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Abstract Background Cell pyroptosis has a strong proinflammatory effect, but it is unclear whether pyroptosis of liver macrophages exacerbates liver tissue damage during liver ischemia‒reperfusion (I/R) injury. Maresin1 (MaR1) has a strong anti-inflammatory effect, and whether it can suppress liver macrophage pyroptosis needs further study. Methods This study aimed to investigate whether MaR1 can alleviate liver I/R injury by inhibiting macrophage pyroptosis. The effects of MaR1 on cell pyroptosis and mitochondrial damage were studied by dividing cells into control, hypoxia/reoxygenation, and hypoxia/reoxygenation + MaR1 groups. Knocking out RORa was used to study the mechanism by which MaR1 exert its protective effects. Transcriptome analysis, qRT‒PCR and Western blotting were used to analyze gene expression. Untargeted metabolomics techniques were used to analyze metabolite profiles in mice. Flow cytometry was used to assess cell death and mitochondrial damage. Results We first found that MaR1 significantly reduced liver I/R injury. We observed that MaR1 decreased liver I/R injury by inhibiting liver macrophage pyroptosis. Then, we discovered that MaR1 promotes mitochondrial oxidative phosphorylation, increases the synthesis of ATP, reduces the generation of ROS, decreases the impairment of mitochondrial membrane potential and inhibits the opening of mitochondrial membrane permeability transition pores. MaR1 inhibits liver macrophage pyroptosis by protecting mitochondria. Finally, we found that MaR1 exerts mitochondrial protective effects through activation of its nuclear receptor RORa and the PI3K/AKT signaling pathway. Conclusions During liver I/R injury, MaR1 can reduce liver macrophage pyroptosis by reducing mitochondrial damage, thereby reducing liver damage.

Background: Broussonetia papyrifera (L.) L′Hér. ex Vent (B. papyrifera) is a deciduous tree widely distributed in Asia. Previous studies have revealed that leaves of B. papyrifera ameliorated atopic dermatitis (AD)-like symptoms and inflammatory response. However, the impact and underlying mechanism of other parts of B. papyrifera on AD remain elusive. Methods: The AD mice induced by 1-Chloro-2,4-dinitrochlorobenzene were used to observe the histopathological alterations in the skin tissues using hematoxylin-eosin staining and toluidine blue staining techniques. Serum levels of inflammatory factors were quantified utilizing ELISA. Pyroptosis was analyzed by lactate dehydrogenase release and flow cytometry in human keratinocytes. The activation of Nod-like receptor protein 3 (NLRP3) inflammasome was analyzed by western blots. Furthermore, the mechanism underlying the inhibition of NLRP3 inflammasome by N-butanol extracts of B. papyrifera root bark (NE-BPRB) was investigated using cellular thermal shift assay and surface plasmon resonance techniques. Results: Treatment with NE-BPRB significantly ameliorated symptoms of AD mice and reduced serum levels of pro-inflammatory factors. NE-BPRB intervention exhibited inhibitory effects on NLRP3 inflammasome activation and pyroptosis in vitro and in vivo. NE-BPRB and its primary bioactive constituent chlorogenic acid (CA) promote the K48-linked ubiquitination of NLRP3, leading to its proteasomal degradation by binding WW domain containing E3 ubiquitin protein ligase 1 (WWP1). Conclusions: The NE-BPRB and its primary bioactive constituent, CA, effectively inhibit the formation of the NLRP3 inflammasome and impede cell pyroptosis by promoting K48-linked ubiquitin-dependent proteasomal degradation of NLRP3 through binding to the E3 ubiquitin ligase WWP1, thereby resulting in improved AD.

