabilities of China are still weak, which lies in the failure to grasp the fundamental laws of technological innovation activities from a philosophical perspective. This study employs the analytical methods of phenomenological eidetic reduction and transcendental reduction to explore the complex philosophical issues underlying the bottleneck of disruptive technological innovation. It traces the lineage of technical philosophy and scientific philosophy, clarifies the dialectical relationship between modern technology and scientific research, and projects the problem of technological innovation into the realm of fundamental spatiotemporal categories. The study reveals that the traditional dynamical spatiotemporal perspective adheres to a mind-body dualistic philosophical thought, viewing space and time as abstract concepts transcending any frame of reference, thereby neglecting the crucial role played by the body and practical activities. Therefore, this study integrates modern science with the theory of spatiotemporal phenomenology to promote the reconstruction of spatiotemporal dimensions characterized by data representation, knowledge flow, and embodied coupling. It actively responds to the strategic needs of future industries and the logical framework of science, establishing an evolutionary framework for future scientific research paradigms termed technological science, intelligent science, and embodied science. It incorporates systems science methodologies to construct a disruptive technological innovation system characterized by engineering application, intelligent integration, and embodied collaboration. Furthermore, based on the quadruple phenomenon structure of philosophy – science – technology–industry and the engineering innovation strategy of new quality–new knowledge, three development recommendations are proposed: establishment of special working groups, enhancement of service support mechanisms, and promotion of technological innovation capabilities of enterprises.

Abstract Background Plant height (PH) is an important agronomic trait influenced by a complex genetic network. However, the genetic basis for the variation in PH in Medicago sativa remains largely unknown. In this study, a comprehensive genome-wide association analysis was performed to identify genomic regions associated with PH using a diverse panel of 220 accessions of M. sativa worldwide. Results Our study identified eight novel single nucleotide polymorphisms (SNPs) significantly associated with PH evaluated in five environments, explaining 8.59–12.27% of the phenotypic variance. Among these SNPs, the favorable genotype of chr6__31716285 had a low frequency of 16.4%. Msa0882400, located proximal to this SNP, was annotated as phosphate transporter 3;1, and its role in regulating alfalfa PH was supported by transcriptome and candidate gene association analysis. In addition, 21 candidate genes were annotated within the associated regions that are involved in various biological processes related to plant growth and development. Conclusions Our findings provide new molecular markers for marker-assisted selection in M. sativa breeding programs. Furthermore, this study enhances our understanding of the underlying genetic and molecular mechanisms governing PH variations in M. sativa.

Aim: Parkinson's disease (PD) tremor is associated with dysfunction in the basal ganglia (BG), cerebellum (CB), and sensorimotor networks (SMN). We investigated tremor-related static functional network connectivity (SFNC) and dynamic functional network connectivity (DFNC) in PD patients. Methods: We analyzed the resting-state functional MRI data of 21 tremor-dominant Parkinson's disease (TDPD) patients and 29 healthy controls. We compared DFNC and SFNC between the three networks and assessed their associations with tremor severity. Results: TDPD patients exhibited increased SFNC between the SMN and BG networks. In addition, they spent more mean dwell time (MDT) in state 2, characterized by sparse connections, and less MDT in state 4, indicating stronger connections. Furthermore, enhanced DFNC between the CB and SMN was observed in state 2. Notably, the MDT of state 2 was positively associated with tremor scores. Conclusion: The enhanced dynamic connectivity between the CB and SMN in TDPD patients suggests a potential compensatory mechanism. However, the tendency to remain in a state of sparse connectivity may contribute to the severity of tremor symptoms.

This study examines the impact of urban–rural integration (URI) on the transition of arable land use functions (TALUF), providing both theoretical and empirical insights into how URI can promote TALUF. Utilizing panel data from 41 cities in the Yangtze River Delta (YRD) from 2003 to 2022, this research employs the entropy method, Durbin model, and spatial threshold model to assess the levels of URI and TALUF in the region and examine the direct impact, spatial spillover effects, and threshold effects of URI on TALUF. The findings are: (1) During the study period, both TALUF and URI levels in the YRD showed continuous improvement, although significant spatial imbalances persisted, with regional differentiation gradually diminishing. (2) URI exerts a significant inhibitory effect on TALUF and produces a negative spatial spillover effect. (3) URI exerts a single threshold effect on TALUF: below the economic development threshold of 0.733, URI and its spatial term inhibit TALUF, whereas above this threshold, they promote it. Consequently, fostering high-quality regional economic development, enhancing intercity cooperation, driving agricultural technological innovation, and increasing agricultural input intensity are essential strategies for arable land use policies in the context of URI.

Abstract Background This study aimed to explore the incidence of occult lymph node metastasis (OLM) in clinical T1 − 2N0M0 (cT1 − 2N0M0) small cell lung cancer (SCLC) patients and develop machine learning prediction models using preoperative intratumoral and peritumoral contrast-enhanced CT-based radiomic data. Methods By conducting a retrospective analysis involving 242 eligible patients from 4 centeres, we determined the incidence of OLM in cT1 − 2N0M0 SCLC patients. For each lesion, two ROIs were defined using the gross tumour volume (GTV) and peritumoral volume 15 mm around the tumour (PTV). By extracting a comprehensive set of 1595 enhanced CT-based radiomic features individually from the GTV and PTV, five models were constucted and we rigorously evaluated the model performance using various metrics, including the area under the curve (AUC), accuracy, sensitivity, specificity, calibration curve, and decision curve analysis (DCA). For enhanced clinical applicability, we formulated a nomogram that integrates clinical parameters and the rad_score (GTV and PTV). Results The initial investigation revealed a 33.9% OLM positivity rate in cT1 − 2N0M0 SCLC patients. Our combined model, which incorporates three radiomic features from the GTV and PTV, along with two clinical parameters (smoking status and shape), exhibited robust predictive capabilities. With a peak AUC value of 0.772 in the external validation cohort, the model outperformed the alternative models. The nomogram significantly enhanced diagnostic precision for radiologists and added substantial value to the clinical decision-making process for cT1 − 2N0M0 SCLC patients. Conclusions The incidence of OLM in SCLC patients surpassed that in non-small cell lung cancer patients. The combined model demonstrated a notable generalization effect, effectively distinguishing between positive and negative OLMs in a noninvasive manner, thereby guiding individualized clinical decisions for patients with cT1 − 2N0M0 SCLC.

Abstract Extensive research has focused on the impact of weather on working capacity and income. However, in regions where income data largely relies on surveys, a pivotal yet underexplored question is whether weather not only influence real income but also introduce biases into survey-collected income data. We analyze longitudinal data from the China Health and Nutrition Survey and corresponding weather records from the Global Surface Summary of the Day, and uncover a negative correlation between survey-day temperature and self-reported annual income from the previous year. With a series of robustness checks, we confirm that the effect is primarily driven by behavioral factors rather than actual income changes. And threshold regression analyses show that the impact of temperature is more pronounced on hot days and relatively subdued or even reversed on cooler days. Further analyses indicate that mood, rather than cognitive capacity, plays a central role in causing the observed downward bias.

