Deficient RPE mitochondrial energetics leads to subretinal fibrosis in age-related neovascular macular degeneration.

Subretinal fibrosis permanently impairs the vision of patients with neovascular age-related macular degeneration. Despite emerging evidence revealing the association between disturbed metabolism in retinal pigment epithelium (RPE) and subretinal fibrosis, the underlying mechanism remains unclear. In the present study, single-cell RNA sequencing revealed, prior to subretinal fibrosis, genes in mitochondrial fatty acid oxidation are downregulated in the RPE lacking very low-density lipoprotein receptor (VLDLR), especially the rate-limiting enzyme carnitine palmitoyltransferase 1A (CPT1A). We found that overexpression of CPT1A in the RPE of Vldlr-/- mice suppresses epithelial-to-mesenchymal transition and fibrosis. Mechanistically, TGFß2 induces fibrosis by activating a Warburg-like effect, i.e. increased glycolysis and decreased mitochondrial respiration through ERK-dependent CPT1A degradation. Moreover, VLDLR blocks the formation of the TGFß receptor I/II complex by interacting with unglycosylated TGFß receptor II. In conclusion, VLDLR suppresses fibrosis by attenuating TGFß2-induced metabolic reprogramming, and CPT1A is a potential target for treating subretinal fibrosis.

Reference Intervals of Renal Function Set Established for Healthy Pregnant Women.

BACKGROUND: This cross-sectional study aimed to explore the variation trend of renal function for healthy pregnant women at different gestational ages and aimed to establish RIs for renal function set tests according to the trimester of pregnancy. METHODS: A total of 120 healthy pregnant women and 40 healthy non-pregnant women were enrolled in this study and divided into early trimester (1 - 13 weeks of gestation, n = 40), second trimester (14 - 27 weeks of gestation, n = 40), third trimester (≥ 28 weeks of gestation, n = 40), and a non-pregnant women group (n = 40). Analytes of UA, BUN, Cr, ß2-MG, Cys-C, RBP, NAG, CO2, HCY, C1q, and NGAL were measured by using the analytical systems of the Second Xiangya Hospital. The RIs were defined by using non-parametric 95% intervals. RESULTS: The RIs for UA, Cr, ß2-MG, NAG, CO2, Hcy, and C1q were established for the first and second trimester group and the third trimester group. There were huge differences after pregnancy. The RIs for BUN were different for the 1 - 13 weeks group and the after 14 weeks group. There were significant differences for NGAL in pregnant and non-pregnant women, but not for Cys-C and RBP. CONCLUSIONS: The RIs for renal function tests in pregnant women were established, thus providing clinical reference intervals for the clinicians.

Gypenoside LXXV Alleviates Colitis by Reprograming Macrophage Polarization via the Glucocorticoid Receptor Pathway.

An imbalance in the macrophage phenotype is closely related to various inflammatory diseases. Here, we discovered that gypenoside LXXV (GP-75), a type of saponin from Gynostemma pentaphyllum, can reprogram M1-like macrophages into M2-like ones. On a mechanistic level, GP-75 inhibits NF-κB-COX2 signaling by targeting the glucocorticoid receptor (GR). Administration of GP-75, either orally or by intraperitoneal injection, significantly alleviates ulcerative colitis in mice, a pathogenesis associated with macrophage polarization. Clodronate liposomes, which deplete macrophages in mice, as well as GR antagonist RU486, abrogate the anticolitis effect of GP-75, thus confirming the pivotal role of macrophages in GP-75 function. We also showed that GP-75 has no toxicity in mice. Overall, this is the first report that demonstrates the effect of GP-75 on macrophage reprograming and as an agent against colitis. Because G. pentaphyllum is gaining popularity as a functional food, our findings offer new perspectives on the use of gypenosides as potential nutraceuticals for medical purposes.

A Zr-hydroxamate metal-organic framework with intrinsic chelating sites for postsynthetic Pd metalation and Suzuki-Miyaura catalysis.

