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In recent years, there have been unparalleled prospects for psychological study due to the swift advancement of generative artificial intelligence (AI) in natural language processing, shown by ChatGPT. This review article looks into the uses and effects of generative artificial intelligence in psychology. We employed a systematic selection process, encompassing papers published between 2015 and 2024 from databases such as Google Scholar, PubMed, and IEEE Xplore, using keywords like "Generative AI in psychology" "ChatGPT and behavior modeling" and "AI in mental health". First, the paper goes over the fundamental ideas of generative AI and lists its uses in data analysis, behavior modeling, and social interaction simulation. A detailed comparison table has been added to contrast conventional research methodologies with GenAI-based approaches in psychology studies. Next, analyzing the theoretical and ethical issues that generative AI raises for psychological research, it highlights how crucial it is to develop a coherent theoretical framework. This study illustrates the benefits of generative AI in handling vast amounts of data and increasing research efficiency by contrasting traditional research methods with AI-driven methodologies. Regarding particular uses, the study explores how generative AI might be used to simulate social interactions, analyze massive amounts of text, and learn about cognitive processes. Section 5 has been expanded to include discussions on political biases, geographic biases, and other biases. In conclusion, the paper looks forward to the future development of generative AI in psychology research and suggests techniques for improving it. We have included methodological solutions such as the Retrieval Augmented Generation (RAG) approach and human-in-the-loop systems, as well as data privacy solutions like open-source local LLMs. In summary, generative AI has the potential to revolutionize psychological research, but in order to maintain the moral and scientific integrity of the field, ethical and theoretical concerns must be carefully considered before applying the technology., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Most coexisting insect species exhibit stunted growth compared to individual species on plants. This phenomenon reflects an interspecific antagonism drawing extensive attention, while the underlying mechanisms remain largely uncharacterized. Mirids (Apolygus lucorum) and cotton bollworms (Helicoverpa armigera) are two common cotton pests. We identified a secretory protein, ASP1, from the oral secretion of mirids, found in the nucleus of mirid-infested cotton leaves. ASP1 specifically targets the transcriptional co-repressor TOPLESS (TPL) and inhibits NINJA-mediated recruitment of TPL, promoting plant defense response and gossypol accumulation in cotton glands. ASP1-enhanced defense inhibits the growth of cotton bollworms on cotton plants, while having limited impact on mirids. The mesophyll-feeding characteristic allows mirids to avoid most cotton glands, invalidating cotton defense. Our investigation reveals the molecular mechanism by which mirids employ cotton defense to selectively inhibit the feeding of cotton bollworms., (Copyright © 2024 The Author. Published by Elsevier Inc. All rights reserved.)

Ribonuclease P (RNase P) plays a vital role in the maturation of tRNA across bacteria, archaea, and eukaryotes. However, how RNase P assembles various components to achieve specific cleavage of precursor tRNA (pre-tRNA) in different organisms remains elusive. In this study, we employed single-molecule fluorescence resonance energy transfer to probe the dynamics of RNase P from E. coli ( Escherichia coli ) and Mja ( Methanocaldococcus jannaschii ) during pre-tRNA cleavage by incorporating five Cy3-Cy5 pairs into pre-tRNA and RNase P. Our results revealed significant differences in the assembly and catalytic mechanisms of RNase P between E. coli and Mja at both the RNA and protein levels. Specifically, the RNA of E. coli RNase P ( Eco RPR) can adopt an active conformation that is capable of binding and cleaving pre-tRNA with high specificity independently. The addition of the protein component of E. coli RNase P (RnpA) enhances and accelerates pre-tRNA cleavage efficiency by increasing and stabilizing the active conformation. In contrast, Mja RPR is unable to form the catalytically active conformation on its own, and at least four proteins are required to induce the correct folding of Mja RPR. Mutation experiments suggest that the functional deficiency of Mja RPR arises from the absence of the second structural layer, and proper intermolecular assembly is essential for Mja RNase P to be functional over a broad temperature range. We propose models to illustrate the distinct catalytic patterns and RNA-protein interactions of RNase P in these two organisms., Competing Interests: Competing interests statement:The authors declare no competing interest.

Nephrite, a historically significant material in Chinese jade culture, varies in elemental composition and spectroscopic properties based on its geographic origin due to differing mineralization environments. This study aims to address the limitations of traditional methods by employing a multi-technique approach that combines XRF mapping, fiber optic reflectance spectroscopy (FORS), near-infrared spectroscopy (NIR), and synchrotron-based X-ray absorption fine structure (XAFS) analysis, focusing on a comprehensive characterization of Fe to understand the properties of nephrite from various provenances. Our results reveal that while major elements like Si, Mg, and Ca are uniformly distributed, elements such as K, Mn, and Fe show significant variability, with Fe and Mn exhibiting nearly identical distribution patterns. Transparency variations in Qinghai nephrite correlate with Ca distribution. Chromaticity analysis indicates that Fe significantly influences the yellow coloration of nephrite, and NIR spectroscopy shows that Fe content affects spectral characteristics. XAFS analysis provides detailed insights into the valence and coordination environment of Fe, highlighting its role in color variation and spectral shifts. This integrated approach bridges the correlation between elemental composition and distribution, structural properties and visual representation, and its non-destructive advantages could hold great promise for jade research., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

An animal's locomotor rate is an important indicator of its motility. In studies of the nematode Caenorhabditis elegans (C. elegans), assays of the frequency of body bending waves have often been used to discern the effects of mutations, drugs, or aging. Traditional manual methods for measuring locomotor frequency are low in throughput and subject to human error. Most current automated methods depend on image segmentation, which requires high image quality and is prone to errors. Here, we describe an algorithm for automated estimation of C. elegans locomotor frequency using image invariants, i.e. shape-based parameters that are independent of object translation, rotation, and scaling. For each video frame, the method calculates a combination of 8 Hu's moment invariants and a set of maximally stable extremal regions (MSER) invariants. The algorithm then calculates the locomotor frequency by computing the autocorrelation of the time sequence of the invariant ensemble. Results of our method show excellent agreement with manual or segmentation-based results over a wide range of frequencies. We show that compared to a segmentation-based method that analyzes a worm's shape and a method based on video covariance, our technique is more robust to low image quality and background noise. We demonstrate the system's capabilities by testing the effects of serotonin and serotonin pathway mutations on C. elegans locomotor frequency., Competing Interests: Conflicts of interest The authors declare no conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Genetics Society of America.)

Assays of behavior in model organisms play an important role in genetic screens, drug testing, and the elucidation of gene-behavior relationships. We have developed an automated, high-throughput imaging and analysis method for assaying behaviors of the nematode C. elegans. We use high-resolution optical imaging to longitudinally record the behaviors of 96 animals at a time in multi-well plates, and computer vision software to quantify the animals' locomotor activity, behavioral states, and egg laying events. To demonstrate the capabilities of our system we used it to examine the role of serotonin in C. elegans behavior. We found that egg-laying events are preceded by a period of reduced locomotion, and that this decline in movement requires serotonin signaling. In addition, we identified novel roles of serotonin receptors SER-1 and SER-7 in regulating the effects of serotonin on egg laying across roaming, dwelling, and quiescent locomotor states. Our system will be useful for performing genetic or chemical screens for modulators of behavior., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Genetics Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: This study aimed to evaluate the utility of 24 single nucleotide polymorphism (SNP) loci associated with iris color and hair color in phenotypic identification of the Han Chinese population in Fujian Province. The selected SNPs, known for their strong correlation with specific human phenotypic features, provide valuable reference data for developing a molecular phenotypic identification system., Methods: A multiplex genotyping assay system was established with primers for the 24 SNPs linked to iris color and hair color synthesized based on existing literature. In total, 235 unrelated individuals of Han Chinese ethnicity in Fujian Province were included in this study. PowerStats v12 was employed to calculate forensic parameters associated with the 24 SNP loci, including gene frequencies, genotype frequencies, minor allele frequencies, discrimination power (DP), polymorphism information content (PIC), and observed heterozygosity (Ho). Hardy-Weinberg equilibrium tests were conducted for each locus. The SNP genotyping results were uploaded to the HIrisPlex model (https://HIrisPlex.erasmusmc.nl/) to predict iris and hair colors, and the inferred results were compared with manually assessed images. The accuracy of pigment phenotype inference was evaluated by using ROC curves in SPSS 26.0 software., Results: The accuracy rates of inferring brown iris and black hair phenotypes were 99.6% and 99.5%. The area under the curve (AUC) values were 0.923 and 0.980, respectively., Conclusions: The 24 SNP loci demonstrated high accuracy in inferring iris color and hair color; it seems to be a useful tool for forensic phenotypic identification and anthropological or evolutionary applications. Establishment of suitable pigment classification criteria and optimized prediction models is based on revealing more phenotypic genetic markers.

