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Ibogaine and its main metabolite noribogaine provide important molecular prototypes for markedly different treatment of substance use disorders and co-morbid mental health illnesses. However, these compounds present a cardiac safety risk and a highly complex molecular mechanism. We introduce a class of iboga alkaloids – termed oxa-iboga – defined as benzofuran-containing iboga analogs and created via structural editing of the iboga skeleton. The oxa-iboga compounds lack the proarrhythmic adverse effects of ibogaine and noribogaine in primary human cardiomyocytes and show superior efficacy in animal models of opioid use disorder in male rats. They act as potent kappa opioid receptor agonists in vitro and in vivo, but exhibit atypical behavioral features compared to standard kappa opioid agonists. Oxa-noribogaine induces long-lasting suppression of morphine, heroin, and fentanyl intake after a single dose or a short treatment regimen, reversal of persistent opioid-induced hyperalgesia, and suppression of opioid drug seeking in rodent relapse models. As such, oxa-iboga compounds represent mechanistically distinct iboga analogs with therapeutic potential. Ibogaine is a natural substance that interrupts opioid addiction but has cardiac risks. This article introduces novel ibogaine analogs that show reduced cardiac risk and enhanced neuroplasticity and therapeutic-like effects in models of opioid use disorder. [ABSTRACT FROM AUTHOR]

Modular Multilevel Converter Virtual Synchronous Generator (MMC-VSG) technology is gaining widespread attention for its ability to enhance the inertia and frequency stability of the power grid integrated with converter-interfaced renewable energy sources. However, the excitation voltage regulation in the MMC-VSG can generate equivalent negative damping torque and cause low-frequency oscillation problems similar to those in synchronous machines. This article aims to improve the system's damping torque and minimize low-frequency oscillations by introducing a Virtual Power System Stabilizer (VPSS) into the power control loop. Building on the study of dynamic interactions between various control links of the MMC, this research establishes a reduced-order model (ROM) and a Phillips–Heffron state equation for the MMC-VSG single machine infinite bus system, using a hybrid modeling approach and a zero-pole truncation method. It also analyzes the mechanism of low-frequency oscillations in the MMC-VSG system through the damping torque method. The analysis reveals that the negative damping torque produced during the excitation voltage regulation process causes changes in the virtual power angle, which in turn increases the risk of low-frequency oscillation in the MMC-VSG. To address this issue, the article proposes an optimized control method for the MMC-VSG dual power loop architecture (power-angle/excitation) VPSS. This strategy compensates for the inadequate damping torque of a single loop VPSS and effectively suppresses low-frequency oscillations in the system. [ABSTRACT FROM AUTHOR]

Purpose: The study employs two independent experimental studies to collect data. It focuses on the matching effect between advertising appeals and product types. The Elaboration Likelihood Model serves as the theoretical framework for understanding the cognitive processing involved in consumers' responses to these advertising appeals and product combinations. Design/methodology/approach: This paper aims to investigate the impact of advertising appeals on consumers' intentions to purchase organic food. We explored the interaction between advertising appeals (egoistic vs altruistic) and product types (virtue vs vice) and purchase intention. The goal is to provide insights that can enhance the advertising effectiveness of organic food manufacturers and retailers. Findings: The analysis reveals significant effects on consumers' purchase intentions based on the matching of advertising appeals with product types. Specifically, when egoistic appeals align with virtuous products, there is an improvement in consumers' purchase intentions. When altruistic appeals match vice products, a positive impact on purchase intention is observed. The results suggest that the matching of advertising appeals with product types enhances processing fluency, contributing to increased purchase intention. Originality/value: This research contributes to the field by providing nuanced insights into the interplay between advertising appeals and product types within the context of organic food. The findings highlight the importance of considering the synergy between egoistic appeals and virtuous products, as well as altruistic appeals and vice products. This understanding can be strategically employed by organic food manufacturers and retailers to optimize their advertising strategies, thereby improving their overall effectiveness in influencing consumers' purchase intentions. [ABSTRACT FROM AUTHOR]

In recent years, cultural tourism has increasingly embraced museum visits. Museums serve as both cultural heritage guardians and integral parts of tourist destinations, significantly impacting visitor satisfaction and experience. Moreover, online museum reviews have become a crucial indicator of museum service quality, visitor experience, and public feedback in the digital age. An analysis of online reviews on major tourism websites and social media platforms can assist museums in developing appropriate management strategies. This study employed the structural topic model (STM) to analyze online museum reviews, identifying three primary attributes of museums and visitors' personal experiences, as well as 19 sub-attributes. The study confirmed that core offerings have a positive impact on visitor experience and satisfaction, while peripheral services and overall ambiance are also positively related to visitor experience and satisfaction. Furthermore, the results of structural equation modeling demonstrated that visitors' personal experiences have a positive impact on satisfaction. The results of structural equation modeling analysis support all seven hypothesized relationships. These findings will assist museum managers in developing effective management strategies and future plans. [ABSTRACT FROM AUTHOR]

Purpose: The crosstalk between hepatocellular carcinoma (HCC) cells and hepatic stellate cells (HSCs) is one of the important mechanisms of liver cancer metastasis. The relationship between liver cancer metastasis and glycolysis has been extensively studied recently. However, the role of von Willebrand factor (vWF) mediated glycolysis mechanism in liver cancer metastasis is currently unknown. Methods: Western blot was used to verify the expression of vWF in HCC cells. PAS staining, glycogen and L-lactate content assays were used to reflect cellular glycolysis levels. The ability of cell migration was explored by Wound-healing and Transwell assays. Besides, the effect of vWF on the progression of HCC in vivo was also studied using subcutaneous xenograft model. Results: vWF derived from HCC cells promoted tumor migration by mediating glycolysis. Besides, vWF participated in the crosstalk between HCC cells and HSCs. HCC cells activated HSCs through vWF-mediated TGFB1 expression and secretion, and activated HSCs upregulated vWF expression in HCC cells through IL-6 secretion feedback. Further, in vitro and in vivo experiments also confirmed the importance of the JAK1/vWF/TGFB1 axis in regulating HSCs-derived IL-6 mediated HCC migration and growth. Conclusion: In summary, this article demonstrated that IL-6 released from hepatic stellate cells enhanced glycolysis and migration ability of liver cancer cells by activating JAK1/vWF/TGFB1 axis which may also be a potential target for inhibiting liver cancer metastasis. [ABSTRACT FROM AUTHOR]

This study aims to investigate the effect of hosts' facial features of different genders on customers' booking intentions on the Airbnb shared accommodation platform. A comprehensive model was built to analyze hosts' facial features in the United States (n = 105,084) through big data combined with an artificial intelligence facial recognition system. Results show that beauty, smile, aging, and wearing glasses positively affect customers' booking intentions. There is gender heterogeneity in the effect of hosts' facial features on customers' booking intentions. Compared to female hosts, smiling is significant for male hosts, and wearing glasses has a greater impact on female hosts. Host reputation somewhat weakens the positive effect of host facial features on customers' booking intentions, and the shared housing type strengthens the positive effect of facial features on customers' booking intentions. This study provides insights into customer decision-making that may be influenced by hosts' facial features. [ABSTRACT FROM AUTHOR]

