Construction of a Functional Nucleic Acid-Based Artificial Vesicle-Encapsulated Composite Nanoparticle and Its Application in Retinoblastoma-Targeted Theranostics.

Retinoblastoma (RB) is an aggressive tumor of the infant retina. However, the ineffective targeting of its theranostic agents results in poor imaging and therapeutic efficacy, which makes it difficult to identify and treat RB at an early stage. In order to improve the imaging and therapeutic efficacy, we constructed an RB-targeted artificial vesicle composite nanoparticle. In this study, the MnO2 nanosponge (hMNs) was used as the core to absorb two fluorophore-modified DNAzymes to form the Dual/hMNs nanoparticle; after loaded with the artificial vesicle derived from human red blood cells, the RB-targeted DNA aptamers were modified on the surface, thus forming the Apt-EG@Dual/hMNs complex nanoparticle. The DNA aptamer endows this nanoparticle to target the nucleolin-overexpressed RB cell membrane specifically and enters cells via endocytosis. The nanoparticle could release fluorophore-modified DNAzymes and supplies Mn2+ as a DNAzyme cofactor and a magnetic resonance imaging (MRI) agent. Subsequently, the DNAzymes can target two different mRNAs, thereby realizing fluorescence/MR bimodal imaging and dual-gene therapy. This study is expected to provide a reliable and valuable basis for ocular tumor theranostics.

Recent theranostic applications of hydrogen peroxide-responsive nanomaterials for multiple diseases.

It is well established that hydrogen peroxide (H2O2) is associated with the initiation and progression of many diseases. With the rapid development of nanotechnology, the diagnosis and treatment of those diseases could be realized through a variety of H2O2-responsive nanomaterials. In order to broaden the application prospects of H2O2-responsive nanomaterials and promote their development, understanding and summarizing the design and application fields of such materials has attracted much attention. This review provides a comprehensive summary of the types of H2O2-responsive nanomaterials including organic, inorganic and organic-inorganic hybrids in recent years, and focused on their specific design and applications. Based on the type of disease, such as tumors, bacteria, dental diseases, inflammation, cardiovascular diseases, bone injury and so on, key examples for above disease imaging diagnosis and therapy strategies are introduced. In addition, current challenges and the outlook of H2O2-responsive nanomaterials are also discussed. This review aims to stimulate the potential of H2O2-responsive nanomaterials and provide new application ideas for various functional nanomaterials related to H2O2.

Mapping the research on desulfurization wastewater: Insights from a bibliometric review (1991-2021).

Desulfurization wastewater in coal-fired power plants (CFPPs) is a great environmental challenge. This study aimed at the current status and future research trends of desulfurization wastewater by bibliometric analysis. The desulfurization wastewater featured with high sulfate (8000 mg/L), chlorite (8505 mg/L), magnesium (2882 mg/L) and calcium (969 mg/L) but low sodium (801.82 mg/L), and the concentrations of the main contaminants were critically summarized. There was an increasing trend in the annual publications of desulfurization wastewater in the period from 1991 to 2021, with an average growth rate of 15%. Water Science and Technology, Desalination and Water Treatment, Energy & Fuels, Chemosphere, and Journal of Hazardous Materials are the top 5 journals in this field. China was the most productive country (58.3% of global output) and the core country in the international cooperation network. Wordcloud analysis and keyword topic trend demonstrated that removal/treatment of pollutants dominated the global research in the field of desulfurization wastewater. The primary technologies for desulfurization wastewater treatment were systematically evaluated. The physicochemical treatment technologies occupied half of the total treatment methods, while membrane-based integrated processes showed potential applications for beneficial reuse. The challenges and outlook on desulfurization wastewater treatment for achieving zero liquid discharge are summarized.

Aptamer-Based Probes for Cancer Diagnostics and Treatment.

Aptamers are single-stranded DNA or RNA oligomers that have the ability to generate unique and diverse tertiary structures that bind to cognate molecules with high specificity. In recent years, aptamer researches have witnessed a huge surge, owing to its unique properties, such as high specificity and binding affinity, low immunogenicity and toxicity, and simplicity of synthesis with negligible batch-to-batch variation. Aptamers may bind to targets, such as various cancer biomarkers, making them applicable for a wide range of cancer diagnosis and treatment. In cancer diagnostic applications, aptamers are used as molecular probes instead of antibodies. They have the potential to detect various cancer-associated biomarkers. For cancer therapeutic purposes, aptamers can serve as therapeutic or delivery agents. The chemical stabilization and modification strategies for aptamers may expand their serum half-life and shelf life. However, aptamer-based probes for cancer diagnosis and therapy still face several challenges for successful clinical translation. A deeper understanding of nucleic acid chemistry, tissue distribution, and pharmacokinetics is required in the development of aptamer-based probes. This review summarizes their application in cancer diagnostics and treatments based on different localization of target biomarkers, as well as current challenges and future prospects.

