Colchicine delivered by a novel nanoparticle platform alleviates atherosclerosis by targeted inhibition of NF-κB/NLRP3 pathways in inflammatory endothelial cells.

Atherosclerosis, a chronic inflammatory disease characterized by arterial plaque formation, is one of the most prominent causes of cardiovascular diseases. However, the current treatments often do not adequately compromise the chronic inflammation-mediated plaque accumulation and the disease progression. Therefore, a new and effective strategy that blocks atherosclerosis-associated inflammation is urgently needed to further reduce the risk. Colchicine, a potent anti-inflammatory medication, has shown great potential in the treatment of atherosclerosis, but its adverse effects have hampered its clinical application. Herein, we developed a novel delivery nanosystem encapsulated with colchicine (VHPK-PLGA@COL), which exhibited improved biosafety and sustained drug release along with the gradual degradation of PLGA and PEG as confirmed both in vitro and in vivo. Surface modification of the nanoparticles with the VHPK peptide ensured its capability to specifically target inflammatory endothelial cells and alleviate atherosclerotic plaque accumulation. In the ApoE - / - atherosclerotic mouse model, both colchicine and VHPK-PLGA@COL treatment significantly decreased the plaque area and enhanced plaque stability by blocking the NF-κB/NLRP3 pathways, while VHPK-PLGA@COL exhibited enhanced therapeutic effects due to its unique ability to target inflammatory endothelial cells without obvious long-term safety concerns. In summary, VHPK-PLGA@COL has the potential to overcome the key translational barriers of colchicine and open new avenues to repurpose this drug for anti-atherosclerotic therapy.

The prolyl isomerase Pin1 stabilizes NeuroD during differentiation of mechanoreceptors.

The peptidyl prolyl cis-trans isomerase Pin1 plays vital roles in diverse cellular processes and pathological conditions. NeuroD is a differentiation and survival factor for a subset of neurons and pancreatic endocrine cells. Although multiple phosphorylation events are known to be crucial for NeuroD function, their mechanisms remain elusive. In this study, we demonstrate that zebrafish embryos deficient in Pin1 displayed phenotypes resembling those associated with NeuroD depletion, characterized by defects in formation of mechanosensory hair cells. Furthermore, zebrafish Pin1 interacts with NeuroD in a phosphorylation-dependent manner. In Pin1-deficient cell lines, NeuroD is rapidly degraded. However, the protein stability of NeuroD is restored upon overexpression of Pin1. These findings suggest that Pin1 functionally regulates NeuroD protein levels by post-phosphorylation cis-trans isomerization during neuronal specification.

Comprehensive pan-cancer analysis reveals NUSAP1 is a novel predictive biomarker for prognosis and immunotherapy response.

Nucleolar and spindle-associated protein 1 (NUSAP1) is a microtubule-associated protein that plays a crucial role in mitosis. Despite initial reports suggesting a potential involvement of NUSAP1 in tumor progression and malignant cell regulation, there has been no systematic analysis of its role in the tumor immune microenvironment, nor its predictive value for prognosis and immunotherapy response across different cancer types. In this study, we analyze NUSAP1 mRNA and protein expression levels in various human normal and tumor tissues, using data from TCGA, GTEx, CPTAC, HPA databases, and clinical samples. Our findings reveal that NUSAP1 is highly expressed in multiple tumor tissues across most cancer types and is primarily expressed in malignant and immune cells, according to single-cell sequencing data from the TISCH database. Prognostic analysis based on curated survival data from the TCGA database indicates that NUSAP1 expression levels can predict clinical outcomes for 26 cancer types. Furthermore, Gene Set Enrichment Analysis (GSEA) suggests that NUSAP1 promotes cell proliferation, tumor cell invasion, and regulation of anti-tumor response. Analysis of immune score, immune cell infiltration, and anti-cancer immunity cycle using ESTIMATE, TIMER, and TIP databases show that high NUSAP1 levels are associated with low CD4+T and NKT cell infiltration but high Th2 and MDSC infiltration, inversely correlated with antigen-presenting molecules and positively correlated with a variety of immune negative regulatory molecules. Notably, patients with melanoma, lung, and kidney cancer with high NUSAP1 expression levels have shorter survival times and lower immunotherapy response rates. Using Cmap analysis, we identify Entinostat and AACOCF3 as potential inhibitors of NUSAP1-mediated pro-oncogenic effects. In vitro and in vivo experiments further confirm that NUSAP1 knockdown significantly reduces the proliferation ability of A549 and MCF-7 cells. Overall, our study highlights the potential of NUSAP1 expression as a novel biomarker for predicting prognosis and immuno-therapeutic efficacy across different human cancers and suggests its potential for developing novel antitumor drugs or improving immunotherapy.

