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Objective·To investigate the effects of trimethylamine oxide (TMAO) on cardiac function in mice with hypertrophic cardiomyopathy (HCM) and its potential molecular mechanism.Methods·Mice with myosin heavy chain 6 (Myh6) c.1211G>A (p.R404Q+/-) point mutation were used as the animal model. According to dietary supplementation of TMAO and TMAO inhibitor iodomethylcholine (IMC), the wild type (WT) mice and HCM mice were divided into WT group, HCM group (HCM-1 group, HCM-2 group), WT+TMAO group, HCM+TMAO group and HCM+IMC group, respectively. Left ventricular fraction shortening (FS) and left ventricular posterior wall thickness (LVPW) were assessed by echocardiography in all mice. Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum TMAO concentration of mice in the HCM-1 group and WT group. The regularity of myocardial cell arrangement of mice was evaluated by hematoxylin and eosin staining (HE staining). The proportion of myocardial fibrosis was evaluated by Masson staining. The activity of protein kinase A (PKA) in mouse myocardial tissue was detected by PKA kit. The expression of ryanodine receptor 2 (RyR2) and p-RyR2(S2808) in mouse myocardial tissue was detected by Western blotting.Results·The results of echocardiography showed that at 12 months of age, the FS of mice in the WT+TMAO group and HCM+TMAO group were lower than those in the corresponding WT group and HCM-1 group, respectively (P

How to effectively maintain costly intra-group cooperation has always been a topic of great concern in society. As we all know, inter-group competition is a constructive way to promote intra-group cooperation. Previous inter-group competition mechanisms are primarily based on the total contribution value of all individuals in the group in the current round, which ignore the historical behavior of the group and its members. For comparison, we argue that the introduction of collective reputation which reflects not only the total contribution of the groups in the current round but also the group's historical behavior is necessary for the construction of an inter-group competition model. Furthermore, an excellent collective reputation can help the group obtain more high-quality resources and help the group stand out from the competition. To this end, we introduce a new mechanism of inter-group transfer payment driven by collective reputation and construct a public goods game (PGG) model of inter-group competition to study the dynamic behavior of intra-group cooperation evolution. Two parameters, the proportion of accepted groups a and the proportion of transferred groups b , are introduced. The simulation results suggest that the effectiveness of this model in promoting cooperation depends largely on the joint settings of a and b. And in most cases, the combination of small a and medium b plays the significant role. [ABSTRACT FROM AUTHOR]

Background: Pulmonary rehabilitation (PR) has been recognized to be an effective therapy for chronic obstructive pulmonary disease (COPD). However, in China, the application of PR interventions is still less promoted. Therefore, this cross-sectional study aimed to understand COPD patients' intention to receive PR, capture the potential personal, social and environmental barriers preventing their willingness of receiving PR, and eventually identify demanding PR services with the highest priority from patients' point of view. Methods: In total 237 COPD patients were recruited from 8 health care facilities in Zhejiang, China. A self-designed questionnaire was applied to investigate patients' intention to participate in PR and potentially associated factors, including personal dimension such as personal awareness, demographic factors, COPD status and health-related literacy/behaviors, as well as social policies and perceived environmental barriers. The demand questionnaire of PR interventions based on the Kano model was further adopted. Results: Among the 237 COPD patients, 75.1% of COPD patients were willing to participate in PR interventions, while only 62.9% of the investigated patients had heard of PR interventions. Over 90% of patients believed that the cost of PR services and the ratio of medical insurance reimbursement were potential obstacles hindering them from accepting PR services. The multiple linear regression analysis indicated that the PR skills of medical staff, knowledge promotion and public education levels of PR in the community, patients' transportation concerns and degree of support from family and friends were significantly associated with willingness of participation in PR interventions. By using the Kano model, the top 9 most-requisite PR services (i.e., one-dimensional qualities) were identified from patients' point of view, which are mainly diet guidance, education interventions, psychological interventions and lower limb exercise interventions. Subgroup analysis also revealed that patients' demographics, such as breathlessness level, age, education and income levels, could influence their choice of priorities for PR services, especially services related to exercise interventions, respiratory muscle training, oxygen therapy and expectoration. Conclusions: This study suggested that PR-related knowledge education among patients and their family, as well as providing basic package of PR services with the most-requisite PR items to COPD patients, were considerable approaches to promote PR attendance in the future. [ABSTRACT FROM AUTHOR]

