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The primary objective of a regional integration strategy is to foster talent agglomeration and knowledge spillover, thereby enhancing the high-quality development of the regional economy. Extant literature predominantly concentrates on talent distribution and the pattern of knowledge spillover under integration policy. However, scant attention has been paid to the causal inference of regional integration policy on talent aggregation and knowledge spillover. Under the new economic structure of establishing a unified national market and high-quality development, a comprehensive understanding of the evolutionary mechanisms of integration policy in relation to talent aggregation and knowledge spillover is pivotal for shaping regional talent policies and refining theories of population mobility. To address this gap, this study employs time-varying Difference-In-Differences (DID) and spatial DID approaches to empirically assess the influence and underlying mechanisms of regional integration policy within the context of the Yangtze River Delta Urban Agglomeration. The analysis reveals three key findings. First, the integration policy demonstrates a substantial facilitative impact on talent aggregation and knowledge diffusion within the Yangtze River Delta Urban Agglomeration, bolstering these processes by 10.5% and 14.8%, respectively, and exhibiting significant spatial spillover effects. This indicates that the policy not only attracts talent to specific regions but also encourages the spread of knowledge beyond the immediate geographical boundaries of the targeted areas. Second, heterogeneity analysis shows that the policy effectively enhances talent aggregation and knowledge spillover in central cities, with no significant influence observed in peripheral cities. This disparity suggests that central cities, with their advanced infrastructure and economic opportunities, are better positioned to capitalize on the benefits of the integration policy. Furthermore, from a demographic perspective, the policy exhibits a more pronounced positive effect on talent aggregation and knowledge spillovers in medium- and large-scale cities. This trend underscores the importance of city size and demographic factors in the successful implementation of integration policies. Third, mechanistic analysis indicates that the beneficial impacts of the policy on talent concentration are more pronounced in cities characterized by higher levels of urbanization, investment, market integration, education, income level, public service provision, and transportation infrastructure. These factors collectively create an environment conducive to talent attraction and retention, amplifying the effects of the integration policy. Furthermore, the policy has significantly enhanced talent agglomeration by increasing the stock of human capital, highlighting the role of education and skill development in fostering regional economic growth. In conclusion, this study provides a theoretical basis and practical reference for urban agglomerations aiming to spearhead the high-quality advancement of regional economies. By revealing the intrinsic laws and influence mechanisms of regional integration policy, the findings offer valuable insights for policymakers seeking to optimize talent policies and promote sustainable economic development. The empirical evidence highlights the importance of targeted policy interventions that consider the unique characteristics of different urban areas, thereby ensuring a balanced and inclusive approach to regional development. Future research should continue to explore the long-term effects of integration policies and their potential to drive innovation and economic resilience in an increasingly interconnected world.

In spite of the sudden onset of the COVID-19 pandemic, many instructors who used team-based pedagogies shifted them online rather than suspending them entirely, but with limited time and resources. To examine the difference in team dynamics and outcomes for courses in Spring 2019 and Spring 2020 of over 1500 first-year engineering students per semester, Wilcoxon signed-rank tests and random forests method were used. Results show that students reported less improvement in team-member effectiveness, lower psychological safety, and less satisfaction in the semester with the emergency transition. However, students also reported lower conflict. The most important factor predicting project grades shifted from 'Interacting with teammates' to 'Having relevant knowledge, skills, and abilities' amid the emergency shift, accompanied by a reduction in team interdependence. In spite of the collection of data during an emergency transition, the foundation of face-to-face interaction before moving to virtual cooperation represents a useful contribution to research that has focused exclusively on virtual learning circumstances.