Assays of behavior in model organisms play an important role in genetic screens, drug testing, and the elucidation of gene-behavior relationships. We have developed an automated, high-throughput imaging and analysis method for assaying behaviors of the nematode C. elegans . We use high-resolution optical imaging to longitudinally record the behaviors of 96 animals at a time in multi-well plates, and computer vision software to quantify the animals' locomotor activity, behavioral states, and egg laying events. To demonstrate the capabilities of our system we used it to examine the role of serotonin in C. elegans behavior. We found that egg-laying events are preceded by a period of reduced locomotion, and that this decline in movement requires serotonin signaling. In addition, we identified novel roles of serotonin receptors SER-1 and SER-7 in regulating the effects of serotonin on egg laying across roaming, dwelling, and quiescent locomotor states. Our system will be useful for performing genetic or chemical screens for modulators of behavior.

Introduction: The aging of the skin, which is affected by both external and internal causes, can reflect the external age and the internal health status. While the aging characteristics differ across ethnic groups, the specific changes in skin aging within the Chinese population have been underexplored. Moreover, investigating the similarity of aging skin characteristics between parent-offspring pairs remains uncharted territory. This study aims to fill these gaps by examining the skin aging features of Chinese women and assessing the similarity in aging skin characteristics between mother-daughter pairs., Methods: A total of 40 mother-daughter pairs were recruited and analyzed. The perceived ages of the participants were evaluated, and their aging skin traits were systematically graded. Statistical methods were employed to discern the trends of the aging skin characteristics. By introducing a novel similarity parameter, we compared whether various skin aging characteristics have similar patterns between mothers and daughters., Results: Our findings indicate that age 50 represents a pivotal point in skin aging. Beyond this age, the increase in rhytides and laxity scores accelerated noticeably, whereas the escalation in dyschromia scores became less marked. By introducing similar parameters between mother-daughter pairs and the radar map, we discovered that the skin aging characteristics are remarkably consistent between mother-daughter pairs., Conclusion: Understanding the main aging skin characteristics of different age groups can allow caregivers to devise treatments for preventing skin aging in women of various ages. The mother's skin aging trend is also significant for the daughter's skin aging prevention., Competing Interests: The authors have no conflicts of interest to declare for this work., (© 2024 Zhang et al.)

KCNA1 is the coding gene for Kv1.1 voltage-gated potassium-channel α subunit. Three variants of KCNA1 have been reported to manifest as paroxysmal kinesigenic dyskinesia (PKD), but the correlation between them remains unclear due to the phenotypic complexity of KCNA1 variants as well as the rarity of PKD cases. Using the whole exome sequencing followed by Sanger sequencing, we screen for potential pathogenic KCNA1 variants in patients clinically diagnosed with paroxysmal movement disorders and identify three previously unreported missense variants of KCNA1 in three unrelated Chinese families. The proband of one family (c.496G>A, p.A166T) manifests as episodic ataxia type 1, and the other two (c.877G>A, p.V293I and c.1112C>A, p.T371A) manifest as PKD. The pathogenicity of these variants is confirmed by functional studies, suggesting that p.A166T and p.T371A cause a loss-of-function of the channel, while p.V293I leads to a gain-of-function with the property of voltage-dependent gating and activation kinetic affected. By reviewing the locations of PKD-manifested KCNA1 variants in Kv1.1 protein, we find that these variants tend to cluster around the pore domain, which is similar to epilepsy. Thus, our study strengthens the correlation between KCNA1 variants and PKD and provides more information on genotype-phenotype correlations of KCNA1 channelopathy., Competing Interests: Conflict of interest The authors declare that no competing interests exist., (Copyright © 2024 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.)

Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous sarcoma characterized by the COL1A1-PDGFB fusion gene. This study utilized single-cell RNA sequencing to dissect the cellular and molecular landscape of primary DFSP. Distinct DFSP cell clusters, exhibiting fibroblast-like traits, revealed variations in pathways associated with proliferation, inflammation and metabolism. Differential gene expression analysis during the differentiation from tumour stem cells to DFSP cells unveiled SMOC2, DCN and TGFBR3 as potential regulators of tumour invasion and immune infiltration through VEGF/TGF-β signalling modulation. Cellular communication analysis highlighted interactions within DFSP cell clusters and with endothelial cells, implicating molecules such as NAMPT, ANGPT2 and PTN in pathogenesis and treatment resistance. These findings offer insights into DFSP intratumour heterogeneity, elucidate molecular mechanisms underlying tumour behaviour, and suggest potential therapeutic targets., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Plastics within municipal solid waste (MSW) are non-degradable. As MSW continues to degrade, the relative content of plastics rises, and particle gradation may also change. Moreover, throughout the landfilling process, MSW is subjected to various stress conditions, potentially influencing its mechanical properties. This study explored the effects of varying plastic contents, different particle gradations, and distinct stress paths on the mechanical properties of MSW, and consolidated drained triaxial tests of 42 groups of reconstituted MSW specimens were conducted. The results showed that there was an optimal plastic content of 6-9 % for MSW, where the shear strength of MSW was higher than that of MSW with other plastic contents. When the stress path changed from TC45 to TC72, the optimal plastic content of MSW changed from 6 % to 9 %. As the plastic content increased, both the cohesion and internal friction angle of the MSW initially increased, then subsequently decreased. The impact of plastic content on cohesion was more pronounced than on the internal friction angle, especially at larger strains. Under various stress paths, MSW with distinct particle size distributions demonstrated diverse stress-strain behaviors. Traditional criteria for evaluating well-graded conditions in soils are not suitable for MSW. The effect of gradation on the cohesion of MSW is essentially due to the predominant role of fiber content; the relationship between gradation and the internal friction angle in MSW is complex and correlates closely with the content of both coarse and fine particles, as well as fibers. This study serves as an essential reference for predicting deformations in landfills and analyzing the stability of landfill slopes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Ring-opening polymerization (ROP) offers a striking solution to solve problems encountered in step-growth condensation polymerization, including precise control over molecular weight, molecular weight distribution, and topology. This has inspired our interest in ROP of cycloalkanes with an ultimate goal to rethink polyolefins, which clearly poses a number of challenges. Practicality of ROP of cycloalkanes is actually limited by their low polymerizability and elusive mechanisms which arise from significantly varied ring size and non-polar C-C bonds in monomers. In this work, by using Lewis acid/Brønsted base/C(sp 3 )-H initiator system previously developed in our laboratory, we focus on cyclobutanes and explore the positional and electronic effects of substituents on the ring, namely electron push-pull effect, in promoting controlled polymerization to afford densely functionalized poly(cyclobutanes), as well as catalytic degradation of obtained polymers for upcycling. More importantly, experiments and DFT calculations unveil considerable population of Lewis-acid-induced thermostabilized 1,4-zwitterions, which distinguish cyclobutanes from cyclopropanes and others. All these findings would shed light on catalytic synthesis and degradation of saturated all-carbon main-chain polymers, as well as small molecule transformations of cyclobutanes., (© 2024 Wiley-VCH GmbH.)