objective*To screen new potential pathogenic genes in the course of esophageal squamous cell carcinoma. Methods*The data of miRNA chips GSE122497 and GSE164174 were obtained by GEO database. The differential mirnas of esophageal cancer patients and healthy people were screened by GEO2R, and the intersection was obtained by Venn Diagram Webtool. Target Scan tool and DIANATOOLS tool were used to predict the target genes of differential miRNA, and the intersection of predicted target genes of the two tools was used for gene function analysis. The protein interactions of target genes were analyzed by using STRING tool and Hub genes were selected. Results*(1) A total of 108 differential miRNAs were detected in the chip. (2) After taking the intersection of Target Scan tool and DIANATOOLS tool, there were 1 354 different target genes. (3) Gene Ontology (GO) analysis showed that gene functions of differential target genes were significantly enriched in biological processes such as DNA template transcriptional regulation and RNA polymerase II promoter transcriptional regulation, as well as RNA polymerase II core promoter proximal sequence specific DNA binding, protein binding, metal ion binding and other molecular functions. It mainly existed in nucleus, cytoplasm, cytoplasm and other cellular components. In descending order of the number of enriched genes, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the above genes were significantly enriched in tumor pathway, MAPK signaling pathway, stem cell pluripotency regulation signaling pathway, etc. (4) There were 1 326 nodes and 2 300 edges in the protein interaction network, and the average node connectivity was 3.47. The selected Hub genes were SMAD specific E3 ubiquitin protein ligase 2 (SMURF2), β-transducin repeat containing E3 ubiquitin protein ligase (BTRC), SMAD specific E3 ubiquitin protein ligase 1 (SMURF 1), ubiquitin conjugating enzyme E2 D1 (UBE2D1), and cullin 2 (CUL2). Previous studies have shown that the above genes are related to ubiquitination. Conclusion*SMURF2, BTRC, SMURF1, UBE2D1 and CUL2 genes screened from GEO database may be involved in the disease process of esophageal squamous cell carcinoma through the ubiquitin of targeted regulatory proteins. [ABSTRACT FROM AUTHOR]

Eutrophication, dredging, agricultural and urban runoffs, and epiphyte overgrowth could reduce light availability for seagrass. This may affect "blue carbon" stocks in seagrass beds. However, little research is available on the effect of light intensities on carbon sequestration capacity in seagrass beds, especially small-bodied seagrasses. The dominant seagrass Halophila beccarii , a vulnerable species on the IUCN Red List, was cultured in different light intensities to examine the response of vegetation and sediment carbon in seagrass beds. The results showed that low light significantly reduced leaf length and above-ground biomass, while carbon content in both above-ground and below-ground tissues were not affected. Low light reduced both the above-ground biomass carbon and the total biomass carbon. Interestingly, while under saturating light conditions, the subsurface and surface carbon content was similar, under low light conditions, subsurface sediment carbon was significantly lower than the surface content. The reduction of subsurface sediment carbon might be caused by less release flux of dissolved organic carbon from roots in low light. Taken together, these results indicate that reduced light intensities, to which these meadows are exposed to, will reduce carbon sequestration capacity in seagrass beds. Measures should be taken to eliminate the input of nutrients on seagrass meadows and dredging activities to maintain the "blue carbon" storage service by enhancing light penetration into seagrass. [ABSTRACT FROM AUTHOR]