Abstract Inflammatory arthritis (IA) is a common rheumatic adverse event following immune checkpoint inhibitors treatment. The clinical disparities between IA and rheumatoid arthritis (RA) imply disease heterogeneity and distinct mechanisms, which remain elusive. Here, we profile CD45+ cells from the peripheral blood or synovial fluid (SF) of patients with PD-1-induced IA (PD-1-IA) or RA using single-cell RNA sequencing. We report the predominant expansion of IL1B hi myeloid cells with enhanced NLRP3 inflammasome activity, in both the SF and peripheral blood of PD-1-IA, but not RA. IL1B hi macrophages in the SF of PD-1-IA shared similar inflammatory signatures and might originate from peripheral IL1B hi monocytes. Exhausted CD8+ T cells (Texs) significantly accumulated in the SF of patients with PD-1-IA. IL1B hi myeloid cells communicated with CD8+ Texs possibly via the CCR1-CCL5/CCL3 and CXCL10-CXCR3 axes. Collectively, these results demonstrate different cellular and molecular pathways in PD-1-IA and RA and highlight IL1B hi macrophages as a possible therapeutic target in PD-1-IA.

Abstract Background We aimed to identify some potential biomarkers for elderly osteoporosis (OP) by integral analysis of lncRNA and mRNA expression data. Methods A total of 8 OP cases and 5 healthy participants were included in the study. Fasting peripheral venous blood samples were collected from individuals, and total RNA was extracted. RNA-seq library was prepared and sequenced on the Illumina HiSeq platform. Differential gene expression analysis was performed using “DESeq2” package in R language. Functional enrichment analysis was conducted using the “clusterProfiler” package, and the cis- and trans-regulatory relationships between lncRNA and target mRNA were analyzed by the lncTar software. A protein-protein interaction (PPI) network was constructed using the STRING database, and hub genes were identified through the MCODE plugin in Cytoscape. Results We identified 897 differentially expressed lncRNAs (DELs) and 1366 differentially expressed genes (DEGs) between normal and OP samples. After co-expression network analysis and cis-trans regulatory genes analysis, we identified 69 candidate genes regulated by lncRNAs. Then we further screened 7 genes after PPI analysis. The target gene DOCK4, trans-regulated by two lncRNAs, was found to be significantly upregulated in OP samples. Additionally, 4 miRNAs were identified as potential regulators of DOCK4. The potential diagnostic value of DOCK4 and its two trans-regulatory lncRNAs was supported by ROC analysis, indicating their potential as biomarkers for OP. Conclusion DOCK4 is a potential biomarker for elderly osteoporosis diagnostic. It is identified to be regulated by two lncRNAs and four miRNAs.

Carbon fiber reinforced polymer (CFRP) has been widely used in construction, rehabilitation and maintenance of civil infrastructures. Anchor system is one of the most crucial part ensuring load transfer between CFRP and the structures. However, for CFRP plate anchors, there is a contradiction between the anchor capacity and the anchor size. In this paper, a novel cylinder shaped anchor for thick CFRP plates was developed based on a detailed experimental and numerical study. The proposed anchor weighs only 6 kg and it can develop 98 % strength of the 3 mm thickness CFRP plates. The experimental and numerical results revealed that the anchor efficiency of the proposed cylinder shaped anchor system is significantly affected by wedge shape, anchor material, tooth shape, pretightening force and magnitude of interference. The proposed anchor system can significantly promote application of thick CFRP plates.

Niemann-Pick disease type C1 (NP-C1) is a rare and devastating recessive inherited lysosomal lipid and cholesterol storage disorder caused by mutations in the NPC1 or NPC2 gene. These two proteins bind to cholesterol and cooperate in endosomal cholesterol transport. Characteristic clinical manifestations of NP-C1 include hepatosplenomegaly, progressive neurodegeneration, and ataxia. While the rarity of NP-C1 presents a significant obstacle to progress, researchers have developed numerous potential therapeutic approaches over the past two decades to address this condition. Various methods have been proposed and continuously improved to slow the progression of NP-C1, although they are currently at an animal or clinical experimental stage. This overview of NP-C1 therapy will delve into different theoretical treatment strategies, such as small molecule therapies, cell-based approaches, and gene therapy, highlighting the complex therapeutic challenges associated with this disorder.

Osteoarthritis (OA) is a prevalent chronic degenerative disease that affects the bones and joints, particularly in middle-aged and elderly individuals. It is characterized by progressive joint pain, swelling, stiffness, and deformity. Notably, treatment with a heat shock protein 90 (HSP90) inhibitor has significantly curtailed cartilage destruction in a rat model of OA. Although the monoclonal antibody 9B8 against HSP90 is recognized for its anti-tumor properties, its potential therapeutic impact on OA remains uncertain. This study investigated the effects of 9B8 on OA and its associated signaling pathways in interleukin-1β (IL-1β)−stimulated human chondrocytes and a rat anterior cruciate ligament transection (ACLT) model. A specific concentration of 9B8 preserved cell viability against IL-1β−induced reduction. In vitro, 9B8 significantly reduced the expression of extracellular matrix-degrading enzyme such as disintegrin and metallopeptidase-4 (ADAMTS4) of thrombospondin motifs, matrix metalloproteinase-13 (MMP-13), as well as cellular inflammatory factors such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), which were upregulated by IL-1β.In vivo, 9B8 effectively protected the articular cartilage and subchondral bone of the rat tibial plateau from ACLT-induced damage. Additionally, gene microarray analysis revealed that IL-1β substantially increased the expression of SLC2A1, PFKP, and ENO2 within the HIF-1 signaling pathway, whereas 9B8 suppressed the expression of these genes. Thus, 9B8 effectively mitigates ACLT-induced osteoarthritis in rats by modulating the HIF-1 signaling pathway, thereby inhibiting overexpression involved in glycolysis.These results collectively indicate that 9B8 is a promising novel drug for the prevention and treatment of OA.

Intelligent manufacturing is a systematic engineering and technological innovation that propels the transformation and upgrading of China’s manufacturing industry, enhancing industrial competitiveness. It is a pivotal element in strengthening the manufacturing sector of China. The comprehensive and profound advancement of intelligent manufacturing necessitates adherence to ideological innovation, requiring the formulation of a scientifically grounded development strategy from its philosophical roots. This paper, based on the phenomenological reductionism and ontological perspective method, starts from the perspective of the philosophy of technology, integrates systemic dialectical logical reasoning, investigates and identifies the “hard problems” of human– machine collaborative technology in intelligent manufacturing, and insightfully explores its philosophical essence from the standpoint of the philosophy of scientific epistemology. The research findings indicate that explicit knowledge and tacit knowledge are commonly present in manufacturing technology activities. However, the long-standing technological development has overlooked the significance of tacit knowledge and has made an unreasonable assumption about the existence of “rational people” in human subjects, neglecting their crucial role in manufacturing systems. Therefore, this paper, through ontological reflection, proposes a Cartesian intelligent manufacturing technology development path based on the Internet of Things, Internet of Contents & Knowledge, and Internet of Bodies. Building upon this foundation, it establishes a Heideggerian intelligent manufacturing system architecture grounded in behavior-oriented, deictic representations, and embodied embedding. Through this traceable causal analysis, it constructs a three-stage progressive development knowledge paradigm for resolving the “hard problems” of human – machine collaborative technology. This paradigm is characterized by data-driven, functional representation, and embodied integration. To efficiently promote the development of the new-generation intelligent manufacturing, a knowledge engineering classification assessment system can be established. The application of theoretical cognitive models can drive the resolution of technological challenges and the formulation of industry support policies. Establishing a multi-faceted application-oriented intelligent manufacturing public service platform strengthens knowledge circulation and integrated application.

