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The Beijing Healthy Aging Cohort Study (BHACS) was established to supplement the limited data of a large representative cohort of older people based on the general population and was designed to evaluate the prevalence, incidence, and natural history of cognitive decline, functional disability, and conventional vascular risk factors. The aim was to determine the evolution of these conditions by estimating the rates and determinants of progression and regression to adverse outcomes, including dementia, cardiovascular events, cancer, and all-cause death. It can therefore provide evidence to help policy makers develop better policies to promote healthy aging in China. BHACS consisted of three cohorts (BLSA, CCHS-Beijing, and BECHCS) in Beijing with a total population of 11 235 (6281 in urban and 4954 in rural areas) and an age range of 55 years or older (55-101 years) with a mean age of 70.35 ± 7.71 years (70.69 ± 7.62 years in urban and 69.92 ± 7.80 years in rural areas). BHACS-BLSA conducted the baseline survey in 2009 with a multistage stratification-random clustering procedure for people aged 55 years or older; BHACS-CCHS-Beijing conducted the baseline survey in 2013-2015 with a stratified multistage cluster random sampling method for people aged 55 years or older; and BHACS-BECHCS conducted the baseline survey in 2010-2014 with two-stage cluster random sampling method for people aged 60 years or older. Data were collected through questionnaires, physical measurements, and laboratory analyses. Topics covered by BHACS include a wide range of physical and mental health indicators, lifestyles and personal, family, and socio-economic determinants of health. There are no immediate plans to make the cohort data freely available to the public, but specific proposals for further collaboration are welcome. For further information and collaboration, please contact the corresponding author Yao He (e-mail: yhe301@x263.net).
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Disfunção Cognitiva , Envelhecimento Saudável , Masculino , Humanos , Idoso , Pessoa de Meia-Idade , Pequim/epidemiologia , Estudos de Coortes , China/epidemiologia , Disfunção Cognitiva/epidemiologiaRESUMO
BACKGROUND: This study aimed to investigate the risks of all-cause and cardiovascular mortality associated with blood pressure (BP) levels of 130-139/80-89 mmHg in Chinese adults with different glucose metabolism, during a long-term follow-up of over 20 years. METHODS: A prospective population-based cohort of 2,132 adults in Shanghai was established in 2002 and followed for 21 years. The association between BP categories and mortality was assessed, and the risk was further analyzed using multiple Cox regression analysis by combining BP and blood glucose categories. RESULTS: The final analysis included 2,004 participants, with 397 all-cause and 166 cardiovascular mortality. The incidence of all-cause and cardiovascular mortality per 1,000 person-years for different BP categories were as follows: BP < 130/80 mmHg (4.5 and 1.3), 130-139/80-89 mmHg (7.7 and 2.9), and ≥ 140/90 mmHg or treated groups (19.9 and 8.7), respectively. After adjusting for age, sex, and other factors, BP ≥ 140/90 mmHg was significantly associated with a higher risk of mortality across different blood glucose categories. However, using BP < 130/80 mmHg and normoglycemia as the reference, a BP of 130-139/80-89 mmHg was significantly associated with higher risks of all-cause (hazard ratio 3.30 [95% confidence interval 1.48-7.38], P < 0.01) and cardiovascular mortality (9.60 [1.93-47.7], P < 0.01) in diabetes, but not in those with normoglycemia or prediabetes. CONCLUSIONS: BP of 130-139/80-89 mmHg may lead to a significantly higher risk of all-cause and cardiovascular mortality in Chinese adults with diabetes, but not in those with normoglycemia or prediabetes. This suggests that the targeted BP for people with diabetes should be < 130-139/80-89 mmHg.