A highly crystalline and robust Zr-hydroxamate metal-organic framework (MOF) was prepared from a pyrazine-based ligand, featuring abundant N,N' chelating sites. High-degree Pd(II) metalation of the MOF was achieved through straightforward postsynthetic modification, with detailed coordination chemistry elucidated spectroscopically. The Pd-functionalized MOF was then studied as a heterogeneous Suzuki-Miyaura catalyst, through combined experimental/computational methods.

A Rapid Head Organ Localization System Based on Clinically Realistic Images: A 3D Two Step Progressive Registration Method with CVH Anatomical Knowledge Mapping.

Rapid localization of ROI (Region of Interest) for tomographic medical images (TMIs) is an important foundation for efficient image reading, computer-aided education, and well-informed rights of patients. However, due to the multimodality of clinical TMIs, the complexity of anatomy, and the deformation of organs caused by diseases, it is difficult to have a universal and low-cost method for ROI organ localization. This article focuses on actual concerns of TMIs from medical students, engineers, interdisciplinary researchers, and patients, exploring a universal registration method between the clinical CT/MRI dataset and CVH (Chinese Visible Human) to locate the organ ROI in a low-cost and lightweight way. The proposed method is called Two-step Progressive Registration (TSPR), where the first registration adopts "eye-nose triangle" features to determine the spatial orientation, and the second registration adopts the circular contour to determine the spatial scale, ultimately achieving CVH anatomical knowledge automated mapping. Through experimentation with representative clinical TMIs, the registration results are capable of labeling the ROI in the images well and can adapt to the deformation problem of ROI, as well as local extremum problems that are prone to occur in inter-subject registration. Unlike the ideal requirements for TMIs' data quality in laboratory research, TSPR has good adaptability to incomplete and non-thin-layer quality in real clinical data in a low-cost and lightweight way. This helps medical students, engineers, and interdisciplinary researchers independently browse images, receive computer-aided education, and provide patients with better access to well-informed services, highlighting the potential of digital public health and medical education.

From personality types to social labels: the impact of using MBTI on social anxiety among Chinese youth.

Introduction: As the Myers-Briggs Type Indicator (MBTI) gains popularity among Chinese young people, it has undergone a gradual transition from being perceived as a personality assessment tool to being regarded as a social label. The objective of this study was to ascertain whether the use of the MBTI as a social label has an impact on social anxiety among Chinese youth groups. Methods: A questionnaire survey was conducted on social media platforms to recruit Chinese youth aged 18 to 35. A total of 247 males and 222 females participated in the study, and the data was analyzed quantitatively using SPSS software and the Process macro plugin. Results: The study found no strong correlation between MBTI as a social label and social anxiety. Moreover, this study introduced ego identity, belonging, and impression management as mediating variables and found that, under the influence of ego identity and impression management, the use of MBTI has a significant impact on social anxiety. Discussion: The research reveals the complex role of MBTI among Chinese youth and provides a new perspective for understanding the impact of online social labels on the mental health of youth groups. Of course, this study also has limitations in terms of sample size and variable control. Future research should expand the sample size, introduce more potential influencing factors, and further validate and expand the existing conclusions.

Urban residential greenness and cancer mortality: Evaluating the causal mediation role of air pollution in a large cohort.

Evidence linking greenness to all-site and site-specific cancers remains limited, and the complex role of air pollution in this pathway is unclear. We aimed to fill these gaps by using a large cohort in southern China. A total of 654,115 individuals were recruited from 2009 to 2015 and followed-up until December 2020. We calculated the normalized difference vegetation index (NDVI) in a 500-m buffer around the participants' residences to represent the greenness exposure. Cox proportional-hazards models were used to evaluate the impact of greenness on the risk of all-site and site-specific cancer mortality. Additionally, we assessed both the mediation and interaction roles of air pollution (i.e., PM2.5, PM10, and NO2) in the greenness-cancer association through a causal mediation analysis using a four-way decomposition method. Among the 577,643 participants, 10,088 cancer deaths were recorded. We found a 10% (95% CI: 5-16%) reduction in all-site cancer mortality when the NDVI increased from the lowest to the highest quartile. When stratified by cancer type, our estimates suggested 18% (95% CI: 8-27%) and 51% (95% CI: 16-71%) reductions in mortality due to respiratory system cancer and brain and nervous system cancer, respectively. For the above protective effect, a large proportion could be explained by the mediation (all-site cancer: 1.0-27.7%; respiratory system cancer: 1.2-32.3%; brain and nervous system cancer: 3.6-109.1%) and negative interaction (all-site cancer: 2.1-25.7%; respiratory system cancer: 2.0-25.7%; brain and nervous system cancer: not significant) effects of air pollution. We found that particulate matter (i.e., PM2.5 and PM10) had a stronger causal mediation effect (25.0-109.1%) than NO2 (1.0-3.6%), while NO2 had a stronger interaction effect (25.7%) than particulate matter (2.0-2.8%). In summary, greenness was significantly beneficial in reducing the mortality of all-site, respiratory system, and brain and nervous system cancer in southern China, with the impact being modulated and mediated by air pollution.