Abstract Objectives To compare color Doppler ultrasound and contrast-enhanced ultrasound (CEUS) in evaluating vascular invasion in pancreatic ductal adenocarcinoma (PDAC). Materials and methods This retrospective study included 210 patients with PDAC who were evaluated by color Doppler ultrasound, CEUS, and contrast-enhanced computed tomography (CECT) at our institution between January 2017 and December 2020. Pathologic results were used as the gold standard in patients who underwent surgical and intraoperative exploration. For nonsurgical patients, CECT results were used as the reference standard. The vessels evaluated included those in the peripancreatic arterial system and venous system. The diagnostic performances of color Doppler ultrasound and CEUS for vascular invasion were compared. Results In 51 patients who underwent surgery and intraoperative exploration, color Doppler ultrasound and CEUS differed only in assessing venous system invasion in patients with PDAC of the pancreatic body and tail, with the former being superior to the latter. In 159 nonsurgical patients, there was no difference between CEUS and color Doppler ultrasound in assessing superior mesenteric arteriovenous invasion. CEUS was superior to color Doppler ultrasound in evaluating the celiac artery and its branches, with an accuracy of up to 97.8% for some vessels. Color Doppler ultrasound was ideal for evaluating the splenic and portal veins. Conclusion CEUS is more suitable for the evaluation of peripancreatic arteries than color Doppler. CEUS combined with color Doppler ultrasound can be used as a potential supplement to CECT and is also expected to be used to evaluate vascular invasion of PDAC after chemotherapy. Critical relevance statement Contrast-enhanced US and color Doppler in the assessment of vascular invasion in pancreatic ductal adenocarcinoma have their respective advantages, through standardized ultrasound processes are expected to improve the efficiency of inspection. Key Points Contrast-enhanced US has unique advantages in assessing pancreatic ductal adenocarcinoma invasion of the celiac artery. Doppler imaging is of high value in assessing venous system invasion. Standardization of ultrasound imaging procedures for pancreatic ductal adenocarcinoma is expected to improve efficiency. Graphical Abstract

Abstract Background The insulin/insulin-like signalling (IIS) pathway is common in mammals and invertebrates, and the IIS pathway is unknown in Fasciola gigantica. In the present study, the IIS pathway was reconstructed in F. gigantica. We defined the components involved in the IIS pathway and investigated the transcription profiles of these genes for all developmental stages of F. gigantica. In addition, the presence of these components in excretory and secretory products (ESPs) was predicted via signal peptide annotation. Results The core components of the IIS pathway were detected in F. gigantica. Among these proteins, one ligand (FgILP) and one insulin-like molecule binding protein (FgIGFBP) were analysed. Interestingly, three receptors (FgIR-1/FgIR-2/FgIR-3) were detected, and a novel receptor, FgIR-3, was screened, suggesting novel functions. Fg14-3-3ζ, Fgirs, and Fgpp2a exhibited increased transcription in 42-day-old juveniles and 70-day-old juveniles, while Fgilp, Fgigfb, Fgsgk-1, Fgakt-1, Fgir-3, Fgpten, and Fgaap-1 exhibited increased transcription in metacercariae. FgILP, FgIGFBP, FgIR-2, FgIR-3, and two transcription factors (FgHSF-1 and FgSKN-1) were predicted to be present in FgESPs, indicating their exogenous roles. Conclusions This study helps to elucidate the signal transduction pathway of IIS in F. gigantica, which will aid in understanding the interaction between flukes and hosts, as well as in understanding fluke developmental regulation, and will also lay a foundation for further characterisation of the IIS pathways of trematodes.

Ex vivo tissue culture of the human corpus cavernosum (CC) can be used to explore the tissue structural changes and complex signaling networks. At present, artificial CC-like tissues based on acellular or three-dimensional (3D)-printed scaffolds are used to solve the scarcity of primary penis tissue samples. However, inconvenience and high costs limit the wide application of such methods. Here, we describe a simple, fast, and economical method of constructing artificial CC-like tissue. Human CC fibroblasts (FBs), endothelial cells (ECs), and smooth muscle cells (SMCs) were expanded in vitro and mixed with Matrigel in specific proportions. A large number of bubbles were formed in the mixture by vortexing combined with pipette blowing, creating a porous, spongy, and spatial structure. The CC FBs produced a variety of signaling factors, showed multidirectional differentiation potential, and grew in a 3D grid in Matrigel, which is necessary for CC-like tissue to maintain a porous structure as a cell scaffold. Within the CC-like tissue, ECs covered the surface of the lumen, and SMCs were located inside the trabeculae, similar to the structure of the primary CC. Various cell components remained stable for 3 days in vitro, but the EC content decreased on the 7th day. Wingless/integrated (WNT) signaling activation led to lumen atrophy and increased tissue fibrosis in CC-like tissue, inducing the same changes in characteristics as in the primary CC. This study describes a preparation method for human artificial CC-like tissue that may provide an improved experimental platform for exploring the function and structure of the CC and conducting drug screening for erectile dysfunction therapy.

Abstract NLR family proteins act as intracellular receptors. Gene duplication amplifies the number of NLR genes, and subsequent mutations occasionally provide modifications to the second gene that benefits immunity. However, evolutionary processes after gene duplication and functional relationships between duplicated NLRs remain largely unclear. Here, we report that the rice NLR protein Pit1 is associated with its paralogue Pit2. The two are required for the resistance to rice blast fungus but have different functions: Pit1 induces cell death, while Pit2 competitively suppresses Pit1-mediated cell death. During evolution, the suppression of Pit1 by Pit2 was probably generated through positive selection on two fate-determining residues in the NB-ARC domain of Pit2, which account for functional differences between Pit1 and Pit2. Consequently, Pit2 lost its plasma membrane localization but acquired a new function to interfere with Pit1 in the cytosol. These findings illuminate the evolutionary trajectory of tandemly duplicated NLR genes after gene duplication.