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Doenças Cardiovasculares , Diabetes Mellitus , Hipertensão , Estado Pré-Diabético , Adulto , Humanos , Pressão Sanguínea , Hipertensão/epidemiologia , Estado Pré-Diabético/complicações , Doenças Cardiovasculares/epidemiologia , Glicemia/metabolismo , Estudos Prospectivos , China/epidemiologia , Diabetes Mellitus/epidemiologia , Fatores de RiscoRESUMO
OBJECTIVE: To investigate the mechanism and efficacy of transarterial viroembolization (TAVE) with an oncolytic virus (OH2) for the treatment of liver cancer in rabbit VX2 tumor models. MATERIALS AND METHODS: Subcutaneous tumor and liver cancer models were established to determine the optimal viral titer and administration modality of OH2. Different liver cancer models were established to evaluate the locoregional tumor response, synergistic and standby effects, survival benefit, and specific antitumor immune memory after TAVE treatment. The immune cell densities in tumor tissues were measured. RESULTS: The optimal viral titer of OH2 was 1 × 107 CCID50. TAVE was the most effective modality with greater homogeneous OH2 distribution and therapeutic efficacy compared to other administration routes of transarterial virus infusion (TAVI), commonly adopted intratumor injection (TI), and intravenous injection (IV). Additionally, TAVE treatment significantly improved the locoregional tumor response, standby effect, and survival benefit compared to the TAVI, transarterial embolization (TAE), and control groups. TAVE modified the immune cell densities for immune-excluded liver cancer, partially destroyed vessel metastases, and established antitumor immune memory. The synergistic treatment efficacy of TAVE was superior to the simple addition of two independent monotherapies. CONCLUSION: TAVE was the optimal and a safe modality for treating immune-excluded liver cancer, and its synergistic effect achieved a remarkable tumor response, standby effect, survival benefit, and antitumor immune memory, which providing an innovative therapeutic modality for clinical practice. DATA AVAILABILITY: Data is available from the corresponding author upon requirement.
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Embolização Terapêutica , Neoplasias Hepáticas , Animais , Coelhos , Neoplasias Hepáticas/tratamento farmacológicoRESUMO
INTRODUCTION AND OBJECTIVES: This study aims to explore the association between Klotho and Non-Alcoholic Fatty Liver Disease (NAFLD), a condition affecting millions worldwide. Klotho may have a protective effect against NAFLD mechanisms like inflammation, oxidative stress, and fibrosis. The study will use FLI and FIB-4 score to diagnose NAFLD in a large population for investigating the link between Klotho and NAFLD. MATERIALS AND METHODS: The study aimed to explore the association between Klotho and NAFLD by measuring the α-Klotho protein levels in the participants' blood using ELISA. Patients with underlying chronic liver diseases were excluded. The severity of NAFLD was evaluated using FLI and FIB-4, and logistic regression models were used to analyze the data obtained from NHANES. Subgroup analyses were conducted to study Klotho's effect on hepatic steatosis and fibrosis in diverse subpopulations. RESULTS: The study found that low levels of α-Klotho were associated with NAFLD, with ORs ranging from 0.72 to 0.83. However, high levels of α-Klotho were associated with NAFLD-related fibrosis. The Q4 group showed significant results in individuals aged 51 years or younger and in females. Non-Hispanic White ethnicity, education level of high school or above, non-smoking, non-hypertension, and non-diabetic groups showed negative correlations. CONCLUSIONS: Our study suggests a potential correlation between α-Klotho levels in the blood and NAFLD in adult patients, especially among younger individuals, females and Non-Hispanic Whites. Elevated α-Klotho levels may have therapeutic benefits in treating NAFLD. Further research is required to validate these findings, but they provide new insights for managing this condition.
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Hepatopatia Gordurosa não Alcoólica , Adulto , Feminino , Humanos , Etnicidade , Inflamação , Cirrose Hepática/diagnóstico , Cirrose Hepática/epidemiologia , Cirrose Hepática/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/complicações , Inquéritos Nutricionais , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Selectively replicating herpes simplex virus-2 (HSV-2) vector is a promising treatment for cancer therapy. The insertion of multiple transgenes into the viral genome has been performed to improve its oncolytic activity. METHODS: Herein, we simultaneously constructed five "armed" oncolytic viruses (OVs), designated oHSV2-IL12, -IL15, GM-CSF, -PD1v, and IL7 × CCL19. These OVs delete the ICP34.5 and ICP47 genes with the insertion of transgenes into the deleted ICP34.5 locus. The anti-tumor efficacy in vivo was tested in the syngeneic 4T1 and CT26 tumor-bearing mice model. RESULTS: The OVs showed comparable oncolytic capability in vitro. The combination therapy of oHSV2-IL12, -IL15, GM-CSF, -PD1v, and IL7 × CCL19 exhibited the highest tumor inhibition efficacy compared with the treatment of single OV or two OVs combination. CONCLUSIONS: The OVs armed with different transgenes combination therapy also named 5-valent oHSV2 (also called cocktail therapy) might be an effective therapeutic strategy for solid tumors.
