Porous Agarose Layered Magnetic Graphene Oxide Nanocomposite for Virus RNA Monitoring in Wastewater.

The detection of virus RNA in wastewater has been established as a valuable method for monitoring Coronavirus disease 2019. Carbon nanomaterials hold potential application in separating virus RNA owing to their effective adsorption and extraction capabilities. However, carbon nanomaterials have limited separability under homogeneous aqueous conditions. Due to the stabilities in their nanostructure, it is a challenge to efficiently immobilize them onto magnetic beads for separation. Here, we develop a porous agarose layered magnetic graphene oxide (GO) nanocomposite that is prepared by agglutinating ferroferric oxide (Fe3O4) beads and GO with agarose into a cohesive whole. With an average porous size of approximately 500 nm, the porous structure enables the unhindered entry of virus RNA, facilitating its interaction with the surface of GO. Upon the application of a magnetic field, the nucleic acid can be separated from the solution within a few minutes, achieving adsorption efficiency and recovery rate exceeding 90% under optimized conditions. The adsorbed nucleic acid can then be preserved against complex sample matrix for 3 days, and quantitatively released for subsequent quantitative reverse transcription polymerase chain reaction (RT-qPCR) detection. The developed method was successfully utilized to analyze wastewater samples obtained from a wastewater treatment plant, detecting as few as 10 copies of RNA molecules per sample. The developed aMGO-RT-qPCR provides an efficient approach for monitoring viruses and will contribute to wastewater-based surveillance of community infections.

[Clinical Practice of Multiple Disciplinary Team Care Model Following the Concept of Palliative Care for Advanced Head and Neck Cancer:Report of One Case].

We provided the palliative care of a multiple disciplinary team care mode to a patient diagnosed with advanced head and neck cancer and her caregivers.People-centered integrated health services were provided according to the specific needs and preferences of individuals.The team-based palliative care relieved the suffering and improved the quality of life of the patient and that of her family who were facing challenges associated with life-threatening illness.

[Standard Process for Palliative Sedation in Peking Union Medical College Hospital].

End-stage patients experience unbearable pain because of refractory symptoms.Palliative sedation is a form of palliative care which relieves patients' agony by lowering their consciousness.Standard palliative sedation can help patients die with dignity.It is distinct from euthanasia and does not alter the survival of patients.Sufficient palliative care is the premise of palliative sedation.Repeated and detailed clinical evaluation,as well as multidisciplinary involvement,is necessary for the standardized implementation of palliative sedation.Here,we proposed the standard process and specifications of palliative sedation in Peking Union Medical College Hospital.Furthermore,we reported a case of palliative sedation for an advanced cancer patient with refractory delirium and living pain to demonstrate its application in clinical practice.

[Community-based Home Hospice Care Model under the Guidance of Tertiary Hospitals].

Community-based home hospice care provided by community service centers and family physician teams aims to alleviate the suffering of terminally ill patients and help them to receive end-of-life care and pass away at home.The Puhuangyu Community Health Service Center established the home hospice care model of PUMCH-Puhuangyu Coordination at the end of 2019.The model has been practiced and improved to date.This paper introduces this model of home hospice care.

[Experience of Community-based Home Hospice Care Practice for 24 Patients in Beijing Puhuangyu Community].

Objective To investigate the feasibility of home hospice care based on the practical experience in Puhuangyu community of Beijing.Methods We selected the patients assessed by hospice care team and receiving home hospice care from Puhuangyu Community Health Service Center of Beijing from January 1,2020 to December 31,2021.The clinical manifestations,hospice services received,and place of death of the patients were analyzed. Results A total of 24 patients were included in this study.They mainly suffered from malignant tumors(18 patients,75.0%),with pain as the most common symptom(12 patients,50.0%).The patients received a variety of hospice services through a combination of outpatient visits,home visits,and WeChat follow-up.The service time of each patient was(2.8±1.7) h each week on average and 57.9%(11/19) of the patients passed away at home. Conclusions The home hospice care in Puhuangyu community has a stable source of patients.The members of this hospice team can provide a variety of home hospice services.With this model,the wish to pass away at home can be achievable for most patients.Therefore,this model of community-based home hospice care is feasible.