Introduction: Breast cancer (BC) is a malignant disease that occurs worldwide and poses serious health burden. Objectives: To assess the prevalence of BC burden in the Western Pacific region (WPR) from 1990 to 2019, and to predict trends from 2020 to 2044. To analyze the driving factors and put forward the region-oriented improvement. Methods: Based on the Global Burden of Disease Study 2019, BC cases, deaths, disability-adjusted life years (DALYs) cases, age-standardized incidence rate (ASIR), age-standardized death rate (ASDR), and age-standardized DALYs rate in WPR from 1990 to 2019 was obtained and analysed. Age-period-cohort (APC) model was used to analyze age, period, and cohort effects in BC, and Bayesian APC (BAPC) was used to predict trends over the next 25 years. Results: In conclusion, BC incidence and deaths in the WPR have increased rapidly over the past 30 years and are expected to continue to increase between 2020 and 2044. Among behavioral and metabolic factors, high body-mass index was the main risk factor for BC mortality in middle-income countries, whereas alcohol use was the main risk factor in Japan. Age is a key factor in the development of BC, with 40 years being the critical point. Incidence trends coincide with the course of economic development. Conclusions: The BC burden remains an essential public health issue in the WPR and will increase substantially in the future. More efforts should be made in middle-income countries to prompt the health behavior and minimize the burden of BC because these nations accounts for the majority of BC burden in the WPR.

In this study, single factor experiments were employed to determine the effects of various factors on yields of total flavonoids and polyphenols from Broussonetia papyrifera root bark. Then Box-Behnken design and response surface methodology were used to optimize the ethanol reflux extraction process using the Design-Expert 11 software. Moreover, the antioxidant activity of the ethanol extract of Broussonetia papyrifera root bark was evaluated by determining the scavenging capacity of DPPH·, ABTS+·, and the hydroxyl free radical, as well as the total reducing power. Results showed that the optimal conditions were as follows: Extraction temperature 75 ℃, extraction time 117 min, solid-liquid ratio 1:16 g/mL, and ethanol concentration 70%. Under these conditions, the experimental extraction yield values of total flavonoids and polyphenols from Broussonetia papyrifera root bark were 23.93±0.30 mg/g and 14.69±0.56 mg/g, respectively, which was not significantly different in comparison to predicted values. The IC50 values of scavenging rates on DPPH·, ABTS+·, and the hydroxyl free radical were 5.256 μg/mL, 0.259 mg/mL, and 0.310 mg/mL, respectively, and the scavenging rates showed a certain dose-effect relationship with the sample concentration. In addition, the total reducing power of 1.0 mg/mL ethanol extract of the root bark was 1.484±0.062. These results indicated that this optimization test was effective and feasible, and the ethanol extract of Broussonetia papyrifera root bark had good antioxidant activity in vitro. The present study provides supplement information for the comprehensive utilization of Broussonetia papyrifera in food and medicine ingredients.

Abstract Background The transmission of 2019 novel coronavirus (COVID-19) has caused global panic in the past three years. Countries have learned an important lesson in the practice of responding to COVID-19 pandemic: timely and accurate diagnosis is critical. As an important technology of virus diagnosis, nucleic acid testing (NAT) is also widely used in the identification of other infectious diseases. However, geographic factors often constrain the provision of public health services such as NAT services, and the spatial nature of their resource allocation is a significant problem. Methods We used OLS, OLS-SAR, GWR, GWR-SAR, MGWR, and MGWR-SAR models to identify the determinants of spatial difference and spatial heterogeneity affecting NAT institutions in China. Results Firstly, we identify that the distribution of NAT institutions in China shows a clear spatial agglomeration, with an overall trend of increasing distribution from west to east. There is significant spatial heterogeneity in Chinese NAT institutions. Secondly, the MGWR-SAR model results show that city level, population density, number of tertiary hospitals and number of public health emergency outbreaks are important factors influencing the spatial heterogeneity of NAT institutions in China. Conclusions Therefore, the government should allocate health resources rationally, optimise the spatial layout of testing facilities, and improve the ability to respond to public health emergencies. Meanwhile, third-party testing facilities need to focus on their role in the public health emergency response system as a market force to alleviate the inequitable allocation of health resources between regions. By taking these measures to prepare adequately for possible future public health emergencies.