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Neoplasias , Terapia Viral Oncolítica , Vírus Oncolíticos , Animais , Vetores Genéticos/genética , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Herpesvirus Humano 2/genética , Interleucina-12/genética , Interleucina-15/genética , Interleucina-7/genética , Camundongos , Neoplasias/tratamento farmacológico , Terapia Viral Oncolítica/métodos , Vírus Oncolíticos/genéticaRESUMO
BACKGROUND: The tumor microenvironment (TME) is critical in the progression and metastasis of skin cutaneous melanoma (SKCM). Differences in tumor-infiltrating immune cells (TICs) and their gene expression have been linked to cancer prognosis. Given that immunotherapy can be effective against SKCM, we aimed to identify key genes that regulate the immunological state of the TME in SKCM. METHODS: Data from 471 SKCM patients in the The Cancer Genome Atlas were analyzed using ESTIMATE algorithms to generate an ImmuneScore, StromalScore, and EstimateScore for each patient. Patients were classified into low- or high-score groups based on median values, then compared in order to identify differentially expressed genes (DEGs). Then a protein-protein interaction (PPI) network was developed, and a prognostic model was created using uni- and multivariate Cox regression as well as the least absolute shrinkage and selection operator (LASSO). Key DEGs were identified using the web-based tool GEPIA. Profiles of TIC subpopulations in each patient were analyzed using CIBORSORT, and possible correlations between key DEG expression and TICs were explored. Levels of CCL8 were determined in SKCM and normal skin tissue using immunohistochemistry. RESULTS: Two scores correlated positively with the prognosis of SKCM patients. Comparison of the low- and high-score groups revealed 1684 up-regulated and 18 down-regulated DEGs, all of which were enriched in immune-related functions. The prognostic model identified CCL8 as a key gene, which CIBERSORT found to correlate with M1 macrophages. Immunohistochemistry revealed strong expression in SKCM tissue, but failed to detect the protein in normal skin tissue. CONCLUSIONS: CCL8 is a potential prognostic marker for SKCM, and it may become an effective target for melanoma in which M1 macrophages play an important role.
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The treatment of tumors with oncolytic viruses is an important cancer immunotherapy strategy. Interleukin-15 (IL-15) can enhance the antitumor effect of natural killer cells and T cells. An oncolytic herpes simplex type II virus (oHSV2-mIL-15CherryFP) expressing mouse IL-15 was constructed using the CRISPR/Cas9 system, and its antitumor activity in vitro and in vivo was evaluated. In vitro, the mouse interleukin-15 (mIL-15) present in the culture supernatant expressed by oHSV2-mIL-15CherryFP was able to enhance the killing of CT26-GFP tumor cells by T cells. In addition, the intratumoral injection of oHSV2-mIL-15CherryFP inhibited tumor growth in the CT26-iRFP and BGC823-iRFP model. These results indicate that the use of oncolytic herpes simplex virus expressing IL-15 may be a potential therapeutic strategy in tumor immunotherapy.
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The stimulator of interferon genes (STING) connects the innate and adaptive immune system and plays a significant role in antitumor immunity. Over the past decades, endogenous and CDN-derived STING agonists have been a hot topic in the research of cancer immunotherapies. However, these STING agonists are either in infancy with limited biological effects or have failed in clinical trials. In 2020, a non-nucleotide STING agonist MSA-2 was identified, which exhibited satisfactory antitumor effects in animal studies and is amenable to oral administration. Due to its distinctive binding mode and enhanced bioavailability, there have been accumulating interests and an array of studies on MSA-2 and its derivatives, spanning its structure-activity relationship, delivery systems, applications in combination therapies, etc. Here, we provide a comprehensive review of MSA-2 and interventional strategies based on this family of STING agonists to help more researchers extend the investigation on MSA-2 in the future.