Long non-coding RNA X-Inactive Specific Transcript (XIST) interacting with USF2 promotes osteogenic differentiation of periodontal ligament stem cells through regulation of WDR72 transcription.

BACKGROUND: Periodontal ligament stem cells (PDLSCs) are the most potential cells in periodontal tissue regeneration and bone tissue regeneration. Our prior work had revealed that WD repeat-containing protein 72 (WDR72) was crucial for osteogenic differentiation of PDLSCs. Here, we further elucidated its underlying mechanism in PDLSC osteogenic differentiation. METHODS: Human PDLSCs, isolated and identified by flow cytometry, were prepared for osteogenic differentiation induction. Levels of WDR72, long non-coding RNA X-Inactive Specific Transcript (XIST), upstream stimulatory factor 2 (USF2), and osteogenic marker genes (Runx2, Osteocalcin, and Collagen I) in human PDLSCs and clinical specimens were detected by RT-qPCR. Protein expressions of WDR72, Runx2, Osteocalcin, and Colla1 were tested by Western blot. The interactions among the molecules were verified by RIP, RNA pull-down, ChIP, and luciferase reporter assays. Osteogenic differentiation was evaluated by alkaline phosphatase (ALP) and alizarin red staining (ARS). RESULTS: WDR72 was decreased in periodontal tissues of periodontitis patients, and overexpression reversed TNF-α-mediated suppressive effects on PDLSC osteogenic differentiation. Mechanically, XIST recruited the enrichment of USF2 to the WDR72 promoter region, thereby positively regulating WDR72. WDR72 silencing overturned XIST-mediated biological effects in PDLSCs. CONCLUSION: WDR72, regulated by the XIST/USF2 axis, enhances osteogenic differentiation of PDLSCs, implying a novel strategy for alleviating periodontitis.

Optical properties and molecular composition of wintertime atmospheric water-soluble organic carbon in different coastal cities of eastern China.

To evaluate the optical properties and molecular composition of water-soluble organic carbon (WSOC) in the atmosphere of coastal cities, particle samples were collected in Tianjin, Qingdao and Shanghai, three coastal cities in eastern China. Subsequent analysis by ultraviolet visible and fluorescence spectrometer and electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry were performed. The results showed that the concentration levels and light absorption ability of WSOC decreased from the north to south cities, ranking as Tianjin > Qingdao > Shanghai. Three major fluorescent components including less­oxygenated humic-like substances (52-60 %), highly­oxygenated humic-like substances (15-31 %) and protein-like substances (17-31 %) were identified in WSOC based on the fluorescence spectroscopy and parallel factor analysis, which might be closely related to anthropogenic emissions and continental sources as well as secondary formation processes. Five subgroups of molecular components were further identified in WSOC, including the predominant CHON compounds (35-43 %), sulfur-containing compounds (i.e., CHONS and CHOS compounds, 24-43 %), CHO compounds (20-26 %) and halogen-containing compounds (1-7 %). Compared to marine air masses influenced samples, WSOC affected by continental air masses exhibited higher light absorption coefficients and generally had a higher degree of aromaticity and unsaturation, as well as contained more molecular formulas of WSOC, especially enriched with sulfur-containing compounds. In contrast, relatively more abundant halogen-containing compounds were identified in the marine air masses influenced samples. Overall, this study provided new insights into the light-absorbing and chemical properties of WSOC in coastal cities, especially under the influences of continental and marine air masses.

Sex-specific effect of perfluoroalkyl substances exposure on liver and thyroid function biomarkers: A mixture approach.