Correction: Open-flow microperfusion combined with mass spectrometry for in vivo liver lipidomic analysis.

Correction for 'Open-flow microperfusion combined with mass spectrometry for in vivo liver lipidomic analysis' by Tuo Li et al., Analyst, 2021, 146, 1915-1923, https://doi.org/10.1039/D0AN02189J.

Analysis of the microecological mechanism of diabetic kidney disease based on the theory of "gut-kidney axis": A systematic review.

Diabetic kidney disease (DKD) is one of the main microvascular complications of diabetes mellitus, as well as the leading cause of end-stage renal disease. Intestinal microbiota has emerged as a crucial regulator of its occurrence and development. Dysbiosis of the intestinal microbiota can disrupt the intestinal mucosal barrier, abnormal immunological response, reduction in short-chain fatty acid metabolites, and elevation of uremic toxins, all closely related to the occurrence and development of DKD. However, the underlying mechanisms of how intestinal microbiota and its metabolites influence the onset and progression of DKD has not been fully elucidated. In the current review, we will try to summarize the microecological mechanism of DKD by focusing on three aspects: the intestinal microbiota and its associated metabolites, and the "gut-kidney axis," and try to summarize therapies targeted at managing the intestinal microbiota, expecting to provide theoretical basis for the subsequent study of the relationship between intestinal homeostasis and DKD, and will open an emerging perspective and orientation for DKD treatment.

Multifunctional human serum albumin-crosslinked and self-assembling nanoparticles for therapy of periodontitis by anti-oxidation, anti-inflammation and osteogenesis.

Periodontitis is a chronic inflammatory disease that can result in the irreversible loss of tooth-supporting tissues and elevate the likelihood and intensity of systemic diseases. The presence of reactive oxygen species (ROS) and associated related oxidative stress is intricately linked to the progression and severity of periodontal inflammation. Targeted removal of local ROS may serve to attenuate inflammation, improve the unfavorable periodontal microenvironment and potentially reverse ensuing pathological cascades. These ROS scavenging nanoparticles, which possess additional characteristics such as anti-inflammation and osteogenic differentiation, are highly sought after for the treatment of periodontitis. In this study, negative charged human serum albumin-crosslinked manganese-doped self-assembling Prussian blue nanoparticles (HSA-MDSPB NPs) were fabricated. These nanoparticles demonstrate the ability to scavenge multiple ROS including superoxide anion, free hydroxyl radicals, singlet oxygen and hydrogen peroxide. Additionally, HSA-MDSPB NPs exhibit the capacity to alleviate inflammation in gingiva and alveolar bone both in vitro and in vivo. Furthermore, HSA-MDSPB NPs have been shown to play a role in promoting the polarization of macrophages from the M1 to M2 phenotype, resulting in reduced production of pro-inflammatory cytokines. More attractively, HSA-MDSPB NPs have been demonstrated to enhance cellular osteogenic differentiation. These properties of HSA-MDSPB NPs contribute to decreased inflammation, extracellular matrix degradation and bone loss in periodontal tissue. In conclusion, the multifunctional nature of HSA-MDSPB NPs provides a promising therapeutic approach for the treatment of periodontitis.