We study electromagnetic ion cyclotron (EMIC) waves based on observations from the ionosphere, magnetosphere, and ground during a geomagnetic storm recovery phase on 28 August 2018. In this case, multiple ducting EMIC waves in the ionosphere show higher frequencies in the post‐midnight than those in the pre‐midnight. Ionospheric EMIC wave frequency differences in magnetic local time (MLT) are consistent with MLT frequency differences in the equatorial magnetosphere, which are mainly caused by different background magnetic field at different L‐shells. Moreover, we report the first observation of frequency range selections in ionospheric ducting EMIC waves and find that frequency selections depend on the magnetic field intensity in the main part of the ionospheric waveguide, with higher frequency corresponding to larger magnetic field. This study reveals the important role of background magnetic field in regulating ducting EMIC wave frequencies in the ionosphere. Plain Language Summary: Electromagnetic ion cyclotron (EMIC) waves are in the frequency range of 0.2–5 Hz, and they may occur in three different bands, which are named as H+, He+, and O+ bands from high to low frequencies. In this paper, He+ band EMIC waves in the nightside during a geomagnetic storm are observed by satellites in the ionosphere, and their frequencies are different, that is, frequencies are higher in the post‐midnight than those in the pre‐midnight. Ionospheric EMIC wave frequency differences in local time have been noticed before but have not yet been explained. We discover that ionospheric EMIC wave frequency differences in local time agree well with frequency differences in the magnetosphere. Besides frequency discrepancies in local time, in the post‐midnight, ionospheric EMIC waves tend to select higher or lower frequency range relative to frequencies in the magnetosphere. We find that these frequency selections mainly depend on the magnetic field intensity in the ionosphere. The frequency selections in ionospheric EMIC waves have not been identified before, and it is important to understand variations of EMIC waves in the ionosphere. Key Points: Ionospheric EMIC wave frequency differences in magnetic local time (MLT) are consistent with MLT frequency differences in the equatorial magnetosphereHigher/lower wave frequencies in the equatorial magnetosphere are at lower/higher L‐shells with larger/smaller background magnetic fieldFrequency selections of ducting EMIC waves depend on local magnetic field, and frequency is higher when the magnetic field is larger [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to analyze the effects of carbon reduction efforts and preservation efforts on system benefits in the cold chain industry of fresh products. Design/methodology/approach: This study develops an optimal decision game model for the fresh products in the cold chain, incorporating the retailer's preservation effort and the supplier's carbon emission reduction effort. It quantifies the relationship between carbon emission reduction effort, preservation effort and system profit. The model considers parameters like carbon trading price, consumer low-carbon preference and consumer freshness preference, reflecting real-world conditions and market trends. Numerical simulations are conducted by varying these parameters to observe their impact on system profit. Findings: Under the carbon cap-and-trade policy, the profit of the fresh cold chain system is higher than that of the fresh cold chain system without carbon constraints, and the profit of the supplier under decentralized decision-making is increased by nine times in the simulation results. The increase in carbon trading prices can effectively improve the freshness level of fresh products cold chain, carbon emission reduction level and system profit. Originality/value: This study comprehensively considers the factors of freshness and carbon emission reduction, provides the optimal low-carbon production decision-making reference for the fresh food cold chain and promotes the sustainable development of the fresh food cold chain. [ABSTRACT FROM AUTHOR]

Aims: To analyze the clinical characteristics of acute symptomatic seizures and predict the risk factors for seizure recurrence in patients with anti-N-methyl-d-aspartate receptor (NMDAR), anti-leucine-rich glioma-inactivated 1 (LGI1), and anti-gamma-aminobutyric acid B receptor (GABABR) encephalitis. Methods: In this retrospective study, we included hospitalized patients who had been diagnosed with anti-NMDAR, anti-LGI1, and anti-GABABR encephalitis between November 2014 and April 2021. Binary logistic regression analysis was performed to identify the potential risk factors for seizure recurrence. Results: In total, 262 patients with anti-NMDAR, anti-LGI1, and anti-GABABR encephalitis were included, 197 (75.2%) of whom presented with acute symptomatic seizures. During follow-up, 42 patients exhibited seizure recurrence. In anti-NMDAR encephalitis, frontal lobe abnormality on brain magnetic resonance imaging, delayed immunotherapy, early seizures, and focal motor onset were associated with seizure recurrence. Conclusions: Acute symptomatic seizure is a common clinical feature observed in patients with anti-NMDAR, anti-LGI1, and anti-GABABR encephalitis, with 50% of patients presenting with seizures as an initial symptom. The prognosis of patients with acute symptomatic seizures can be improved after receiving immunotherapy. Nevertheless, a minority of patients will experience seizure recurrence; therefore, restarting immunotherapy is recommended. [ABSTRACT FROM AUTHOR]

OBJECTIVE To assess the feasibility and safety of the minimalistic approach to left atrial appendage occlusion (LAAO) guided by cardiac computed tomography angiography (CCTA). METHODS Ninety consecutive patients who underwent LAAO, with or without CCTA-guided, were matched (1:2). Each step of the LAAO procedure in the computed tomography (CT) guidance group (CT group) was directed by preprocedural CT planning. In the control group, LAAO was performed using the standard method. All patients were followed up for 12 months, and device surveillance was conducted using CCTA. RESULTS A total of 90 patients were included in the analysis, with 30 patients in the CT group and 60 matched patients in the control group. All patients were successfully implanted with Watchman devices. The mean ages for the CT group and the control group were 70.0 ± 9.4 years and 68.4 ± 11.9 years (P = 0.52), respectively. The procedure duration (45.6 ± 10.7 min vs. 58.8 ± 13.0 min, P < 0.001) and hospital stay (7.5 ± 2.4 day vs. 9.6 ± 2.8 day, P = 0.001) in the CT group was significantly shorter compared to the control group. However, the total radiation dose was higher in the CT group compared to the control group (904.9 ± 348.0 mGy vs. 711.9 ± 211.2 mGy, P = 0.002). There were no significant differences in periprocedural pericardial effusion (3.3% vs. 6.3%, P = 0.8) between the two groups. The rate of postprocedural adverse events (13.3% vs. 18.3%, P = 0.55) were comparable between both groups at 12 months follow-up. CONCLUSIONS CCTA is capable of detailed LAAO procedure planning. Minimalistic LAAO with preprocedural CCTA planning was feasible and safe, with shortened procedure time and acceptable increased radiation and contras consumption. For patients with contraindications to general anesthesia and/or transesophageal echocardiography, this promising method may be an alternative to conventional LAAO. [ABSTRACT FROM AUTHOR]

The digital economy plays an important role in reducing the global warming process. This paper explores the spatiotemporal heterogeneity impacts of the digital economy on provincial carbon emissions and its underlying mechanisms. Initially, this paper examines the inhibitory impact of the digital economy on carbon emissions, alongside the mediating role of economic agglomeration, at a theoretical level. Subsequently, it empirically explores the quantitative associations among the digital economy, economic agglomeration, and carbon emissions by utilizing Chinese provincial panel data spanning from 2000 to 2021. This investigation employed static and dynamic spatial Durbin models as well as mediation models to analyze the interrelationships. The results firstly revealed that the digital economy notably diminishes carbon emissions, with economic agglomeration playing a significant mediating role. This conclusion remained consistent even after substituting the explanatory variables and weight matrix, modifying the sample period, and conducting other robustness tests. Secondly, the impact of the digital economy on carbon emissions exhibited spatial spillovers. Compared with the impact on the local area, the impact on neighboring provinces was found to be weaker. Thirdly, carbon emissions showed a significant "snowball" effect in the time dimension. This paper emphasizes the important role of digital technology in curbing carbon emissions, and it provides some policy insights for studying the digital economy, economic agglomeration, and carbon emissions. Furthermore, it offers valuable insight and suggestions to reduce carbon emissions and realize the goal of the "dual-carbon" strategy. [ABSTRACT FROM AUTHOR]