[Obstacles in the Practice of Palliative Care Consultation Services in Grade A Tertiary Hospitals].

Objective To explore the obstacles in palliative care consultation services and put forward the suggestions for improving the services in grade A tertiary hospitals. Methods A semi-structured interview was conducted with 17 medical workers who had requested palliative care consultation services in Peking Union Medical College Hospital. Results The palliative care consultation services were hindered by five obstacle factors including insufficient knowledge of patients and their families about palliative care,unsound understanding of medical workers about palliative care,poor implementation of consultation opinions,limited labor of palliative care team,and poor economic benefits from palliative care.In view of such obstacles,the following suggestions were put forward,which included increasing the acceptance of palliative care by patients and their families,enriching the knowledge of medical staff on palliative care,establishing a new cooperation model between consultation team and medical staff,strengthening the institutional guarantee for the development of palliative care,and establishing and perfecting the laws and policies related to palliative care. Conclusion Although there are many difficulties in the in-hospital palliative care consultation services in grade A tertiary hospitals,the demand and expectation of medical staff for palliative care are still increasing.

[Exploration and Practice of the Whole-course Care Mode from Hospital to Home for an Advanced Malignant Tumor Patient].

This paper depicted the whole-course care for an advanced cancer patient from hospital to home.In this case,telemedicine was employed to provide guidance on the symptom control,comfort care,psychotherapy,and bereavement counseling.The patient got the holistic care from the whole family and team.The holistic care finally gave a good death of the patient and aided in the recovery of the family members from grief.

Blood Circulation-Prolonging Peptides for Engineered Nanoparticles Identified via Phage Display.

Sustaining blood retention for theranostic nanoparticles is a big challenge. Various approaches have been attempted and have demonstrated some success but limitations remain. We hypothesized that peptides capable of increasing blood residence time for M13 bacteriophage, a rod-shaped nanoparticle self-assembled from proteins and nucleic acids, should also prolong blood circulation for engineered nanoparticles. Here we demonstrate the feasibility of this approach by identifying a series of blood circulation-prolonging (BCP) peptides through in vivo screening of an M13 peptide phage display library. Intriguingly, the majority of the identified BCP peptides contained an arginine-glycine-aspartic acid (RGD) motif, which was necessary but insufficient for the circulation-prolonging activity. We further demonstrated that the RGD-mediated specific binding to platelets was primarily responsible for the enhanced blood retention of BCP1. The utility of the BCP1 peptide was demonstrated by fusion of the peptide to human heavy-chain ferritin (HFn), leading to significantly improved pharmacokinetic profile, enhanced tumor cell uptake and optimum anticancer efficacy for doxorubicin encapsulated in the HFn nanocage. Our results provided a proof-of-concept for an innovative yet simple strategy, which utilizes phage display to discover novel peptides with the capability of substantially prolonging blood circulation for engineered theranostic nanoparticles.

Predictive and prognostic value of ZEB1 protein expression in breast cancer patients with neoadjuvant chemotherapy.