An animal's locomotor rate is an important indicator of its motility. In studies of the nematode C. elegans, assays of the frequency of body bending waves have often been used to discern the effects of mutations, drugs, or aging. Traditional manual methods for measuring locomotor frequency are low in throughput and subject to human error. Most current automated methods depend on image segmentation, which requires high image quality and is prone to errors. Here, we describe an algorithm for automated estimation of C. elegans locomotor frequency using image invariants, i.e., shape-based parameters that are independent of object translation, rotation, and scaling. For each video frame, the method calculates a combination of 8 Hu's moment invariants and a set of Maximally Stable Extremal Regions (MSER) invariants. The algorithm then calculates the locomotor frequency by computing the autocorrelation of the time sequence of the invariant ensemble. Results of our method show excellent agreement with manual or segmentation-based results over a wide range of frequencies. We show that compared to a segmentation-based method that analyzes a worm's shape and a method based on video covariance, our technique is more robust to low image quality and background noise. We demonstrate the system's capabilities by testing the effects of serotonin and serotonin pathway mutations on C. elegans locomotor frequency.

The blood brain barrier (BBB) limits the application of most therapeutic drugs for neurological diseases (NDs). Hybrid cell membrane-coated nanoparticles derived from different cell types can mimic the surface properties and functionalities of the source cells, further enhancing their targeting precision and therapeutic efficacy. Neuroinflammation has been increasingly recognized as a critical factor in the pathogenesis of various NDs, especially Alzheimer's disease (AD). In this study, a novel cell membrane coating is designed by hybridizing the membrane from platelets and chemokine (C-C motif) receptor 2 (CCR2) cells are overexpressed to cross the BBB and target neuroinflammatory lesions. Past unsuccessful endeavors in AD drug development underscore the challenge of achieving favorable outcomes when utilizing single-mechanism drugs.Two drugs with different mechanisms of actions into liposomes are successfully loaded to realize multitargeting treatment. In a transgenic mouse model for familial AD (5xFAD), the administration of these drug-loaded hybrid cell membrane liposomes results in a significant reduction in amyloid plaque deposition, neuroinflammation, and cognitive impairments. Collectively, the hybrid cell membrane-coated nanomaterials offer new opportunities for precise drug delivery and disease-specific targeting, which represent a versatile platform for targeted therapy in AD., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Lung injury leads to respiratory dysfunction, low quality of life, and even life-threatening conditions. Circular RNAs (circRNAs) are endogenous RNAs produced by selective RNA splicing. Studies have reported their involvement in the progression of lung injury. Understanding the roles of circRNAs in lung injury may aid in elucidating the underlying mechanisms and provide new therapeutic targets. Thus, in this review, we aimed to summarize and discuss the characteristics and biological functions of circRNAs, and their roles in lung injury from existing research, to provide a theoretical basis for the use of circRNAs as a diagnostic and therapeutic target for lung injury., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gao, Chen, Jiang, Han, Lin, Yang, Quan, Xiong and Chen.)

Introduction: Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnoea (OSA) are prevalent respiratory diseases in China and impose significant burdens on the healthcare system. Moreover, the co-occurrence of COPD and OSA exacerbates clinical outcomes significantly. However, comprehensive epidemiological investigations in China remain scarce, and the defining characteristics of the population affected by COPD and OSA, alongside their intrinsic relationship, remain ambiguous., Methods and Analysis: We present a protocol for a prospective, multicentre, observational cohort study based on a digital health management platform across three different healthcare tiers in five sites among Chinese patients with COPD. The study aims to establish predicative models to identify OSA among patients with COPD and to predict the prognosis of overlap syndrome (OS) and acute exacerbations of COPD through the Internet of Things (IoT). Moreover, it aims to evaluate the feasibility, effectiveness and cost-effectiveness of IoT in managing chronic diseases within clinical settings. Participants will undergo baseline assessment, physical examination and nocturnal oxygen saturation measuring. Specific questionnaires screening for OSA will also be administered. Diagnostic lung function tests and polysomnography will be performed to confirm COPD and OSA, respectively. All patients will undergo scheduled follow-ups for 12 months to record the changes in symptoms, lung functions and quality of life. Primary outcomes include the prevalence and characteristics of OS, while secondary outcomes encompass OS prognosis and the feasibility of the management model in clinical contexts. A total of 682 patients with COPD will be recruited over 12-24 months., Ethics and Dissemination: The study has been approved by Peking University Third Hospital, and all study participants will provide written informed consent. Study results will be published in an appropriate journal and presented at national and international conferences, as well as relevant social media and various stakeholder engagement activities., Trial Registration Number: NCT04833725., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To investigate the effects of overexpressed keratin 17 (KRT17) on the biology of human dermal fibroblasts (HDFs) and to explore the mechanism of KRT17 in diabetic wound healing., Methods: KRT17 expression was tested in diabetic keratinocytes, animal models, and patient skin tissues (Huazhong University of Science and Technology Ethics Committee, [2022] No. 3110). Subsequently, HDFs were stimulated with different concentrations of KRT17 in vitro. Changes in the proliferation and migration of HDFs were observed. Then, identification of KRT17-induced changes in dermal fibroblast of RNA sequencing-based transcriptome analysis was performed., Results: KRT17 expression was upregulated under pathological conditions. In vitro stimulation of HDFs with different concentrations of KRT17 inhibited cell migration. RNA-seq data showed that enriched GO terms were extracellular matrix components and their regulation. KEGG analysis revealed that the highest number of enriched genes was PI3K-Akt, in which integrin alpha-11 (ITGA11) mRNA, a key molecule that regulates cell migration, was significantly downregulated. Decreased ITGA11 expression was observed after stimulation of HDFs with KRT17 in vitro., Conclusion: Increased expression of KRT17 in diabetic pathological surroundings inhibits fibroblast migration by downregulating the expression of ITGA11. Thus, KRT17 may be a molecular target for the treatment of diabetic wounds., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

The low patency rate after artificial blood vessel replacement is mainly due to the ineffective use of anticoagulant factors and the mismatch of mechanical compliance after transplantation. Electrospun nanofibers with biomimetic extracellular matrix three-dimensional structure and tunable mechanical strength are excellent carriers for heparin. In this work, we have designed and synthesized a series of biodegradable poly(ester-ether-urethane)ureas (BEPU), following compound with optimized constant concentration of heparin by homogeneous emulsion blending, then spun into the hybrid BEPU/heparin nanofibers tubular graft for replacing rats' abdominal aorta in situ for comprehensive performance evaluation. The results in vitro demonstrated that the electrospun L-PEUUH (LDI-based PEUU with heparin) vascular graft was of regular microstructure, optimum surface wettability, matched mechanical properties, reliable cytocompatibility, and strongest endothelialization in situ. Replacement of resected abdominal artery with the L-PEUUH vascular graft in rat showed that the graft was capable of homogeneous hybrid heparin and significantly promoted the stabilization of vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs), as well as stabilizing the blood microenvironment. This research demonstrates the L-PEUUH vascular graft with substantial patency, indicating their potential for injured vascular healing., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2023. Published by Elsevier B.V.)

Objective: This study aimed to investigate the safety and efficacy of endovascular aortic repair (EVAR) for the treatment of an abdominal aortic aneurysm (AAA) with a hostile neck anatomy (HNA)., Methods: From January 1, 2015 to December 31, 2019, a total of 259 patients diagnosed with an AAA who underwent EVAR were recruited into this study. Based on the morphological characteristics of the proximal neck anatomy, the patients were divided into the HNA group and the friendly neck anatomy (FNA) group. The patients were followed up for up to 4 years., Results: The average follow-up time was 1056.1±535.5 days. Type I endoleak occurred in 4 patients in the HNA group, and 2 patients in the FNA group. Neither death nor intraoperative switch to open repair occurred in either group. The time of the operation was significantly longer in the HNA group (FNA vs. HNA, 99.2±51.1 min vs. 117.5±63.8 min, P=0.011). There were no significant differences in short-term clinical success rate (P=0.228) or midterm clinical success rate (P=0.889) between the two groups. The overall mortality rate was 10.4%, and Kaplan-Meier survival analysis indicated that the two groups had similar cumulative survival rates at the end of the follow-up period (P=0.889)., Conclusion: EVAR was feasible and safe in patients with an AAA with a proximal HNA. The early and midterm results were promising; however, further studies are needed to verify the long-term effectiveness of EVAR., (© 2023. Huazhong University of Science and Technology.)