The effect of residential greenness on cardiovascular mortality from a large cohort in South China: An in-depth analysis of effect modification by multiple demographic and lifestyle characteristics.

BACKGROUND: The potential for residential greenness to improve cardiovascular health through both physical and psychological mechanisms is well recognized. However, evidence from rapidly urbanizing developing countries and cohort-based causal inference approaches, remains limited. We aim to examine the effect of residential greenness and time to cardiovascular mortality in South China. METHODS: We utilized data from a community-based population survey involving 748,209 participants at baseline from 2009 to 2015, followed up until 2020. Residential greenness exposure was assessed by the annual Normalized Difference Vegetation Index (NDVI) in the 500 m radius of each participant's residence. We used time-varying proportional hazard Cox models coupled with inverse probability weighting to fit marginal structural models and obtain hazard ratios (HRs) for cardiovascular disease (CVD) mortality after adjusting for confounders. Multiple effect modifiers on both additive and multiplicative scales were further explored. RESULTS: A total of 15,139 CVD-related deaths were identified during a median of 7.9 years of follow-up. A protective effect was found between higher greenness exposure and reduced CVD mortality, with a 9.3 % lower rate of total CVD mortality (HR 0.907, 95 % CI 0.859-0.957) based on a 0.1 increase in annual average NDVI. Demographic (age, marital status) and lifestyle factors (smoking, drinking status) were found to modify the association between residential greenness and CVD mortality (all P interaction values < 0.05 or 95 %CI for RERI excluded the value 0). Notably, this effect was more pronounced among older adults, married, and individuals having healthier lifestyles, indicating a greater benefit from greenness for these subgroups. CONCLUSIONS: Our findings support a causal link between increased residential greenness exposure and a reduced risk of CVD mortality in South China with marked heterogenous effects, which has public health implications for cultivating greener urban environments to mitigate the impact of CVD within the context of rapid urbanization.

Risk of stroke admission after long-term exposure to PM1: Evidence from a large cohort in South China.

BACKGROUND: Limited attention has been paid to the health effects of long-term PM1 exposure on stroke admission. Current investigations exploring the long-term PM exposure effect are largely based on observational studies, and PM generally is not allocated randomly to participants. Using traditional regression models might confuse messaging and hinder policy recommendations for pollution control and disease prevention policies. METHODS: We conducted a cohort study among 36,271 adults from one of the largest cities in China in 2015 and followed up through 2020. Hazard ratios of stroke admissions following long-term PM1 exposure were estimated via a causal inference approach, marginal structural time-varying Cox proportional hazard model, accounting for multiple confounders. Additionally, several sensitivity analyses and impact modification analyses were carried out. RESULTS AND DISCUSSION: Associations with 1 µg/m3 increase in long-term PM1 were identified for total (HR, 1.079; 95 %CI, 1.012-1.151) and ischemic stroke admissions (HR, 1.092; 95 %CI, 1.018-1.171). The harmful associations varied with exposure duration, initially increasing and then decreasing. The 2-3 years cumulative exposure was associated with a 3.3-5.4 % raised risk for total stroke. For every 1 µg/m³ increase in long-term PM1 exposure, females exhibited a higher risk of both total and ischemic stroke (13 % and 16 %) than men (4 % and 5 %). Low-exposure individuals (whose annual PM1 concentrations were under the third quartile among the annual concentrations for all the participants) exhibited greater sensitivity to PM1 effects (total stroke: 1.079 vs. 1.107; ischemic stroke: 1.092 vs. 1.116). The results underline the importance of safeguarding low-exposed people in highly polluted areas and suggest that long-term PM1 exposure may increase stroke admission risk, warranting attention to vulnerable groups.

Invasive Fusarium solani infection diagnosed by traditional microbial detection methods and metagenomic next-generation sequencing in a pediatric patient: a case report and literature review.