BACKGROUND: Zinc finger E-box binding homeobox 1 (ZEB1) is a molecule involved in the progression of epithelial-to-mesenchymal transition (EMT) in various kinds of cancers. Here, we aimed to determine whether the expression of the ZEB1 protein is related to the response of patients to neoadjuvant therapy as well as their survival outcome. METHODS: Immunohistochemistry (IHC) was performed on paraffin-embedded tumor samples from core needle biopsy before neoadjuvant therapy (NAT). Univariate and multivariate logistic regression analyses were used to analyze the associations between the protein expression of ZEB1 and the pathological complete response (pCR) outcome. Kaplan-Meier plots and log-rank tests were used to compare disease-free survival (DFS) between groups. A Cox proportional hazards model was used to calculate the adjusted hazard ratio (HR) with a 95% confidential interval (95% CI). RESULTS: A total of 75 patients were included in the IHC test. High ZEB1 protein expression was associated with a low pCR rate in both univariate (OR = 0.260, 95% CI 0.082-0.829, p = 0.023) and multivariate (OR = 0.074, 95% CI 0.011-0.475, p = 0.006) logistic regression analyses. High ZEB1 protein expression was also associated with a short DFS according to both the log-rank test (p = 0.023) and Cox proportional hazard model (HR = 9.025, 95% CI 1.024-79.519, p = 0.048). In hormone receptor positive (HorR-positive) patients, high ZEB1 protein expression was also associated with a lower pCR (OR = 0.054, 95% CI 0.007-0.422, p = 0.005) and a poorer DFS (HR = 10.516, 95% CI 1.171-94.435, p = 0.036) compared with low ZEB1 protein expression. In HER2-overexpressing patients, ZEB1 protein expression was also associated with poor survival (p = 0.042). CONCLUSIONS: Our results showed that high ZEB1 protein expression was a negative predictive marker of pCR and DFS in neoadjuvant therapy in breast cancer patients and in HorR-positive and HER2-overexpressing subgroups.Trial registration NCT, NCT02199418. Registered 24 July 2014-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02199418?term=NCT02199418&rank=1. NCT, NCT 02221999. Registered 21 August 2014-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02221999?term=NCT02221999&rank=1.

2,3,7,8-Tetrachlorodibenzo-p-dioxin promotes migration ability of primary cultured rat astrocytes via aryl hydrocarbon receptor.

Emerging evidence showed that 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) could induce expression of certain reactivation-associated genes in astrocytes, however, the consequent cellular effects and molecular mechanisms are still unclear. During the process of astrocyte reactivation, migration is a critical cellular event. In the present study, we employed wound-healing assay and Transwell® motility assay to explore the effects of TCDD on cell migration in primary cultured rat cortical astrocytes. We found that upon TCDD treatments at relative low concentrations (10-10 and/or 10-9 mol/L), the ability of primary astrocytes to migrate horizontally and vertically was promoted. In line with this cellular effect, the mRNA expression of two pro-migratory genes, including cell division cycle 42 (CDC42) and matrix metalloproteinase 2 (MMP2) was induced by TCDD treatment. Dioxin exerts its toxic effects mainly through aryl hydrocarbon receptor (AhR) pathway. So the role of AhR pathway in the pro-migratory effects of TCDD was examined using an AhR antagonist, CH223191. We found that application of CH223191 significantly reversed the pro-migratory effects of TCDD. Interestingly, the basal ability of horizontal migration as well as basal levels of CDC42 and MMP2 expression were dramatically reduced suggesting a possible physiological role of AhR in maintaining the endogenous migration ability of the primary astrocytes. These findings support the notion that dioxin promotes astrocyte reactivation at molecular and cellular levels.

Dioxin induces expression of hsa-miR-146b-5p in human neuroblastoma cells.

Dioxin can cause a series of neural toxicological effects. MicroRNAs (miRs) play important roles in regulating nervous system function and mediating cellular responses to environmental pollutants, such as dioxin. Hsa-miR-146b-5p appears to be involved in neurodegenerative diseases and brain tumors. However, little is known about effects of dioxin on the expression of hsa-miR-146b-5p. We found that the hsa-miR-146b-5p expression and its promoter activity were significantly increased in dioxin treated SK-N-SH cells, a human-derived neuroblastoma cell line. Potential roles of hsa-miR-146b-5p in mediating neural toxicological effects of dioxin may be due to the regulation of certain target genes. We further confirmed that hsa-miR-146b-5p significantly suppressed acetylcholinesterase (AChE) activity and targeted the 3'-untranslated region of the AChE T subunit, which has been down-regulated in dioxin treated SK-N-SH cells. Functional bioinformatic analysis showed that the known and predicted target genes of hsa-miR-146b-5p were involved in some brain functions or cyto-toxicities related to known dioxin effects, including synapse transmission, in which AChE may serve as a responsive gene for mediating the effect.