Chronic obstructive pulmonary disease (COPD) and asthma are chronic inflammatory diseases of the airways. Galectin-13 has recently been forwarded as a biomarker for airway eosinophilic inflammation in asthma. However, the association between galectin-13 and COPD remains unknown. To examine the changes in galectin-13 expression in acute exacerbations of COPD (AECOPD) and the stable phase of COPD and unveil the association between galectin-13 expression and eosinophilic inflammation in COPD, we measured plasma galectin-13 expression in different phases of COPD patients ( n  = 60, 44 AECOPD patients, and 16 stable COPD patients) and healthy controls ( n  = 15). Plasma levels of galectin-13 in 60 COPD patients were further analyzed and compared to systemic inflammation, airway eosinophilic inflammation, and lung function. The plasma galectin-13 level was markedly increased in subjects with AECOPD compared to stable COPD patients and healthy controls. Plasma galectin-13 levels in COPD subjects were positively correlated with serum CRP ( r s  = 0.46, p  = 0.0003), peripheral blood eosinophilia count ( r s  = 0.57, p <0.0001), and FeNO ( r s  = 0.46, p  = 0.0002). In addition, the level of galectin-13 was negatively correlated with FEV 1 ( r s  = -0.43, p  = 0.0001), FEV 1 pred (%) ( r s  = -0.544, p <0.0001), as well as FEV 1 /FVC ( r s  = -0.46, p <0.0001). Multiple linear regression analysis suggested that plasma galectin-13 levels were affected by FEV 1 pred (%), peripheral blood eosinophilia count, and FeNO. We concluded that galectin-13 levels were increased in COPD patients, and elevated galectin-13 expressions related to airway eosinophilic inflammation. Galectin-13 may facilitate the identification of COPD endotypes and may become a potential therapeutic target.

Background: Severe asthma is associated with substantial mortality and has unmet therapeutic need. A subset of severe asthma is characterized by neutrophilic airway inflammation. Classically activated (or M1) macrophages which express IL-12 and IL-23 are associated with airway neutrophilia in asthma. Exogenous IL-25 was reported to suppress intestinal inflammation in animal models of inflammatory bowel diseases via suppressing IL-12 and IL-23 production. We hypothesize that IL-25 ameliorates airway neutrophilia via inhibiting macrophage M1 polarization and the expression of IL-12 and IL-23 in asthma., Methods: In a mouse model of neutrophil-dominant allergic airway inflammation, the effect of mouse recombinant IL-25 on airway inflammation were assessed by H&E staining and bronchoalveolar lavage (BAL) cell counting. The percentage of M1 macrophages in lung tissue and BAL cells were analyzed by flow cytometry. Quantitative PCR and immunostaining were performed to measure the expression of Il12, Il23, and inflammatory cytokines. Mechanistic experiments were performed in primary culture of macrophages from mouse lungs. The expression of IL-12, IL-23 and IL-25 in sputum was analyzed in a cohort of severe asthma and subjects with eosinophilic or non-eosinophilic asthma., Results: Intranasal administration of IL-25 markedly decreased the number of neutrophils in BAL cells in a murine model of neutrophil-dominant allergic airway inflammation. Moreover, exogenous IL-25 decreased the number of M1 macrophages, and reduced the expression of IL-12, IL-23 in the lungs of the mouse model. Exogenous IL-25 also inhibited the expression of inflammatory cytokines IL-1β, IFN-γ, TNF-α and IL-17 A. In vitro, IL-25 suppressed IL-12 and IL-23 expression in lipopolysaccharide (LPS)-stimulated primary culture of mouse pulmonary macrophages. Mechanistically, IL-25 inhibited LPS-induced c-Rel translocation to nucleus via STAT3-dependent signaling. In a cohort of severe asthma, IL-25 protein levels in sputum were significantly lower than control subjects. The transcript levels of IL-12 and IL-23 were increased whereas IL-25 transcripts were decreased in sputum cells from subjects with non-eosinophilic asthma compared to eosinophilic asthma., Conclusions: IL-25 expression is downregulated in subjects with severe or non-eosinophilic asthma. Exogenous IL-25 ameliorates airway neutrophilia, at least in part, via inhibiting macrophage M1 polarization and the expression of IL-12 and IL-23., (© 2023. The Author(s).)

Introduction: Adult patients with atrial septal defects (ASD), the most common form of adult congenital heart disease, often die of arrhythmias, and the immaturity of cardiomyocytes contributes significantly to arrhythmias. ASD typically induces a left-to-right shunt, which then leads to the right atrium (RA) volume overload (VO). Whether or not VO contributes to RA cardiomyocyte immaturity and thereby causes arrhythmias in adult patients with ASD remains unclear. Methods: Here, we developed the first neonatal RA VO mouse model by creating a fistula between the inferior vena cava and abdominal aorta on postnatal day 7. RA VO was confirmed by increases in the mean flow velocity, mean pressure gradient, and velocity time integral across the tricuspid valve, and an increase in the RA diameter and RA area middle section. Results: We found that VO decreased the regularity and length of sarcomeres, and decreased the T-element density, regularity, and index of integrity of T-tubules in RA cardiomyocytes, suggesting that the two most important maturation hallmarks (sarcomere and T-tubules) of RA cardiomyocytes were impaired by VO. Accordingly, the calcium handling capacity of cardiomyocytes from postnatal day 21 (P21) RA was decreased by VO. VO caused a significant elongation of the PR interval. The expression of connexin 43 (Cx43) was decreased in RA VO. Moreover, gene ontology (GO) analysis of the downregulated genes in RA demonstrated that there was an abundance of enriched terms associated with sarcomeres and T-tubules exposed to VO. The results were further verified by qRT-PCR. Conclusions: In conclusion, the first neonatal RA VO mouse model was developed; furthermore, using this neonatal RA VO mouse model, we revealed that VO impeded RA sarcomere and T-tubule maturation, which may be the underlying causes of atrial arrhythmias in adult patients with ASD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Dong, Chen, Zheng, Wang, Li, Xiao, Sun, Ye, Qiu, Hu and Hong.)

In clinic, controlling acute coagulation after small-diameter vessel grafts transplantation is considered a primary problem. The combination of heparin with high anticoagulant efficiency and polyurethane fiber with good compliance is a good choice for vascular materials. However, blending water-soluble heparin with fat-soluble poly (ester-ether-urethane) urea elastomer (PEEUU) uniformly and preparing nanofibers tubular grafts with uniform morphology is a huge challenge. In this research, we have compounded PEEUU with optimized constant concentration of heparin by homogeneous emulsion blending, then spun into the hybrid PEEUU/heparin nanofibers tubular graft (H-PHNF) for replacing rats' abdominal aorta in situ for comprehensive performance evaluation. The in vitro results demonstrated that H-PHNF was of uniform microstructure, moderate wettability, matched mechanical properties, reliable cytocompatibility, and strongest ability to promote endothelial growth. Replacement of resected abdominal artery with the H-PHNF in rat showed that the graft was capable of homogeneous hybrid heparin and significantly promoted the stabilization of vascular smooth muscle cells (VSMCs) as well as stabilizing the blood microenvironment. This research demonstrates the H-PHNF with substantial patency, indicating their potential for vascular tissue engineering., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Zhang, Du, Zhu, Chen, Liu and Dong.)