Although studies have investigated the effects of perfluoroalkyl substances (PFASs) on liver and thyroid function, little is known about its combined and sex-specific effect. A total of 688 participants were interviewed and serum PFASs concentration was measured using liquid chromatography/mass spectrometry. Five biomarkers of liver and thyroid function (ALT, GGT, TSH, FT3 and FT4) were chosen as outcomes. A restriction cubic spline function was applied to capture the dose-response relationship between PFASs and liver enzymes and thyroid hormones. Multivariable regression and Bayesian kernel machine regression (BKMR) models were performed to assess the single and overall associations of PFASs with targeted biomarkers. Single-pollutant analyses indicated that increased PFASs concentrations were associated with elevated ALT and GGT levels. BKMR models suggested positive dose-response relationships between PFASs mixtures and ALT and GGT levels. Significant associations were only detected between several PFASs and thyroid hormones, and joint effect of PFASs mixtures on FT3 levels was found at higher concentrations. Meanwhile, sex differences were found in the associations of PFASs with ALT and GGT levels, with significant results only in males. Our findings provide epidemiological evidence for combined and sex-specific effects of PFASs on ALT and GGT levels.

Efficacy of Continuous Renal Replacement Therapy and Intermittent Hemodialysis in Patients with Renal Failure in Intensive Care Unit: A Systemic Review and Meta-analysis.

Objective: This study aimed to compare the clinical efficacy of continuous renal replacement therapy (CRRT) and intermittent hemodialysis (IHD) in patients with renal failure in intensive care unit (ICU). Methods: Relevant studies were searched in the databases including EMBASE, Cochrane Library, and MEDLINE (PubMed) from inception to January 04, 2021. The inclusion of available studies and the collection of data were independently conducted by two authors after reviewing the full text. Pooled analyses of relative risk (RR) and weighted mean difference (WMD) were performed to compare the outcomes of renal recovery, short-term mortality, length of ICU stays, and length of in-hospital stays between the two different treatment groups. Publication bias was assessed by the funnel plot. Results: A total of 11 RCT studies including 1740 patients with renal failure were eligible for final analysis. Among them, 894 patients (51.4%) underwent CRRT and 846 patients (48.6%) received IHD. Pooled analysis did not find significant differences in renal recovery and short-term mortality between the two groups. Interestingly, patients underwent CRRT showed significantly shorter length of ICU stay and in-hospital stay than those who underwent IHD (ICU stay: RR: -0.61, 95%CI: -1.10--0.11, P < 0.05; I2 = 93.6%; in-hospital stay: RR: -0.56, 95%CI: -1.41-0.28, P < 0.05; I2 = 97.7%). No significant publication biases were observed on the funnel plots. Conclusion: Compared with IHD, CRRT had similar effects on renal recovery and short-term mortality in patients with renal failure in ICU. As a promising technique in clinical practice, CRRT could significantly reduce the length of ICU stay and in-hospital stay of patients, which was of great significance for the reduction of medical costs and the long-term benefits of patients, thereby reducing the burden on society and individuals.

Characteristics of wintertime carbonaceous aerosols in two typical cities in Beijing-Tianjin-Hebei region, China: Insights from multiyear measurements.

In order to investigate the impact of "Blue Sky War" implemented during 2018-2020 on carbonaceous aerosols in Beijing-Tianjin-Hebei (BTH) region, China, fine particulate matter (PM2.5) samples were collected simultaneously in Tianjin and Handan in three consecutive winters from 2018 to 2020. Organic carbon (OC) and elemental carbon (EC) in PM2.5 were measured with the same thermal-optical methods and analysis protocols. Significant reductions in primary organic carbon (POC) and EC concentrations were observed both in Tianjin and Handan, with decreasing rates of 0.65 and 2.95 µg m-3 yr-1 for POC and 0.13 and 0.64 µg m-3 yr-1 for EC, respectively. The measured absorption coefficients of EC (babs, EC) also decreased year by year, with a decreasing rate of 1.82 and 6.16 Mm-1 yr-1 in Tianjin and Handan, respectively. The estimated secondary organic carbon (SOC) concentrations decreased first and then increased in both Tianjin and Handan, accounting for more than half of the total OC in winter of 2020-2021 and with increasing contributions especially in highly polluted days. SOC was recognized as one of key factors influencing EC light absorption. EC in the two cities was relatively more related to coal combustion and industrial sources. The reductions of primary carbonaceous components may be attributed to the air quality regulations targeting coal combustion and industrial sources emissions in BTH area. Potential source contribution function (PSCF) analysis results indicated that the major source areas of OC and EC in Tianjin were the southwest region of the sampling site, while the southeast areas for Handan. These findings demonstrated the effectiveness of air quality regulation in primary emissions in typical polluted cities in BTH region and highlighted the needs for further control and in-depth investigation of SOC formation along with implementation of air pollution control act in the future.

