Search

Simple Summary: Myomaker has been reported to play an important role in regulating myoblast fusion. However, the role of Myomaker gene in skeletal muscle growth in economic fish during post-hatching stage is unclear. This study showed that the growth of Chinese perch was significantly decreased when Myomaker was inhibited by Myomaker-siRNA. Furthermore, both the diameter of muscle fibers and the number of nuclei in single muscle fibers were significantly reduced in the Myomaker-siRNA group, whereas, there was no significant difference in the number of proliferating cells between the control and Myomaker-siRNA groups. Together, these findings indicate that Myomaker may promote the hypertrophy of muscle fibers and growth of fast muscle in Chinese perch by promoting myoblast fusion. The fusion of myoblasts is a crucial stage in the growth and development of skeletal muscle. Myomaker is an important myoblast fusion factor that plays a crucial role in regulating myoblast fusion. However, the function of Myomaker in economic fish during posthatching has been poorly studied. In this study, we found that the expression of Myomaker in the fast muscle of Chinese perch (Siniperca chuatsi) was higher than that in other tissues. To determine the function of Myomaker in fast muscle, Myomaker-siRNA was used to knockdown Myomaker in Chinese perch and the effect on muscle growth was determined. The results showed that the growth of Chinese perch was significantly decreased in the Myomaker-siRNA group. Furthermore, both the diameter of muscle fibers and the number of nuclei in single muscle fibers were significantly reduced in the Myomaker-siRNA group, whereas there was no significant difference in the number of BrdU-positive cells (proliferating cells) between the control and the Myomaker-siRNA groups. Together, these findings indicate that Myomaker may regulate growth of fast muscle in Chinese perch juveniles by promoting myoblast fusion rather than proliferation. [ABSTRACT FROM AUTHOR]

Cancer is a heterogeneous disease. Although both tumor metabolism and tumor immune microenvironment are recognized as driving factors in tumorigenesis, the relationship between them is still not well-known, and potential combined targeting approaches remain to be identified. Here, we demonstrated a negative correlation between the expression of NAMPT, an NAD+ metabolism enzyme, and PD-L1 expression in various cancer cell lines. A clinical study showed that a NAMPTHigh PD-L1Low expression pattern predicts poor prognosis in patients with various cancers. In addition, pharmacological inhibition of NAMPT results in the transcription upregulation of PD-L1 by SIRT-mediated acetylation change of NF-κB p65, and blocking PD-L1 would induce NAMPT expression through a HIF-1-dependent glycolysis pathway. Based on these findings, we designed and synthesized a dual NAMPT/PD-L1 targeting compound, LZFPN-90, which inhibits cell growth in a NAMPT-dependent manner and blocks the cell cycle, subsequently inducing apoptosis. Under co-culture conditions, LZFPN-90 treatment contributes to the proliferation and activation of T cells and blocks the growth of cancer cells. Using mice bearing genetically manipulated tumors, we confirmed that LZFPN-90 exerted target-dependent antitumor activities, affecting metabolic processes and the immune system. In conclusion, our results demonstrate the relevance of NAD+-related metabolic processes in antitumor immunity and suggest that co-targeting NAD+ metabolism and PD-L1 represents a promising therapeutic approach. Synopsis: The proposed interaction of NAMPT and PD-L1 and their dual targeting by LZFPN-90 were explored, raising the possibility that the pharmacological blockade of NAMPT and simultaneous immune checkpoint blockade represent a promising strategy for cancer therapy. The expression of PD-L1 and NAMPT is negatively correlated by epigenetic and glycolysis regulatory mechanisms. Pharmacological inhibition of NAMPT results in the transcription upregulation of PD-L1 by SIRT-mediated acetylation change of NF-κB p65. Blocking PD-L1 induces NAMPT expression through a HIF-1-dependent glycolysis pathway. The PD-1/PD-L1 interaction and NAMPT activity are effectively inhibited by the dual NAMPT/PD-L1 targeting compound LZFPN-90. The proposed interaction of NAMPT and PD-L1 and their dual targeting by LZFPN-90 were explored, raising the possibility that the pharmacological blockade of NAMPT and simultaneous immune checkpoint blockade represent a promising strategy for cancer therapy. [ABSTRACT FROM AUTHOR]