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory airway disease that affects the quality of life of nearly one-tenth of the global population. Due to irreversible airflow obstruction and progressive lung function decline, COPD is characterized by high mortality and disability rates, which imposes a huge economic burden on society. In recent years, the importance of intervention in the early stage of COPD has been recognized and the concept of early COPD has been proposed. Identifying and intervening in individuals with early COPD, some of whom have few or no symptoms, might halt or reverse the progressive decline in lung function, improve the quality of life, and better their prognosis. However, understanding of early COPD is not yet well established, and there are no unified and feasible diagnostic criteria, which complicates clinical research. In this article, we review evolution of the definition of early COPD over the past 20 years, describe the changes in awareness of this concept, and propose future research directions., Competing Interests: Dr. Curtis participated in the following COPD-relevant industry-sponsored activities: AstraZeneca PLC, consultant, AstraZeneca Respiratory Advisory Council, 09/16/2020–12/31/2021, $1362, paid to University of Michigan; CSL Behring, LLC 199240, consultant, Virtual Nebulized Immunoglobulin (NebIg) Advisory Board, 02/01/2021–2/23/2022, $2500, paid to University of Michigan., (© 2023 Published by Elsevier B.V. on behalf of Chinese Medical Association.)

Growing RNAs fold differently as they are transcribed, which modulates their finally adopted structures. Riboswitches regulate gene expression by structural change, which are sensitive to co-transcriptionally structural biology. Here we develop a strategy to track the structural change of RNAs during transcription at single-nucleotide and single-molecule resolution and use it to monitor individual transcripts of the SAM-VI riboswitch (riboSAM) as transcription proceeds, observing co-existence of five states in riboSAM. We report a bifurcated helix in one newly identified state from NMR and single-molecule FRET (smFRET) results, and its presence directs the translation inhibition in our cellular translation experiments. A model is proposed to illustrate the distinct switch patterns and gene-regulatory outcome of riboSAM when SAM is present or absent. Our strategy enables the precise mapping of RNAs' conformational landscape during transcription, and may combine with detection methods other than smFRET for structural studies of RNAs in general., (© 2023. The Author(s).)

Objective: Hirschsprung disease (HSCR) is one of the common neurocristopathies in children, which is associated with at least 20 genes and involves a complex regulatory mechanism. Transcriptional regulatory network (TRN) has been commonly reported in regulating gene expression and enteric nervous system development but remains to be investigated in HSCR. This study aimed to identify the potential TRN implicated in the pathogenesis and diagnosis of HSCR., Methods: Based on three microarray datasets from the Gene Expression Omnibus database, the multiMiR package was used to investigate the microRNA (miRNA)-target interactions, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Then, we collected transcription factors (TFs) from the TransmiR database to construct the TF-miRNA-mRNA regulatory network and used cytoHubba to identify the key modules. Finally, the receiver operating characteristic (ROC) curve was determined and the integrated diagnostic models were established based on machine learning by the support vector machine method., Results: We identified 58 hub differentially expressed microRNAs (DEMis) and 16 differentially expressed mRNAs (DEMs). The robust target genes of DEMis and DEMs mainly enriched in several GO/KEGG terms, including neurogenesis, cell-substrate adhesion, PI3K-Akt, Ras/mitogen-activated protein kinase and Rho/ROCK signaling. Moreover, 2 TFs ( TP53 and TWIST1 ), 4 miRNAs ( has-miR-107 , has-miR-10b-5p , has-miR-659-3p , and has-miR-371a-5p ), and 4 mRNAs ( PIM3 , CHUK , F2RL1 , and CA1 ) were identified to construct the TF-miRNA-mRNA regulatory network. ROC analysis revealed a strong diagnostic value of the key TRN regulons (all area under the curve values were more than 0.8)., Conclusion: This study suggests a potential role of the TF-miRNA-mRNA network that can help enrich the connotation of HSCR pathogenesis and diagnosis and provide new horizons for treatment., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Background: Anoikis resistance is recognized as a crucial step in the metastasis of cancer cells. Most epithelial tumors are distinguished by the ability of epithelial cells to abscond anoikis when detached from the extracellular matrix. However, no study has investigated the involvement of anoikis in the small airway epithelium (SAE) of chronic obstructive pulmonary disease (COPD)., Methods: Anoikis-related genes (ANRGs) exhibiting differential expression in COPD were identified using microarray datasets obtained from the Gene Expression Omnibus (GEO) database. Unsupervised clustering was performed to classify COPD patients into anoikis-related subtypes. Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, gene set enrichment analysis (GSEA), and gene set variation analysis (GSVA) were used to annotate the functions between different subtypes. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were leveraged to identify key molecules. The relative proportion of infiltrating immune cells in the SAE was quantified using the CIBERSORT and ssGSEA computational algorithms, and the correlation between key molecules and immune cell abundance was analyzed. The expression of key molecules in BEAS-2B cells exposed to cigarette smoke extract (CSE) was validated using qRT-PCR., Results: A total of 25 ANRGs exhibited differential expression in the SAE of COPD patients, based on which two subtypes of COPD patients with distinct anoikis patterns were identified. COPD patients with anoikis resistance had more advanced GOLD stages and cigarette consumption. Functional annotations revealed a different immune status between COPD patients with pro-anoikis and anoikis resistance. Tenomodulin (TNMD) and long intergenic non-protein coding RNA 656 (LINC00656) were subsequently identified as key molecules involved in this process, and a close correlation between TNMD and the infiltrating immune cells was observed, such as activated CD4 + memory T cells, M1 macrophages, and activated NK cells. Further enrichment analyses clarified the relationship between TNMD and the inflammatory and apoptotic signaling pathway as the potential mechanism for regulating anoikis. In vitro experiments showed a dramatic upregulation of TNMD and LINC00656 in BEAS-2B cells when exposed to 3% CSE for 48 hours., Conclusion: TNMD contributes to the progression of COPD by inducing anoikis resistance in SAE, which is intimately associated with the immune microenvironment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Yi, Hong, Wang and Chen.)