Fusarium solani, as an opportunistic pathogen, can infect individuals with immunosuppression, neutropenia, hematopoietic stem cell transplantation (HSCT), or other high-risk factors, leading to invasive or localized infections. Particularly in patients following allogeneic HSCT, Fusarium solani is more likely to cause invasive or disseminated infections. This study focuses on a pediatric patient who underwent HSCT for severe aplastic anemia. Although initial blood cultures were negative, an abnormality was detected in the 1,3-ß-D-glucan test (G test) post-transplantation. To determine the causative agent, blood samples were subjected to metagenomic next-generation sequencing (mNGS) and blood cultures simultaneously. Surprisingly, the results of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and mNGS differed slightly, with mNGS identifying Nectria haematonectria, while MALDI-TOF MS based on culture showed Fusarium solani. To clarify the results, Sanger sequencing was performed for further detection, and the results were consistent with those of MALDI-TOF MS. Since the accuracy of Sanger sequencing is higher than that of mNGS, the diagnosis was revised to invasive Fusarium solani infection. With advancements in technology, various detection methods for invasive fungi have been developed in recent years, such as mNGS, which has high sensitivity. While traditional methods may be time-consuming, they are important due to their high specificity. Therefore, in clinical practice, it is essential to utilize both traditional and novel detection methods in a complementary manner to enhance the diagnosis of invasive fungal infections.

Genome-wide analysis of the SWEET gene family in Hemerocallis citrina and functional characterization of HcSWEET4a in response to salt stress.

Sugars will be eventually effluxed transporters (SWEETs) have been confirmed to play diverse physiological roles in plant growth, development and stress response. However, the characteristics and functions of the SWEET genes in Hemerocallis citrina remain unclear and poorly elucidated. In this study, the whole genome of Hemerocallis citrina was utilized to conduct bioinformatics analysis and a total of 19 HcSWEET genes were successfully identified. Analysis of the physicochemical properties indicated dominant differences among these HcSWEETs. A phylogenetic analysis revealed that HcSWEET proteins can be divided into 4 clades ranging from Clade I to IV, where proteins within the same clade exhibited shared conserved motifs and gene structures. Five to six exons were contained in the majority of HcSWEET genes, which were unevenly distributed across 11 chromosomes. The gene duplication analysis showed the presence of 4 gene pairs. Comparative syntenic maps revealed that the HcSWEET gene family might present more closed homology in monocotyledons than dicotyledons. Cis-acting element analysis of HcSWEET genes indicated key responsiveness to various hormones, light, and stresses. Additionally, transcriptome sequencing analysis suggested that most HcSWEET genes had a relatively higher expression in roots, and HcSWEET4a was significantly up-regulated under salt stress. Overexpression further verified the possibility that HcSWEET4a was involved in response to salt stress, which provides novel insights and facilitates in-depth studies of the functional analysis of HcSWEETs in resistance to abiotic stress.

Assessing the modification impact of vaccination on the relationship of the Discomfort Index with hand, foot, and mouth disease in Guizhou: A multicounty study.

BACKGROUND: Hand, foot, and mouth disease (HFMD) is a major public health issue in China while temperature and humidity are well-documented predictors. However, evidence on the combined effect of temperature and humidity is still limited. It also remains unclear whether such an effect could be modified by the enterovirus 71 (EV71) vaccination. METHODS: Based on 320,042 reported HFMD cases during the summer months between 2012 and 2019, we conducted a study utilizing Distributed Lag Non-Linear Models (DLNM) and time-varying DLNM to examine how China's HFMD EV71 vaccine strategy would affect the correlation between meteorological conditions and HFMD risk. RESULTS: The incidence of HFMD changed with the Discomfort Index in an arm-shaped form. The 14-day cumulative risk of HFMD exhibited a statistically significant increase during the period of 2017-2019 (following the implementation of the EV71 vaccine policy) compared to 2012-2016 (prior to the vaccine implementation). For the total population, the range of relative risk (RR) values for HFMD at the 75th, 90th, and 99th percentiles increased from 1.082-1.303 in 2012-2016 to 1.836-2.022 in 2017-2019. In the stratified analyses, Han Chinese areas show stronger relative growth, with RR values at the 75th, 90th, and 99th percentiles increased by 14.3%, 39.1%, and 134.4% post-vaccination, compared to increases of 22.7%, 41.6%, and 38.8% in minority areas. Similarly, boys showed greater increases (24.4%, 47.7%, 121.5%) compared to girls (8.1%, 28.1%, 58.3%). Additionally, the central Guizhou urban agglomeration displayed a tendency for stronger relative growth compared to other counties. CONCLUSIONS: Although the EV71 vaccine policy has been implemented, it hasn't effectively controlled the overall risk of HFMD. There's been a shift in the main viral subtypes, potentially altering population susceptibility and influencing HFMD occurrences. The modulating effects of vaccine intervention may also be influenced by factors such as race, sex, and economic level.