ABSTRACT Background Dexamethasone (Dex), a synthetic glucocorticoid that acts by binding to the glucocorticoid receptor (GR), has been widely applied to treat leukemia and lymphoma; however, the precise mechanism underlying Dex action is still not well elucidated. DOT1L, a histone H3‐lysine79 (H3K79) methyltransferase, has been linked to multiple cancer types, particularly mixed lineage leukemia (MLL) gene rearranged leukemia, but its contribution to lymphoma is yet to be delineated. Analysis from the TCGA database displayed that DOT1L was highly expressed in lymphoma and leukemia. Results We initially demonstrated that DOT1L served as a new target gene controlled by GR, and the downregulation of DOT1L was critical for the killing of B‐lymphoma cells by Dex. Further study revealed that Dex had no impact on the transcriptional activity of the DOT1L promoter, rather it reduced the mRNA level of DOT1L at the posttranscriptional level. In addition, knockdown of DOT1L remarkably inhibited the B‐lymphoma cell growth. Conclusions Overall, our findings indicated that DOT1L may serve as a potential drug target and a promising biomarker of Dex sensitivity when it comes to treating B lymphoma.

BackgroundMetagenomic next-generation sequencing (mNGS) has been widely reported to identify pathogens in infectious diseases (IDs). In this work, we intended to investigate the diagnostic value and clinical acceptance of paired-samples mNGS as compared to the culture method.MethodsA total of 361 patients with suspected infection were retrospectively included. With reference to the clinical diagnosis, we compared the diagnostic performance and clinical acceptance in pathogen detection between mNGS and culture tests. Moreover, the pathogen concordance of paired blood and respiratory tract (RT) samples in mNGS assay was investigated.ResultsAmong 511 samples, 62.04% were shown to be pathogen positive by mNGS, and that for clinical diagnosis was 51.86% (265/511). When compared to culture assay (n = 428), mNGS had a significantly higher positivity rate (51.87% vs. 33.18%). With reference to the clinical diagnosis, the sensitivity of mNGS outperformed that of culture (89.08% vs. 56.72%). Importantly, mNGS exhibited a clinically accepted rate significantly superior to that of culture. In addition, the mNGS result from 53 paired blood and RT samples showed that most pairs were pathogen positive by both blood and RT, with pathogens largely being partially matched.ConclusionThrough this large-scale study, we further illustrated that mNGS had a clinically accepted rate and sensitivity superior to those of the traditional culture method in diagnosing infections. Moreover, blood and paired RT samples mostly shared partial-matched positive pathogens, especially for pathogens with abundant read numbers in RT, indicating that both blood and RT mNGS can aid the identification of pathogens for respiratory system infection.

The taxonomic validity of Dolichovespula kuami, especially in relation to D. flora, has been the subject of a long-term debate. Herein, the valid specific status of the former was supported through an integrated analysis of morphological characters and DNA barcodes. The pronotal rugae and male genitalia of the two species are different, and partial mitochondrial genes (cytochrome oxidase subunit I, COI) indicate that they form significantly distinct lineages. The hitherto unknown male of D. kuami is described for the first time, and a brief discussion of the D. maculata species group is provided.

This review provides a comprehensive overview of the distinguished academic career and scientific accomplishments of Prof. Noritatsu Tsubaki at the University of Toyama. For over 35 years, he has dedicated himself to the research field of one-carbon (C1) chemistry, including catalytic conversion of C1 molecules to valuable chemicals and superclean fuels, innovative catalyst and reactor development, and the design of new catalytic reactions and processes. Organized chronologically, this review highlights Prof. Tsubaki's academic contributions from 1990, when he studied and worked at The University of Tokyo, to his current role as a full professor at the University of Toyama. The academic section of this review is divided into three main parts, focusing on Prof. Tsubaki's pioneering work in C1 chemistry. We believe that this review will serve as a highly valuable reference for colleagues in the fields of C1 chemistry and catalysis, and inspire the development of more original and groundbreaking research.