This study aimed to identify the specimen type that has high positivity and its proper sampling time for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing to promote diagnostic efficiency. All SARS-CoV-2-infected patients with a laboratory-confirmed diagnosis in Zhoushan City were followed up for viral shedding in respiratory tract specimens and faecal samples. Positivity was analysed both qualitatively and quantitatively by proper statistical approaches with strong testing power. Viral shedding in respiratory tract and faecal specimens was prolonged to 45 and 40 days after the last exposure, respectively. The overall positive rate in respiratory tract specimens was low and relatively unstable, being higher in the early-to-mid stage than in the mid-to-late stage of the disease course. Compared with respiratory tract specimens, faecal samples had a higher viral load, higher overall positive rate, and more stable positivity in different disease courses and varied symptomatic status. Faecal specimens have the potential ability to surpass respiratory tract specimens in virus detection. Testing of faecal specimens in diagnosis, especially for identifying asymptomatic carriers, is recommended. Simultaneously, testing respiratory tract specimens at the early-to-mid stage is better than testing at the mid-to-late stage of the disease course. A relatively small sample size was noted, and statistical approaches were used to address it. Information was missing for both specimen types at different stages of the disease course due to censored data. Our research extends the observed viral shedding in both specimen types and highlights the importance of faecal specimen testing in SARS-CoV-2 diagnosis. Healthcare workers, patients, and the general public may all benefit from our study findings. Disposal of sewage from hospitals and residential areas should be performed cautiously because the virus sheds in faeces and can last for a long time. [ABSTRACT FROM AUTHOR]

Cooperation is ubiquitous in real world, even in a fierce competitive environment, which is in contrast with natural selection theory. To address this contradiction, many scholars pay more attention to researching the emergence and maintenance of cooperation. In recent decades, lots of mechanisms about individual behavior are put forward to promote cooperation in spatial prisoner's dilemma game. However, fewer studies focus on the effects of behavior inertia on cooperation. For example, insistence is the key to habit formation, and every extra day you insist, the more motivation you have to keep going, the bigger the inertia of the same behavior is, and the weaker the intention you have to make a change. In other words, it is easier to insist than to change. To this end, we propose a new mechanism, called inertia mechanism of individual behavior to explore the evolution of cooperation, in which each player's behavior inertia relies on the persistence of his/her current strategy: the longer the strategy duration is, the bigger his/her behavior inertia is, and, as a result, the weaker the willingness he/she has to update strategy. Moreover, a reinforcement parameter, α, which characterizes the degree of the impact of the strategy persistence on the behavior inertia, is introduced. The results of numerical simulation show that our inertia mechanism can promote cooperation effectively, compared with the traditional model, and the mechanism performs better with the decrease of α. [ABSTRACT FROM AUTHOR]

Exploring the emergence and maintenance of cooperation in social dilemma is valuable and it arises considerable concerns of many researchers. In this paper, we propose a mechanism to promote cooperation, called benefit community, in which cooperators linking together form a common benefit community and all their payoffs obtained from game are divided coequally. The robustness of conclusions is tested for the PDG (prisoners' dilemma game) on square lattice and WS small world network. We find that cooperation can be promoted by this typical mechanism, especially, it can diffuse and prevail more easily and rapidly on the WS small world network than it on the square lattice, even if a big temptation to defect b. Our research provides a feasible direction to resolve the social dilemma. [ABSTRACT FROM AUTHOR]

Considering congestion effects in realistic network environments, we give a new method to adjust dynamically adjust the weight of the congested edge. We calculate the load on an edge based on the revised betweenness method and propose a novel model with three states of edges to investigate the dynamics of cascading failures in the ring network, the BA scale-free network, and the real traffic networks in London. By two robust metrics, we surprisingly observe the abnormal dynamics of cascading propagation, especially compared with that in the unadjustable weight, the curves of cascading dynamics in the adjustable weight are more irregular, which means that enhancing the capacity of each edge is not always better to avoid the cascading propagation. In addition, our simulation results show that the dynamical change of the edge's weight makes the heterogeneous BA networks more vulnerable. [ABSTRACT FROM AUTHOR]