Energy-related CO2 emissions are mainly concentrated in urban areas. Quantitative research on the relationship between CO2 emissions and economic growth at city and sub-city level is of great importance. Based on the Tapio’s decoupling model, this paper analyzes the decoupling status of CO2 emissions from economic growth in the 16 districts of Beijing during the period of 2006–2017. The decoupling state of the 16 districts showed obvious phased improvement characteristics. In 2017, 93.75% districts achieved decoupling state, including strong decoupling and weak decoupling, of CO2 emissions from economic growth and 37.50% districts achieve strong decoupling, the most desirable decoupling state. The effect of urban functional zoning and industrial structure transition on the total CO2 emissions and the direct influences of the national environmental protection policies and big public event on the decoupling of CO2 emissions from economic growth were observed. This study will enrich the body of decoupling research at the district level and will provide scientific support to the achievement of the “double carbon” target in Beijing and other Chinese cities.

Lung squamous cell carcinoma (LUSC) treatment response is poor and treatment alternatives are limited. Palbociclib, a cyclin-dependent kinase (CDK) 4/6 inhibitor, has recently been approved for hormone receptor-positive breast cancer patients and applied in multiple preclinical models, but its use for LUSC therapy remains elusive. Here, we investigated whether palbociclib induced cell apoptosis and dissected the underlying mechanism in LUSC. We found that palbociclib induced LUSC cell apoptosis through inhibition of Src tyrosine kinase/signal transducers and activators of transcription 3 (STAT3). Interestingly, palbociclib reduced STAT3 signaling in LUSC cells interfered by retinoblastoma tumor-suppressor gene (RB), suggesting that pro-apoptosis effect of palbociclib was independent of classic CDK4/6-RB signaling. Furthermore, palbociclib could suppress IL-1β and IL-6 expression, and therefore blocked Src/STAT3 signaling, which were rescued by either recombinant human IL-1β or IL-6. Moreover, Myc mediated the sensitivity of LUSC cells to palbociclib. Our discoveries demonstrated that palbociclib induces apoptosis of LUSC cells through the Src/STAT3 axis in an RB-independent manner, and provided a reliable experimental basis of clinical studies in LUSC patients.

Spatial transcriptome technology acquires gene expression profiles while retaining spatial location information, it displays the gene expression properties of cells in situ. Through the investigation of cell heterogeneity, microenvironment, function, and cellular interactions, spatial transcriptome technology can deeply explore the pathogenic mechanisms of cell-type-specific responses and spatial localization in neurological diseases. The present article overviews spatial transcriptome technologies based on microdissection, in situ hybridization, in situ sequencing, in situ capture, and live cell labeling. Each technology is described along with its methods, detection throughput, spatial resolution, benefits, and drawbacks. Furthermore, their applications in neurodegenerative disease, neuropsychiatric illness, stroke and epilepsy are outlined. This information can be used to understand disease mechanisms, pick therapeutic targets, and establish biomarkers.

BackgroundCurrently, breast cancer (BC) is ranked among the top malignant tumors in the world, and has attracted widespread attention. Compared with the traditional analysis on biological determinants of BC, this study focused on macro factors, including light at night (LAN), PM2.5, per capita consumption expenditure, economic density, population density, and number of medical beds, to provide targets for the government to implement BC interventions.MethodsA total of 182 prefecture-level cities in China from 2013 to 2016 were selected as the sample of the study. The geographically and temporally weighted regression (GTWR) model was adopted to describe the spatiotemporal correlation between the scale of BC and macro factors.ResultsThe results showed that the GTWR model can better reveal the spatiotemporal variation. In the temporal dimension, the fluctuations of the regression coefficients of each variable were significant. In the spatial dimension, the positive impacts of LAN, per capita consumption expenditure, population density and number of medical beds gradually increased from west to east, and the positive coefficient of PM2.5 gradually increased from north to south. The negative impact of economic density gradually increased from west to east.ConclusionThe fact that the degree of effect of each variable fluctuates over time reminds the government to pay continuous attention to BC prevention. The spatial heterogeneity features also urge the government to focus on different macro indicators in eastern and western China or southern and northern China. In other words, our research helps drive the government to center on key regions and take targeted measures to curb the rapid growth of BC.