General purpose technologies (GPTs) are seen as engines of economic growth, which is achieved through diffusion in various application sectors. The diffusion of GPTs is the key to unleashing their potential value. However, the market and organisational failure of GPT diffusion are seen as hurdles to realise this potential. To address this issue, a single-group evolutionary game model was established to analyse the GPT diffusion process and its influencing factors and reveal the evolutionary mechanism of GPT diffusion. The main findings of the study show that the GPT diffusion is an evolutionary process influenced by many factors. GPT diffusion is negatively related to adoption and commercial development costs and positively related to the success rate of commercial development. In addition, government support is found to be positive for GPT diffusion, but a disproportionate share of government funding supports dampens the diffusion process. It is also found that government funds, knowledge and technological support are conducive to GPT diffusion. The effect of knowledge and technological support on GPT diffusion is positively regulated by the technology conversion coefficient, but the intellectual property rights system has a negative impact. The study sheds light on strategic choices for the diffusion and supply of GPTs. [ABSTRACT FROM AUTHOR]

Background: To demonstrate the effectiveness and feasibility of robotic portal resection (RPR) for mediastinal tumour using a prospectively collected database. Methods: Data from 73 consecutive patients with mediastinal tumours who underwent RPRs were prospectively collected from August 2018 to April 2023. All patients underwent chest and abdominal enhanced computed tomography (CT) and preoperative multidisciplinary team (MDT) discussion. The patients were stratified into two groups based on tumour size: Group A (tumour size < 4 cm) and Group B (tumour size ≥ 4 cm). General clinical characteristics, surgical procedures, and short outcomes were promptly recorded. Results: All of the cases were scheduled for RPRs. One patient (1/73, 1.4%) was switched to a small utility incision approach because of extensive pleural adhesion. Two patients (2.8%) converted to sternotomy, however, no perioperative deaths occurred. Most of the tumours were located in the anterior mediastinum (51/73, 69.9%). Thymoma (27/73, 37.0%) and thymic cyst (16/73, 21.9%) were the most common diagnoses. The median diameter of tumours was 3.2 cm (IQR, 2.4–4.5 cm). The median total operative time was 61.0 min (IQR, 50.0–90.0 min). The median intraoperative blood loss was 20 mL (IQR, 5.0–30.0 ml), and only one patient (1.4%) experienced an intraoperative complication. The median length of hospital stay was 3 days (IQR, 2–4 days). Compared with Group A, the median total operative time and console time of Group B were significantly longer (P = 0.006 and P = 0.003, respectively). The volume of drainage on the first postoperative day was greater in group B than in group A (P = 0.013). Conclusion: RPR is a safe and effective technique for mediastinal tumour treatment, which can expand the application of minimally invasive surgery for the removal of complicated mediastinal tumours. [ABSTRACT FROM AUTHOR]

Background: The aging global population has led to an increased burden of cognitive impairment in older adults. Objective: This study examined the relationship between fermented dairy intake and cognitive function in this population. Methods: Yogurt, cheese, and fermented dairy consumption were assessed through two 24-hour dietary recall interviews, categorized into low, medium, and high intake groups. Multivariate linear regression was employed to examine the relationship between fermented dairy intake and cognitive tests, including the Alzheimer's Disease Word Learning Immediate Recall Test (CERAD-IRT), CERAD Delayed Recall Test (CERAD-DRT), Animal Fluency Test (AFT), Digit Symbol Substitution Test (DSST), and global cognitive z-scores, adjusting for potential confounding factors. Results: The study comprised 2,462 participants (average age 69.34±6.75 years, 52.07% female). Among yogurt consumers, global cognition and AFT z-scores are notably higher than non-consumers. Conversely, individuals who consume cheese display significantly lower CERAD-DRT z-scores. Compared to participants not intake fermented dairy, consumers of fermented dairy show significantly higher AFT and DSST z-scores and lower CERAD-DRT z-scores. Moreover, when categorizing individuals based on their intake of fermented dairy, those with low and medium consumption show significantly higher AFT and DSST z-scores, as well as significantly lower CERAD-DRT z-scores compared to non-consumers. Conclusions: Our study suggests that moderate consumption of fermented dairy products is associated with better executive function and verbal fluency in the elderly. [ABSTRACT FROM AUTHOR]

Runt-related transcription factors (RUNX) are a family of transcription factors that are essential for normal and malignant hematopoietic processes. Their most widely recognized role in malignancy is to promote the occurrence and development of acute myeloid leukemia. However, it is worth noting that during the last decade, studies of RUNX proteins in solid tumors have made considerable progress, suggesting that these proteins are directly involved in different stages of tumor development, including tumor initiation, progression, and invasion. RUNX proteins also play a role in tumor angiogenesis, the maintenance of tumor cell stemness, and resistance to antitumor drugs. These findings have led to the consideration of RUNX as a tumor biomarker. All RUNX proteins are involved in the occurrence and development of solid tumors, but the role of each RUNX protein in different tumors and the major signaling pathways involved are complicated by tumor heterogeneity and the interacting tumor microenvironment. Understanding how the dysregulation of RUNX in tumors affects normal biological processes is important to elucidate the molecular mechanisms by which RUNX affects malignant tumors. [ABSTRACT FROM AUTHOR]

This study aims to explore thematic influences on theme park visitors' satisfaction through user‐generated data. To this end, we first used an unsupervised machine learning method, structural topic modeling, and analyzed 112,000 reviews post by visitors to Shanghai Disney Resort from June 16, 2016 to March 4, 2022. Our findings are of great significance for reflecting consumer behavior through user‐generated data. Specifically, we find that visitors' satisfaction is highly related to service in the theme park and their playing feeling, and early tourists pay more attention to the experience of specific playing items while later tourists focus on the overall playing experience. In addition, an empirical study is conducted by treating the ratings associated with each review as dependent variable and each topic represented by comments as independent variables, which shows that the relationship between the customer reviews and ratings by tourists becomes less pronounced over time. In other words, as time goes, customers review can reflect their subjective feelings or experience, but the rating is not. We discover the "dynamics" of user‐generated data over time and gain a better understanding of the aspects and concerns of visitors' satisfaction over time. The findings of the study contribute to the literature on tourism, service, and consumer behavior while also providing valuable practical implications. [ABSTRACT FROM AUTHOR]

Familial exudative vitreoretinopathy (FEVR) is a severe inherited disease characterized by defective retinal vascular development. With genetic and clinical heterogeneity, FEVR can be inherited in different patterns and characterized by phenotypes ranging from moderate visual defects to complete vision loss. This study was conducted to unravel the genetic and functional etiology of a 4-month-old female FEVR patient. Targeted gene panel and Sanger sequencing were utilized for genetic evaluation. Luciferase assays, western blot, quantitive real-time PCR, and immunocytochemistry were performed to verify the functional defects in the identified candidate variant. Here, we report a 4-month-old girl with bilateral retinal folds and peripheral avascularization, and identified a novel frameshift heterozygous variant c.37dup (p.Leu13ProfsTer13) in NDP. In vitro experiments revealed that the Leu13ProfsTer13 variant led to a prominent decrease in protein levels instead of mRNA levels, resulting in compromised Norrin/β-catenin signaling activity. Human androgen receptor assay further revealed that a slight skewing of X chromosome inactivation could partially cause FEVR. Thus, the pathogenic mechanism by which heterozygous frameshift or nonsense variants in female carriers cause FEVR might largely result from a loss-of-function variant in one X chromosome allele and a slightly skewed X-inactivation. Further recruitment of more FEVR-affected females carrying NDP variants and genotype–phenotype correlation analysis can ultimately offer valuable information for the prognosis prediction of FEVR. [ABSTRACT FROM AUTHOR]