Objective To explore the value of computed tomography (CT) imaging features and texture analysis in the differential diagnosis of acinar cell carcinoma of the pancreas (ACCP). Methods The clinical data of patients who were patholo-gically diagnosed with ACCP, pancreatic ductal adenocarcinoma (PDAC), or solid pseudopapillary neoplasm (SPN) of the pancreas in our hospital from January 2017 to October 2018 were retrospectively analyzed. The clinical manifestations, tumor markers, CT imaging features, and texture parameters were compared and analyzed. Results The contrast-enhanced CT images of 5 patients with ACCP showed that most of the lesions were solid-cystic masses with a large size and more solid components. The CT images of 12 patients with PDAC showed that most of the lesions were solid masses with a small size. The CT images of 12 patients with SPN showed that most of the lesions were solid-cystic masses with a size greater than that of ACCP lesions and fewer solid components, showing the “floating cloud sign”. Eight texture parameters were valuable for the differential diagnosis between ACCP and PDAC (Z=2.015-2.530,P

Objectives Analyzing the lower limb coronal morphological parameters in populations without knee osteoarthritis (KOA) holds significant value in predicting, diagnosing, and formulating surgical strategies for KOA. This study aimed to comprehensively analyze the variability in these parameters among Chinese non‐KOA populations, employing a substantial sample size. Methods A cross‐sectional retrospective analysis was performed on the Chinese non‐KOA populations (n = 407; 49.9% females). The study employed an in‐house developed artificial intelligence software to meticulously assess the coronal morphological parameters of all 814 lower limbs. The parameters evaluated included the hip‐knee‐ankle angle (HKAA), weight‐bearing line ratio (WBLR), joint line convergence angle (JLCA), mechanical lateral‐proximal‐femoral angle (mLPFA), mechanical lateral‐distal‐femoral angle (mLDFA), mechanical medial‐proximal‐tibial angle (mMPTA), and mechanical lateral‐distal‐tibial angle (mLDTA). Differences in these parameters were compared between left and right limbs, different genders, and different age groups (with 50 years as the cut‐off point). Results HKAA and JLCA exhibited left–right differences (left vs. right: 178.2° ± 3.0° vs. 178.6° ± 2.9° for HKAA, p = 0.001; and 1.8° ± 1.5° vs. 1.4° ± 1.6° for JLCA, p

Abstract Background The identification of biomarkers predicting the treatment response of rheumatoid arthritis (RA) is important. [68 Ga]Ga-FAPI-04 showed markedly increased uptake in the joints of patients with RA. The purpose of this study is to investigate whether [68 Ga]Ga-FAPI-04 PET/CT can be a predictor of treatment response in RA. Results Nineteen patients diagnosed with RA in the prospective cohort study were finally enrolled. Both total synovitis uptake (TSU) and metabolic synovitis volume (MSV) in [68 Ga]Ga-FAPI-04 and [18F]FDG PET/CT of the responders were significantly higher than those in non-responders according to Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) response criteria at 3-months’ follow-up (P cutoff values in [68 Ga]Ga-FAPI-04 PET/CT successfully discriminated CDAI and SDAI responders and non-responders at 3-months’ follow-up. Conclusion [68 Ga]Ga-FAPI-04 uptake at baseline were significantly higher in early responders than those in non-responders. Trial registration ClinicalTrials. NCT04514614. Registered 13 August 2020, https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000A4PN&selectaction=Edit&uid=U0001JRW&ts=2&cx=-x9t7cp

To improve the real-time image acquisition and stabilization ability of dynamic robotic dog video acquisition devices, a dynamic robotic dog video image stabilization algorithm based on local low-rank regularization is proposed. Firstly, by studying the image acquisition system of a dynamic robotic dog video acquisition device, a real-time image acquisition and stabilization algorithm suitable for this system was developed based on the prior knowledge of motion morphology components. Then, the rolling curtain effect of the loading video capture device was eliminated through the principle of grid. These results confirmed that the improved algorithm achieved stable performance with approximate Gaussian weights between 170 frames and 230 frames, with the highest ITF value at $\tau =1$ and an average IFT value of 33.42 after 20 iterations. Then, $r=30$ , $\beta =1000$ , and $\omega _{2}$ were selected as the default parameters. The average cropping rate of the improved algorithm was only 0.61, the average distortion was 0.42, and the average stability was 0.69. The improved algorithm scored 3.33 in the “crowd” category of videos, ranking first. After verification, the real-time image acquisition and stabilization algorithm designed by the research institute had good real-time performance and stability. It can meet the real-time image acquisition and stabilization requirements of dynamic robotic dog video acquisition devices.

Abstract Osteoarthritis (OA) is the most common degenerative joint disease. Currently, no satisfactory pharmacological treatment exists for OA. The potential anti-inflammatory properties of Dihydrotanshinone I (DHT) have been reported, but its effects on OA are unclear. In this study, we assess the impact of DHT on the viability of human chondrocytes in vitro. We then use a guinea pig model to investigate the effects of DHT on knee osteoarthritis progression. Twelve-week-old Dunkin Hartley guinea pigs spontaneously developing OA were intraperitoneally injected with different doses of DHT for eight weeks. Micro-CT analysis was performed on the subchondral bone in the knee, and histological assessment of the knee joint was done using stained sections, the ratio of hyaline to calcified cartilage, and Mankin scores. DHT successfully restored IL-1β-induced decreases in cell viability in human primary chondrocytes. In the guinea pig model, intraperitoneal injections of DHT ameliorated age-induced OA, effectively reduced the expression level of two cartilage metabolism-related genes (ADAMTS4 and MMP13) and decreased the inflammatory biomarker IL-6 in the serum of guinea pigs developing spontaneous osteoarthritis. These findings demonstrate DHT’s protective effects on chondrocytes and suggest that it alleviates cartilage degradation and proteoglycan loss in OA.

The cultivated land requisition–compensation balance (CLRCB) policy is an important policy implemented by China to address the reduction in cultivated land and ensure food security. Although this policy has alleviated the loss of cultivated land quantity, it has had complex and diverse impacts on ecosystem services. Taking Hubei Province as the study area, this research explores the impact of the implementation of the CLRCB on ecosystem services and simulates the changes in ecosystem services in the study area in 2030 and the impact of CLRCB on the interactions among various services. The results show the following: (1) from 2000 to 2020, Hubei Province achieved a balance in the quantity of cultivated land through excessive compensation but failed to reach the goals of balancing cultivated land yield and productivity. (2) During the requisition–compensation process, habitat quality decreased by 501,862, and carbon storage lost 1.3 × 107 t, indicating negative ecological impacts; soil conservation services increased by 184.2 × 106 t, and water production increased by 21.29 × 108 m3. Within the cultivated land requisition–compensation area, habitat quality and carbon storage, as well as soil conservation and water production, exhibited synergistic relationships, while the remaining pairs of ecosystem services showed trade-off relationships. (3) The simulation of ecosystem services in 2030 indicates that soil conservation and water production are highest under the natural development scenario, while habitat quality and carbon storage are highest under the ecological protection scenario, both of which are superior to the urban development scenario. Under the natural development scenario, the trade-off and synergistic relationships among various ecosystem services in the cultivated land requisition–compensation area remain unchanged, while these relationships change significantly under the other two scenarios. This study emphasizes that future CLRCB should not only focus on maintaining the quantity of cultivated land but also consider the comprehensive benefits of ecosystem services, in order to achieve sustainable land-use management and ecological conservation.