Association of urinary polycyclic aromatic hydrocarbon metabolites with symptoms among autistic children: A case-control study in Tianjin, China.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous pollutants that are associated with altered neurodevelopment and various neurodevelopmental disorders. However, studies evaluating internal biomarkers of PAH exposure in reference to the severity of autism spectrum disorder (ASD) symptomology and autistic behaviors are scarce. Hence, we conducted a case-control study evaluating 12 urinary hydroxylated PAH metabolites (i.e., hydroxy-PAHs) in 101 children with autism and 101 neurotypical children, matching according to sex and age in a 1:1 ratio. In children with ASD, the severity of symptomology and autistic behaviors were assessed using the child autism rating scale (CARS) and the autism behavior checklist (ABC). We found that urinary levels of nine of the hydroxy-PAHs were statistically significantly higher in the ASD group, with the exception of 2-hydroxynaphthalene (2-OHNap) and 4-hydroxyphenanthrene (4-OHPhe). Moreover, urinary hydroxy-PAH levels were associated with ASD risk, with odds ratios ranging from 1.86 to 17.19. Exposures to 1-hydroxynaphthalene (1-OHNap, ß = 3.32), hydroxyphenanthrenes (1/2/3 + 9-OHPhes, ß = 3.41-5.12), 1-hydroxypyrene (1-OH-Pyr; ß = 3.91), 2-hydroxybenzofuran (2-OHDBF; ß = 3.93), and ∑OH-PAHs (ß = 4.67) were positively associated with CARS scores after adjusting for covariates (all p < 0.05). When applying the ABC scale, 1-OHPyr levels were positively associated with ABC total scores (ß = 18.54), with the strongest associations evidenced in regard to the social relatedness (ß = 6.51) and language domains (ß = 6.51) (all p < 0.05). Bayesian kernel machine regression (BKMR) showed consistent positive exposure responses for 1-OHNap, 1-OHPhe, and 3 + 9-OHPhe levels in regard to CARS scores, and for 1-OHPyr levels in regard to ABC total scores. Our findings suggest that children with ASD may have higher urinary levels of hydroxy-PAHs, and that these biomarker levels are associated with an increased odds of ASD, an increased severity of autism symptomology, and increased autistic behaviors in children with autism. LAY SUMMARY: We conducted an epidemiologic study evaluating the associations of urinary hydroxy-PAH levels with autism spectrum disorder (ASD), autism symptomology, and autistic behaviors. We found that urinary hydroxy-PAHs were statistically significantly associated with ASD. We note strong statistically significant associations between 1-OHNap, 1-OHPhe, and 3 + 9-OHPhe levels and increased severity of autism symptomology, as well as a strong statistically significant association between 1-OHPyr levels and behavioral characteristics within the social and linguistic domains. This work, if confirmed, will contribute to the future development of diagnostics for children with mild autism, as well as to environmental measures to promote the health and wellbeing of children with autism spectrum disorders.

Perfluoroalkyl substances (PFASs) as risk factors for breast cancer: a case-control study in Chinese population.