Digital infrastructure considers the advantages of traditional infrastructure and high‐tech information technology and can optimize the allocation of green resources in the service industry to a large extent. Based on the calculation of the level of digital infrastructure in 30 provinces and cities in China from 2011 to 2020, this study analyzes the impact of digital infrastructure on the resource allocation efficiency of the service industry from a theoretical and empirical perspective. The study found that digital infrastructure can improve the efficiency of green resource allocation in the service industry; however, at the subdivision level, only its operation dimension has a significant and positive impact on the efficiency of green resource allocation in the service industry, and the improvement effect of the construction dimension is insignificant. Analyzing the mechanism of action shows that digital infrastructure can indirectly optimize the allocation of green resources in the service industry by deepening the degree of informatization and improving the level of innovation. Further analysis shows that the impact of digital infrastructure on the efficiency of green resource allocation in the service industry presents a complex nonlinear trend and regional heterogeneity. The research conclusions provide a policy reference for optimizing the allocation of green resources in the service industry and promoting high‐quality economic growth under the background of digital infrastructure. [ABSTRACT FROM AUTHOR]

Limonene was identified as green media for amide formation through quantum chemistry calculation. An environmentally benign and sustainable protocol for amide formation was developed with simple filtration without the need for extensive isolation and purification. Additionally, the scope and general compatibility of the proposed method were explored with aromatic and aliphatic substrates, giving moderate to excellent yields, and a gram-scale synthesis of SHP1 activator 3a-18 were easily performed for further biological evaluation. [ABSTRACT FROM AUTHOR]

Purpose: The primary objective of this study was to construct competing endogenous RNA (ceRNA) networks and evaluate the prognostic significance of tumor-infiltrating immune cells (TIICs) and key biomarkers within the ceRNA networks in colon adenocarcinoma (COAD) patients. Methods: Comprehensive bioinformatics tools were used to screen differentially expressed genes (DEGs), miRNAs (DEMs), and lncRNAs (DELs) related to COAD, leading to the creation of ceRNA networks. The CIBERSORT technique was employed to assess the significance of TIICs in COAD, and an immune-related prognosis prediction model was subsequently developed. Co-expression analyses were conducted to determine the relationship between key genes in ceRNA networks and immunologically significant TIICs. The study also utilized 5 GEO datasets and web-based databases to externally validate the findings. Results: The study revealed a statistically significant relationship between key hub genes and immune cells, as determined through co-expression analysis. Two hub regulators (SOX12 and H19) demonstrated significant prognostic value in the ceRNA-related prognostic model, and their elevated expression levels were verified across multiple CRC cell lines. Additionally, the knockdown of SOX12 led to a suppression of proliferation, migration, and invasion in colon cancer cells. Conclusion: Through the construction of ceRNA networks and evaluation of TIICs, the study successfully established two risk score models and nomograms. These models serve as valuable tools for understanding the molecular processes and predicting the prognosis of COAD patients. Further validation of hub regulators SOX12 and H19 substantiates their potential role as key biomarkers in COAD. [ABSTRACT FROM AUTHOR]

Introduction: Aging, an inevitable physiological process, leads to morphological and histological degenerative changes in the mandibular condylar cartilage (MCC); however, the molecular mechanism has not yet been elucidated, and little information is available on age-related factors. Therefore, this study was designed to identify age-related factors by investigating the age-related differentially expressed genes (DEGs) and localization of their translated protein expression in the mandibular condyle. Methods: Mandibular condyles were collected from 10- and 50-week-old mice. Total RNA was extracted from the samples and then analyzed using cap analysis of gene expression (CAGE) to identify age-related DEGs. Gene ontology (GO) enrichment analysis was performed to determine which biological processes were most affected by aging in terms of gene expression using Metascape. The mandibular condyle samples were processed for histology to investigate morphological changes caused by aging and for immunohistochemistry to localize the protein expression encoded by age-related genes identified with CAGE. Semi-quantitative immunohistochemistry was performed to assess age-related extracellular matrix (ECM) protein levels in the MCC. The histological sections were also used for Alcian blue histochemistry to detect glycosaminoglycans (GAGs). Results: GO enrichment analysis revealed that the genes related to "extracellular matrix organization," including Acan, Col1a1, Col1a2, Col2a1, Mmp3, Mmp9, and Mmp13, were most differentially expressed in the aged mandibular condyle. Among these seven genes, Mmp3 was upregulated, and the others were downregulated with aging. Histological examination showed the age-related morphological and histological changes in the MCC. Immunohistochemical investigation showed the localization of matrix metalloproteinases (MMPs)-3, -9, and -13 and their substrate proteins, aggrecan, type I collagen, and type II collagen, in the mandibular condyle at 10 and 50 weeks, indicating different localizations between the young and the aged. In the aged MCC, semi-quantitative immunohistochemistry showed a significant decrease in the aggrecan protein level, and Alcian blue histochemistry showed a decrease in GAGs. Conclusion: MMP-3, MMP-9, and MMP-13 contribute to the remodeling of the ECM of the MCC and subchondral bone during aging by degrading ECM proteins at specific times and sites under the regulation of their production and secretion. [ABSTRACT FROM AUTHOR]

Background: Mean platelet volume (MPV), as a marker of platelet activity, has been shown to be an efficient prognostic biomarker in several types of cancer. Using MPV, this study aimed to create and validate a prognostic nomogram to the overall survival in esophageal squamous cell carcinoma (ESCC) patients. Methods: The nomogram was constructed and tested using data from a retrospective study of 1893 patients who were randomly assigned to the training and testing cohorts with a 7:3 randomization. In order to screen out the optimal predictors for overall survival (OS), we conducted the LASSO‐cox regression, univariate, and multivariate cox regression analyses. Subsequently, the predictive accuracy of the nomogram was validated in both the training and the testing cohorts. Finally, decision curve analysis (DCA) was used to confirm clinical validity. Results: Age, MPV, nerve invasion, T stage, and N stage were found as independent prognostic variables for OS and were further developed into a nomogram. The nomogram's prediction accuracy for 1‐, 3‐, and 5‐year OS was 0.736, 0.749, 0.774, and 0.724, 0.719, 0.704 in the training and testing cohorts, respectively. Furthermore, DCA results indicated that nomograms outperformed the AJCC 8th and conventional T, N staging systems in both the training and testing cohorts. Conclusions: The nomogram, in conjunction with MPV and standard clinicopathological markers, could improve the accuracy of prediction of OS in ESCC patients. [ABSTRACT FROM AUTHOR]

Policymakers were surprised to find increases in sales tax revenues in 2020 due to expectations that they would drop 8–20%. We investigate this puzzle and provide novel insights into consumption taxes based on this experience. Using a case study from the State of Utah, we document that shifts in the structure of consumption played a significant role in the robustness of sales tax revenue. Two factors stand out in our results. The first factor is the structure of the tax base for sales taxes in the USA. This tax base covers only a subset of personal consumption, excluding, for example, many services. During the pandemic, when services were restricted or shut down, this caused a shift in spending toward goods that are more likely to be in the sales tax base. The second factor is the boom in e-commerce during the pandemic, which boosted sales tax collections. This was catalyzed by recent legal changes that made the collection of sales taxes in e-commerce easier. Interestingly, this e-commerce boost also shifted the point of sale and related sales tax revenues away from urban areas toward suburban areas. Our case study of the pandemic's effect on sales taxes in the USA generally, and Utah's experience specifically, provides lessons for consumption taxes, such as the VAT more broadly, and lessons on the role of consumption taxes for tax revenue volatility. [ABSTRACT FROM AUTHOR]