BackgroundThere are huge differences in female breast cancer mortality between urban and rural China. In order to better prevent breast cancer equally in urban and rural areas, it is critical to trace the root causes of past inequities and predict how future differences will change. Moreover, carcinogenic factors from micro-individual to macro-environment also need to be analyzed in detail. However, there is no systematic research covering these two aspects in the current literature.MethodsBreast cancer mortality data in urban and rural China from 1994 to 2019 are collected, which from China Health Statistical Yearbook. The Age-Period-Cohort model is used to examine the effects of different age groups, periods, and birth cohorts on breast cancer mortality. Nordpred project is used to predict breast cancer mortality from 2020 to 2039.ResultsThe age effect gradually increases and changes from negative to positive at the age of 40–44. The period effect fluctuates very little and shows the largest difference between urban and rural areas in 2019. The birth cohort effect gradually decreases with urban-rural effects alternating between strong and weak. In the predicted results, the urban-rural mortality gap becomes first narrow and then wide and shows a trend of younger death.ConclusionsFrom the perspective of a temporal system, the changing trend of breast cancer mortality is highly consistent with the history of social and economic structural changes in China. From the perspective of the theory of social determinants of health, individuals, families, institutions and governments need to participate in the prevention of breast cancer.

Fibroblasts in the heart, traditionally recognized as interstitial cells, have long been overlooked in the study of cardiac physiology and pathology [...]

In responding to climate change, energy efficiency is one of the key factors for sustainable development, where the high-tech industry can play an important role. However, whether the development of high-tech industry impacts energy efficiency as well as the mechanisms behind still remain unclear. Thus, based on the dynamic spatial Durbin model, this study aims to investigate: 1) the impact of high-tech industry development on energy efficiency from three perspectives of high-tech industry development, i.e., scale, productivity, and agglomeration, and 2) the mechanisms behind such impact especially through technological innovation and industrial structure. The results confirm the influence of high-tech industry development on energy efficiency both directly and indirectly. On the one hand, our analysis contributes on the existing body of scientific knowledge by expounding the relationship between scale, productivity, and agglomeration of high-tech industry development and energy efficiency. On the other hand, it further deepens the understanding on such relationship by revealing two underlying mechanisms behind, i.e., through promoting technological innovation, the productivity and agglomeration of high-tech industries can either completely or partially improve energy efficiency, while the scale and agglomeration of high-tech industries can hinder energy efficiency to a certain level through the industrial restructuring. Based on these findings, this paper provides some policy implications, which are believed to facilitate the practices of energy conservation and emission reduction in China.

Harmonizing human activities with the natural environment has received much attention as a development goal and is a longstanding pursuit of human society. In this study, we investigated the sustainability of green development from the perspective of the coordination between economic and environmental subsystems at the place-based scale, with 290 cities in China as research objects. An interdisciplinary method combining an improved data envelopment analysis model and Lotka-Volterra model was conducted to examine the two subsystems’ development efficiency and their correlation (i.e., mutualism, commensalism, amensalism, sacrifice, competition, independence). The results indicate that one-third of the cities’ economic and environmental subsystems are in a mutualistic state, with a relatively stable social-ecological system. However, the two subsystems are in a state of competition in one-fourth of the cities, with rather intense vulnerability, where the harmonious coexistence of humans and nature is facing more significant challenges. In addition, vulnerability of the social-ecological system in economically developed cities shows substantial polarization. The two subsystems in most of these cities are in mutualism or amensalism relations, whereas the social-ecological system in economically underdeveloped cities shows even greater vulnerability.