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Proteínas de Membrana , Humanos , Proteínas de Membrana/agonistas , Animais , Neoplasias/tratamento farmacológico , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Antineoplásicos/farmacocinética , Antineoplásicos/química , Antineoplásicos/uso terapêuticoRESUMO
The occurrence and progression of skin cutaneous melanoma (SKCM) is strongly associated with immune cells infiltrating the tumor microenvironment (TME). This study examined the expression, prognosis, and immune relevance of SIGLEC9 in SKCM using multiple online databases. Analysis of the GEPIA2 and Ualcan databases revealed that SIGLEC9 is highly expressed in SKCM, and patients with high SIGLEC9 expression had improved overall survival (OS). Furthermore, the mutation rate of SIGLEC9 in SKCM patients was found to be 5.41%, the highest observed. The expression of SIGLEC9 was positively correlated with macrophages, neutrophils and B cells, CD8 + T cells, CD4 + T cells, and dendritic cells, according to TIMER. Based on TCGA-SKCM data, we verified that high SIGLEC9 expression is closely associated with a good prognosis for SKCM patients, including overall survival, progression-free interval, and disease-specific survival. This positive prognosis could be due to the infiltration of immune cells into the TME. Additionally, our analysis of single-cell transcriptome data revealed that SIGLEC9 not only played a role in the normal skin immune microenvironment, but is also highly expressed in immune cell subpopulations of SKCM patients, regulating the immune response to tumors. Our findings suggest that the close association between SIGLEC9 and SKCM prognosis is primarily mediated by its effect on the tumor immune microenvironment.
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Biomarcadores Tumorais , Melanoma , Neoplasias Cutâneas , Microambiente Tumoral , Humanos , Microambiente Tumoral/imunologia , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/mortalidade , Melanoma/imunologia , Melanoma/genética , Melanoma/mortalidade , Melanoma/patologia , Prognóstico , Biomarcadores Tumorais/genética , Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido Siálico/metabolismo , Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido Siálico/genética , Melanoma Maligno Cutâneo , Antígenos CD/genética , Antígenos CD/metabolismo , Linfócitos do Interstício Tumoral/imunologiaRESUMO
Enhancing the synergistic interplay between adsorption and catalytic oxidation to amplify Fenton-like effects remains a pivotal challenge in advancing water pollution remediation strategies. In this study, a suite of novel carriers (SH) composed of silica (SiO2) and hydroxyapatite (HAp) in different ratios were synthesized through an amalgamation of the sol-gel and co-precipitation techniques. Notably, various forms of copper (Cu) species, including Cu2+ ions and Cu nanoclusters (Cu NCs), could be stably incorporated onto the SH surface via meticulous loading and doping techniques. This approach has engendered a new class of Fenton-like catalysts (Cu NCs-SH1-5) characterized by robust acid-base tolerance stability and remarkable recyclability. Compared with the previously reported Cu NCs-HAp, this catalyst with lower Cu species content could achieve better performance in adsorbing and degrading dyes under the aid of hydrogen peroxide (H2O2). The catalyst's dual action sites, specifically the adsorption sites (SiOH, POH, slit pores) and catalytic centers (multivalent Cu species), had clear division of labor and collaborate with each other. Further, reactive oxygen species (ROS) identification and astute electrochemical testing have unveiled the mechanism underpinning the cooperative degradation of dyes by three types of ROS, spawned through electron transfer between the Fenton-like catalyst (Cu NCs-SH) and H2O2. From these insights, the mechanism of synergistic adsorption-catalytic removal was proposed.