Understanding the biotic mechanisms of community stability in variable environments has been a focal point of fundamental ecological research. A multitude of mechanisms, encompassing compensatory dynamics arising from negative species covariance, portfolio effect linked to species richness and evenness, and dominant species stability, have been found to collectively enhance community stability. However, it is not clear how their stabilizing effects change and contribute to the maintenance of community stability along environmental gradients. We performed a ten-year investigation in a large shallow lake with a eutrophic gradient across space. With the dataset, we quantified the role of the three stability mechanisms, and their changes in effect size along the eutrophic gradient to determine their relative importance in biomass stability. Our results showed that the biomass stability shifted from one stable state at eutrophic sites to another stable state at hypertrophic sites, and biomass stability was positively correlated with composition stability. In the relatively stable state, biomass stability exhibited a closely synchronized variation along with compositional stability in response to environmental changes. Conversely, in the unstable state, biomass stability displayed weaker sensitivity to environmental changes compared to compositional stability. The effect sizes of different biotic mechanisms of biomass stability varied across the eutrophic gradient. Compensatory dynamics emerged as the primary force governing biomass stability in eutrophic waters, overshadowing the relatively weak impact of the portfolio effect, which might help resist the shift from turbid state to clear state with decreasing nutrient concentrations. However, as nutrient levels increased, the primary force shifted from compensatory dynamics toward the dominant species stability. This study improves our understanding for the biotic mechanisms of phytoplankton community responding to nutrients mitigation in eutrophic waters, which might be one of the most important ecological components for managing communities to maintain ecosystem functioning. [ABSTRACT FROM AUTHOR]

Air pollution and lake eutrophication have led to a reduction in incident total radiation and water transparency in many lakes, resulting in a decrease in available underwater light. This reduction in available light depends significantly on the dynamics of spring phytoplankton communities. However, the process and mechanisms behind these effects are not yet well understood. In this study, we conducted a field mesocosm experiment to observe the responses of the phytoplankton community to varying levels of light intensity (100%, 85%, and 65% photosynthetically active radiation, PAR). Our study revealed that reducing PAR resulted in an earlier peak of cyanobacterial biomass in spring, while the biomass of chlorophytes and bacillariophytes declined with decreasing light intensity. The weakening of light intensity promoted the recovery of photosynthetic activity in cyanobacteria but reduced the photosynthetic activity in chlorophytes and bacillariophytes. Additionally, the decrease in light intensity reduced the diversity of phytoplankton communities, accelerating the rate of species turnover. However, the rate of species turnover slowed down as the dominance of cyanobacteria was established in the later stages of the experiment. Therefore, the weakening of light intensity is beneficial to the early establishment of the dominance of cyanobacteria in the phytoplankton community structure, accelerating the succession process of phytoplankton community. These findings contribute to the exploration of the effects of reduced light intensity on the establishment of cyanobacterial dominance in spring, providing valuable insights for the management of lake ecosystems. [ABSTRACT FROM AUTHOR]