Identification of differentially expressed genes response to TCDD in rat brain after long-term low-dose exposure.

Several cohort studies have reported that dioxin and dioxin-like polychlorinated biphenyls might impair the nervous system and lead to neurological or neurodegenerative diseases in the elder people, but there is limited research on the involved mechanism. By using microarray analysis, we figured out the differentially expressed genes between brain samples from SD rats after low-dose (0.1µg/(kg▪bw)) dioxin exposure for six months and controls. To investigate the function changes in the course of dioxin exposure, Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on the differentially expressed genes. And the changes of several picked genes have been verified by real-time PCR. A total of 145 up-regulated and 64 down-regulated genes were identified. The metabolic processes, interleukin-1 secretion and production were significantly associated with the differentially expressed genes. And the genes regulated by dioxin also clustered to cholinergic synapse and long-term potentiation. Candidate biomarker genes such as egr1, gad2, gabrb3, abca1, ccr5 and pycard may be toxicological targets for dioxin. Furthermore, synaptic plasticity and neuro-immune system may be two principal affected areas by dioxin.

Inpatient care burden due to cancers in Anhui, China: a cross-sectional household survey.

BACKGROUND: The financial burden of cancers has profound effects and there is a clear need to explore the issue from different perspectives and for different population groups. This study aimed at investigating inpatient cancer care (ICC) burden in Anhui, a typical inland province of China. METHODS: The study collected data through a household survey conducted during April to November, 2014 using cluster-randomized sampling and a structured questionnaire administered face-to-face by trained interviewers. RESULTS: The survey covered 60,678 urban and rural residents and 318 person-times of ICC during the past year. Age-adjusted annual person-times and days of ICC per thousand population added up to 4.24 and 76.78 respectively and urban residents showed significantly greater admission rates and length of stay than that of rural ones. Total ICC expenditures accounted for 13.30 % of all that of inpatient care for the whole population. Per-case direct and indirect costs of all types of cancers were estimated as 10365.1 and 929.9 RMB. Per-case total cost on ICC at township hospitals was 2142.3 RMB and at province level hospitals, 17133.0 RMB. Significant variations in per-case ICC expenditures also existed between patients with different household income and type of medical insurance systems, but patients suffering from different types of cancers. Out-of-pocket payment due to ICC turned out to be catastrophic for 20.6 % of all cancer patients and 65.2 % for other medical insurance, 45.6 % for enrollees of urban and rural medical insurance, 43.2 % for the 65 to 74 years old. Multi regression revealed statistically significant association between ICC costs and education, reimbursement ratio, household income and level of hospital. CONCLUSIONS: Cancers characterize low incidence, moderate service use and high expenses. There exist substantial differences between subgroups and part of these variations cannot be explained by pathological factors. ICC expenses are catastrophic in nature to a large part of patients. There is a clear need for more effectively regulating cancer-related medical practices and service seeking behaviors.

Assessment and model guided cancer screening promotion by village doctors in China: a randomized controlled trial protocol.