Small-diameter blood vascular transplantation failure is mainly caused by the vascular materials' unreliable hemocompatibility and histocompatibility and the unmatched mechanical properties, which will cause unstable blood flow. How to solve the problems of coagulation and intimal hyperplasia caused by the above factors is formidable in vascular replacement. In this work, we have synthesized poly(ferulic acid) (PFA) and prepared poly(ester-urethane)urea (PEUU)/silk fibroin (SF)/poly(ferulic acid) (PFA) hybrid nanofibers vascular graft (PSPG) by random electrospinning and post-double network bond crosslinking for process optimization. The results in vitro demonstrated that the graft is of significant anti-oxidation, matched mechanical properties, reliable cytocompatibility, and blood compatibility. Replacing resected rat abdominal aorta and rabbit carotid artery models with PSPG vascular grafts indicated that the grafts are capable of homogeneous hybrid PFA significantly promoted the stabilization of endothelial cells and the ingrowth of smooth muscle cells, meanwhile stabilizing the immune microenvironment. This research demonstrates the PSPG vascular graft with substantial patency, indicating their potential for injured vascular healing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Frontotemporal dementia (FTD) is the second most common cause of dementia after Alzheimer's disease, characterized by distinct changes in behavior, personality, and language. Our study performed whole exome sequencing and repeat-primed PCR analysis in 29 unrelated FTD patients. Consequently, 2 known pathogenic variants (MAPT: p.P301L; TBK1: p.I450Kfs), and 4 novel variants (MAPT: p.R406Q, p.D430H, p.A330D; GRN: c.350-2A>G) were identified. The functional analysis results showed that phosphorylated tau levels were higher in cells expressing p.R406Q and p.D430H tau than those expressing wild-type tau, especially at the Thr205, Thr231, and Ser396 phosphorylation epitopes. Besides, the p.R406Q and p.D430H variants of MAPT impaired the ability of tau to bind to the microtubules and increased tau self-aggregation. Furthermore, we found that the c.350-2A>G variant caused exon 5 skipping. Our results showed that p.R406Q, p.D430H, and c.350-2A>G variants were classified as pathogenic. Finally, we summarized the clinical characterization of patients carrying pathogenic variants of MAPT in the East Asia populations. Our results broaden the genetic spectrum of FTD with MAPT and GRN variants., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Several predictors of COVID-19 severity have been reported. However, chronic airway inflammation characterised by accumulated lymphocytes or eosinophils may affect the pathogenesis of COVID-19., Methods: In this retrospective cohort study, we reviewed the medical records of all patients with laboratory-confirmed COVID-19 with chronic bronchitis, chronic obstructive pulmonary disease (COPD) and asthma admitted to the Sino-French New City Branch of Tongji Hospital, a large regional hospital in Wuhan, China, from 26 January to 3 April. The Tongji Hospital Ethics Committee approved this study., Results: There were 59 patients with chronic bronchitis, COPD and asthma. When compared with non-severe patients, severe patients were more likely to have decreased lymphocyte counts (0.6×10⁹/L vs 1.1×10⁹/L, p<0.001), eosinopaenia (<0.02×10⁹/L; 73% vs 24%, p<0.001), increased lactate dehydrogenase (LDH) (471.0 U/L vs 230.0 U/L, p<0.001) and elevated interleukin 6 level (47.4 pg/mL vs 5.7 pg/mL, p=0.002) on admission. Eosinopaenia and elevated LDH were significantly associated with disease severity in both univariate and multivariate regression models including the above variables. Moreover, eosinophil count and LDH level tended to return to normal range over time in both groups after treatment and severe patients recovered slower than non-severe patients, especially in eosinophil count., Conclusions: Eosinopaenia and elevated LDH are potential predictors of disease severity in patients with COVID-19 with underlying chronic airway diseases. In addition, they could indicate disease progression and treatment effectiveness., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: CYP2C19 gene polymorphisms have been described to have an important influence on the drug metabolism observed in human populations. A series of PCR-based molecule detection methods are applied to identify CYP2C19 genotype. The aim of the study is to validate the novel CYP2C19 genotyping approach with other methods and reveal the allele frequency distribution of CYP2C19 in Chinese Han population., Methods: We applied a novel genotyping approach for CYP2C19 gene which was combining direct PCR and capillary electrophoresis (CE) technique. A series of fluorescent labeled primers were designed to amplify the particular DNA fragments which indicated the wild type of CYP2C19 genotype. The variants consist of CYP2C19*2, CYP2C19*3 and CYP2C19*17 alleles. Both the novel PCR-based CE method and real-time quantitative PCR (RT-qPCR) method were used to identify the CYP2C19 genotypes in 324 whole blood samples originated from Chinese Han population. According to the different criterions for judgement of two methods, we can obtain the CYP2C19 alleles and genotypes of the same participants. Kappa statistics was used to evaluate the consistency of the two results and the frequencies of CYP2C19 alleles. The genotypes in Chinese Han population were calculated using EXCEL. Furthermore, to ensure the accuracy and reliability of the CYP2C19 genotypes obtained by using the novel approach, Sanger sequencing was conducted to validate the CYP2C19 genotypes *1/*17 and *2/*3., Results: Among the 324 specimens, 111 were *1/*1, 141 were *1/*2, 10 were *1/*3, 4 were *1/*17, 46 were *2/*2, 10 were *2*/3, 1 was *2/*17, and 1 was *3/*17. Allele distributions for CYP2C19 were *1, *2, *3, and *17 at 58.18%, 37.65%, 3.24%, and 0.93%, respectively. Both PCR-based CE method and RT-qPCR methods had good consistency in the genotypes of CYP2C19 polymorphism (Kappa value = 1.000, p < 0.05). The DNA sequences of CYP2C19 genotype *1/*17 were composed of c.681 G/G, c.636 G/G, and c.-806 C>T. In the same way, the DNA sequences of CYP2C19 genotype *2/*3 were composed of c.681 G>A, c.636 G>A, and c.-806 C/C., Conclusions: The variants including the CYP2C19*2 allele were the most common mutations in Chinese Han unrelated individuals. Both PCR-based CE method and RT-qPCR method had good consistency in the genotypes of CYP2C19 polymorphism. Nevertheless, because of more convenience and higher throughput, the novel PCR-based capillary electrophoresis approach showed to be more suitable for clinical gene screening.

Activation of IL-4R (IL-4 receptor) signaling in airway epithelial cells leads to airway hyperresponsiveness and mucus overproduction in asthma. CDH26 (cadherin-26), a cadherin implicated in the polarization of airway epithelial cells, is upregulated in asthma. However, the role of CDH26 in asthma remains unknown. In this study, we demonstrated that Cdh26 deficiency significantly reduced airway mucus overproduction, airway hyperresponsiveness, and airway eosinophilia in a murine model of allergic airway disease. Interestingly, allergen-induced Il-4Rα upregulation in airway epithelium was markedly reduced in Cdh26 -/- mice. In cultured human bronchial epithelial cells, CDH26 knockdown inhibited IL-13, a ligand for IL-4R; induced IL-4Rα and IL-13Rα1 (IL-13 receptor α1) upregulation; and suppressed downstream Jak1 (Janus kinase 1) and Stat6 (signal transducer and activator of transcription 6) phosphorylation. Moreover, CDH26 knockdown inhibited IL-13-induced MUC5AC and eosinophilic chemokine expression. These results suggest that CDH26 plays a key role in epithelial IL-4R signaling activation and downstream effectors. In contrast, CDH26 overexpression amplified IL-13-activated IL-4R signaling in BEAS-2B cells. In the airway epithelium of patients with asthma, IL-4Rα expression was elevated, and CDH26 was the only cadherin that was upregulated among 11 cadherin family members. CDH26 expression was strongly correlated with epithelial IL-4Rα and MUC5AC expression, sputum eosinophilia, and fractional exhaled nitric oxide in patients with asthma. Taken together, we identified CDH26 as a key regulator of epithelial IL-4R signaling in asthma and a potential therapeutic target for IL-4R-mediated allergic diseases.

Nasopharyngeal carcinoma (NPC) is not only a common malignant disease of the head and neck, but also presented as locoregionally advanced NPC at diagnosis with poor prognosis. The efficacy of current chemoradiotherapy is unsatisfactory; therefore, in this study, we evaluated the safety and efficacy of treating locally advanced NPC using recombinant human endostatin injection (Endostar), combined with a cisplatin plus 5-fluorouracil (PF) regimen and sequential intensity-modulated radiotherapy (IMRT), and compared it with PF plus IMRT regimen. This phase II study included 83 eligible patients with stages III-IVa NPC (8th AJCC/UICC) who were randomized 1:1 into control (n = 42) and experimental (n = 41) groups. The control group received PF chemotherapy and IMRT for locally advanced NPC; One cycle of induction chemotherapy (IC) was administered before IMRT, and three cycles of adjuvant chemotherapy (AC) were administered four weeks post-radiotherapy. The experimental group received additional Endostar therapy. All patients were followed up for at least 5 years. The primary endpoints were progression-free survival (PFS) and the objective response rate. The secondary endpoints included overall survival and treatment-related toxicities. The short-term efficacy was evaluated at the end of the fourth chemotherapy cycle. Our results showed that the complete response rate of nasopharyngeal lesions was not significantly different between the experimental and control groups (80.5 vs. 71.4%, P = 0.335); however, there were significant differences in the complete response rates of cervical metastatic lymph nodes (75.6 vs. 40.5%, P = 0.001), especially for cervical N3 lymph nodes in the experimental group (55.6 vs. 9.5%, P = 0.004). The overall median follow-up time was 69.7 months. Patients in the experimental group showed significantly prolonged PFS by about four months (hazard ratio [HR] = 0.64, 95% CI: 0.41-0.99, P = 0.045). There was no significant difference in the median overall survival ( P = 0.374). Furthermore, subgroup analysis indicated that the risk of death in patients with cervical N3 lymph nodes in the experimental group was reduced by 52% (HR = 0.48, 95% CI: 0.23-0.99, P = 0.046). Moreover, the incidence of radiation-induced grades 3-4 oral mucositis was significantly lower in the experimental group (29.3% vs. 54.8%, P = 0.019), while no significant differences in other severe adverse reactions were observed between the two groups ( P >0.05). Taken together, our study indicated that, in patients with locally advanced NPC, Endostar in combination with PF chemotherapy and sequential IMRT significantly improved PFS, had tolerable treatment-related toxicities, improved the prognoses of patients with cervical N3 lymph nodes, and reduced the incidence of radiation-related oral mucositis., Competing Interests: None., (AJCR Copyright © 2022.)