JASMONATE ZIM domain (JAZ) proteins, inhibitors of the jasmonic acid (JA) signaling pathway, are identified in different plants, such as rice and Arabidopsis. These proteins are crucial for growth, development, and abiotic stress responses. However, limited information is available regarding the JAZ family in alfalfa. This study identified 11 JAZ genes (MsJAZs) in the “Zhongmu No.1” reference genome of alfalfa. The physical and chemical properties, chromosome localization, phylogenetic relationships, gene structure, cis-acting elements, and collinearity of the 11 MsJAZ genes were subsequently analyzed. Tissue-specific analysis revealed distinct functions of different MsJAZ genes in growth and development. The expression patterns of MsJAZ genes under salt stress conditions were validated using qRT-PCR. All MsJAZ genes responded to salt stress, with varying levels of upregulation over time, highlighting their role in stress responses. Furthermore, heterogeneous expression of MsJAZ1 in Arabidopsis resulted in significantly lower seed germination and survival rates in OE-2 and OE-4 compared to the WT under 150 mM NaCl treatment. This study establishes a foundation for further exploration of the function of the JAZ family and provides significant insights into the genetic improvement of alfalfa.

The prestressed active reinforcement of concrete structures using iron-based shape memory alloys (Fe-SMAs) is investigated in this experimental study through three connecting methods: adhesive–bolted hybrid connection, bolted connection, and adhesively bonded connection by activating at elevated temperatures (heating and cooling) and constraining deformation to generate prestress inside Fe-SMAs, through which compressive stress is generated in the parent concrete structures. In tests, the Fe-SMA is activated at 250 °C using a hot air gun, generating a prestress of 184.6–246 MPa. The experimental results show that local stress concentration in the concrete specimen and Fe-SMA plate around the hole is caused by the bolted connection. The adhesively bonded connection is prone to softening and slip of the structural adhesive during the activation process, thereby reducing the overall recovery force of Fe-SMAs. The adhesive–bolted hybrid connection effectively mitigates the local stress concentration problem of concrete and Fe-SMAs at anchor holes, while avoiding the prestress loss caused by the softening and slip of structural adhesive during elevated-temperature activation, achieving good reinforcement effect. This study on the connection methods of an Fe-SMA for reinforcing concrete structures provides both experimental support and practical guidance for its engineering application, offering new perspectives for future research.

This study builds a refined finite element (FE) model to research the flexural behavior of a reinforced beam with prestressed CFRP tendons. The precision of the FE model is validated through a comparison with the experimental outcomes. The numerical findings align well with the experimental outcomes, encompassing the failure mode, load-deflection curve, load-strain curves of concrete, steel reinforcements and CFRP tendons. The variances between predicted values and experimental results are within 10%. Leveraging the verified FE model, an extensive parametric study has been carried out to examine the effects of various parameters, including the CFRP tendon prestress, the CFRP tendon diameter, the deviator layout, the anchorage height and the prestressing strand prestress. Leveraging the findings from the parametric study, some refined design recommendations are proposed for practical reinforcement applications: Increasing the CFRP tendon prestress in practical reinforcement designs is recommended; CFRP tendons with larger diameters are recommended for use in practical reinforcement designs; Employing a linear CFRP tendon profile for reinforcement is not considered optimal in practical applications; The prestress loss in the prestressing strands of PC beams should be considered in practice.

Abstract Background Breast phyllodes tumours (PTs) are a unique type of fibroepithelial neoplasms with metastatic potential and recurrence tendency. However, the precise nature of heterogeneity in breast PTs remains poorly understood. This study aimed to elucidate the cell subpopulations composition and spatial structure and investigate diagnostic markers in the pathogenesis of PTs. Methods We applied single‐cell RNA sequencing and spatial transcriptomes on tumours and adjacent normal tissues for integration analysis. Immunofluorescence experiments were conducted to verify the tissue distribution of cells. Tumour cells from patients with PTs were cultured to validate the function of genes. To validate the heterogeneity, the epithelial and stromal components of tumour tissues were separated using laser capture microdissection, and microproteomics data were obtained using data‐independent acquisition mass spectrometry. The diagnostic value of genes was assessed using immunohistochemistry staining. Results Tumour stromal cells harboured seven subpopulations. Among them, a population of widely distributed cancer‐associated fibroblast‐like stroma cells exhibited strong communications with epithelial progenitors which underwent a mesenchymal transition. We identified two stromal subpopulations sharing epithelial progenitors and mesenchymal markers. They were inferred to further differentiate into transcriptionally active stromal subpopulations continuously expressing COL4A1/2. The binding of COL4A1/2 with ITGA1/B1 facilitated a growth pattern from the stroma towards the surrounding glands. Furthermore, we found consistent transcriptional changes between intratumoural heterogeneity and inter‐patient heterogeneity by performing microproteomics studies on 30 samples from 11 PTs. The immunohistochemical assessment of 97 independent cohorts identified that COL4A1/2 and CSRP1 could aid in accurate diagnosis and grading. Conclusions Our study demonstrates that COL4A1/2 shapes the spatial structure of stromal cell differentiation and has important clinical implications for accurate diagnosis of breast PTs.

Primary pulmonary osteosarcoma is one of the extraskeletal osteosarcomas originating from the lung with an extremely low incidence and highly invasive potential. Here we report a case of primary pulmonary osteosarcoma treated in our hospital with a literature review. The patient, a 17-year-old male, had a cough and hemoptysis for 20 days. Computed tomography (CT) and positron emission tomography (PET)/CT were performed in our hospital. According to pathological examination after surgery, the tumor was diagnosed as a high-grade sarcoma with remarkable osteogenesis and necrosis. Based on radiological and histological examinations, a diagnosis of primary pulmonary osteosarcoma originating was considered. The patient underwent surgery and adjuvant chemotherapy. This patient has been under consecutive follow-up for nearly 8 years, showing no signs of recurrence or distant metastasis. Primary pulmonary osteosarcoma is a rare lung malignancy that shows rapid progression, nonspecific symptoms and inapparent signs at an early stage. The diagnosis of primary pulmonary osteosarcoma highly relies on imaging and histological examinations, among which chest CT is the predominant method to check this disease.

Summary: Emerging studies have demonstrated the link between RNA modifications and various cancers, while the predictive value and functional mechanisms of RNA modification-related genes (RMGs) in esophageal squamous cell carcinoma (ESCC) remain unclear. Here we established a prognostic signature for ESCC based on five RMGs. The analysis of ESCC clinical samples further verified the prognostic power of the prognostic signature. Moreover, we found that the knockdown of NSUN6 promotes ESCC progression in vitro and in vivo, whereas the overexpression of NSUN6 inhibits the malignant phenotype of ESCC cells. Mechanically, NSUN6 mediated tRNA m5C modifications selectively enhance the translation efficiency of CDH1 mRNA in a codon dependent manner. Rescue assays revealed that E-cadherin is an essential downstream target that mediates NSUN6’s function in the regulation of ESCC progression. These findings offer additional insights into the link between ESCC and RMGs, as well as provide potential strategies for ESCC management and therapy.