Purpose: Sleep disturbances exacerbate the progression of Alzheimer's disease (AD), but disturbances of non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep may have different effects. Neurofilament light chain (NfL), an axon-specific protein, is an indicator of the severity of neuronal apoptosis. To investigate whether or not NREM or REM sleep is crucial to neuronal survival, we examined the effects of induced NREM or REM sleep loss on NfL levels in APP/PS1 mice, a model of AD, and their wild-type (WT) C57BL/6 J littermates. Methods: At 6 months of age, WT mice and AD mice were equally divided into six groups, namely, the WT-normal sleep (S), WT-total sleep deprivation (TSD), WT-REM deprivation (RD), AD-S, AD-TSD and AD-RD groups, according to the type of sleep intervention applied. All mice underwent 6 days of sleep intervention. Cerebrospinal fluid (CSF) and plasma NfL levels were measured at baseline and on days 2, 4 and 6, and spatial memory was assessed in the Morris water maze (MWM) test. Results: Among the 18 WT and 18 AD mice, CSF and plasma NfL levels were higher in AD-TSD mice than in AD-S or AD-RD mice, while no significant difference was observed between the latter two groups. In AD-TSD mice, CSF and plasma NfL levels increased with the duration of sleep deprivation. A similar pattern of results was observed for the WT groups. Conclusions: NREM sleep loss may increase CSF and plasma NfL levels in both WT and AD mice. [ABSTRACT FROM AUTHOR]

With the flourishing development of the urban metro system, the topology of important nodes changes as the metro network structure evolves further. The identical important node has distinct impacts on various metro networks' resilience. At present, the dynamic influences of important station evolution on the resilience of metro networks remain to be studied further. Taking Shenzhen Metro Network (SZMN) as an example, the dynamic influences of the structure evolution of important nodes on the resilience of the metro network were investigated in this study. Firstly, the dynamic evolution characteristics of complex network topology and node centralities in metro systems were mined. Then, combined with the node interruption simulation and the resilience loss triangle theory, the resilience levels of distinct metro networks facing the failure of the same critical node were statistically assessed. Additionally, suggestions for optimal network recovery strategies for diverse cases were made. Finally, based on the evaluation results of node importance and network resilience, the dynamic influences of the topological evolution of important nodes on the resilience of metro networks were thoroughly discussed. The study's findings help us comprehend the metro network's development features better and can assist the metro management department in making knowledgeable decisions and taking appropriate action in an emergency. This study has theoretical and practical significance for the resilient operation and sustainable planning of urban metro network systems. [ABSTRACT FROM AUTHOR]

An urban metro network is susceptible to becoming vulnerable and difficult to recover quickly in the face of an unexpected attack on account of the system's complexity and the threat of various emergencies. Therefore, it is necessary to assess the resilience of urban metro networks. However, the research on resilience assessment of urban metro networks is still in the development stage, and it is better to conduct said research using a technique which combines many attributes, multiple methods, and several cases. Therefore, based on the complex network modeling and topological characteristics analysis of metro systems, a metro network's robustness and vulnerability measurement method under node interruption and edge failure is proposed for the first time in this study. Then, considering the three cases of general station interruption, interchange station interruption, and traffic tunnel failure, a quantitative resilience assessment model of metro networks is put forward, and the corresponding recovery strategies are discussed. Finally, a case study of the Zhengzhou Metro Network (ZZMN) under an extreme rainstorm is conducted to demonstrate the viability of the proposed model. The results show that ZZMN possesses scale-free and small-world network properties, and it is robust to random interruptions but vulnerable to deliberate attacks. ZZMN still needs to improve its effectiveness in information transmission. The centrality distribution for each node in the ZZMN network differs significantly, and each node's failure has a unique impact on the network. The larger the DC, BC, and PR of a node is, the lower the network's robustness after its removal is, and the stronger the vulnerability is. Compared with the three cases of general station interruption, interchange station interruption, and traffic tunnel failure, the network loss caused by tunnel failure was the lowest, followed by general station interruption, and the interruption at interchange stations was the most costly. Given the failures under various cases, the metro management department should prioritize selecting the optimal recovery strategy to improve the resilience of the metro network system. This study's findings can assist in making urban metro systems less vulnerable to emergencies and more resilient for a quick recovery, which can provide scientific theoretical guidance and decision support for the safety and resilient, sustainable development of urban metro systems. [ABSTRACT FROM AUTHOR]