BACKGROUND: Proven cost-effectiveness contrasted by low uptake of cancer screening (CS) calls for new methodologies promoting the service. Contemporary interventions in this regard relies primarily on strategies targeting general or specific groups with limited attention being paid to individualized approaches. This trial tests a novel package promoting CS utilization via continuous and tailored counseling delivered by primary caregivers. It aims at demonstrating that high risk individuals in the intervention arm will, compared to those in the delayed intervention condition, show increased use of CS service. METHODS/DESIGN: The trial adopts a quasi-randomized controlled trial design and involves 2160 high risk individuals selected, via rapid and detailed risk assessments, from about 72,000 farmers aged 35+ in 36 administrative villages randomized into equal intervention and delayed intervention arms. The CS intervention package uses: a) village doctors and village clinics to deliver personalized and thus relatively sophisticated CS counseling; b) two-stage risk assessment models in identifying high risk individuals to focus the intervention on the most needed; c) standardized operation procedures to guide conduct of counseling; d) real-time effectiveness and quality monitoring to leverage continuous improvement; e) web-based electronic system to enable prioritizing complex determinants of CS uptake and tailoring counseling sessions to the changing needs of individual farmers. The intervention arm receives baseline and semiannual follow up evaluations plus CS counseling for 5 years; while the delayed intervention arm, only the same baseline and follow-up evaluations for the first 5 years and CS counseling starting from the 6th year if the intervention proved effective. Evaluation measures include: CS uptake by high risk farmers and changes in their knowledge, perceptions and self-efficacy about CS. DISCUSSION: Given the complexity and heterogeneity in the determinant system of individual CS service seeking behavior, personalized interventions may prove to be an effective strategy. The current trial distinguishes itself from previous ones in that it not only adopts a personalized strategy but also introduces a package of pragmatic solutions based on proven theories for tackling potential barriers and incorporating key success factors in a synergetic way toward low cost, effective and sustainable CS promotion. TRIAL REGISTRATION: ISRCTN33269053.

eCROPS-CA: a systematic approach toward effective and sustainable cancer prevention in rural China.

BACKGROUND: Effective prevention against cancers depends heavily on sustained individual efforts practicing protective behaviors and avoiding risk factors in a complex sociocultural context, which requires continuous and personalized supports. Contemporary prevention relies primarily on strategies targeting general population with limited attention being paid to individualized approaches. This study tests a novel package called, in acronym of core intervention components, eCROPS-CA that leverages protective behaviors against over 80% leading cancers among high risk individuals via continuous and tailored counseling by village doctors. METHODS/DESIGN: The study utilizes a quesi-RCT design involving 4320 high risk individuals selected, via rapid and detailed risk assessments, from about 72,000 farmers aged 35+ in 36 administrative villages randomized into equal intervention and delayed intervention arms. The intervention arm receives baseline and semiannual follow up evaluations plus eCROPS-CA for 5 years; while the control arm, only the baseline and follow-up evaluations for the first 5 years and eCROPS-CA starting from the 6(th) year if the intervention is proved effective. eCROPS-CA comprises electronic supports and supervision (e), counseling cancer prevention (C), recipe for objective behaviors (R), operational toolkit (O), performance-based incentives (P), and screening and assessment (S). Evaluation measures include: incidence and stage of the leading cancers, cancer-related knowledge, attitudes and practices; easy biophysical indicators (e.g., body mass index, blood pressure); intervention compliance, acceptance of the package. DISCUSSION: The prevention package incorporates key success factors in a synergetic way toward cost-effectiveness and long-term sustainability. It targets a set rather than any single cancer; choses village doctors as key solution to the widespread lack of professional manpower in implementing personalized and thus relatively sophisticated prevention; adopts real-time monitoring in reaching continuous improvement; utilizes smart web aids to enable prioritizing complex determinants of objective behaviors, linking counseling sessions happened at different time points and hence delivering highly coordinated prevention; uses 2-stage risk assessment models in identifying high risk individuals so as to focus on the most needed; applies standardized operation procedures in simplifying and smoothing behavior intervention yet ensuring delivery of essential steps and key elements. TRIALS REGISTRY: ISRCTN33269053.

Cuproptosis-related genes predict prognosis and trastuzumab therapeutic response in HER2-positive breast cancer.