The aim of this study was to present current research trends on the synergistic use of radiotherapy and immunotherapy (IRT) for cancer treatment. On March 1, 2023, we conducted a literature search for IRT papers using the Web of Science database. We extracted information and constructed two databases – the Core Database (CD) with 864 papers and Generalized Database (GD) with 6344 papers. A bibliometric analysis was performed to provide insights into the research landscape, to identify emerging trends and highly cited papers and journals in the field of IRT. The CD contained 864 papers that were collectively cited 31,818 times. Prominent journals in this area included the New England Journal of Medicine, Lancet Oncology, and the Journal of Clinical Oncology. Corresponding authors from the USA contributed the most publications. In recent years, lung cancer, melanoma, stereotactic radiotherapy, immune checkpoint inhibitors, and the tumor microenvironment emerged as hot research areas. This bibliometric analysis presented quantitative insights into research concerning IRT and proposed potential avenues for further exploration. Moreover, researchers can use our findings to select appropriate journals for publication or identify prospective collaborators. In summary, this bibliometric analysis provides a comprehensive overview of the historical progression and recent advancements in IRT research that may serve as inspiration for future investigations.

Information extraction (IE) aims to discover and extract valuable information from unstructured text. This problem can be decomposed into two subtasks: named entity recognition (NER) and relation extraction (RE). Although the IE problem has been studied for years, most work efforts focused on jointly modeling these two subtasks, either by casting them into a structured prediction framework or by performing multitask learning through shared representations. However, since the contextual representations of entity and relation models inherently capture different feature information, sharing a single encoder to capture the information required by both subtasks in the same space would harm the accuracy of the model. Recent research (Zhong and Chen, 2020) has also proved that using two separate encoders for NER and RE tasks respectively through pipeline method are effective, with the model surpassing all previous joint models in accuracy. Thus, in this paper, we design An Pipeline method Information Extraction module called APIE, APIE combines the advantages of both pipeline methods and joint methods, demonstrating higher accuracy and powerful reasoning abilities. Specifically, we design a multi-level feature NER model based on attention mechanism and a document-level RE model based on local context pooling. To demonstrate the effectiveness of our proposed approach, we conducted tests on multiple datasets. Extensive experimental results have shown that our proposed model outperforms state-of-the-art methods and improves both accuracy and reasoning abilities.

Abstract Root hairs are extensions of epidermal cells on the root tips that increase the root contract surface area with the soil. For polar tip growth, newly synthesized proteins and other materials must be incorporated into the tips of root hairs. Here, we report the characterization of PRX102, a root hair preferential endoplasmic reticulum peroxidase. During root hair growth, PRX102 has a polar localization pattern within the tip regions of root hairs but it loses this polarity after growth termination. Moreover, PRX102 participates in root hair outgrowth by regulating dense cytoplasmic streaming toward the tip. This role is distinct from those of other peroxidases playing roles in the root hairs and regulating reactive oxygen species homeostasis. RNA-seq analysis using prx102 root hairs revealed that 87 genes including glutathione S-transferase were downregulated. Our results therefore suggest a new function of peroxidase as a player in the delivery of substances to the tips of growing root hairs.

Abstract Diagnostic imaging is an essential and indispensable part of medical diagnosis and treatment, and diagnostic errors or biases are also common in the department of radiology, sometimes even having a severe impact on the diagnosis and treatment of patients. There are various reasons for diagnostic errors or biases in imaging. In this review, we analyze and summarize the causes of diagnostic imaging errors and biases based on practical cases. We propose solutions for dealing with diagnostic imaging errors and reducing their probability, thereby helping radiologists in their clinical practice. Critical relevance statement Diagnostic errors or bias contribute to most medical errors in the radiology department. Solutions for dealing with diagnostic imaging errors are pivotal for patients. Key points • Diagnostic errors or bias contribute to most medical errors in radiology department. • Solutions for dealing with diagnostic imaging errors are pivotal for patients. • This review summarizes the causes of diagnostic errors and offers solutions to them. Graphical Abstract

Flowering, the transition from the vegetative to the reproductive stage, is vital for reproductive success, affecting forage quality, the yield of aboveground biomass, and seed production in alfalfa. To explore the transcriptomic profile of alfalfa flowering transition, we compared gene expression between shoot apices (SAs) at the vegetative stage and flower buds (FBs) at the reproductive stage by mRNA sequencing. A total of 3,409 DEGs were identified, and based on gene ontology (GO), 42.53% of the most enriched 15 processes were associated with plant reproduction, including growth phase transition and floral organ development. For the former category, 79.1% of DEGs showed higher expression levels in SA than FB, suggesting they were sequentially turned on and off at the two test stages. For the DEGs encoding the components of circadian rhythm, sugar metabolism, phytohormone signaling, and floral organ identity genes, 60.71% showed higher abundance in FB than SA. Among them, MsAP1, an APETALA1 (AP1) homolog of Arabidopsis thaliana, showed high expression in flower buds and co-expressed with genes related to flower organ development. Moreover, ectopic expression of MsAP1 in Arabidopsis resulted in dwarfism and early flowering under long-day conditions. The MsAP1-overexpression plant displayed morphological abnormalities including fused whorls, enlarged pistils, determinate inflorescence, and small pods. In addition, MsAP1 is localized in the nucleus and exhibits significant transcriptional activity. These findings revealed a transcriptional regulation network of alfalfa transition from juvenile phase to flowering and provided genetic evidence of the dual role of MsAP1 in flowering and floral organ development.

Prestressed spun high-strength concrete (PHC) piles are commonly used in various types of structures, including bridges, buildings and marine infrastructures. However, piles installed in aggressive environments are vulnerable to corrosion of the steel, which can lead to rapid degradation of the piles. As a corrosion-resistant material, carbon fiber-reinforced polymer (CFRP) is considered an alternative to steel tendons for durability enhancement. In this study, a new pile system with CFRP was proposed. Experimental tests of three full-scale piles and a numerical analysis of eight piles with various parameters were performed to investigate the flexural performance of CFRP prestressed spun high-strength concrete pile. The proposed piles were loaded under four-point bending after prestressing. The experimental and numerical results verified the feasibility of the proposed system, and the CFRP pile exhibited twice of flexural capacity of that of steel-reinforced piles. The flexural performance of the CFRP PHC pile was significantly affected by the reinforcement ratio, prestressing level and modulus of the CFRP. An analytical approach predicting the flexural capacity of the CFRP PHC pile was proposed based on the parametric study. Ninety percent accuracy was achieved for the proposed analytical approach. The presented study can significantly promote the application of CFRP in pile foundations and improve the durability of PHC piles.