In recent years, blood pumps have become the bridge to heart transplantation for patients with heart failure. Portability and wearability of blood pumps should be considered to ensure patient satisfaction in everyday life. To date, the focus has been on the development of portable and wearable peripheral components, little attention has been paid to the portable and wearable performance of the blood pump itself. This study reported a novel design of a wearable and portable extracorporeal centrifugal blood pump. Based on an in-house centrifugal maglev blood pump, the wearable and portable blood pump was designed with parallel inlet and outlet pipes to improve the wearable performance. A ring cavity was set at the inlet to convert the circumferential velocity of the inlet pipe to an axial velocity. The hydraulic and hemolytic performance of the baseline and portable blood pumps were analyzed and compared. Compared with the baseline pump, the hydrodynamic and hemolytic performance of the portable pump has been maintained without serious degradation. The results of this study will improve the life quality of patients with heart failure, and enhance the clinical benefits of artificial heart.

Angiogenesis is a vital endogenous brain self-repair processes for neurological recovery after intracerebral hemorrhage (ICH). Increasing evidence suggests that leptin potentiates angiogenesis and plays a beneficial role in stroke. However, the proangiogenic effect of leptin on ICH has not been adequately explored. Moreover, leptin triggers post-ICH angiogenesis through pericyte, an important component of forming new blood vessels, which remains unclear. Here, we reported that exogenous leptin infusion dose-dependent promoted vascular endothelial cells survival and proliferation at chronic stage of ICH mice. Additionally, leptin robustly ameliorated pericytes loss, enhanced pericytes proliferation and migration in ICH mice in vivo, and in ICH human brain microvascular pericytes (HBVPC) in vitro. Notably, we showed that pericytes-derived pro-angiogenic factors were responsible for enhancing the survival, proliferation and tube formation followed leptin treatment in human brain microvascular endothelial cells (HCMEC/D3)/HBVPC co-culture models. Importantly, considerable improvements in neurobehavioral function and hostile microenvironment were observed in leptin treatment ICH mice, indicating that better vascular functionality post ICH improves outcome. Mechanistically, this study unveiled that leptin boost post-ICH angiogenesis potentially through modulation of leptin receptor (leptinR)/Signal Transducer and Activator of Transcription 3 (STAT3) signaling pathway in pericyte. Thus, leptin may be a lucrative option for the treatment of ICH.

Chlamydial infection causes a number of clinically relevant diseases and induces significant morbidity in humans. Immune and inflammatory responses contribute to both the clearance of Chlamydia infection and pathology in host tissues. Chlamydia infection stimulates host cells to produce a large number of cytokines that trigger and regulate host immune responses against Chlamydia. However, inappropriate responses can occur with excessive production of cytokines, resulting in overreactive inflammatory responses and alterations in host or Chlamydia metabolism. As a result, Chlamydia persists and causes wound healing delays, leading to more severe tissue damage and triggering long-lasting fibrotic sequelae. Here, we summarize the roles of cytokines in Chlamydia infection and pathogenesis, thus advancing our understanding chlamydial infection biology and the pathogenic mechanisms involved.