Heterozygous de novo loss-of-function mutations in the gene expression regulator HNRNPU cause an early-onset developmental and epileptic encephalopathy. To gain insight into pathological mechanisms and lay the potential groundwork for developing targeted therapies, we characterized the neurophysiologic and cell-type-specific transcriptomic consequences of a mouse model of HNRNPU haploinsufficiency. Heterozygous mutants demonstrated global developmental delay, impaired ultrasonic vocalizations, cognitive dysfunction and increased seizure susceptibility, thus modeling aspects of the human disease. Single-cell RNA-sequencing of hippocampal and neocortical cells revealed widespread, yet modest, dysregulation of gene expression across mutant neuronal subtypes. We observed an increased burden of differentially-expressed genes in mutant excitatory neurons of the subiculum—a region of the hippocampus implicated in temporal lobe epilepsy. Evaluation of transcriptomic signature reversal as a therapeutic strategy highlights the potential importance of generating cell-type-specific signatures. Overall, this work provides insight into HNRNPU-mediated disease mechanisms and provides a framework for using single-cell RNA-sequencing to study transcriptional regulators implicated in disease. Author summary: The brain relies on strict regulation of gene expression for proper functioning. Mutations in genes that influence the expression of other genes are linked to neurological conditions such as epilepsy, autism, intellectual disability, and neurodegenerative disorders. Identifying targeted therapies for these genetic causes of disease are increasingly difficult since they often lead to a wide array of molecular and cellular effects from the widespread disturbance in gene expression. One potential approach is to identify therapies that shift the abnormal gene expression signature to a more normal state. To explore this 'transcriptome-guided' approach, we characterized the consequences of the loss of one copy of the gene expression regulator, HNRNPU, from the molecular to the whole organism level using a genetic mouse model. We generated disease-associated gene expression signatures and compared them to signatures obtained from cells treated with different drugs to pinpoint compounds with the potential to rescue abnormal gene expression. [ABSTRACT FROM AUTHOR]

Proteasomal degradation of intrinsically disordered proteins, such as tau, is a critical component of proteostasis in both aging and neurodegenerative diseases. In this study, we investigated proteasomal activation by MK886 (MK). We previously identified MK as a lead compound capable of modulating tau oligomerization in a cellular FRET assay and rescuing P301L tau-induced cytotoxicity. We first confirmed robust proteasomal activation by MK using 20S proteasomal assays and a cellular proteasomal tau-GFP cleavage assay. We then show that MK treatment can significantly rescue tau-induced neurite pathology in differentiated SHSY5Y neurospheres. Due to this compelling result, we designed a series of seven MK analogs to determine if proteasomal activity is sensitive to structural permutations. Using the proteasome as the primary MOA, we examined tau aggregation, neurite outgrowth, inflammation, and autophagy assays to identify two essential substituents of MK that are required for compound activity: (1) removal of the N-chlorobenzyl group from MK negated both proteasomal and autophagic activity and reduced neurite outgrowth; and (2) removal of the indole-5-isopropyl group significantly improved neurite outgrowth and autophagy activity but reduced its anti-inflammatory capacity. Overall, our results suggest that the combination of proteasomal/autophagic stimulation and anti-inflammatory properties of MK and its derivatives can decrease tau-tau interactions and help rebalance dysfunctional proteostasis. Further development of MK to optimize its proteasomal, autophagic, and anti-inflammatory targets may lead to a novel therapeutic that would be beneficial in aging and neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

BACKGROUND: Amitraz is a broad‐spectrum formamidine acaricide proven to be effective against mites in all development stages. Under acidic conditions, amitraz is hydrolyzed to N2‐(2,4‐dimethylphenyl)‐N1‐methyformamidine (DPMF), an active metabolite for mite control. Octopamine and tyramine receptors are well known targets of amitraz. Until now, no research has been conducted about the amitraz target in Tetranychus cinnabarinus. This study aimed to identify the target genes of amitraz in T. cinnabarinus and reveal the mechanisms behind the differential acaricidal activities of amitraz and DPMF. RESULTS: Analysis of the toxicity, stress expression, target sensitivity and binding site of amitraz against T. cinnabarinus showed that TcOctβ2R was the main target gene of amitraz. DPMF had more potent acaricidal activity against T. cinnabarinus and was more effective at activating TcOctβ2R than amitraz. Furthermore, the three synergists had no significant effect on amitraz and DPMF, indicating that the detoxification metabolism was not related to the difference in acaricidal activity. CONCLUSION: In this study, TcOctβ2R was identified as the main target gene of amitraz against T. cinnabarinus. The divergence of target binding was responsible for the difference in acaricidal activity between amitraz and DPMF. The results also revealed the physiological and pharmacological functions of octopamine receptors (OARs) in T. cinnabarinus and could provide a basis for the design of new acaricides, with OARs as a special target. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Although robotic segmentectomy has been applied for the treatment of small pulmonary lesions for many years, studies on the learning curve of robotic segmentectomy are quite limited. Thus, we aim to investigate the learning curve of robotic portal segmentectomy with 4 arms (RPS-4) using prospectively collected data in patients with small pulmonary lesions. One hundred consecutive patients with small pulmonary lesions who underwent RPS-4 between June 2018 and April 2021 were included in the study. Da Vinci Si/Xi systems were used to perform RPS-4. The mean operative time, console time, and docking time for the entire cohort were 119.2 ± 41.6, 85.0 ± 39.6, and 6.6 ± 2.8 min, respectively. The learning curve of RPS-4 can be divided into three different phases: 1–37 cases (learning phase), 38–78 cases (plateau phase), and > 78 cases (mastery phase). Moreover, 64 cases were required to ensure acceptable surgical outcomes. The total operative time (P < 0.001), console time (P < 0.001), blood loss (P < 0.001), and chest tube duration (P = 0.014) were reduced as experience increased. In conclusion, the learning curve of RPS-4 could be divided into three phases. 37 cases were required to pass the learning phase, and 78 cases were needed to truly master this technique. [ABSTRACT FROM AUTHOR]

In endemic areas, EBV DNA is used to guide diagnosis, detect recurrence and distant metastasis of NPC. Until now, the importance of EBV DNA in the prediction of NPC has received little attention in non-endemic regions. To explore the prognostic value of EBV DNA alone or in combination with PNI in NPC patients from a non-endemic area of China. In this retrospective study, 493 NPC patients were enrolled. Clinical pathologic data, pre-treatment plasma EBV DNA, and laboratory tests were all performed. A standard anticancer treatment was prescribed, and follow up data were collected. EBV DNA was found to be positively related to clinical stage (r = 0.357, P < 0.001), T stage (r = 0.193, P < 0.001), N stage (r = 0.281, P < 0.001), and M stage (r = 0.215, P < 0.001). The difference in EBV DNA loads between clinical stage, T, N and M stage was statistically significant (P < 0.001). In this study, the best cutoff value for EBV-DNA to distinguish the prognosis of NPC was 262.7 copies/ml. The 5-year OS of patients in the EBV-DNA ≤ 262.7 copies/ml group and EBV-DNA > 262.7 copies/ml group was 88% and 65.3%, respectively (P < 0.001). EBV-DNA and PNI were found to be independent prognostic factors for OS in multivariate analysis (P < 0.05). EBV-DNA was independent prognostic factors for PFS. In predicting NPC patients OS, the novel combination marker of EBV DNA and PNI outperformed TNM staging (AUC: 0.709 vs. 0.675). In addition, the difference between EBV + PNI and EBV + TNM was not statistically significant for OS or PFS (P > 0.05). This novel combination biomarker was a promising biomarker for predicting NPC survival and may one day guide treatment option. [ABSTRACT FROM AUTHOR]