In 2000, Seligman and Csikszentmihalyi published the highly influential “Positive Psychology: An Introduction” in American Psychologist, and with it, they advocated for a strengths-based approach for helping people live a “good life”. Building on that work, positive psychology was further conceptualized as consisting of meta-psychological and practical aspects. The meta-psychological constitutes the aims or “grand vision” of what positive psychology stands for, whereas the practical constitutes the “nuts-and-bolts” elements that should be focused on in developing interventions. In the present commentary, we build on this previous work to propose a “positive psychology pragmatic framework” to develop strengths-based interventions (SBIs) for use with special student populations; in this case, students with special needs and P-3 and gifted students. Relatedly, we review the empirical and theoretical/conceptual literature relevant to the use of SBIs within each subpopulation as well as discuss some characteristics that make each subpopulation unique. Consequently, to the highest degree possible, we advocate for integrating intrapersonal, interpersonal, contextual/environmental, systemic, and developmental factors in developing SBIs and we make specific recommendations for future research through the lens of this proposed framework.

Abstract Purpose A Disintegrin and Metalloproteinase (ADAM) and A Disintegrin and Metalloproteinase with Thrombospondin Motif (ADAMTS) have been reported potentially involved in bone metabolism and related to bone mineral density. This Mendelian Randomization (MR) analysis was performed to determine whether there are causal associations of serum ADAM/ADAMTS with BMD in rid of confounders. Methods The genome-wide summary statistics of four site-specific BMD measurements were obtained from studies in individuals of European ancestry, including forearm (n = 8,143), femoral neck (n = 32,735), lumbar spine (n = 28,498) and heel (n = 426,824). The genetic instrumental variables for circulating levels of ADAM12, ADAM19, ADAM23, ADAMTS5 and ADAMTS6 were retrieved from the latest genome-wide association study of European ancestry (n = 5336 ~ 5367). The estimated causal effect was given by the Wald ratio for each variant, the inverse-variance weighted model was used as the primary approach to combine estimates from multiple instruments, and sensitivity analyses were conducted to assess the robustness of MR results. The Bonferroni-corrected significance was set at P

In the realm of Chinese traditional arts, paper-cutting symbols embody deep-seated aesthetic and cultural values. Within the framework of artificial intelligence, the fusion of these conventional symbols with contemporary pattern design through intelligent reconstruction processes promotes innovation in modern design. This paper introduces a novel pattern feature extraction algorithm specifically designed for identifying and extracting the essence of traditional paper-cutting art. Utilizing Deep Convolutional Generative Adversarial Networks (DCGAN), an automated method for generating woven patterns is developed, integrating conventional motifs with modern design elements. Additionally, a segmentation model based on DeepLabV3+ semantics is constructed to facilitate this integration. The study focuses on the fusion of traditional paper-cutting symbols with fabric patterns, providing a new direction for textile design research. The empirical evaluation involved seven experimenters who predominantly favored patterns that blended abstract and traditional styles, with the average style rating exceeding 3.2. Moreover, the color performance analysis of the reconstructed fabric patterns across five regions showed color difference values greater than 4, indicating superior color fidelity. These findings underscore the potential of combining AI-driven techniques with traditional art forms to enhance and revolutionize modern design practices.

BackgroundParkinson’s disease (PD) symptoms deteriorate with disease progression. Although deep brain stimulation (DBS) can effectively improve the motor signs of PD patients, it is not yet known whether DBS surgery, which is an invasive treatment modality, may change the progression of PD.ObjectiveThe aim of this work was to compare the effect of DBS with that of drug treatment on the progression of PD.MethodsA total of 77 patients with PD with the Hoehn and Yahr scale (HY) stage of 2.5 or 3 were included, and were divided into 34 in the drug therapy alone group (Drug-G) and 43 in the DBS therapy group (DBS-G). All patients were subjected to a follow-up of 2 years, and disease severity was assessed by the Unified Parkinson’s Disease Rating Scale part III (UPDRS-III), the Montreal Cognitive Assessment (MOCA), the Hamilton Anxiety Scale (HAMA), and the Hamilton Depression Scale (HAMD) scores. In addition, the quality of life of patients and the burden on their family were assessed by the 39-item PD questionnaire (PDQ-39) scores, daily levodopa equivalent dose (LED), patient’s annual treatment-related costs, and the Zarit Caregiver Burden Scale (ZCBS) score. The changes in relevant scale scores between the two groups were compared at each follow-up stage.ResultsThe UPDRS-III score of the patients in the “off” state increased from year to year in both groups, and the degree of increase of this score was greater in the DBS-G than in the Drug-G group. The MOCA score in both groups began to decline in the 2nd year of follow-up, and the decline was greater in the Drug-G than in the DBS-G group. DBS treatment did not affect patients’ psychiatric disorders. The PDQ39, LED, costs, and ZCBS were negatively correlated with the follow-up time in patients in the DBS-G group, and positively correlated with the follow-up time in patients in the Drug-G.ConclusionPD is progressive regardless of treatment. The findings from this follow-up study suggest that the disease progression of patients in DBS-G may be slightly faster compared to the drug-G, but the advantages of DBS are also evident. Indeed, DBS better improves patient’s motor signs and quality of life and reduces the family burden. In addition, DBS has less impact on patients in terms of cognitive and mental effects.

Objectives: Patients with epidermal growth factor receptor (EGFR) mutations in lung adenocarcinoma (LUAD) can benefit from individualized targeted therapy. This study aims to develop, compare, analyse prediction models based on dual-energy spectral computed tomography (DESCT) and CT-based radiomic features to non-invasively predict EGFR mutation status in LUAD. Materials and methods: Patients with LUAD (n = 175), including 111 patients with and 64 patients without EGFR mutations, were enrolled in the current study. All patients were randomly divided into a training dataset (122 cases) and validation dataset (53 cases) at a ratio of 7:3. After extracting CT-based radiomic, DESCT and clinical features, we built seven prediction models and a nomogram of the best prediction. Receiver operating characteristic (ROC) curves and the mean area under the curve (AUC) values were used for comparisons among the models to obtain the best prediction model for predicting EGFR mutations. Results: The best distinguishing ability is the combined model incorporating radiomic, DESCT and clinical features for predicting the EGFR mutation status with an AUC of 0.86 (95 % CI: 0.79–0.92) in the training group and an AUC value of 0.83 (95 % CI: 0.73, 0.96) in the validation group. Conclusions: Our study provides a predictive nomogram non-invasively with a combination of CT-based radiomic, DESCT and clinical features, which can provide image-based biological information for targeted therapy of LUAD with EGFR mutations.

Due to the uniqueness and interactivity of its scenario, the cultural and tourism commercial space consistently enriches and enhances the user experience while satisfying users' consumption and shopping. However, there is limited research on the participatory aspect of cultural tourism business spaces from the perspective of users. To this end, the present study investigates the participatory experience of cultural tourism commercial spaces by selecting 305 tourists who visited Huaihai Street in Suzhou for consumption and entertainment and quantifies the relationship between the public's flow experience, aesthetic judgments, and behavioral outcomes using a structural equation modeling approach. The results of the study confirm that aesthetic judgments and flow experiences positively impact behavioral outcomes and that flow experiences also affect aesthetic judgments and behavioral outcomes. These findings contribute to a better understanding of the significance of user participation in cultural tourism business spaces.