Integrating Molecular Biology and Network Pharmacology to Analyze the Antidepressant Mechanism of Glycyrrhizaglabra.

INTRODUCTION: Antidepressants have adverse effects and induce drug resistance when used excessively or frequently. Therefore, adjuvants are needed to reduce the use of antidepressants during treatment. Traditional Chinese medicine (TCM) is an important adjunctive approach to depression with safety, environmental protection, and low toxicity. Glycyrrhizaglabra (licorice, GG) is a plant commonly used in various herbal remedies. METHOD: We investigated the antidepressant activity of GG, its active constituents, and potential depression-related targets. We combined animal behavioral and molecular biological assays with network pharmacology to analyze the antidepressant mechanism of GG. GG extracts reversed lipopolysaccharide (LPS)-induced depression-like behavior in behavioral tests. We selected 56 active compounds and 695 target compounds of licorice from TCMSP. The PPI network screened 80 core targets for enrichment analysis. It shows that GG significantly affected neurodegeneration pathways, neuroactive ligand-receptor interaction, cAMP signaling pathway, serotonergic synapse, dopaminergic synapse, and MAPK signaling pathway. RESULT: Mechanistic studies showed that GG reduced IL-1ß, IL-6, and TNF-α levels, 5-HTRA1 expression, and GSK3ß phosphorylation in mouse hippocampus. It also increased BDNF and DRD1 expression and CREB and ERK1/2 phosphorylation. CONCLUSION: It shows that GG acted on these proteins to affect multiple pathways that mediate the pathogenesis of depression.

Membrane-based optical fiber Bragg grating pressure sensor for health monitoring of pile foundations.

A fiber Bragg grating (FBG) pressure sensor is proposed, designed, and fabricated for lateral earth pressure sensing, in which the FBG sensor is mounted on a 3D printed trestle structure combined with a membrane. The applied pressure can cause a deformation on the membrane, and then this deformation applied on the trestle structure causes tensile strain on the FBG. The proposed sensor is functionalized as a high-sensitive pressure transducer capable of converting the pressure into strain on the FBG. Here, the performance of the proposed sensor is numerically and experimentally investigated. The results show that the pressure sensitivity at 30°C is 10.62 pm/kPa within a range of 0-0.6 MPa. Due to the thermal expansion of the structure, the pressure sensitivity coefficient decreases with the increase of temperature; however, the cross effect between the temperature and strain on the sensing sensitivity is investigated and can be eliminated. The fabricated sensor has advantages of high sensitivity, good stability, and high pressure resolution, so it has potential in the field of structural health monitoring.

Epimedii Folium decoction ameliorates osteoporosis in mice through NLRP3/caspase-1/IL-1ß signalling pathway and gut-bone axis.