Breast cancer is the most common diagnosed cancer, the HER2-positive subtype account for 15% of all breast cancer. HER2-targeted therapy is the mainstay treatment for HER2-positive breast cancer. Cuproptosis is a novel form of programmed cell death, and is caused by mitochondrial lipoylation and destabilization of iron-sulfur proteins triggered by copper, which was considered as a key player in various biological processes. However, the roles of cuproptosis-related genes in HER2-positive breast cancer remain largely unknown. In the present study, we constructed a prognostic prediction model of HER2-positive breast cancer patients using TCGA database. Dysregulated genes for cells resistant to HER2-targeted therapy were analyzed in the GEO dataset. KEGG pathway, GO enrichment and GSEA was performed respectively. The immune landscape of DLAT was analyzed by CIBERSORT algorithm and TIDE algorithm. HER2-positive breast cancer patients with high CRGs risk score showed shorter OS. DLAT was downregulated and correlated with better survival of HER2-positive breast cancer patients (HR = 3.30, p = 0.022). High expressed DLAT was associated with resistant to HER2-targeted therapy. Knocking down DLAT with siRNA increased sensitivity of breast cancer to trastuzumab. KEGG pathway and GO enrichment of DEGs indicated that DLAT participates in various pathways correlated with organelle fission, chromosome segregation, nuclear division, hormone-mediated signaling pathway, regulation of intracellular estrogen receptor signaling pathway, condensed chromosome and PPAR signaling pathway. There was a negative correlation between TIDE and DLAT expression (r = - 0.292, p < 0.001), which means high DLAT expression is an indicator of sensitivity to immunotherapy. In conclusion, our study constructed a four CRGs signature prognostic prediction model and identified DLAT as an independent prognostic factor and associated with resistant to HER2-targeted therapy for HER2-positive breast cancer patients.

Application of carbon nanoparticles combined with refined extracapsular anatomy in endoscopic thyroidectomy.

Objective: To evaluate the value of refined extracapsular anatomy combined with carbon nanoparticle suspension tracing technology for protecting parathyroid function and the thoroughness of lymph node dissection in the central region during endoscopic thyroid cancer surgery. Patients and methods: Retrospective clinical data analysis was performed on 108 patients who underwent endoscopic thyroid cancer surgery at the First Affiliated Hospital of Wannan Medical College (Yijishan Hospital) from November 2019 to November 2022. Before surgery, thyroid function tests, color Doppler ultrasounds and neck-enhanced CT scans were performed on all patients. Cytopathological diagnosis obtained via ultrasound-guided fine-needle aspiration served as confirmation for the primary diagnosis. It was determined whether to perform a total thyroidectomy or a hemithyroidectomy (HT) together with preventive unilateral (ipsilateral) central neck dissection. Follow-up times were 1 to 34 months. Results: Transient neuromuscular symptoms were present in 3.70% (4/108) cases, with no permanent neuromuscular symptoms or permanent hypoparathyroidism. Regarding transient hypoparathyroidism, the patients recovered after three months and did not need long-term calcium supplementation. The number of harvested LNs (mean± SD) was 5.54 ± 3.84, with ≤5 in 57.41% (62/108) and >5 in 42.59% (46/108) cases. The number of patients with metastatic LNs was 37.96% (41/108), with ≤2 in 65.85% (27/41) and >2 in 34.15% (14/41) cases. Conclusions: Fine extracapsular anatomy combined with carbon nanoparticle suspension tracing is effective in endoscopic thyroid cancer surgery. It can improve the thoroughness of prophylactic central neck dissection and recognition of the parathyroid gland and avoid parathyroid injury and other complications to effectively protect parathyroid function.

Effects of perinatal TCDD exposure on colonic microbiota and metabolism in offspring and mother mice.