Background: Children under five are the vulnerable population most at risk of being infected with Plasmodium parasites, especially in the Sahel region. Seasonal malaria chemoprevention (SMC) recommended by World Health Organization (WHO), has proven to be a highly effective intervention to prevent malaria. Given more deaths reported during the COVID-19 pandemic than in previous years due to the disruptions to essential medical services, it is, therefore, necessary to seek a more coordinated and integrated approach to increasing the pace, coverage and resilience of SMC. Towards this end, fully leverage the resources of major players in the global fight against malaria, such as China could accelerate the SMC process in Africa. Methods: We searched PubMed, MEDLINE, Web of Science, and Embase for research articles and the Institutional Repository for Information Sharing of WHO for reports on SMC. We used gap analysis to investigate the challenges and gaps of SMC since COVID-19. Through the above methods to explore China's prospective contribution to SMC. Results: A total of 68 research articles and reports were found. Through gap analysis, we found that despite the delays in the SMC campaign, 11.8 million children received SMC in 2020. However, there remained some challenges: (1) a shortage of fully covered monthly courses; (2) lack of adherence to the second and third doses of amodiaquine; (3) four courses of SMC are not sufficient to cover the entire malaria transmission season in areas where the peak transmission lasts longer; (4) additional interventions are needed to consolidate SMC efforts. China was certified malaria-free by WHO in 2021, and its experience and expertise in malaria elimination can be shared with high-burden countries. With the potential to join the multilateral cooperation in SMC, including the supply of quality-assured health commodities, know-how transfer and experience sharing, China is expected to contribute to the ongoing scale-up of SMC. Conclusions: A combination of necessary preventive and curative activities may prove beneficial both for targeted populations and for health system strengthening in the long run. More actions are entailed to promote the partnership and China can be one of the main contributors with various roles. [ABSTRACT FROM AUTHOR]

Three-dimensional porous network encapsulation strategy is an effective means to obtain composite phase-change materials (PCMs) with high heat storage capacity and enhanced thermal conductivity. Herein, macroporous reduced graphene oxide (rGO) aerogels with adjustable pore size are prepared by the emulsion template method and hydrothermal reduction process. Further, the shape-stabilized rGO-aerogel-based composite PCMs are constructed after the combination of 3D porous rGO supports and paraffin wax (PW) through vacuum melting infiltration. By regulating the pore structure of the rGO aerogel network, the rGO-based composite PCMs achieve excellent energy storage properties with a phase-change enthalpy of 179.94 J/g for the loading amount of 95.61 wt% and an obvious enhancement in thermal conductivity of 0.412 W/m−1·K−1, which is 54.89% higher than pristine PW and enduring thermal cycling stability. The obtained macroporous rGO-aerogel-based composite PCMs with high thermal storage and heat transfer performance effectively broaden the application of PCMs in the field of thermal energy storage. [ABSTRACT FROM AUTHOR]

Background: To explore whether robotic lobectomy (RL) is superior to video‐assisted lobectomy (VAL) in terms of short‐term outcomes in patients with pulmonary neoplasms. Methods: From January 30, 2019 to February 28, 2022, a series of consecutive minimally invasive lobectomies were performed for patients with pulmonary neoplasms. Perioperative outcomes such as operation time, blood loss, dissected lymph nodes (LNs), surgical complications, postoperative pain control, length of postoperative stay in hospital, and total cost of hospitalization were compared. Results: A total of 336 cases including 173 RLs and 163 VALs were enrolled. Baseline characteristics were comparable between groups. RLs were associated with shorter operation time (median [interquadrant range, IQR], 107 min [90–130] vs. 120 min [100–149], p < 0.001), less blood loss (median [IQR], 50 mL [30–60] vs. 50 mL [50–80], p = 0.02), and lower blood transfusion rate (3.5% vs. 9.8%, p = 0.02) compared with VALs. More LNs were harvested by the robotic approach (median [IQR], 29 [20–41] vs. 22 [15–45], p = 0.04). The incidences of conversion, major postoperative complications, extra analgesic usage, and postoperative length of stay were all comparable between the RL and VAL groups. As predicted, the total cost of hospitalization was greater in the RL group (median [IQR], $16728.35 [15682.16–17872.15] vs. $10713.47 [9662.13–11742.15], p < 0.001). Conclusion: RL improved surgical efficacy with shortened operative time, less blood loss, and more thorough LN dissection compared with VAL, compromised by higher cost. [ABSTRACT FROM AUTHOR]

The deep reinforcement learning (DRL) technique has gained attention for its potential in designing "virtual network" controllers. This skill utilizes a novel solution that can avoid the specific parameters and system model required in classical dynamic programming algorithms. However, addressing the issue of system uncertainties and performance deterioration remains a challenge. To overcome this challenge, the authors propose a new control prototype using a twin delayed deep deterministic policy gradient (TD3)-based adaptive controller, which replaces the conventional virtual synchronous generator (VSG) module in the modular multilevel converter (MMC) control. In this approach, an adaptive programming module is developed using a critic fuzzy network point of view to determine the optimal control policy. The modification presented in this framework is able to improve the system stability and resist disruptions while retaining the merits of the conventional VSG control model. The proposed approach is implemented and tested using the DRL toolbox in MATLAB/Simulink. [ABSTRACT FROM AUTHOR]

We used pyroptosis-related genes to establish a risk–score model for prognostic prediction of liver hepatocellular carcinoma (LIHC) patients. A total of 52 pyroptosis-associated genes were identified. Then, data for 374 LIHC patients and 50 normal individuals were acquired from the TCGA database. Through gene expression analyses, differentially expressed genes (DEGs) were determined. The 13 pyroptosis-related genes (PRGs) confirmed as potential prognostic factors through univariate Cox regression analysis were entered into Lasso and multivariate Cox regression to build a PRGs prognostic signature, containing four PRGs (BAK1, GSDME, NLRP6, and NOD2) determined as independent prognostic factors. mRNA levels were evaluated by qRT-PCR, while overall survival (OS) rates were assessed by the Kaplan–Meier method. Enrichment analyses were done to establish the mechanisms associated with differential survival status of LIHC patients from a tumor immunology perspective. Additionally, a risk score determined by the prognostic model could divide LIHC patients into low- and high-risk groups using median risk score as cut-off. A prognostic nomogram, derived from the prognostic model and integrating clinical characteristics of patients, was constructed. The prognostic function of the model was also validated using GEO, ICGC cohorts, and online databases Kaplan–Meier Plotter. Small interfering RNA-mediated knockdown of GSDME, as well as lentivirus-mediated GSDME knockdown, were performed to validate that knockdown of GSDME markedly suppressed growth of HCC cells both in vivo and in vitro. Collectively, our study demonstrated a PRGs prognostic signature that had great clinical value in prognosis assessment. [ABSTRACT FROM AUTHOR]