The epitranscriptomic mark N6-methyladenosine (m6A) is the most common type of messenger RNA (mRNA) post-transcriptional modification in eukaryotes. With the discovery of the demethylase FTO (FAT MASS AND OBESITY-ASSOCIATED PROTEIN) in Homo Sapiens, this modification has been proven to be dynamically reversible. With technological advances, research on m6A modification in plants also rapidly developed. m6A modification is widely distributed in plants, which is usually enriched near the stop codons and 3′-UTRs, and has conserved modification sequences. The related proteins of m6A modification mainly consist of three components: methyltransferases (writers), demethylases (erasers), and reading proteins (readers). m6A modification mainly regulates the growth and development of plants by modulating the RNA metabolic processes and playing an important role in their responses to environmental signals. In this review, we briefly outline the development of m6A modification detection techniques; comparatively analyze the distribution characteristics of m6A in plants; summarize the methyltransferases, demethylases, and binding proteins related to m6A; elaborate on how m6A modification functions in plant growth, development, and response to environmental signals; and provide a summary and outlook on the research of m6A in plants.

Context: Ultrasound (US) is the most economical and widely used method for detecting lesions in parathyroid regions. Identifying typically parathyroid adenomas as hypoechoic nodules with clear margins. However, 10 % of lesions exhibit atypical features, such as the dual concentric sign, and the cognition of them still needs to be improved. Objective: To promote understanding of clinical and histopathological features for parathyroid lesions with the dual concentric echo sign and to investigate its pathogenesis and methods for distinguishing from cervical lymph nodes to improve US diagnostic accuracy. Methods: Retrospectively, patients were categorized into three groups: Group 1, with 36 patients showing parathyroid lesions with dual concentric echo signs; Group 2, with 40 patients displaying classic hypoechoic parathyroid lesions; and Group 3, comprising 36 patients with identified lymph nodes, which were all examined from January 2018 to December 2019. The clinical data on demographics, clinical symptoms, serum levels, histopathologic findings, and US image characteristics were thoroughly reviewed. Results: According to the clinical data, no significant differences in demographics or lesion sizes were observed in Group 1 and Group 2 (p > 0.05). No significant variances were noted in biochemical markers, including PTH, T-25OHD, and ALP. However, a notable difference was identified in adjusted serum calcium levels, which were significantly lower in Group 1 compared to Group 2 (p

Objectives: Metagenomic next-generation sequencing (mNGS) is a powerful tool for pathogen detection. The accuracy depends on both wet lab and dry lab procedures. The objective of our study was to assess the influence of read length and dataset size on pathogen detection. Methods: In this study, 43 clinical BALF samples, which tested positive via clinical mNGS and were consistent with the diagnosis, were subjected to re-sequencing on the Illumina NovaSeq 6000 platform. The raw re-sequencing data, consisting of 100 million (M) paired-end 150 bp (PE150) reads, were divided into simulated datasets with eight different data sizes (5 M, 10 M, 15 M, 20 M, 30 M, 50 M, 75 M, 100 M) and five different read lengths (single-end 50 bp (SE50), SE75, SE100, PE100, and PE150). Both Kraken2 and IDseq bioinformatics pipelines were employed to analyze the previously diagnosed pathogens in the simulated data. Detection of pathogens was based on read counts ranging from 1 to 10 and RPM values ranging from 0.2 to 2. Results: Our results revealed that increasing dataset sizes and read lengths can enhance the performance of mNGS in pathogen detection. However, a larger data sizes for mNGS require higher economic costs and longer turnaround time for data analysis. Our findings indicate 20 M reads being sufficient for SE75 mode to achieve high recall rates. Additionally, high nucleic acid loads in samples can lead to increased stability in pathogen detection efficiency, reducing the impact of sequencing strategies. The choice of bioinformatics pipelines had a significant impact on recall rates achieved in pathogen detection. Conclusions: Increasing dataset sizes and read lengths can enhance the performance of mNGS in pathogen detection but increase the economic and time costs of sequencing and data analysis. Currently, the 20 M reads in SE75 mode may be the best sequencing option.

In deep strata, there is a risk that geotechnical engineering is simultaneously subjected to chemical corrosion and dynamic loading, which seriously affects the safety of engineering. In this study, Split Hopkinson Pressure Bar (SHPB) was utilized to conduct dynamic loading tests on chemically corroded sandstone, which investigated the dynamic metamorphic properties and chemical damage of sandstone in this condition. Based on the effective bearing area and strain equivalence principles, the damage variables were determined by changes in the porosity of sandstone that were indicated by nuclear magnetic resonance (NMR). The microstructure and particle size distribution of sandstone were quantitatively analyzed by Scanning Electron Microscopy (SEM) and Nano Measurer software. Furthermore, the failure mechanisms of sandstone were explained by chemical reactions between rocks and solutions. The results showed that the porosity of sandstone corroded by chemical solutions increases. With the increase of damage variables, the dynamic compressive strength linearly decreases while the dynamic destructive strain gradually increases. The distribution of particle size has good self-similarity at the micro level and the fractal dimension was positively correlated with the damage variable. Microstructural metamorphism and chemical damage mechanisms of sandstones were revealed through microstructure testing and mineralization analysis. Findings are necessary for the safe operation of rock engineering.