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BACKGROUND: Cardiometabolic diseases (CMDs) increases the risk of cognitive decline, but the extent to which this can be offset by adherence to an active integrated lifestyle is unknown. METHODS: This prospective study used the baseline and 2-year follow-up data of 2537 dementia-free elderly ≥60 from PINDEC Project. Lifestyle factors (including physical exercise, social interaction, leisure activities, sleep quality, smoking, and alcohol consumption) were collected and the integrated score was calculated. Participants were divided into three groups based on integrated score tertiles (inactive, ≤3 score; intermediate, 4 score; and active, ≥5). Logistic regression was used in data analysis. RESULTS: 35.2 % participants had 5-6 healthy components, while only 5.4 % had all 6 healthy lifestyles. The multiadjusted odds ratios (ORs, 95 % confidence interval) of early cognitive decline was 1.223 (0.799-1.871) and 1.832 (1.140-2.943) for participants with only one CMD and any two or more CMDs, respectively. An inverse dose-response relationship was found between lifestyle scores and early cognitive decline (Ptrend = 0.017). In participants with active lifestyle, the OR for early cognitive decline comparing the CMDs status of any two or more CMDs vs. CMDs-free was 0.778 (95%CI: 0.302-2.007). Participants with inactive lifestyle and any two or more CMDs had a near 3.4-fold increased risk of early cognitive decline than those without CMDs who had intermediate to active lifestyle (OR = 3.422, 95%CI: 1.764-6.638). LIMITATIONS: Our research lacks information about nutrition. CONCLUSIONS: A dose-response relationship exists between CMDs status and risk of early cognitive decline. However, adherence to an active integrated lifestyle may mitigate this risk.
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Doenças Cardiovasculares , Disfunção Cognitiva , Humanos , Idoso , Estudos Prospectivos , Disfunção Cognitiva/epidemiologia , Estilo de Vida , Encéfalo , Doenças Cardiovasculares/epidemiologiaRESUMO
Background: As the focal point of epidemic prevention and control, the mental health of COVID-19 patients cannot be ignored. Online Mindfulness-Based Stress Reduction (MBSR) allows for the provision of conveniently accessible, effective and low-cost interventions on a large scale. We aim to evaluate the effectiveness of an online MBSR intervention in alleviating anxiety and depression among asymptomatic/mild patients limited by COVID-19-related restrictions. Methods: Fifty-eight patients treated in Sanya Fangcang hospital were randomly allocated to either to the experimental group (n = 29) following daily, for 5 days, an online-based mindfulness intervention or to the control group (n = 29). Patients from both groups underwent online questionnaires including assessment of anxiety and depression status at pre- and post-tests using Self-rating Anxiety Scale and Self-Rating Depression Scale. Results: After the online-based MBSR program, the anxiety and depression scores of the patients in the MBSR group decreased significantly in comparison to the scores of those in the control group (respectively η2 = 0.175, η2 = 0.215, p < 0.001). And the proportion of severe anxiety and depression patients in the MBSR group decreased to 0% which lower than the control group, and the proportion of light anxiety and depression patients was significantly more than that in the control group after the MBSR intervention. Conclusion: The online-based MBSR intervention appears to be an effective way of alleviating anxiety and depression symptoms among COVID-19 patients with associated quarantine in Fangcang hospital. Given the seriousness of mental health threat that could be posed by this ongoing pandemic, our study provides a new idea and method for cost-effective and time-efficient interventions in the future of epidemic prevention and control.
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IMPORTANCE: Little evidence on the association between adiposity measures and all-cause mortality was observed among centenarians, and no targeted development of optimal weight recommendations for them. OBJECTIVE: To comprehensively assess the association between adiposity indices and all-cause mortality among centenarians. DESIGN SETTING, AND PARTICIPANTS: This prospective population-based cohort study included 1002 centenarians registered in 18 counties and cities in Hainan Province from June 2014 to May 2021. The age of participants at baseline was provided by the civil affairs bureau and verified before enrollment. MAIN OUTCOMES AND MEASURES: All-cause mortality was rigorously confirmed as the primary outcome. BMI was calculated by height and weight. BRI was calculated by height and waist circumference. RESULTS: At baseline, the mean (SD) age was 102.8 ± 2.7 years, and 180 participants (18.0%) were men. The median follow-up time was 5.0 (4.8-5.5) years, with 522 deaths. In BMI categories, compared with the lowest group (mean BMI = 14.2 kg/m2), the highest group (mean BMI = 22.2 kg/m2) had lower mortality (hazard ratio [HR], 0.61; 95%CI, 0.47-0.79) (P for trend = 0.001). In BRI categories, compared with the lowest group (mean BRI = 2.3), the highest group (mean BRI = 5.7) had lower mortality (hazard ratio [HR], 0.66; 95%CI, 0.51-0.85) (P for trend = 0.002), and the risk did not decrease after BRI exceeded 3.9 in women. Higher BRI was associated with lower HRs after adjusting for interaction with comorbidities status. E-values analysis suggested robustness to unmeasured confounding. CONCLUSIONS AND RELEVANCE: BMI and BRI were inverse linear associated with mortality risk in the whole population, while BRI was observed to be J-shaped in women. The interaction of lower multiple complication incidence and BRI had a significant effect on the reduced risk of all-cause mortality.