Background: Our study aimed to compare the short-term outcomes between robot-assisted segmentectomy (RAS) and video-assisted segmentectomy (VAS) for small pulmonary nodules. Methods: The study included of 299 segmentectomies (132 RAS and 167 VAS procedures) for small pulmonary nodules between June 2018 and November 2021. The patients were divided into two groups: the RAS group and the VAS group. Propensity score-matching (PSM) analysis was performed to minimize bias. A logistic regression model was performed to identify the independent risk factors associated with complications. Results: Before PSM, the following clinical variables were not balanced: age (P = 0.004), tumor size (P < 0.001), forced expiratory volume for 1 s (FEV1), and FEV1 percentage (P < 0.001). The patients with RAS had a shorter operative time (P = 0.014), less blood loss, a shorter postoperative hospital stay, less use of strong opioids, less drainage on postoperative day 1, and less postoperative total drainage, but more cost (all P < 0.001). Conversion to open surgery was performed for two patients in the VAS group but none in the RAS group. After PSM, 53 pairs were successfully matched. The data again suggested that the patients with RAS had less blood loss, a shorter postoperative hospital stay, and less use of strong opioids, but more cost (all P < 0.001). The operation time also was shorter in the RAS group, with a borderline statistically significant P value (0.053). Conclusions: In our study, RAS had better short-term outcomes than VAS, indicating a safer and more efficient technique than VAS. [ABSTRACT FROM AUTHOR]

Background: Post-stroke depression (PSD) is a common psychiatric complication of mental disorders after stroke. Acupuncture for PSD is effective and has few adverse effects. As a classical complementary and alternative therapy, acupuncture is often used in combination with antidepressants for PSD. However, there is a wide variety of acupuncture therapies, and the efficacy of different acupuncture varies. In this study, a network meta-analysis (NMA) was used to assess the clinical efficacy of different acupuncture combined with antidepressants for the treatment of PSD. Methods: A comprehensive search of PubMed, The Cochrane Library, EMbase, Web of Science, CNKI, CBM, VIP, and Wan-Fang databases for published randomized controlled trials of acupuncture combined with antidepressants for the treatment of PSD was conducted. The time frame for the literature search was from the date of database creation to April 30, 2022. The Cochrane risk of bias tool for randomized trials (RoB 2.0) was used to evaluate the bias risk of the included studies. Data analysis was performed by STATA 14.0 software. Results: A total of 38 literatures with 2,898 patients involving nine acupuncture therapies were included. NMA results were as follows: moxibustion plus antidepressants had the best efficacy in terms of improving total effective rate. Conventional acupuncture plus antidepressants was the most effective in improving HAMD scores. In terms of improving SDS scores, acupressure plus antidepressants was the most effective. In terms of improving NIHSS scores, moxibustion plus antidepressants showed the best results. Conclusion: A comparison of the efficacy indicators of the nine different acupuncture therapies combined showed that moxibustion plus antidepressants, conventional acupuncture plus antidepressants and acupressure plus antidepressants were superior in the treatment of PSD. Based on the shortcomings of the existing studies, this conclusion needs to be validated by additional highquality randomized controlled trials. [ABSTRACT FROM AUTHOR]

The human retina serves as a light detector and signals transmission tissue. Advanced insights into retinal disease mechanisms and therapeutic strategies require a deep understanding of healthy retina molecular events. Here, we sequenced the mRNA of over 0.6 million single cells from human retinas across six regions at nine different ages. Sixty cell sub-types have been identified from the human mature retinas with unique markers. We revealed regional and age differences of gene expression profiles within the human retina. Cell-cell interaction analysis indicated a rich synaptic connection within the retinal cells. Gene expression regulon analysis revealed the specific expression of transcription factors and their regulated genes in human retina cell types. Some of the gene's expression, such as DKK3, are elevated in aged retinas. A further functional investigation suggested that over expression of DKK3 could impact mitochondrial stability. Overall, decoding the molecular dynamic architecture of the human retina improves our understanding of the vision system. [ABSTRACT FROM AUTHOR]

Familial exudative vitreoretinopathy (FEVR) is an inherited blinding disorder; however, the known FEVR‐associated variants account for approximately only 50% cases. Currently, the pathogenesis of most reported variants is not well studied, we aim to identify novel variants from FEVR‐associated genes and perform a comprehensive functional analysis to uncover the pathogenesis of variants that cause FEVR. Using targeted gene panel and Sanger sequencing, we identified six novel and three known variants in TSPAN12 and NDP. These variants were demonstrated to cause significant inhibition of Norrin/β‐catenin pathway by dual‐luciferase reporter assay and western blot analysis. Structural analysis and co‐immunoprecipitation revealed compromised interactions between missense variants and binding partners in the Norrin/β‐catenin pathway. Immunofluorescence and subcellular protein extraction were performed to reveal the abnormal subcellular trafficking. Additionally, over‐expression of TSPAN12 successfully enhanced the Norrin/β‐catenin signaling activity by strengthening the binding affinity of mutant Norrin with FZD4 or LRP5. Together, these observations expanded the spectrum of FEVR‐associated variants for the genetic counseling and prenatal diagnosis of FEVR, as well providing a potential therapeutic strategy for the treatment of FEVR. [ABSTRACT FROM AUTHOR]

The ever-increasing trend of greenhouse gas (GHG) emissions is accelerating global warming and threatening food security. Environmental benefits and sustainable food production must be pursued locally and globally. Thus, a field experiment was conducted in 2015 to understand how to balance the trade-offs between agronomic productivity and environment quality in the North China Plain (NCP). Eight treatments consisted of two factors, i.e., (1) tillage practices: rotary tillage (RT) and no-till (NT), and (2) cropping sequences (CS): maize–wheat–soybean–wheat (MWSW), soybean–wheat–maize–wheat (SWMW), soybean–wheat (SW), and maize–wheat (MW). The economic and environmental benefits were evaluated by multiple indicators including the carbon footprint (CF), maize equivalent economic yield (MEEY), energy yield (EY), and carbon sustainability index (CSI). Compared with NT, RT increased the EY and MEEY, but emitted 9.4% higher GHGs. Among different CSs, no significant reduction was observed in CF. The lowest (2.0 Mg CO2-eq ha−1 year−1) and the highest (5.6 Mg CO2-eq ha−1 year−1) CF values were observed under MW and SWMW, respectively. However, CSs with soybean enhanced MEEY and the net revenue due to their higher price compared to that of MW. Although the highest CSI was observed under RT-MW, soybean-based crop rotation could offset the decline in CSI under NT when compared to that for RT. These findings suggest that conservation agriculture (CA) could enhance the balance in trade-offs between economic and environmental benefits. Additional research is needed on how to achieve high crop production by establishing a highly efficient CA system in the NCP. [ABSTRACT FROM AUTHOR]

NAFLD is a series of liver disorders, and it has become the most prevalent hepatic disease to date. However, there are no approved and effective pharmaceuticals for NAFLD owing to a poor understanding of its pathological mechanisms. While emerging studies have demonstrated that m6A modification is highly associated with NAFLD. In this review, we summarize the general profile of NAFLD and m6A modification, and the role of m6A regulators including erasers, writers, and readers in NAFLD. Finally, we also highlight the clinical significance of m6A in NAFLD. [ABSTRACT FROM AUTHOR]