With the prosperous development of the urban metro network, the characteristics of the topological structure and node importance are changing dynamically. Most studies focus on static comparisons, and dynamic evolution research is rarely conducted. It is necessary to track the dynamic evolution mechanism of the metro network from the perspective of development. In this paper, the Shenzhen Metro Network (SZMN) topology from 2004 to 2021 was first modeled in Space L. Five kinds of node centralities in eight periods were measured. Then, the dynamic evolution characteristics of the SZMN network topology and node centralities were compared. Finally, an improved multi-attribute decision-making method (MADM) was used to evaluate the node importance, and the spatiotemporal-evolution mechanism of the node importance was discussed qualitatively and quantitatively. The results show that, with the spatiotemporal evolution of the SZMN, the nodes became more and more intensive, and the network tended to be assortative. The different kinds of node centralities changed variously over time. Moreover, the node importance of the SZMN gradually dispersed from the core area of Chegongmiao–Futian to the direction of the Airport and Shenzhen North. The node importance evolves dynamically over time, and it is closely related to the changes in the node type, surrounding nodes and whole network environment. This study reveals the dynamic evolution mechanism of the complex topology and node importance in the SZMN, which can provide scientific suggestions and decision support for the planning, construction, operation management and resilient sustainable development of the urban metro. [ABSTRACT FROM AUTHOR]

Harmful cyanobacterial blooms in eutrophic water bodies pose a major threat to the environment and to human health. The morphological functional traits of cyanobacteria play important roles in maintaining their competitive advantages. To explore the regulatory mechanisms of the morphological functional traits of different bloom-forming cyanobacteria, we performed a one-year-long phytoplankton survey from November 2016 to October 2017 in Lake Chaohu, China. The colony size and cell diameter of the dominant cyanobacteria were measured, and their relationships were analyzed. The results showed that Dolichospermum flos-aquae and Microcystis aeruginosa were the dominant cyanobacteria in the lake. Microcystis was the dominant species during the summer; the growth of Dolichospermum growth surpassed that of Microcystis, and Dolichospermum became the dominant species in the late autumn, winter and spring. From winter to spring, the colony size of Dolichospermum decreased from 222.25 μm to 10.51 μm, and the individual cell diameter increased from 6.5 μm to 7.4 μm. From summer to autumn, Dolichospermum showed enlarged colony sizes and reduced cell diameters. The Microcystis colony size increased from 83.71 μm in the spring to 196.71 μm in the summer and autumn, while cells diameter remained essentially at 3–4 μm from March to October in Lake Chaohu. The relationship between colony size and cell diameter in Dolichospermum was significantly positive, while that of Microcystis was not significant. These results suggest that Dolichospermum may maintain biomass through a trade-off between cell diameter and colony size, and that a flexible morphological regulatory mechanism exists. This study seeks to improve our understanding of how bloom-forming cyanobacteria maintain their dominance by regulating their morphological traits. [ABSTRACT FROM AUTHOR]