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Adiposidade , Centenários , Masculino , Idoso de 80 Anos ou mais , Humanos , Feminino , Estudos Prospectivos , Índice de Massa Corporal , Estudos de Coortes , Obesidade/epidemiologia , Circunferência da Cintura , Fatores de RiscoRESUMO
OBJECTIVE: To evaluate the associations of lipid indicators and mortality in Beijing Elderly Comprehensive Health Cohort Study. METHODS: A prospective cohort was conducted based on Beijing Elderly Comprehensive Health Cohort Study with 4499 community older adults. After the baseline survey, the last follow-up was March 31, 2021 with an average 8.13 years of follow-up. Cox proportional hazard model was used to estimate the hazard ratios (HR) with 95% CI for cardiovascular disease (CVD) death and all-cause death in associations with baseline lipid indicators. RESULTS: A total of 4499 participants were recruited, and the mean levels of uric acid, body mass index, systolic blood pressure, diastolic blood pressure, fasting plasma glucose, total cholesterol (TC), triglyceride, and low-density lipoprotein cholesterol (LDL-C) showed an upward trend with the increasing remnant cholesterol (RC) quarters (Ptrend < 0.05), while the downward trend was found in high-density lipoprotein cholesterol (HDL-C). During the total 36,596 person-years follow-up, the CVD mortality and all-cause mortality during an average 8.13 years of follow-up was 3.87% (95% CI: 3.30%-4.43%) and 14.83% (95% CI: 13.79%-15.86%) with 174 CVD death participants and 667 all-cause death participants. After adjusting for confounders, the higher level of TC (HR = 0.854, 95% CI: 0.730-0.997), LDL-C (HR = 0.817, 95% CI: 0.680-0.982) and HDL-C (HR = 0.443, 95% CI: 0.271-0.724) were associated with lower risk of CVD death, and the higher level of HDL-C (HR = 0.637, 95% CI: 0.501-0.810) were associated with lower risk of all-cause death. The higher level of RC (HR = 1.276, 95% CI: 1.010-1.613) increase the risk of CVD death. Compared with the normal lipid group, TC ≥ 6.20 mmol/L group and LDL-C ≥ 4.10 mmol/L group were no longer associated with lower risk of CVD death, while RC ≥ 0.80 mmol/L group was still associated with higher risk of CVD death. In normal lipid group, the higher levels of TC, LDL-C and HDL-C were related with lower CVD death. CONCLUSIONS: In community older adults, higher levels of TC and HDL-C were associated with lower CVD mortality in normal lipid reference range. Higher RC was associated with higher CVD mortality, which may be a better lipid indicator for estimating the CVD death risk in older adults.
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The widespread use of halogenated flame retardants in recent years has led to the accumulation of TBBPA in water, which may cause potential harm to living organisms. The phototransformation of the flame retardant TBBPA in alkaline saline water under simulated sunlight irradiation was investigated. The effects of abiotic factors such as the initial concentration of TBBPA, chloride ion concentration, solution pH, inorganic anions and cations, dissolved organic matter (DOM) were studied. The results showed that the phototransformation rate of TBBPA accelerated with the decrease of the initial concentration of TBBPA, the increase of chloride ion concentration and solution pH. The scavenging experiments showed that â¢OH, 1O2, O2â¢- and 3TBBPA* all participated in the phototransformation of TBBPA. The presence of NO3-, CO32-, SO42-, Mg2+, Ca2+, Fe3+ and fulvic acid (FA) all inhibited the phototransformation of TBBPA in the present study. The phototransformation products of TBBPA were detected by liquid chromatography-mass spectrometry (LC-MS), and the phototransformation pathways were proposed. This is the first report on the photo-induced generation of halogen exchange products from TBBPA in saline solutions, which will contribute to a better understanding of the environmental behavior and risks of BFRs in water.