The performance of small-diameter vascular grafts adapted to vascular replacement is commonly hindered by stenosis. To address this issue, a graft featuring rapid remodeling with degradation is warranted. In this work, a 1.8-mm-diameter graft was constructed by fabricating a decellularized human amniotic membrane (HAM) with polycaprolactone (PCL)/silk fibroin (SF) around it through electrospinning, namely, an HPS graft, and applied in a rat aortic grafting model for comparison to a decellularized porcine small intestinal submucosa (SIS)-integrated PCL/SF (SPS) graft and an autologous aorta. In vitro studies demonstrated that HAM provided a bioactive milieu for rapid endothelial cell proliferation and resisting fibroblast-induced collagen secretion. PCL/SF provides a biocompatible microenvironment for cellular infiltration with mechanical properties resembling those of the rat aorta. In vivo studies showed that the HPS graft induced functional endothelialization more rapidly, along with less intensive ECM deposition than the SPS graft upon the histologically weaker inflammatory response and foreign body reaction 4 weeks after implantation, and maintained patency by progressively stabilizing the remodeling structure approximating the native counterparts over 24 weeks. The bioengineered graft expands the applicability of allogeneic matrices with degradable electrospun polymers for long-term in situ vascular applications. STATEMENT OF SIGNIFICANCE: An orchestrated remodeling of the vascular graft, featuring rapid endothelialization and resisting extracellular matrix (ECM) deposition on the luminal surface, with a mechanically stable structure, is requisite for long-term vascular patency. Nevertheless, off-the-shelf grafts might not fulfil the criteria under abdominal aortic pressure. Herein, we fabricated a 1.8-mm-diameter vascular graft through the integration of a decellularized human amniotic membrane (HAM) with electrospun polycaprolactone (PCL)/silk fibroin (SF). In a rat aortic grafting model, the graft is capable of rapid endothelialization and resisting collagen deposition and provides a native-like mechanical structure for stabilizing the remodeling process towards that of the native aorta. This bioengineered graft has potential for small-diameter vascular regeneration, and provides advanced strategies to facilitate full-remodeling tissue applications., Competing Interests: Declaration of Competing Interest There are no conflicts of interest relating to this work., (Copyright © 2022. Published by Elsevier Ltd.)

Dialectical thinking is an overarching and sophisticated thinking style that involves accepting and resolving contradictions. The current study examined whether the dispositional tendency of dialectical thinking is mediated by organizational patterns of intrinsic brain networks. Based on previous theoretical and empirical works, we hypothesized that the dorsal anterior cingulate cortex (dACC), the hub for conflict processing, shows increased couplings with nodes in the default mode network (DMN). A sample of 380 young and healthy participants completed a self-reported measure of dialectical thinking and underwent resting-state functional magnetic resonance imaging scanning. Results of seed-based correlational ROI and whole-brain analyses supported our hypothesis that trait dialectical thinking was positively correlated with the strength of the dACC-DMN couplings. These findings demonstrate the possibility of identifying network-level neural representations of sociocultural orientations., (© 2022. The Psychonomic Society, Inc.)

Purpose: Tigecycline is an agent for carbapenemase-producing Klebsiella pneumonia (KPC-KP), given its penetration into lung tissues. Our study focused on the molecular and clinical efficacy of tigecycline for hospital-acquired pneumonia (HAP) in the ICU., Patients and Methods: A retrospective cohort study of 52 adult KPC-KP HAP patients by searching hospital medical records from January 2018 to December 2020 was established to investigate the epidemiology of KPC-KP infections for tigecycline treatment and the associated clinical efficacy of tigecycline. The KPC-KP isolates underwent multilocus sequence typing. Molecular typing, antimicrobial resistance, and virulence profiling were also analyzed by whole-genome sequencing of KPC-KP., Results: Among 52 patients with KPC-KP, the ICU mortality rate was 14/52 (27%), and there was no significant statistical difference in mortality between the effective group and failure group ( p = 0.754). However, the duration of tigecycline was statistically different between the two groups of patients (14.4 vs 10 days, p =0.046). The total bacterial clearance rate was 6/52 (11.5%). There was no significant statistical difference in both groups ( p =0.416). Antibiotic resistance genes ( aac3iia ) and virulence gene ( AREO-iutA, Capsule-wzc ) were negatively correlated with clinical efficacy ( p = 0.011, OR = 1.237)., Conclusions: Bla kpc was the main carbapenemase in all K. pneumoniae strains. ST11-KL64 KPC-KP was the most common virulence factors in KPC-KP isolates. This study suggested that antibiotic resistance genes ( aac3iia ) and virulence gene ( AREO-iutA, Capsule-wzc ) were independent mortality risk factors for patients with Klebsiella pneumoniae carbapenemase-2 producing K. pneumoniae infections, when during the tigecycline treatment. Molecular analysis of K. pneumoniae may provide an option when choosing the antimicrobial treatment., Competing Interests: The authors declare no competing interests., (© 2022 Bai et al.)

Oxygenases, which catalyze the reductive activation of O 2 and incorporation of oxygen atoms into substrates, are widely distributed in aerobes. They function by switching the redox states of essential cofactors that include flavin, heme iron, Rieske non-heme iron, and Fe(II)/α-ketoglutarate. This review summarizes the catalytic features of flavin-dependent monooxygenases, heme iron-dependent cytochrome P450 monooxygenases, Rieske non-heme iron-dependent oxygenases, Fe(II)/α-ketoglutarate-dependent dioxygenases, and ring-cleavage dioxygenases, which are commonly involved in pesticide degradation. Heteroatom release (hydroxylation-coupled hetero group release), aromatic/heterocyclic ring hydroxylation to form ring-cleavage substrates, and ring cleavage are the main chemical fates of pesticides catalyzed by these oxygenases. The diversity of oxygenases, specificities for electron transport components, and potential applications of oxygenases are also discussed. This article summarizes our current understanding of the catalytic mechanisms of oxygenases and a framework for distinguishing the roles of oxygenases in pesticide degradation.

Purpose: To investigate the clinical value of CD133 and CD44 as putative cancer stem cell markers in distinguishing between basal cell carcinoma (BCC) and trichoblastomas (TB)., Patients and Methods: Tumor samples from 24 BCC and 23 TB patients were retrospectively retrieved for immunohistochemical staining of CD133 and CD44. The results were interpreted using a semiquantitative scoring system (H score). A receiver operating characteristic (ROC) curve was developed to identify an optimal cutoff value for differentiating between BCC and TB., Results: Expression of CD133 was significantly higher in BCC patients than in TB patients (median H score: 30 [IQR: 12.5-56.3] vs 0 [IQR: 0-2], P < 0.001). However, there was no significant difference in CD44 expression between the two groups (median H score: 105 [IQR: 63.8-155.0] vs 60 [IQR: 30-120], P = 0.095). The ROC analysis of CD133 immunostaining yielded an area under the curve (AUC) of 0.881 (95% CI: 0.756-1.000) for differentiating between BCC and TB by using a H score of 7 as the cut-off value (98.5% sensitivity and 87.0% specificity). By contrast, immunostaining of CD44 showed a lower diagnostic value, with an AUC of 0.642 (95% CI: 0.476-0.808) at the optimal cut-off value of 85 (62.5% sensitivity and 73.9% specificity). The positive and negative predictive values were 88.5% and 95.2% for CD133 and 71.4% and 65.4% for CD44, respectively. Additionally, CD133 expression was significantly associated with mitotic activity in BCC patients ( r = 0.549, P = 0.005)., Conclusion: Our study expanded upon previous studies of CD133 and CD44 expressions in skin tumors, suggesting that CD133, but not CD44, may serve as a novel biomarker for differential diagnosis of BCC, although future studies using a larger number of patients are needed to justify it further., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Bi et al.)