Background: Irritable bowel syndrome (IBS) is a functional gut disease characterized by visceral hypersensitivity and gut motor dysfunction. Serotonin (5-hydroxytryptamine, 5-HT) is an important enteric neurotransmitter. High levels of 5-HT aggravate IBS symptoms. The serotonin reuptake transporter (SERT) is a membrane-embedded transporter involved in IBS pathogenesis that plays an important role in regulating 5-HT signaling. Aim: We investigated whether gut motor function was altered in SERT-knockout (SERT-KO) rats. Additionally, we sought to determine whether Shugan decoction (SGD), a clinically experienced prescription for the treatment of IBS, exerts regulatory effects on intestinal motility in SERT-KO rats, and attempted to identify the mechanisms involved. Method: SERT-KO rats were produced by transcription activator-like effector nuclease (TALEN) technology. Fecal pellet output was measured for ten consecutive days to estimate distal colonic motility. Small intestinal motility was measured by charcoal-meal experiments. The colonic and small intestinal muscle contractile activities were measured by organ bath study. Western blot was used to analyze the muscarinic receptor expression in colon tissue. Result: Compared with that in wild-type (WT) rats, the defecation amount, amplitude of spontaneous contraction, and the tension of ACh-induced contraction of colonic longitudinal smooth muscle in SERT-KO rats were significantly increased. The expression of muscarinic receptor subtype-3 (M3R) in the colons of SERT-KO rats was also elevated. SGD can decrease defecation of SERT-KO rats. Moreover, SGD reduced the amplitude of spontaneous contraction, the frequency and tension of ACh-induced contraction of colonic longitudinal smooth muscle, and the expression of M3R in the colon in SERT-KO rats. Conclusions: SERT-KO rats showed increased defecation accompanied by enhanced colonic motility and M3R expression. The findings suggest that SGD modifies colonic dysmotility and reduces defecation in SERT-KO rats by down-regulating M3R expression in the colon. [ABSTRACT FROM AUTHOR]

Purpose: Sleep disturbances are common in Alzheimer's disease (AD) and mild cognitive impairment (MCI) patients. Non-rapid eye movement stage 3 (N3), rapid eye movement stage (REM), spindle density, and K-complex (KC) density are decreased in MCI and AD patients. Periodic limb movements in sleep (PLMS) are increased in other neurodegenerative diseases. We aimed to distinguish amnestic mild cognitive impairment (aMCI) patients from the overall population of MCI patients by comparing the N3 and REM proportions, the morphological characteristics of spindles and KCs and the periodic limb movement index (PLMI) among control, aMCI and AD subjects. Methods: In 92 subjects (30 controls, 32 aMCI and 30 AD), sleep stages, spindles, KCs and PLMS were recorded during the second of two nights of polysomnography (PSG). We compared the above parameters among the three groups. Results: AD and aMCI subjects had lower proportions of N3 and REM, poorer spindle and KC activities and more frequent PLMS than controls. These alterations were associated with decreased Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores. We determined cut-off values for distinguishing aMCI and AD using logistic regression and receiver operating characteristic (ROC) analyses. Conclusions: AD and aMCI patients have abnormal sleep stage proportions, spindles, KCs and PLMS. The combination of the above alterations may distinguish aMCI and AD patients from controls with high specificity and sensitivity. [ABSTRACT FROM AUTHOR]

An inverse association may exist between cancers and neurodegenerative diseases, although convenient biomarkers for verifying this inverse association are lacking. Plasma neurofilament light chain (NfL) is a novel biomarker for neurodegenerative diseases, such as Alzheimer's disease (AD), but it has not been measured in patients with cancers, such as gastric cancer (GC). We aimed to explore whether plasma NfL could be a biomarker for GC and AD and whether an inverse association of NfL exists between GC and AD. In this study, plasma NfL levels of 60 normal controls (NC), 91 GC subjects, and 74 AD subjects were measured by a highly sensitive single-molecule array assay. We found that GC subjects expressed lower plasma NfL levels but AD subjects expressed higher plasma NfL levels than NCs. After controlling for confounding factors, plasma NfL levels in the GC group were associated with serum tumor marker levels, and plasma NfL levels in the AD group were associated with cognitive performance and cerebrospinal fluid (CSF) pathological marker levels. Across the entire cohort, plasma NfL levels were associated with cognitive performance, CSF pathological marker levels and serum tumor marker levels. These results suggest thatplasma NfL may be a potential biomarker for GC and AD and may be convenient for evaluating the inverse association between cancers and neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