PurposeParkinson's disease (PD) patients frequently experience visual hallucinations (VHs) and obstructive sleep apnea (OSA). The aim of this study was to describe the prevalence and clinical correlates of VHs and OSA in the Chinese population with PD.Materials and methodsA sample of 489 PD patients was recruited for the present study. Patients were categorized as having formed VHs (FVHs) or minor VHs (MVHs) or as non-hallucinators (NVHs) according to the Unified Parkinson's Disease Rating Scale (UPDRS) and an initial questionnaire. Polysomnography (PSG) was used for objective assessment of sleep.ResultsVHs were observed in 143 (29.2%) patients. Among them, 75 of the hallucinators experienced MVHs, and 68 experienced FVHs. The disease duration, UPDRS Part III score, Hoehn and Yahr (H–Y) stage, Pittsburgh Sleep Quality Index (PSQI) score and rapid eye movement (REM) sleep behavior disorder (RBD) score of hallucinators were significantly greater than those of non-hallucinators (P < 0.05). We also observed OSA in 38.7, 54.7, and 63.3% of the NVH, MVH, and FVH groups, respectively. PSG showed that the VH groups had a lower total sleep time, lower sleep efficiency, higher arousal index, lower sleep latency, lower N1%, higher apnea-hypopnea index (AHI), higher average duration of apnea, higher respiratory-related arousal (RRA), and lower values of the lowest O2 and mean O2. The forward binary logistic regression model showed that AHI, N1%, RRA and lowest O2 were independently associated with VHs in PD patients.ConclusionsOur results confirm the high prevalence of VHs and OSA as well as their relationship in patients with PD.

Non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of the metabolic syndrome, remains without approved pharmacological treatment. Food-derived bioactive peptides can aid in the management of metabolic conditions including hypertension, obesity and insulin resistance. IRW (isoleucine-arginine-tryptophan) is a tripeptide produced from egg white with angiotensin converting enzyme-inhibitory properties. IRW supplementation elicits antihypertensive effects, improves skeletal muscle insulin signaling and glucose tolerance while reducing body weight gain. In this study, we hypothesized that IRW supplementation would prevent high-fat diet (HFD)-induced NAFLD by modulating hepatic lipid metabolism and increasing mitochondrial content. We found that IRW prevents diet-induced NAFLD, while rosiglitazone (ROSI) treatment worsens it. IRW decreases hepatic triglyceride content and lipid droplet size compared to HFD and ROSI. IRW increases the hepatic mitochondrial complexes and citrate synthase activity, phosphorylation of 5'-AMP-activated protein kinase and microsomal triglyceride transfer protein abundance compared to HFD. Compared with ROSI, IRW increases phosphorylated acetyl CoA carboxylase and mitochondrial complexes. Overall, the hypothesis is supported by these findings.

BackgroundClonorchis sinensis (C. sinensis) is a epidemiologically significant food-borne parasite, causing several hepatobiliary diseases. Biliary microbiota community structure might be influenced by infection with pathogens. However, the biliary microbiome of biliary obstruction patients infected with C. sinensis is still an unexplored aspect.MethodsA total of 50 biliary obstruction patients were enrolled, including 24 infected with C. sinensis and 26 non-infected subjects. The bile samples were collected by Endoscopic Retrograde Cholangiopancretography. Biliary microbiota alteration was analyzed through high-throughput 16S ribosomal RNA (rRNA) gene sequencing.ResultsOur findings revealed that there was significant increase in both richness and diversity, as well as changes in the taxonomic composition of the biliary microbiota of C. sinensis infected patients. At the phylum level, C. sinensis infection induced Proteobacteria increased and Firmicutes reduced. At the genus level, the relative abundance of Pseudomonas and Staphylococcus increased significantly, while Enterococcus decreased prominently in infected groups (P < 0.05). The PICRUSt analysis further showed remarkably different metabolic pathways between the two groups.ConclusionC. sinensis infection could modify the biliary microbiota, increasing the abundance and changing the phylogenetic composition of bacterial in biliary obstruction patients. This study may help deepen the understanding of the host-biliary microbiota interplay with C. sinensis infection on the background of biliary obstruction and provide new insights into understanding the pathogenesis of clonorchiasis.

Carbon fiber reinforced polymer (CFRP) has been proved effective in flexural strengthening of reinforced concrete (RC) beams. Various anchor systems have been developed to prevent premature debonding of CFRP plates for structural reinforcement applications. In this study, a novel circular wedged anchor system was proposed and tested under tensile load. The new anchor system includes circular barrel, connector and toothed wedges. Parameters such as intensity and height of tooth, gap between wedges and wedge angle were investigated in order to optimize the proposed anchor system. Effects of above parameters on capacity of the proposed anchor system are presented in the paper. The test results indicate full tensile strength of the tested CFRP plate could be developed using the optimized anchor system. A practical application of the proposed anchor system has been employed in the structural reinforcements of Tongyu River Bridge in China, and this system is found very effective in bridge cracking control via the practical long-term bridge inspections after strengthening.

In fire, ignoring the axial force acting on the high strength steel (HSS) beam-column endplate connections when considering catenary action may lead to a safety risk for the whole steel structure. Hence, a nonlinear analysis is conducted to reveal the actual performance of HSS T-stubs and HSS extended endplate connections in fire using the software ABAQUS. The ultimate displacement, failure mode and bearing capacity of HSS T-stubs under tension-shear combined action are investigated. The failure modes and moment–rotation curves of HSS endplate connections obtained by the numerical study are verified with test results in fire. Furthermore, the effects of bolt diameter, endplate thickness, endplate strength, the combination of endplate thickness and endplate strength, as well as temperature on the mechanical behaviour of HSS endplate connections considering axial force are studied. The results of nonlinear analysis are verified against Eurocode 3 Part 1–8 in various situations. The results indicate that when the shear-to-tension ratio is 2.0, the tensile bearing capacity and ultimate displacement of HSS T-stubs at 600 °C decreased to 38% and 31% of the pure tension, respectively. The parametric analysis shows that when the temperature is 600 °C, the initial stiffness and ultimate flexural capacity of connections are only about 40% and 31% of that at 20 °C.

In order to ensure the safe production of the oil field，scanning electron microscopy (SEM) and X-ray diffraction (XRD)，combined with wire beam electrodes，were used to observe the corrosion morphology and analyze the corrosion products under the scale in accordance with the actual operating conditions of an oil field in northern Shaanxi.The influence mechanism of Cl-，CO2 and O2 on corrosion under scale was explored by polarization curve and electrochemical impedance spectroscopy，and the corrosion inhibition performance of corrosion inhibitors on corrosion under scale was clarified.Results showed that Cl-，CO2 and O2 could easily penetrate the scale layer and reach the surface of the metal substrate to form corrosion cells，which increased the corrosion tendency.The corrosion inhibitor CH-1 had a small adsorption capacity on the scale sample surface，and had a strong anodic inhibition effect on the corrosion under scale.It could achieve the corrosion inhibition effect through negative catalytic effect，and had good corrosion inhibition performance under scale.

Understanding the relationship between the intake of sugars and diet quality can inform public health recommendations. This systematic review synthesized recent literature on associations between sugar intake and diet quality in generally healthy populations aged 2 years or older. We searched databases from 2010 to 2022 for studies of any design examining associations between quantified sugar intake in the daily diet and dietary indexes (DIs) or micronutrient intakes. Different sugar types and diet quality measures were analyzed separately. We converted DI results to Pearson’s r correlations and grouped indexes with or without a free or added sugar component to facilitate cross-study comparisons. Meta-analysis was deemed inappropriate. From 13,869 screened records, we included 27 cross-sectional studies. NUQUEST risk of bias ratings were neutral (n = 18 studies) or poor (n = 9), and strength of evidence by the GRADE approach was very low due to study design. Most studies reported negative associations for added and free sugars with diet quality indexes (r ranging from −0.13 to −0.42) and nutrients of public health concern (fiber, vitamin D, calcium, potassium), while associations with total sugars were mixed. Due to cross-sectional study designs, the clinical relevance of these findings is unclear. Prospective studies are needed to minimize confounding and inform causal relationships.