Emerging evidence supports that exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) impacts the gut microbiota and metabolic pathways. TCDD can be transmitted from mother to child; thus, we hypothesize that maternal exposure to TCDD may affect the gut microbiota in mothers and offspring. To acquire in vivo evidence supporting this hypothesis, female C57BL/6 mice were administered with TCDD (0.1 and 10 µg/kg body weight (bw)) during pregnancy and lactation periods, and then changes of colonic microbiota in offspring and mothers were evaluated. High-throughput sequencing of the V4 regions of the 16S rRNA gene was performed. The composition and structure of the colonic microbiota in offspring and mothers were significantly influenced by 10 µg/kg bw TCDD as demonstrated by upregulation of harmful bacteria and downregulation of beneficial bacteria. Paradoxically, pathogenic bacteria and opportunistic pathogens were conversely decreased in the offspring of the low-dose TCDD treatment group. Tryptophan (Trp) metabolism exhibited a noticeable change caused by the alteration of colonic microbiota in offspring after maternal exposure to 10 µg/kg bw TCDD, which showed a linear dependence, demonstrating that pathogens or opportunistic pathogens may accelerate the dysbiosis of Trp metabolism. Trp metabolism dysregulation caused by the changed colonic microbiota may subsequently impact other intestinal segments or even living organisms. Our study provides new evidence indicating a potential influence of early TCDD exposure on the colonic microbiota and metabolism.

HIF-1alpha/VEGF pathway mediates 1,3,6,8-tetrabromo-9 H-carbazole-induced angiogenesis: a potential vascular toxicity of an emerging contaminant.

The dioxin-like substances polyhalogenated carbazoles (PHCZs) may trigger the aryl hydrocarbon receptor (AhR) signaling pathway. Although the crosstalk between AhR and the hypoxia inducible factor-1 (HIF-1) pathways is generally believed to occur, the exact mechanisms of the HIF-1 pathway in PHCZ toxicity have not been determined. We aimed to elucidate the effect of PHCZs on the HIF-1 pathway and its involvement in the regulation of target genes of HIF-1. Herein, we employed human HepG2 cells transiently transfected with a hypoxia response element (HRE) luciferase reporter to identify PHCZs that could influence HIF-1 pathway. We found that exposure to one of the four selected PHCZs, specifically 1,3,6,8-tetrabromo-9 H-carbazole (1368-BCZ), induced a significant enhancement of the activity of HRE activity. In silico data supported 1368-BCZ-induced HIF-1α activity preferentially. Moreover, 1368-BCZ significantly upregulated the expression of HIF-1 target genes, including endothelial growth factor (VEGF) and erythropoietin. Importantly, the stimulated secretion of VEGF by 1368-BCZ promoted the angiogenesis in human umbilical vein endothelial cells. Therefore, the present experimental and computational studies provide new and direct evidence of 1368-BCZ - HIF-1 interaction, which sheds light on the HIF-mediated cardiovascular toxicity and allows a knowledge-based risk assessment of emerging pollutants.

Mobility speed predicts new-onset hypertension: a longitudinal study.

OBJECTIVE: The aim of this study was to investigate whether declining mobility and muscle strength predict new-onset hypertension in suburban-dwelling elderly individuals. METHODS: This study was designed as a longitudinal prospective cohort study. It was comprised of 362 individuals (mean age = 67.8 ± 6.2; 157 men) without hypertension at baseline. At baseline, all participants completed health questionnaires and underwent measurements of mobility [the Timed Up and Go test (TUGT) and 4-m walking test] and muscle strength (grip strength). At 1-year follow-up, we determined the number of participants who had developed new-onset hypertension. We then evaluated the relationship between above metrics and the development of hypertension. RESULTS: In the present study, 94 (26.0%) participants developed hypertension after 1 year. After adjusting for mixed factors, the TUGT scores [hazard ratio = 1.15; 95% confidence interval (CI), 1.10-1.31; P = 0.030] were positively associated with the development of hypertension, while the 4-m walking test scores (hazard ratio = 0.07; 95% CI, 0.01-0.47; P = 0.007) showed an inverse relationship with hypertension incidence. Grip strength (hazard ratio = 1.03; 95% CI, 0.99-1.06; P = 0.098) was not significantly associated with hypertension incidence. CONCLUSION: Our results indicate that people with declining mobility are significantly more likely to develop hypertension. Hence, improving mobility could be protective against hypertension for elderly individuals.