Simple Summary: Immunogenic cell death (ICD) is an important mechanism underlying anti-cancer therapy response by activating the immune system. However, the landscape and predictive value of ICD among cancers remain to be elucidated. In this study, we carried out a comprehensive analysis integrating genomic, proteomic and epigenetics data across 33 cancer types, 31 normal tissue types and 1406 cancer cell lines. We found that the expression level of ICD-related genes was regulated by methylation and transcriptional regulators. We figured out the most valuable ICD-related markers in predicting prognosis in cancer patients and developed a model for practical use. We also defined the ICD score and found that it was a reliable marker in predicting survival, chemotherapy and immunotherapy across cancer patients. Further exploration using single-cell RNA-seq data indicated that T cell might remodel the tumor microenvironment by turning a "cold" tumor into a "hot" one in an ICD-dependent manner. Moreover, we also discovered several ICD-related therapeutic targets including IGF2BP3 which might benefit cancer patients who could hardly respond to immunotherapy. Immunogenic cell death (ICD), a form of regulated cell death, is related to anticancer therapy. Due to the absence of widely accepted markers, characterizing ICD-related phenotypes across cancer types remained unexplored. Here, we defined the ICD score to delineate the ICD landscape across 33 cancerous types and 31 normal tissue types based on transcriptomic, proteomic and epigenetics data from multiple databases. We found that ICD score showed cancer type-specific association with genomic and immune features. Importantly, the ICD score had the potential to predict therapy response and patient prognosis in multiple cancer types. We also developed an ICD-related prognostic model by machine learning and cox regression analysis. Single-cell level analysis revealed intra-tumor ICD state heterogeneity and communication between ICD-based clusters of T cells and other immune cells in the tumor microenvironment in colon cancer. For the first time, we identified IGF2BP3 as a potential ICD regulator in colon cancer. In conclusion, our study provides a comprehensive framework for evaluating the relation between ICD and clinical relevance, gaining insights into identification of ICD as a potential cancer-related biomarker and therapeutic target. [ABSTRACT FROM AUTHOR]

Free-standing two-dimensional (FS-2D) materials of covalent or ionic bonds can be prepared through mechanical exfoliation by virtue of their intrinsic layered crystal structures. Here, following this strategy, it was reported the fabrication of large-area FS-2D Au films with controllable lattice orientations via an electrochemical hydrogen-detaching method. It was further characterized the catalytic properties of FS-2D Au. The (111)-oriented FS-2D Au with 20 nm in thickness shows a catalytic conversion up to 43.8% for the oxidation of cyclohexane as a model reaction system, a result of more than double of generally reported values. The exceptionally high catalytic activity could be attributed to the flexible structure of the FS-2D Au catalyst, which differs from the rigid structure of general catalysts. The results give useful implications for large-scale productions of a variety of FS-2D metals with controllable orientations, by which their applications may not be confined to catalysis chemistry. [ABSTRACT FROM AUTHOR]

Potato is the most important non-grain food in the world, while late blight caused by Phytophthora infestans seriously threatens the production of potato. Since pathogen-associated molecular patterns (PAMPs) are relatively conserved, PAMP-triggered immunity (PTI) can provide durable resistance to late blight for potato. However, knowledge of the regulatory mechanisms of PTI against oomycete pathogens at protein levels remains limited due to the small number of identified proteins. In the present work, changes in the proteome profile of Nicotiana benthamiana leaves upon P. infestans PAMP induction were examined using the SWATH-MS (sequential windowed acquisition of all theoretical mass spectra) approach, which provides quantification of protein abundances and large-scale identification of PTIrelated proteins. A total of 4401 proteins have been identified, of which 1429 proteins were differentially expressed at least at one time point of 8, 12, 24 and 48 h after PAMP induction, compared with the expression at 0 h when immediately after PAMP induction. They were further analyzed by expression clustering and gene ontology (GO) enrichment analysis. Through functional verification, six novel DEPs of 19 candidates were proved to be involved in PTI responses, including mitochondrial phosphate carrier protein (MPT) 3, vesicleassociated membrane protein (VAMP) 714, lysophospholipase (LysoPL) 2, ascorbate peroxidase (APX) 1, heat shock 70 kDa protein (HSP) 2 and peptidyl-prolyl cis-trans isomerase FKBP (FKBP) 15-1. Taken together, the time course approach and the resulting large-scale proteomic analyses have enlarged our understanding of PTI mechanisms and provided a valuable resource for the discovery of complex protein networks involved in the resistance response of potato to late blight. [ABSTRACT FROM AUTHOR]

Trichomes are differentiated epidermal cells and exist on above-ground organs of nearly all land plants with important roles in resistance to a wide range of biotic and abiotic stresses. We attempted to obtain candidate gene (s) for Hairy glume (Hg), responsible for the trichome on wheat glume, by using bulked segregant exome capture sequencing (BSE-Seq), while Hg was only mapped in 0.52-3.26 Mb of 1AS. To further fine map this gene and identify candidate genes in this region, a near isogenic line-derived population consisting of 2,050 F2 lines was generated in the present study. By analyzing this population, Hg was fine mapped into a 0.90 cM region covering a physical distance of ~825.03 Kb encompassing 6 high- and 23 low-confidence genes in the reference genome of Chinese Spring. A presence-absence variation was identified in the fine mapping region through analyses of sequence-tagged sites markers and genome sequences of the hairy glume parent of the near isogenic lines. The results presented here will be useful for further cloning Hg in wheat. [ABSTRACT FROM AUTHOR]

Combined inhibition of vascular endothelial growth factor receptor (VEGFR) and the programmed cell death protein 1 (PD-1) pathways has shown efficacy in multiple cancers; however, the clinical outcomes show limited benefits and the unmet clinical needs still remain and require improvement in efficacy. Using murine colon carcinoma (CT26) allograft models, we examined the efficacy and elucidated novel tumor microenvironment (TME) remodeling mechanisms underlying the combination of chidamide (a benzamide-based class l histone deacetylase inhibitor; brand name in Taiwan, Kepida®) with VEGF receptor tyrosine kinase inhibitor (TKIs; cabozantinib/regorafenib, etc.) and immune checkpoint inhibitors (ICIs; anti-PD-1/anti-PD-L1/anti-CTLA-4 antibodies). The TME was assessed using flow cytometry and RNA-sequencing to determine the novel mechanisms and their correlation with therapeutic effects in mice with significant treatment response. Compared with ICI alone or cabozantinib/regorafenib + ICI, combination of chidamide + cabozantinib/regorafenib + ICI increased the tumor response and survival benefits. In particular, treatment of CT26-bearing mice with chidamide + regorafenib + anti-PD-1 antibody showed a better objective response rate (ORR) and overall survival (OS). Similar results were observed in anti-PD-1 treatment-resistant mice. After treatment with this optimal combination, in the TME, RNA-sequencing revealed that downregulated mRNAs were correlated with leukocyte migration, cell chemotaxis, and macrophage gene sets, and flow cytometry analysis showed that the cell numbers of myeloid-derived polymorphonuclear suppressor cells and tumor-associated macrophages were decreased. Accordingly, chidamide + regorafenib + anti-PD-1 antibody combination therapy could trigger a novel TME remodeling mechanism by attenuating immunosuppressive cells, and restoring T-cell activation to enhance ORR and OS. Our studies also showed that the addition of Chidamide to the regorafenib + anti-PD-1 Ab combination could induce a durable tumor-specific response by attenuating immune suppression in the TME. In addition, this result suggests that TME remodeling, mediated by epigenetic immunomodulator combined with TKI and ICI, would be more advantageous for achieving a high objective response rate, when compared to TKI plus ICI or ICI alone, and maintaining long-lasting antitumor activity. [ABSTRACT FROM AUTHOR]

The overall structure of a network is determined by its micro features, which are different in both syntactic and non-syntactic networks. However, the fact that most language networks are small-world and scale-free raises the question: does syntax play a role in forming the scale-free feature? To answer this question, we build syntactic networks and co-occurrence networks to compare the generation mechanisms of nodes, and to investigate whether syntactic and non-syntactic factors have distinct roles. The results show that frequency is the foundation of the scale-free feature, while syntax is beneficial to enhance this feature. This research introduces a microscopic approach, which may shed light on the scale-free feature of language networks. [ABSTRACT FROM AUTHOR]