In order to enhance Chinese workers’ occupational safety awareness, it is essential to learn from developed countries’ experiences. This article investigates thoroughly occupational safety and health (OSH) in China and the UK; moreover, the article performs a comparison of Chinese and British OSH training-related laws, regulations and education system. The following conclusions are drawn: China’s work safety continues to improve, but there is still a large gap compared with the UK. In China a relatively complete vocational education and training (VET) system has been established. However, there exist some defects in OSH. In the UK, the employer will not only pay attention to employees’ physiological health, but also to their mental health. The UK’s VET is characterized by classification and grading management, which helps integrate OSH into the whole education system. China can learn from the UK in the development of policies, VET and OSH training. [ABSTRACT FROM AUTHOR]

Soil nitrification and denitrification are key nitrogen (N) removal processes in riparian wetlands in extremely arid regions, but the driving factors of the two N processes in these wetlands are still unclear. We measured soil nitrification and denitrification rates and related environmental properties in a typical riparian wetland in the middle reaches of the Heihe River, northwestern China. Our results showed that rates of soil nitrification and denitrification exhibited moderate variability, ranging from 52.77 to 221.18 μg kg−1 h−1 and 91.25 to 428.26 μg kg−1 h−1, respectively. Soil salinity was high, with mean electrical conductivity (EC) of 6.8 mS cm−1. Soil salinity and moisture were the key factors influencing nitrification and denitrification in this riparian wetland in an extremely arid region. Soil salinity exerted significant inhibitory impact on soil nitrification when EC was > 4.05 mS cm−1. Soil nitrification increased with an increase in soil moisture when soil water content < 27.03% and decreased with an increase in soil moisture when soil water content > 27.03%. Denitrification had a significantly negative relationship with soil salinity, and significantly positive relationship with soil moisture. The interaction of soil salinity and moisture played a central role in regulating soil denitrification. Based on these results, we propose that water consumption of riparian wetlands, and the planting of halophytes, should be increased to reduce soil salinity and increase soil moisture, which is essential for sustaining soil N removal function in riparian wetlands in extremely arid regions. [ABSTRACT FROM AUTHOR]

Many kinds of spatial–temporal data collected by transportation systems, such as user order systems or automated fare-collection (AFC) systems, can be discretized and converted into time-series data. With the technique of time-series data mining, certain travel-demand patterns of different areas in the city can be detected. This study proposes a data-mining model for understanding the patterns and regularities of human activities in urban areas from spatiotemporal datasets. This model uses a grid-based method to convert spatiotemporal point datasets into discretized temporal sequences. Time-series analysis technique dynamic time warping (DTW) is then used to describe the similarity between travel-demand sequences, while the clustering algorithm density-based spatial clustering of applications with noise (DBSCAN), based on modified DTW, is used to detect clusters among the travel-demand samples. Four typical patterns are found, including balanced and unbalanced cases. These findings can help to understand the land-use structure and commuting activities of a city. The results indicate that the grid-based model and time-series analysis model developed in this study can effectively uncover the spatiotemporal characteristics of travel demand from usage data in public transportation systems. [ABSTRACT FROM AUTHOR]

With the recent rapid development of cities, the dynamics of urban road-traffic commuting are becoming more and more complex. In this research, we study urban road-traffic commuting dynamics based on clustering analysis and a new proposed urban commuting electrostatics model. As a case study, we investigate the characteristics of urban road-traffic commuting dynamics during the morning rush hour in Beijing, China, using over 1.3 million Global Positioning System (GPS) data records of vehicle trajectories. The hotspot clusters are identified using clustering analysis, after which the urban commuting electric field is simulated based on an urban commuting electrostatics model. The results show that the areas with high electric field intensity tend to have slow traffic, and also that the vehicles in most areas tend to head in the same direction as the electric field. The results above verify the validity of the model, in that the electric field intensity can reflect the traffic pressure of an area, and that the direction of the electric field can reflect the traffic direction in that area. This new proposed urban commuting electrostatics model helps greatly in understanding urban road-traffic commuting dynamics and has broad applicability for the optimization of urban and traffic system planning. [ABSTRACT FROM AUTHOR]