Background: Port-wine stain (PWS) is a congenital capillary malformation that often occurs on the face. Feasible and quantitative evaluation of facial port-wine stain (FPWS) can significantly impact its clinical management and aid in future research., Aim: To develop and validate an easy-to-use scoring system for FPWS evaluation., Methods: A facial port-wine stain area and severity index (FSASI) scoring system was proposed. To determine the FSASI score, the face was divided into four regions: forehead, right malar, left malar, and perioral. The severity of FPWS in each region was evaluated by three factors: percentage of the area affected, lesion color, and thickness. To evaluate the intra- and inter-rater reliability of FSASI, two separate FSASI assessments on 111 clinical pictures were conducted by each rater in a one-week interval, and the results from 6 independent raters at different time points were compared. Validity of the FSASI scores was assessed by comparing it with physician global assessment (PGA) and traditional classification data. Validity of the area and color elements of FSASI was also determined. The changes in FSASI scores after vascular-targeted photodynamic therapy (V-PDT) were analyzed to evaluate the treatment effect., Results: The FSASI scoring system showed good intra- and inter-rater reliability (ICC >0.75, p < 0.001) and was found to be comparable to PGA scores (Spearman's r = 0.752-0.907, p < 0.001) and traditional classification data (Spearman's r = 0.426-0.662, p < 0.001). Efficacy analysis indicated that FSASI scores decreased after V-PDT treatment., Conclusion: The results of this study demonstrated the reliability and validity of FSASI, which may be applied to assess the severity of FPWS and to evaluate treatment effects in clinical practice and research., (© 2021 Wiley Periodicals LLC.)

Objective: Ross procedure is considered as the "gold standard" for aortic valve replacement, but the conduits used for right ventricular outflow tract (RVOT) reconstruction, such as homografts and bovine jugular vein (BJV) conduits, are of limited availability in China. Handmade expanded polytetrafluoroethylene-valved conduits (HVCs) have been used recently as the alternative for RVOT reconstruction, but their specific experience in Ross procedure is limited in the literature., Methods: This was a retrospective review of 27 children who underwent Ross procedure in our center from January 2018 to January 2022., Results: Mean age at surgery was 8.0 ± 3.8 years. During the study period, BJV conduits were used for RVOT reconstruction in 6 patients (22%), and HVCs were used in 21 patients (78%). Median conduit size was 20 mm (range, 16-24 mm), and mean conduit Z-score was +0.8 ± 0.9. Median time for cardiopulmonary bypass was 158 min (range, 109-275 min), and mean time for aortic crossclamping was 110 ± 21 min. There was no early mortality. During a median follow-up time of 1.4 years (range, 0.1-3.7 years), 3 patients (11%) with BJV conduits had peak conduit velocity of > 3.5 m/s; 3 patients (11%) with HVCs developed moderate conduit insufficiency; no patients had more than moderate conduit insufficiency. Three patients with BJV conduits had 5 reinterventions, and all received conduit replacement with HVCs., Conclusion: HVC is an appealing alternative to BJV conduit for RVOT construction for children undergoing Ross procedure, with favorable short-term outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dong, Chen, Jiang, Hu, Qiu, Zhu, Zhang and Zhang.)

Background: Immunotherapy is a promising strategy for ovarian cancer (OC), and this study aims to identify biomarkers related to CD8 + T cell infiltration to further discover the potential therapeutic target. Methods: Three datasets with OC transcriptomic data were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Two immunotherapy treated cohorts were obtained from the Single Cell Portal and Mariathasan's study. The infiltration fraction of immune cells was quantified using three different algorithms, Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT), and microenvironment cell populations counter (MCPcounter), and single-sample GSEA (ssGSEA). Weighted gene co-expression network analysis (WGCNA) was applied to identify the co-expression modules and related genes. The nonnegative matrix factorization (NMF) method was proposed for sample classification. The mutation analysis was conducted using the "maftools" R package. Key molecular markers with implications for prognosis were screened by univariate COX regression analysis and K-M survival analysis, which were further determined by the receiver operating characteristic (ROC) curve. Results: A total of 313 candidate CD8 + T cell-related genes were identified by taking the intersection from the TCGA-OV and GSE140082 cohorts. The NMF clustering analysis suggested that patients in the TCGA-OV cohort were divided into two clusters and the Cluster 1 group showed a worse prognosis. In contrast, Cluster 2 had higher amounts of immune cell infiltration, elevated ssGSEA scores in immunotherapy, and a higher mutation burden. CSMD3, MACF1, PDE4DIP, and OBSCN were more frequently mutated in Cluster 1, while SYNE2 was more frequently mutated in Cluster 2. CD38 and CXCL13 were identified by univariate COX regression analysis and K-M survival analysis in the TCGA-OV cohort, which were further externally validated in GSE140082 and GSE32062. Of note, patients with lower CXCL13 expression showed a worse prognosis and the CR/PR group had a higher expression of CXCL13 in two immunotherapy treated cohorts. Conclusion: OC patients with different CD8 + T cell infiltration had distinct clinical prognoses. CXCL13 might be a potential therapeutic target for the treatment of OC., Competing Interests: Author HY was employed by the company 3D Medicines, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Chen, Luo, Wang, Yu, Gao and Zhong.)

Labeling RNA molecules at specific positions is critical for RNA research and applications. Such methods are in high demand but still a challenge, especially those that enable native co-synthesis rather than post-synthesis labeling of long RNAs. The method we developed in this work meets these requirements, in which a leader RNA is extended on the hybrid solid-liquid phase by an engineered transcriptional complex following the pause-restart mode. A custom-designed short oligonucleotide is used to functionalize the engineered complex. This remarkable co-transcriptional labeling method incorporates labels into RNAs in high yields with great flexibility. We demonstrate the method by successfully introducing natural modifications, a fluorescent nucleotide analogue and a donor-acceptor fluorophore pair to specific sites located at an internal loop, a pseudoknot, a junction, a helix, and the middle of consecutive identical nucleotides of various RNAs. This newly developed method overcomes efficiency and position-choosing constraints that have hampered routine strategies to label RNAs beyond 200 nucleotides (nt).

The single-molecule magnet {Mn 84 } is a challenge to theory because of its high nuclearity. We directly compute two experimentally accessible observables, the field-dependent magnetization up to 75 T and the temperature-dependent heat capacity, using parameter-free theory. In particular, we use first-principles calculations to derive short- and long-range exchange interactions and compute the exact partition function of the resulting classical Potts and Ising spin models for all 84 Mn S = 2 spins to obtain observables. The latter computation is made possible by using hyperoptimized tensor network contractions, a technique developed to simulate quantum supremacy circuits. We also synthesize the magnet and measure its heat capacity and magnetization, observing qualitative agreement between theory and experiment and identifying an unusual bump in the heat capacity and a plateau in the magnetization. Our work also identifies some limitations of current theoretical modeling in large magnets, such as sensitivity to small, long-range exchange couplings.

Background: Mutations in proline-rich transmembrane protein 2 (PRRT2) are the major cause of paroxysmal kinesigenic dyskinesia (PKD). We recently reported transmembrane protein 151A (TMEM151A) mutations caused PKD. Herein, we aimed to conduct phenotypic comparisons of patients with PKD carrying PRRT2 variants, carrying TMEM151A variants, and carrying neither the PRRT2 nor TMEM151A variant., Methods: Sanger sequencing of PRRT2 and TMEM151A was performed, and phenotypic characteristics were analyzed., Results: In a cohort of 131 PKD probands (108 without PRRT2 variants and 23 newly recruited), five novel TMEM151A variants were identified and one (c.647C > A) occurred de novo. Together with our previous studies, PRRT2 and TMEM151A variants accounted for 34.7% (85/245) and 6.9% (17/245) of PKD probands, respectively. Compared with patients carrying PRRT2 variants, those with TMEM151A variants tended to exbibit dystonia with shorter durations, have no history of benign infantile epilepsy, and have residual attacks/aura when treated with carbamazepine/oxcarbazepine., Conclusions: Patients with TMEM151A variants have different features from patients with PRRT2 variants. © 2022 International Parkinson and Movement Disorder Society., (© 2022 International Parkinson and Movement Disorder Society.)