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Retardadores de Chama , Bifenil Polibromatos , Matéria Orgânica Dissolvida , Bifenil Polibromatos/análise , Águas Salinas , Luz SolarRESUMO
BsAb (bispecific antibody)-armed oncolytic viruses (OVs) are effective in regulating tumor microenvironment. However, oHSV2 (oncolytic herpes simplex virus type 2) expressing immune checkpoints targeting BsAb molecules are not reported. Here, we generated oHSV2-armed PD-L1/CD3 BsAb and established pharmacodynamic evaluation models, which suggested that our oHSV2-BsAb molecules have an improved oncolytic potency in vitro and in vivo. The oHSV2 viruses armed with BsAb molecules targeting programmed cell death ligand 1 (PD-L1)/CD3 or CD19/CD3 (oHSV2-PD-L1/CD3-BsAb or oHSV2-CD19/mCD3-BsAb) were constructed; besides inducing oncolysis in virus-infected tumor cells, the modified oncolytic virus oHSV2-PD-L1/CD3-BsAb can also activate peripheral blood mononuclear cells (PBMCs) by releasing PD-L1/CD3 BsAb and thereby induce PBMC-mediated killing of PD-L1-positive tumor cells, regardless of PD-L1 expression level. The expressed PD-L1/CD3 BsAb can upregulate the activation markers of T cells in PBMCs and induce different cytokine secretion. The activation of T cells and the enrichment of related immune regulatory pathways are further confirmed by proteomics. It also demonstrated that the OVs or PBMCs could upregulate PD-L1 expression on the surface of tumor cells through transforming "cold tumors" with low PD-L1 expression into "hot tumors" with high PD-L1 expression, which can facilitate the targeting of BsAb molecules and enhance the effect of oncolysis. oHSV2-PD-L1/CD3-BsAb or oHSV2-CD19/mCD3-BsAb showed an enhanced oncolytic effect in vitro and in vivo compared to backbone virus oHSV2-GFP. Our results showed that the newly designed oHSV2-BsAb had enhanced therapeutic effects against solid tumors and provided a new option of immunotherapy.
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Anticorpos Biespecíficos , Neoplasias , Vírus Oncolíticos , Anticorpos Biespecíficos/genética , Antígenos CD19 , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Herpesvirus Humano 2/genética , Humanos , Leucócitos Mononucleares/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Linfócitos T , Microambiente Tumoral/genéticaRESUMO
Single antigen-targeted chimeric antigen receptor (CAR) T-cell therapy may be insufficient to induce a durable response in pediatric aggressive B-cell lymphomas. This clinical trial examined the feasibility of sequential different B-cell antigen-targeted CAR T-cell therapy for pediatric relapsed/refractory (R/R) Burkitt lymphoma. Twenty-three patients received the first CD19 CAR T-cell infusion. The patients who did not achieve an ongoing complete response (CR) underwent 1 or more sequential infusions of CAR T-cell therapy that targeted CD22 followed by CD20 according to their disease status and CAR T-cell persistence after each infusion. The median time from the last infusion to the cutoff date was 17 months (range, 15-23 months). The estimated 18-month CR rate was 78% (95% confidence interval [CI], 54%-91%). The estimated 18-month progression-free survival rate was 78% (95% CI, 55%-90%), with 78% (95% CI, 37%-94%) in patients with bulky disease and 60% (95% CI, 25%-83%) in patients with central nervous system (CNS) involvement. During the first CD19 CAR T-cell infusion, grade ≥3 cytokine release syndrome (CRS) occurred in 34.8% and neurotoxicity occurred in 21.7% of all patients. During subsequent infusions, there were only a few incidences of grade >2 CRS and neurotoxicity. All adverse events were reversible. The severity of neurotoxicity was not significantly different between patients with CNS involvement and those who did not have CNS involvement. Sequential CAR T-cell therapy may result in a durable response and is safe in pediatric R/R Burkitt lymphoma. Patients with CNS involvement may benefit from sequential CAR T-cell therapy. This trial was registered at www.chictr.org.cn/index.aspx as #ChiCTR1800014457.