Empagliflozin is a sodium–glucose cotransporter 2 (SGLT2) inhibitor that is commonly used for the treatment of type 2 diabetes mellitus (T2DM). CKD-370 was newly developed as a cocrystal formulation of empagliflozin with co-former L-proline, which has been confirmed to be bioequivalent in South Korea. This study aimed to quantify the differences in the absorption phase and pharmacokinetic (PK) parameters of two empagliflozin formulations in healthy subjects by using population PK analysis. The plasma concentration data of empagliflozin were obtained from two randomized, open-label, crossover, phase 1 clinical studies in healthy Korean subjects after a single-dose administration. A population PK model was constructed by using a nonlinear mixed-effects (NLME) approach (Monolix Suite 2021R1). Interindividual variability (IIV) and interoccasion variability (IOV) were investigated. The final model was evaluated by goodness-of-fit (GOF) diagnostic plots, visual predictive checks (VPCs), prediction errors, and bootstrapping. The PK of empagliflozin was adequately described with a two-compartment combined transit compartment model with first-order absorption and elimination. Log-transformed body weight significantly influenced systemic clearance (CL) and the volume of distribution in the peripheral compartment (V2) of empagliflozin. GOF plots, VPCs, prediction errors, and the bootstrapping of the final model suggested that the proposed model was adequate and robust, with good precision at different dose strengths. The cocrystal form did not affect the absorption phase of the drug, and the PK parameters were not affected by the different treatments.

BackgroundStroke, which is a common clinical cerebrovascular disease, causes approximately 83% of survivors to suffer from balance impairments. Balance and gait training (BGT) is widely used to restore balance in patients with stroke. However, its wide variety presents clinicians with a dilemma when selecting interventions. This study aimed to compare and rank BGT interventions by quantifying information based on randomized controlled trials (RCTs).MethodsWe conducted a network meta-analysis (NMA) of non-gait-trained controls and head-to-head RCTs and compared the effects of 12 BGT interventions. A total of nine literature databases, including Medline, Embase, Cochrane Library, Web of Science, Scopus, SPORTDiscus, ClinicalTrials.gov, CNKI, and Chinese biomedical literature databases, were searched from their database inception to August 2023. Two authors independently selected studies and extracted data. The difference in outcomes, which were expressed as standardized mean differences and confidence intervals (CIs) of 95%, were explored in this meta-analysis.ResultsA total of 66 studies with 1,933 participants were included. Effect size estimates showed that not all BGT interventions were more effective than controls, with treadmill training as the least effective for balance test batteries (SMD = −0.41, 95% CI [−1.09, 0.27]) and proactive balance (SMD = −0.50, 95% CI [−1.14, 0.14]). Body-weight-supported treadmill training with external stimulation was most effective for proactive balance and dynamic steady-state balance (SMD = 1.57, 95% CI [−0.03, 3.16]); SMD = 1.18, 95% CI [0.67, 1.68]. Virtual reality gait training (SMD = 1.37, 95% CI [0.62, 2.11]) had the best effect on improving balance test batteries, while dual-task BGT (SMD = 1.64, 95% CI [0.50, 2.78]) had the best effect on static steady-state balance. After analyses for possible impact covariates, the findings through the outcomes did not change substantially. Confidence in the evidence was generally low or very low.ConclusionThis NMA suggested that virtual reality gait training was the most effective BGT modality for improving balance test batteries. Body-weight support treadmill training with external stimulation was the most effective for improving active and dynamic balance. In addition, dual-task BGT was the best choice for improving static balance. However, balance is a multidimensional concept, and patients’ different needs should be considered when selecting BGT.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022316057, ID: CRD42022316057.

Existing clinical treatments for tendinopathy mainly focus on reducing pain, whereas inhibiting or reversing disease progression remains challenging. Local therapeutic drugs, such as glucocorticoids, cause adverse effects on the metabolism of tendon tissues and injection-related complications. Therefore, new administration modalities for tendinopathy need to be developed. In this study, we designed a hydrogel-based microneedle (MN) system for the long-term transdermal delivery of our novel biological cell-free fat extract (CEFFE) to treat tendinopathies. We found that CEFFE-loaded MNs (CEFFE-MNs) had good biosafety and inhibited lipopolysaccharide (LPS)-induced apoptosis and matrix degradation in Achilles tendon cells of rats. The Achilles tendons of rats returned to their maximum mechanical strength after applying CEFFE-MNs. The administration of CEFFE-MNs had better anti-apoptosis and tendon repair-promoting effects than CEFEF injections in vivo. Transcriptome sequencing indicated that the anti-apoptosis effect of CEFFE-MNs was highly related to tumor necrosis factor (TNF) signaling. CEFFE-MNs inhibited the expression of TNF, TNF receptor 1, and downstream nuclear factor-kappa B signaling. Additionally, CEFFE-MNs rescued LPS-induced mitochondrial dynamics in tendon cells via the TNF-Drp1 axis. Our study reports a novel CEFFE-MN system that exhibits long-term anti-inflammatory and anti-apoptotic effects, suggesting it as a new treatment route for tendinopathy with broad clinical translation prospects.

BackgroundClonorchiasis is an important foodborne parasitic disease. However, eggs of Clonorchis sinensis (C. sinensis) cannot be detected in feces during biliary obstruction. Moreover, many diseases can cause biliary obstruction, such as gallstones, adenocarcinoma, cholangiocarcinoma and Ascaris lumbricoides infection. Therefore, it is of great significance to distinguish between patients of biliary obstruction and biliary obstruction with C. sinensis infection.MethodsA total of 48 biliary obstruction patients were enrolled, including 23 infected with C. sinensis (C. sinensis) (OB+C.s) and 25 non-infected subjects (OB). The bile samples were collected by endoscopic retrograde cholangiopancreatography and analyzed using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF MS). Additionally, multivariate statistical analysis methods were employed to identify differential metabolites. Next, bile amino acid levels were determined by targeted metabolomics analysis.ResultA total of 146 and 132 significant metabolites were identified in electrospray ionization (ESI)+ and ESI− modes, respectively. The levels of amino acids (asparagine, glutamate, ornithine) and polyamines (spermidine and spermine) were significantly changed. Targeted analysis showed that the levels of amino acids (such as L-arginine, L-glutamine, L-lysine, L-propionic, and L-tyrosine) were lower in OB+C.s patients compared to those in OB patients. Marked metabolic pathways were involved in “Glutathione metabolism”, “Caffeine metabolism”, “Alanine, aspartate and glutamate metabolism”, “Arginine and proline metabolism”, “Purine metabolism”, “Beta-Alanine metabolism”, and “D-glutamine and D-glutamate metabolism”.ConclusionThese results show that there were significant differences between OB+C.s and OB patients, especially in amino acids. The metabolic signature and perturbations in metabolic pathways may help to better distinguish OB+C.s and OB patients.