In repeated games, historical interactions lead to varying environment. Among existing studies, the variation of environment or game is basically considered from the perspective of nodes, while in pairwise game, it is more reasonable to consider the interactive environment from the perspective of edges. In addition, since historical interactive experience of pairwise players has an impact on the current interactive environment, the duration of pairwise strategies produces differentiated results. Therefore, we consider the persistence-dependent dynamic interactive environment where the persistence of pairwise strategy affects the weight between two interacting players, and the game resource of interactive environment is influenced by varying weight. The results suggest that the introduction of persistence-dependent dynamic interactive environment can effectively enhance cooperation, and a larger weight increment of CD link generates a higher cooperation level as it indicates that the reward for cooperative behavior is significant, although a single cooperator for the pairwise interacting players. • We introduce the persistence-dependent dynamic interactive environment in prisoner's dilemma game. • An intermediate variable, weight, is introduced and influenced by the strategy persistence of pairwise players. • The fluctuation scale of weight is dependent on distinct kinds of edge links, and a parameter η for CD link is introduced. • The variation of weight determines the changing resources for the interactive environment. • Our new model can boost cooperation significantly, especially for the larger η. [ABSTRACT FROM AUTHOR]

In previous studies about heterogeneous investment, many researchers only focus on the monodirectional effect of reputation, but ignore the reversed influence about the heterogeneity of reputation fluctuation driven by investment. Given this, considering the interplay between reputation and heterogeneous investment, we explore the evolution of cooperation in public goods game. In detail, each player's reputation situations in different groups determine its differentiated investment amounts, and in turn, the heterogeneity of reputation fluctuation is dependent on how much it invests into each group. Furthermore, we introduce two parameters, α and β , to characterize the effect degree of investment on heterogeneous reputation fluctuation and the one of reputation on heterogeneous investment, respectively. The simulation results suggest that cooperation can be boosted to some extent, especially for the larger α and β , as they magnify the interplay of reputation and heterogeneous investment. • We introduce the interplay between reputation and heterogeneous investment in the public goods game. • Reputation effects unequal investment and heterogeneous reputation fluctuation is effected by investment in turn. • We introduce parameter α to characterize the effect degree of investment on heterogeneous reputation fluctuation. • Parameter β is presented to denote the effect degree of reputation on heterogeneous investment. • Our new model can boost cooperation significantly, especially for the larger α and β. [ABSTRACT FROM AUTHOR]

• A reputation-based strategy persistence mechanism in evolutionary game is proposed. • Our mechanism illuminates that the scale of reputation fluctuation totally depends on the persistence of last strategy. • A parameter, α , illustrating the impact of strategy persistence on reputation variation, is introduced. • Cooperation can be promoted effectively by our new mechanism. Understanding the emergence and maintenance of cooperation in social dilemma has received a lot of attention. In previous research, many scholars found that the reputation mechanism can promote cooperation, and the variation of reputation is consistent. However, in reality, according to both one's current action and past experiences, every individual's impression from others is modified to varying extent everyday. In other words, the length of duration of the same performance influences the diverse scale of their own reputation fluctuation. Therefore, a reputation-based strategy persistence mechanism, in which the increment of current reputation is determined by the persistence of last strategy, is proposed. Moreover, we introduce a parameter α to illustrate the impact of strategy persistence on reputation variation. The results of simulation show that the new mechanism paves the way for cooperation in evolutionary game, and the smaller α is, the better the mechanism performs. [ABSTRACT FROM AUTHOR]

In previous studies of evolutionary games, players change reference objects at each time step. However, in real life, many people tend to consistently imitate outstanding role models instead of changing reference objects frequently. From this, a persistent imitation rule is proposed. In detail, a persistent imitator will persist in imitating his or her reference object until the wealth exceeds that of the reference object or the duration of continuous imitation exceeds a specific value. Furthermore, to reflect inter-individual differences, we divide the players into two categories, persistent imitators and random imitators. The simulation suggests that the presence of a high proportion of persistent imitators has a significant effect on the development of cooperation, and the level of cooperation increases as the maximum duration of imitation increases. However, when the proportion of persistent imitators or the maximum duration of imitation is small, the promotion effect on cooperation is not obvious. • The persistent imitation of reference objects is proposed. • Persistent imitators refresh the role model if their payoff exceeds the last one's. • After the maximum duration, the persistent imitator chooses a new reference object. • The presence of persistent imitators can effectively facilitate cooperation. [ABSTRACT FROM AUTHOR]