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Linfoma de Burkitt , Receptores de Antígenos Quiméricos , Antígenos CD19 , Linfoma de Burkitt/terapia , Criança , Síndrome da Liberação de Citocina , Humanos , Imunoterapia Adotiva/efeitos adversos , Linfócitos TRESUMO
Microplastic (MP) contamination in water has garnered significantly global concerns. The MP removal particularly challenges when the particle size decreases to several microns and other contaminants co-exist. This study used the coagulative colloidal gas aphrons (CCGAs) to simultaneously remove the micron-scale MP particles (~5 µm in diameter) and dissolved organic matter (DOM). Carboxyl-modified poly-(methyl methacrylate) (PMMA) and unsurface-coated polystyrene (PS) were chosen as target MPs. Over 94% of PS particles and almost 100% of color were simultaneously removed with lower CCGA consumption than the scenarios with either contaminant in water. The PMMA removal was not as high as the PS removal since the HA polyanions could compete with the negatively-charged PMMA for CCGAs. High salinity reduced the removal of HA by changing its interfacial behaviors without impacting the MP separation. In river water or influent of wastewater treatment plant, the MP particles were almost completely eliminated whereas the DOM (tyrosine-like or tryptophan-like) was partially removed. The fluorescence quenching titration revealed that CCGAs preferably captured the free DOM and the DOM-coated MP particles through complexation interaction. The study denoted that the CCGA system could be a robust tool for efficiently and synergistically removing micron-scale MPs and DOM from different water matrixes.
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A novel macro-architectures material Fe3O4-N-GO@sodium alginate (SA) gel film was successfully produced, which was used to remove series azo dye wastewater. The optimal adsorption rates were attained, which achieved the maximum removal efficiency of 74.22%, 45.72%, 37.75% for Congo Red, Acid Orange 7 and Amino Black 10B respectively, under the condition that the mass ratio of Fe3O4-N-GO to sodium alginate was 0.11. The optimal adsorption temperature for three dyes was 30 â and the adsorption equilibrium was reached at 150 min. The adsorption kinetic model of Fe3O4-N-GO@SA for the three azo dyes conformed to the quasi-second-order reaction model, and the adsorption isotherm was more in line with the Freundlich adsorption. The adsorption mechanism was multi-layer heterogeneous adsorption under the combined action of physical adsorption and chemisorption, and chemisorption was the main step of controlling the speed. The study would provide theoretical basis for the application of macro-architectures material in environment.
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Águas Residuárias , Poluentes Químicos da Água , Adsorção , Compostos Azo , Corantes , Vermelho Congo , Concentração de Íons de Hidrogênio , CinéticaRESUMO
Enrichment of metallic engineered nanoparticles (MENPs) from environmental waters is a prerequisite for their removal, reliable analyses, and environmental process interpretations. This work investigated the enrichment of typical MENPs with different degrees of lability using surface-functionalized microbbubles. During the process, the transformation/dissolution characteristics of MENPs were considered, and the impact of surfactant or coagulant dose, pH of MENP suspensions, and water matrix was systematically investigated. Results show that the colloidal gas aphrons (CGAs) were capable of enriching over 90.0% of ionic Ag(I) which ended up as AgBr and Ag2CO3 in floats when the pH of suspension was 6.0. The polyaluminum chloride-modified CGAs with positive surface charges were good at capturing the particulate ZnO-NPs (~84.8%) but failed to collect the ionic species. It should be noted that the total MENP enrichment efficiency closely related to the content proportions of different species. In the river water, both of the dissolved natural organic matter (fulvic acids) and the electrolytes might influence the enrichment process by affecting the species transformation of Ag-NPs and ZnO-NPs. For the stable TiO2-NPs, 97.1% of the nanoparticles were captured by CGAs. FAs apparently reinforced the enrichment performance since the molecules acted as bridge and facilitated the attachment between TiO2-NP and CGAs. This work contributes to establishing the robust microbubble-induced enrichment method considering the characteristics of MENP contaminants.