BACKGROUND: Perfluoroalkyl substances (PFASs) are a large family of synthetic chemicals, some of which are mammary toxicants and endocrine disruptors. Recent studies have implicated exposure to PFASs as a risk factor for breast cancer in Europe and America. Little is known about the role of PFASs with respect to breast cancer in the Chinese population. METHODS: Participants who were initially diagnosed with breast cancer at Tianjin Medical University Cancer Institute and Hospital between 2012 and 2016 were recruited as cases. The controls were randomly selected from the participants with available blood samples in the Chinese National Breast Cancer Screening Program (CNBCSP) cohort. Ultimately, we enrolled 373 breast cancer patients and 657 controls. Plasma PFASs were measured by an ultra-performance liquid chromatography (UPLC) system coupled to a 5500 Q-Trap triple quadrupole mass spectrometer. A logistic regression model with least absolute shrinkage and selection operator (LASSO) regularization was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) to assess the relationships between PFASs and breast cancer. The three most predictive variables in the LASSO model were selected from 17 PFASs, which was based on the optimal penalty coefficient (λ = 0.0218) identified with the minimum criterion. Additionally, Bayesian kernel machine regression (BKMR) and quantile g-computation models were applied to evaluate the associations between separate and mixed exposure to PFASs and breast cancer. RESULTS: Perfluorooctanesulfonic acid (PFOS) exhibited the highest concentration in both the cases and controls. Perfluorooctanoic acid (PFOA) and perfluoro-n-decanoic acid (PFDA) were positively associated with breast cancer, and perfluoro-n-tridecanoic acid (PFTrDA) was negatively associated with breast cancer according to both the continuous-PFASs and the quartile-PFASs logistic regression models. Of note, PFOA was associated with the occurrence of estrogen receptor (ER)-, progesterone receptor (PR)-, and human epidermal growth factor receptor 2 (HER2)-positive breast cancer (ORER+ = 1.47, 95% CI: 1.19, 1.80; ORPR+ = 1.36, 95% CI: 1.09, 1.69; ORHER2 = 1.62, 95% CI: 1.19, 2.21). CONCLUSIONS: Overall, we observed that PFASs were associated with breast cancer in Chinese women. Prospective cohort studies and mechanistic experiments are warranted to elucidate whether these associations are causal.

The Longitudinal Plasma Modes of κ-Deformed Kaniadakis Distributed Plasmas Carrying Orbital Angular Momentum.

Based on plasma kinetic theory, the dispersion and Landau damping of Langmuir and ion-acoustic waves carrying finite orbital angular momentum (OAM) were investigated in the κ-deformed Kaniadakis distributed plasma system. The results showed that the peculiarities of the investigated subjects relied on the deformation parameter κ and OAM parameter η. For both Langmuir and ion-acoustic waves, dispersion was enhanced with increased κ, while the Landau damping was suppressed. Conversely, both the dispersion and Landau damping were depressed by OAM. Moreover, the results coincided with the straight propagating plane waves in a Maxwellian plasma system when κ=0 and η→∞. It was expected that the present results would give more insight into the trapping and transportation of plasma particles and energy.

SS31 Ameliorates Oxidative Stress via the Restoration of Autophagic Flux to Protect Aged Mice From Hind Limb Ischemia.

Background: Oxidative stress and impaired autophagic flux play important roles in the development of peripheral artery disease (PAD). SS31 is considered an important antioxidant peptide and autophagy regulator. We aimed to investigate the role of SS31 in PAD myopathy and its possible mechanism both in vivo and in vitro. Methods: A hind limb ischemia (HLI) model was established with old C57BL/6 (14-month-old) mice. Mice in the SS31 group were intraperitoneally injected with SS31 (3 mg/kg) for 4 weeks. We examined skeletal muscle function and histomorphology, autophagy-related protein levels and reactive oxygen species (ROS) content. For the in vitro experiments, after C2C12 myotubes were treated with CoCl2, SS31, and chloroquine (CQ) or rapamycin (RAPA), we measured ROS content, autophagy-related protein levels and antioxidant enzyme expression. Results: SS31 treatment effectively enhanced the recovery of skeletal muscle function, alleviated skeletal muscle injury and suppressed mitochondrial ROS production in ischemic limbs. SS31 reduced apoptosis and oxidative stress, and SS31 restored impaired autophagic flux by inhibiting the AKT-mTOR pathway. In vitro studies showed that SS31 restored autophagic flux and improved oxidative stress in C2C12 cells. Moreover, phosphorylated AKT (p-AKT) and phosphorylated mTOR (p-mTOR) levels were reduced. Conclusion: These experiments indicated that SS31 can inhibit oxidative stress by restoring autophagic flux to reverse hypoxia-induced injury in vivo and in vitro.

Associations between exposure to perfluoroalkyl substances and birth outcomes: A meta-analysis.