Background Microglia play key roles in innate immunity, homeostasis, and neurotropic support in the central nervous system. Similar to macrophages, microglia adopt two different activation phenotypes, the classical and alternative activation. Resolvin D1 (RvD1) is considered to display potent anti-inflammatory and pro-resolving actions in inflammatory models. In this present study, we investigate the effect of RvD1 on IL-4-induced alternative activation in murine BV-2 microglial cells. Methods BV-2 cells were incubated with RvD1 alone, IL-4 alone, or the combination of RvD1 and IL- 4. Western blot and immunofluorescence were performed to detect protein levels of alternative activation markers arginase 1 (Arg1), chitinase 3-like 3 (Ym1). Moreover, we investigated the effects of RvD1 on IL-4-induced activation of signal transducer and activators of transcription 6 (STAT6) and peroxisome proliferator-activated receptor gamma (PPARγ). Results RvD1 promoted IL-4-induced microglia alternative activation by increasing the expression of Arg1 and Ym1. RvD1 also enhanced phosphorylation of STAT6, nuclear translocation of PPARγ and the DNA binding activity of STAT6 and PPARγ. These effects were reversed by butyloxycarbonyl-Phe-Leu-Phe-Leu-Phe (a formyl peptide receptor 2 antagonist). Further, the effects of RvD1 and IL-4 on Arg1 and Ym1 were blocked by the application of leflunomide (a STAT6 inhibitor) or GW9662 (a PPARγ antagonist). Conclusions Our studies demonstrate that RvD1 promotes IL-4-induced alternative activation via STAT6 and PPARγ signaling pathways in microglia. These findings suggest that RvD1 may have therapeutic potential for neuroinflammatory diseases. [ABSTRACT FROM AUTHOR]

Chlamydia muridarum, an obligate intracellular pathogen, was used to establish a murine model of female upper genital tract infection by Chlamydia trachomatis. TC0668 in C. muridarum is a hypothetical chromosomal virulence protein that is involved in upper genital tract pathogenesis. The infection of mice with the C. muridarum TC0668-mutant (G216*) strain results in less pathological damage in the upper genital tract. In this study, an isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomics analysis was performed to identify differentially expressed proteins between TC0668 wild-type (TC0668wt) and TC0668 mutant (TC0668mut) strains at 6, 12, 18, and 24 h post-infection (p.i.). Of the 550 proteins differentially expressed at 18 h p.i., 222 and 328 were up-regulated and down-regulated, respectively, inTC0668mut-infected cells. The expression of seven up-regulated proteins (encoded by SRPRB, JAK1, PMM1, HLA-DQB1, THBS1, ITPR1, and BCAP31) and three down-regulated proteins (encoded by MAPKAPK2, TRAFD1, and IFI16) from the iTRAQ analysis were validated using quantitative real-time (qRT)-PCR. The qRT-PCR results were consistent with those of iTRAQ. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that the differentially expressed proteins primarily participated in inflammatory responses, fibrosis, metabolic processes, and complement coagulation cascades, and were mainly enriched in the phosphatidylinositol 3′-kinase (PI3K)/Akt, nuclear factor kappa-B (NF-κB), and other signaling pathways. Using western-blotting and immunofluorescence detection, significant differences in activation of the PI3K/Akt and NF-κB signaling pathways were observed between the TC0668wt- and TC0668mut-infected cells. Differentially expressed proteins linked with inflammation and fibrosis were used in a protein-protein interaction network analysis. The results suggest that TC0668 may play a pivotal role in C. muridarum-induced genital pathology by inducing inflammatory responses and fibrosis, which may involve the activation of the PI3K/Akt and NF-κB signaling pathways.

Surface roughness is a very important index in silicon direct bonding and it is affected by processing parameters in the wet-activated process. These parameters include the concentration of activation solution, holding time and treatment temperature. The effects of these parameters were investigated by means of orthogonal experiments. In order to analyze the wafer roughness more accurately, the bear ratio of the surface was used as the evaluation index. From the results of the experiments, it could be concluded that the concentration of the activation solution affected the roughness directly and the higher the concentration, the lower the roughness. Holding time did not affect the roughness as acutely as that of the concentration, but a reduced activation time decreased the roughness perceptibly. It was also discovered that the treatment temperature had a weak correlation with the surface roughness. Based on these conclusions, the parameters of concentration, temperature and holding time were optimized respectively as NH4OH:H2O2=1:1 (without water), 70 °C and 5 min. The results of bonding experiments proved the validity of the conclusions of orthogonal experiments.DOI: http://dx.doi.org/10.5755/j01.ms.21.4.9711