AIM OF THE STUDY: This study aimed to determine the effect of Epimedium brevicornu Maxim. (EF) on osteoporosis (OP) and its underlying molecular mechanisms, and to explore the existence of the "Gut-Bone Axis". MATERIAL AND METHODS: The impact of EF decoction (EFD) on OP was evaluated using istopathological examination and biochemical assays. Targeted metabolomics was employed to identify key molecules and explore their molecular mechanisms. Alterations in the gut microbiota (GM) were evaluated by 16S rRNA gene sequencing. The role of the GM was clarified using an antibiotic cocktail and faecal microbiota transplantation. RESULTS: EFD significantly increased the weight (14.06%), femur length (4.34%), abdominal fat weight (61.14%), uterine weight (69.86%), and insulin-like growth factor 1 (IGF-1) levels (59.48%), while reducing serum type I collagen cross-linked carboxy-terminal peptide (CTX-I) levels (15.02%) in osteoporotic mice. The mechanism of action may involve the regulation of the NLRP3/cleaved caspase-1/IL-1ß signalling pathway in improving intestinal tight junction proteins and bone metabolism. Additionally, EFD modulated the abundance of related GM communities, such as Lactobacillus, Coriobacteriaceae, bacteria of family S24-7, Clostridiales, and Prevotella, and increased propionate and butyrate levels. Antibiotic-induced dysbiosis of gut bacteria disrupted OP regulation of bone metabolism, which was restored by the recovery of GM. CONCLUSIONS: Our study is the first to demonstrate that EFD works in an OP mouse model by utilising GM and butyric acid. Thus, EF shows promise as a potential remedy for OP in the future.

CYR61 Acts as an Intracellular Microtubule-Associated Protein and Coordinates Mitotic Progression via PLK1-FBW7 Pathway.

Cysteine-rich angiogenic inducer 61 (CYR61), also called CCN1, has long been characterized as a secretory protein. Nevertheless, the intracellular function of CYR61 remains unclear. Here, we found that CYR61 is important for proper cell cycle progression. Specifically, CYR61 interacts with microtubules and promotes microtubule polymerization to ensure mitotic entry. Moreover, CYR61 interacts with PLK1 and accumulates during the mitotic process, followed by degradation as mitosis concludes. The proteolysis of CYR61 requires the PLK1 kinase activity, which directly phosphorylates two conserved motifs on CYR61, enhancing its interaction with the SCF E3 complex subunit FBW7 and mediating its degradation by the proteasome. Mutations of phosphorylation sites of Ser167 and Ser188 greatly increase CYR61's stability, while deletion of CYR61 extends prophase and metaphase and delays anaphase onset. In summary, our findings highlight the precise control of the intracellular CYR61 by the PLK1-FBW7 pathway, accentuating its significance as a microtubule-associated protein during mitotic progression.

How long-term PM exposure may affect all-site cancer mortality: Evidence from a large cohort in southern China.

BACKGROUND: Evidence of a potential causal link between long-term exposure to particulate matter (PM) and all-site cancer mortality from large population cohorts remained limited and suffered from residual confounding issues with traditional statistical methods. AIMS: We aimed to examine the potential causal relationship between long-term PM exposure and all-site cancer mortality in South China using causal inference methods. METHODS: We used a cohort in southern China that recruited 580,757 participants from 2009 through 2015 and tracked until 2020. Annual averages of PM1, PM2.5, and PM10 concentrations were generated with validated spatiotemporal models. We employed a causal inference approach, the Marginal Structural Cox model, based on observational data to evaluate the association between long-term exposure to PM and all-site cancer mortality. RESULTS: With an increase of 1 µg/m³ in PM1, PM2.5, and PM10, the hazard ratios (HRs) and 95% confidence interval (CI) for all-site cancer were 1.033 (95% CI: 1.025-1.041), 1.032 (95% CI: 1.027-1.038), and 1.020 (95% CI: 1.016-1.025), respectively. The HRs (95% CI) for digestive system and respiratory system cancer mortality associated with each 1 µg/m³ increase in PM1 were 1.022 (1.009-1.035) and 1.053 (1.038-1.068), respectively. In addition, inactive participants, who never smoked, or who lived in areas of low surrounding greenness were more susceptible to the effects of PM exposure, the HRs (95% CI) for all-site cancer mortality were 1.042 (1.031-1.053), 1.041 (1.032-1.050), and 1.0473 (1.025-1.070) for every 1 µg/m³ increase in PM1, respectively. The effect of PM1 tended to be more pronounced in the low-exposure group than in the general population, and multiple sensitivity analyses confirmed the robustness of the results. CONCLUSION: This study provided evidence that long-term exposure to PM may elevate the risk of all-site cancer mortality, emphasizing the potential health benefits of improving air quality for cancer prevention.