Although previous meta-analyses have shown that prenatal PFASs exposure is associated with reduction in birth weight, effects of prenatal PFASs exposure on birth outcomes have not been fully explored. We conducted a meta-analysis of 23 eligible studies searched from Embase, PubMed, and Web of Science before March 21, 2021 to analyze the association between prenatal PFASs exposure and birth outcomes, including premature birth (PTB), low birth weight (LBW), small for gestational age (SGA) and miscarriage. Odds ratio (OR) and corresponding confidence intervals were extracted for analysis. According to the heterogeneity of the included studies, fixed-effects (I2 ≤ 50%) and random-effects (I2 > 50%) models were applied respectively. The significant associations between PFOS and PTB (pooled OR = 1.54, 95% CI: 1.20-1.98), PFOA and miscarriage (pooled OR = 1.40, 95% CI: 1.15-1.70), and PFOS and LBW (pooled OR = 1.52, 95% CI: 1.19-1.94) were obtained. There were differences between included studies with different study regions, sampling time, and samples type used for PFASs assessment. These findings may provide insight in risk assessment and decision-making in producing products that contain PFASs.

Transgenerational male reproductive effect of prenatal arsenic exposure: abnormal spermatogenesis with Igf2/H19 epigenetic alteration in CD1 mouse.

Developmental exposure to environmental toxicants can induce transgenerational reproductive disease phenotypes through epigenetic mechanisms. We treated pregnant CD-1 (F0) mice with drinking water containing sodium arsenite (85 ppm) from days 8 to 18 of gestation. Male offspring were bred with untreated female mice until the F3 generation was produced. Our results revealed that F0 transient exposure to arsenic can cause decreased sperm quality and histological abnormalities in the F1 and F3. The overall methylation status of Igf2 DMR2 and H19 DMR was significantly lower in the arsenic-exposed group than that of the control group in both F1 and F3. The relative mRNA expression levels of Igf2 and H19 in arsenic-exposed males were significantly increased in both F1 and F3. This study indicates that ancestral exposure to arsenic may result in transgenerational inheritance of an impaired spermatogenesis phenotyping involving both epigenetic alterations and the abnormal expression of Igf2 and H19.

A systematic review and meta-analysis of catheter ablation for atrial fibrillation.

BACKGROUND: This study analyzes and compares the efficacy of using catheter ablation (CA) and traditional drug treatments for atrial fibrillation (AF). Through a systematic review and meta-analysis, it seeks to provide a theoretical basis for using clinical CA for patients with AF. METHODS: We searched through articles detailing randomly controlled trials (RCTs) that assessed the surgical effect of CA on the treatment of AF. These articles were published before January 31, 2000 in various English databases, including PubMed, Embase, Medline, Ovid, Springer, and Web of Sciences. The Cochrane Handbook for Systematic Reviews of Intervention 5.0.2 was adopted for the bias risk assessment, and Review Manager 5.3 software was used for the meta-analysis of the articles. RESULTS: A total of 2,098 patients drawn from 13 articles were included in the study. For patients in the experimental group (Exp. group), the meta-analysis showed an increase in the effects of clinical treatment [mean deviation (MD) =3.91; 95% confidence interval (CI), 3.15-4.85; Z=12.36; P<0.00001], an improvement in daily life function (MD =1.45; 95% CI, 1.03-1.87; Z=6.82; P<0.00001), a decrease in body weakness (MD =-2.84; 95% CI, -3.24 to -2.45; Z=14.16; P <0.00001), and an increase in quality of life score (MD =14.15; 95% CI, 7.24-21.05; Z=4.01; P<0.0001). The Exp. group also experienced a reduction in postoperative pain level (MD =-2.5; 95% CI, -3.11 to -1.89; Z=8.04; P<0.00001), reoccurrence of symptomatic AF (OR =0.27; 95% CI, 0.11-0.67; Z=2.82; P=0.005), rehospitalization (MD =0.15; 95% CI, 0.07-0.31; Z=5.11; P<0.00001), other arrhythmia (MD =0.33; 95% CI, 0.18-0.6; Z=3.62; P=0.0003), and pulmonary vein stenosis (PVS) (MD =0.32; 95% CI, 0.14-0.72; Z=2.74; P=0.006). However, in contrast to patients in the control group (Ctrl group), the 'bleeding' mentioned above showed no statistical difference. DISCUSSION: CA has a good postoperative clinical effect on AF patients, reducing incidences of pain, adverse reactions, and rehospitalization. For this reason, CA is a suitable treatment for AF patients who do not effectively respond to drug therapy.