Robotic surgery is known as the "third technological revolution" in the field of surgery, and is an important milestone in the development of modern surgery. However, our country's innovative surgical robot industry is still in its early stages, and it is only being utilized in certain surgical fields. To explore the effectiveness of the application of domestic surgical robot in oral and maxillofacial surgery, the author successfully completed a case of benign parotid tumor resection with the assistance of a domestic autonomous robot. The operation was successful, facial nerve function was preserved, and postoperative wound healing was good.

Purpose: To investigate information-seeking behavior related to urticaria before and during the COVID-19 pandemic in China., Methods: Search query data for terms related to urticaria were retrieved using Baidu Index database from October 23, 2017 to April 23, 2022, and daily COVID-19 vaccination doses data were obtained from the website of the Chinese Center for Disease Control and Prevention. Among the 23 eligible urticaria search terms, four urticaria themes were generated as classification, symptom, etiology, and treatment of urticarial, respectively. Baidu Search Index (BSI) value for each term were extracted to analyze and compare the spatial and temporal distribution of online search behavior for urticaria before and after the COVID-19 pandemic, and to also explore the correlation between search query and daily COVID-19 vaccination doses., Results: The classification of urticaria accounted for nearly half of the urticaria queries on the internet. Regular seasonal patterns of BSI were observed in urticaria-related online search, by attaining its highest level in spring and summer and lowest level in winter. The BSIs of all urticaria themes significantly increased after the COVID-19 pandemic than that before the pandemic (all P <0.05). Xizang, Qinghai and Ningxia are the most active geographical areas for increased urticaria-searching activities after the COVID-19 pandemic. There was also a significant positive correlation between daily BSIs and daily COVID-19 vaccination doses in each urticaria theme. Cross-correlation analysis found that the search of symptom, etiology, and treatment attained their strongest correlation with daily COVID-19 vaccination doses at 11-27 days before the injection of vaccine, imply vaccination hesitation related to concerns of urticaria., Conclusions: This study used the internet as a proxy to provide evidence of public search interest and spatiotemporal characteristics of urticaria, and revealed that the search behavior of urticaria have increased significantly after the COVID-19 pandemic and COVID-19 vaccination. It is anticipated that the findings about such increase in search behavior, as well as the behavior of urticaria-related vaccine-hesitancy, will help guide public health education and policy regulation., 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, Yu, He, Yao, He, Wu, Xu and Ye.)

The mutant form of the guanosine triphosphatase (GTPase) KRAS is a key driver in human tumors but remains a challenging therapeutic target, making KRAS MUT cancers a highly unmet clinical need. Here, we report a class of bottlebrush polyethylene glycol (PEG)-conjugated antisense oligonucleotides (ASOs) for potent in vivo KRAS depletion. Owing to their highly branched architecture, these molecular nanoconstructs suppress nearly all side effects associated with DNA-protein interactions and substantially enhance the pharmacological properties of the ASO, such as plasma pharmacokinetics and tumor uptake. Systemic delivery to mice bearing human non-small-cell lung carcinoma xenografts results in a significant reduction in both KRAS levels and tumor growth, and the antitumor performance well exceeds that of current popular ASO paradigms, such as chemically modified oligonucleotides and PEGylation using linear or slightly branched PEG. Importantly, these conjugates relax the requirement on the ASO chemistry, allowing unmodified, natural phosphodiester ASOs to achieve efficacy comparable to that of chemically modified ones. Both the bottlebrush polymer and its ASO conjugates appear to be safe and well tolerated in mice. Together, these data indicate that the molecular brush-ASO conjugate is a promising therapeutic platform for the treatment of KRAS -driven human cancers and warrant further preclinical and clinical development.