Acinetobacter baumannii has emerged as a multidrug-resistant (MDR) superbug by causing severe infections, with high mortality rates. The ability of A. baumannii to form biofilms significantly contributes to its persistence in diverse environmental and hospital settings. Here we report that farnesol, an FDA-approved commercial cosmetic and flavoring agent, demonstrates efficacy for both inhibition of biofilm formation, and disruption of established A. baumannii biofilms. Moreover, no resistance to farnesol was observed even after prolonged culture in the presence of sub-inhibitory farnesol doses. Farnesol combats A. baumannii biofilms by direct killing, while also facilitating biofilm detachment. Furthermore, farnesol was safe, and effective, for both prevention and treatment of A. baumannii biofilms in an ex vivo burned human skin model. Since current treatment options for A. baumannii biofilm infections were mainly counted on the combination therapy of last-resort antibiotics, and clearly non-sustainable due to robust MDR phenotype of A. baumannii, we propose that farnesol alone can be repurposed as a highly effective agent for both preventing and treating life-threating biofilm-associated infections of A. baumannii due to its proven safety, convenient topical delivery, and excellent efficiency, plus its superiority of evading resistance development.

ObjectiveThe purpose of this study is to investigate the drug safety of three Transthyretin (TTR) inhibitors in the real world using the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database.MethodsThis study extracted reports received by the FAERS database from the first quarter of 2018 to the third quarter of 2023 for descriptive analysis and disproportionality analysis. Safety signal mining was conducted at the Preferred Term (PT) level and the System Organ Class (SOC) level using reporting odds ratio (ROR). The characteristics of the time-to-onset curves were analyzed using the Weibull Shape Parameter (WSP). The cumulative incidence of TTR inhibitors was evaluated using the Kaplan-Meier method. Subgroup analyses were conducted based on whether the reporter was a medical professional.ResultsA total of 3,459 reports of adverse events (AEs) caused by TTR inhibitors as the primary suspect (PS) drug were extracted. The top three reported AEs for patisiran were fatigue, asthenia, and fall, with the most unexpectedly strong association being nonspecific reaction. The top three reported AEs for vutrisiran were fall, pain in extremity and malaise, with the most unexpectedly strong association being subdural haematoma. The top three reported AEs for inotersen were platelet count decreased, blood creatinine increased, and fatigue, with the most unexpectedly strong association being blood albumin decreased. Vitamin A decreased, arthralgia, and dyspnea were the same AEs mentioned in the drug labels of all three drugs, while malaise and asthenia were the same unexpected significant signals. This study offers evidence of the variability in the onset time characteristics of AEs associated with TTR inhibitors, as well as evidence of differences in adverse event reporting between medical professionals and non-medical professionals.ConclusionIn summary, we compared the similarities and differences in drug safety of three TTR inhibitors in the real world using the FAERS database. The results indicate that not only do these three drugs share common AEs, but they also exhibit differences in drug safety profiles. This study contributes to enhancing the understanding of medical professionals regarding the safety of TTR inhibitors.

Summary: Light olefins are key intermediates in the synthesis of petrochemicals, and the conversion of stabilized carbon dioxide to light olefins using catalysts containing halogenated elements such as chlorine is a major challenge. Building on previous reports emphasizing the toxic effects of halogen elements on catalysts, we present the synthesis of FeMnKBr/YNa catalysts. This involved the synthesis of the catalyst by melt permeation using Br-containing potassium salts, other metal nitrates and YNa zeolites. The catalyst performed well in converting syngas (H2/CO2 = 3) to light olefins with a selectivity of 56.2%, CO2 conversion of 34.4%, and CO selectivity of 13.6%. Adding Br aids in reducing the Fe phase, boosts catalyst carburization, and produces more iron carbide species. It also moderately deposits carbon on the active center’s surface, enhancing active phase dispersion. Br’s electronegativity mitigates the influence of K, reducing catalyst’s carbon-carbon coupling ability, leading to more low-carbon olefins generation.