A Bibliometric and Visual Analysis of Global Community Resilience Research.

Resilience is an important issue in urban development, and community resilience (CR) is the most typical representative in building urban resilience, which has become the forefront of international resilience research. This paper presents a bibliometric and visual analysis of community resilience research collected from the WoS Core Collection database over the past two decades. H-index, citation frequency, centrality and starting year were adopted to analyze the research objects by bibliometric tools including CiteSpace, VOSviewer, and Gephi. The national and institutional characteristics of macro-geographical distribution and the characteristics of disciplines, journals, authors, and author cooperation of micro-knowledge network distribution were revealed. Finally, the potential research directions of community resilience in the future were discussed. The results show that there are three stages in community resilience research. Seven intellectual bases constitute the research background for community resilience, including social capital mechanism, the evolution of resilience knowledge, earthquake resistance and disaster mitigation, substance abuse, resilient development in rural communities, resilience-building in the least-developed countries, and emergency preparedness. Our analysis shows that the hottest community resilience research topics are the concept of resilience, climate resilience, the social capital mechanism, macro-environment and disaster-reduction policies, and an evaluation index system for community resilience.

Hyaluronan-Mediated Motility Receptor Governs Chromosome Segregation by Regulating Microtubules Sliding Within the Bridging Fiber.

Accurate segregation of chromosomes during anaphase relies on the central spindle and its regulators. A newly raised concept of the central spindle, the bridging fiber, shows that sliding of antiparallel microtubules (MTs) within the bridging fiber promotes chromosome segregation. However, the regulators of the bridging fiber and its regulatory mechanism on MTs sliding remain largely unknown. In this study, the non-motor microtubule-associated protein, hyaluronan-mediated motility receptor (HMMR), is identified as a novel regulator of the bridging fiber. It then identifies that HMMR regulates MTs sliding within the bridging fiber by cooperating with its binding partner HSET. By utilizing a laser-based cell ablation system and photoactivation approach, the study's results reveal that depletion of HMMR causes an inhibitory effect on MTs sliding within the bridging fiber and disrupts the forced uniformity on the kinetochore-attached microtubules-formed fibers (k-fibers). These are created by suppressing the dynamics of HSET, which functions in transiting the force from sliding of bridging MTs to the k-fiber. This study sheds new light on the novel regulatory mechanism of MTs sliding within the bridging fiber by HMMR and HSET and uncovers the role of HMMR in chromosome segregation during anaphase.

Ghrelin attenuate cerebral microvascular leakage by regulating inflammation and apoptosis potentially via a p38 MAPK-JNK dependent pathway.

Ghrelin is a peptide hormone with strong anti-inflammatory properties. In fact, Ghrelin was reported to improve endothelial dysfunction caused by excessive fat. However, its role in preserving the integrity of brain microvascular, under conditions of lipid dysregulation and inflammation, is not known. The objective of this study is to characterize the role of Ghrelin in the protection of cerebral microvascular integrity, during atherosclerosis, and uncover its underlying molecular mechanism. Our results demonstrated that an atherosclerotic condition, brought on by a high fat diet (HFD), can produce massive increases in serum inflammatory factors, blood lipids, cerebral microvascular leakage, and activation of the p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) (p38 MAPK-JNK) pathway. It also produced significantly damaged pericytes morphology, resulting in pericyte decrease. Ghrelin treatment, on the other hand, protected against cerebral microvascular leakage and pericytes damage. Ghrelin effectively downregulated the expression of pro-inflammatory cytokines, and it also suppressed the p38 MAPK-JNK signaling pathway. Additionally, in isolated mouse cerebral microvascular pericytes, ox-LDL lead to increased apoptosis and secretion of inflammatory factors, along with an elevation in phosphorylated p38 MAPK-JNK proteins. Alternately, Ghrelin administration markedly lowered expression of inflammatory factors, suppressed the p38 MAPK-JNK signaling path, and halted cell apoptosis. However, pretreatment of Hesperetin, a p38 MAPK-JNK agonist, abrogated the Ghrelin-mediated suppression of inflammation and apoptosis in pericytes. Taken together, these results suggest that Ghrelin restored cerebral microvascular integrity and reduced vascular leakage in atherosclerosis mice, in part, by its regulation of inflammatory and apoptotic signaling pathways in pericytes.