Associations of BMI with all-cause mortality in normoglycemia, impaired fasting glucose and type 2 diabetes mellitus among an elderly Chinese population: a cohort study.

AIM: To explore the associations of body mass index (BMI) and mortality among people with normal fasting glucose (NFG), impaired fasting glucose (IFG), and type 2 diabetes mellitus (T2DM) in an elderly Chinese population.  METHODS: A retrospective cohort study was conducted that included 59,874 elderly people who were aged 60 and older at baseline. Data for the study came from a health check-up program in China between 2011 and 2019. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using multivariable Cox proportional hazard models of BMI categories by glycemic status. RESULTS: During the median of 5.96 years of follow-up, 7928 participants died (6457/49057 with NFG, 712/5898 with IFG and 759/4919 with T2DM). In adjusted Cox models, risk of mortality showed a decreasing trend with BMI < 18.5 kg/m2, 24 ≤ BMI < 28 kg/m2, and BMI ≥ 28 kg/m2 compared to 18.5 ≤ BMI < 24 kg/m2: HR (95% CI): 1.33 (1.18 to 1.49), 0.88 (0.83 to 0.93), and 0.90 (0.82 to 0.98), respectively, for NFG; 0.89 (0.55 to 1.46), 0.84 (0.71 to 0.99), and 0.88 (0.70 to 1.11), respectively, for IFG; and 1.42 (0.88 to 2.29), 0.75 (0.64 to 0.89), and 0.76 (0.62 to 0.93), respectively, for T2DM. There were curvilinear-shaped associations between BMI and mortality in the NFG and T2DM groups (P overall < 0.001 and P overall < 0.001, respectively; P nonlinearity < 0.001 and P nonlinearity = 0.027, respectively) and no significantly association between BMI and all-cause mortality was observed in the IFG group (P overall = 0.170). CONCLUSION: High BMI compared to normal BMI was associated with decreased mortality, especially in the old populations with NFG and T2DM. Future studies are needed to explain the obesity paradox in elderly patients with T2DM.

Fouling and chemically enhanced backwashing performance of low-pressure membranes during the treatment of shale gas produced water.

The treatment of shale gas produced water (SGPW) for beneficial reuse is currently the most dominant and economical option. Membrane filtration is one preferred method to deal with SGPW, but membrane fouling is an unavoidable problem. In this study, two types of ultrafiltration (UF) membranes and one type of microfiltration (MF) membrane were investigated to treat SGPW from Sichuan basin. Results showed that increased total dissolved solid (31-40 g/L) and UV254 (10-42.9 m-1) were observed for the same shale gas plays, and the primary fluorescent organic substances were humic acid-like components. Compared to UF membranes with the flux decline by 2% to 60%, MF membranes with larger pore size were more likely to be fouled with the flux decline by 43% to 95%. Cake layer filtration was verified to be the primary membrane fouling mechanism. Statistical analysis showed that UV254 played the most significant role in membrane fouling which had the highest correlation (0.76 to 0.93). Compared to permeate backwashing (13%), deionized water backwashing and chemically enhanced backwashing (CEB) using NaClO, H2O2 and citric acid improved the cleaning efficiencies (31%-95%). CEB using NaOH prepared by deionized water aggravated membrane fouling, while excellent cleaning efficiencies (39%-79%) were observed for CEB using NaOH prepared by permeate. The difference in cleaning behaviors for fouled membranes by SGPW was verified by morphology observation and element composition analysis.

Hypertension modifies the associations of body mass index and waist circumference with all-cause mortality among older Chinese: a retrospective cohort study.

BACKGROUND: The effect of baseline hypertension status on the BMI-mortality association is still unclear. We aimed to explore the relationships of body mass index (BMI) and waist circumference (WC) with all-cause mortality among older hypertensive and normotensive Chinese individuals. METHODS: This retrospective cohort study was conducted in Xinzheng, Henan Province, Central China. The data came from the residents' electronic health records of the Xinzheng Hospital Information System. A total of 77,295 participants (41,357 hypertensive participants and 35,938 normotensive participants) aged ≥ 60 years were included from January 2011 to November 2019. Cox proportional hazard regression model was used to examine the relationships. RESULTS: During a mean follow-up of 5.3 years, 10,755 deaths were identified (6,377 in hypertensive participants and 4,378 in normotensive participants). In adjusted models, compared with a BMI of 18.5-24 kg/m2, the hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of BMI < 18.5, 24-28 and ≥ 28 kg/m2 for mortality in hypertensive participants were 1.074 (0.927-1.244), 0.881 (0.834-0.931) and 0.856 (0.790-0.929), respectively, and 1.444 (1.267-1.646), 0.884 (0.822-0.949) and 0.912 (0.792-1.051), respectively, in normotensive participants. Compared with normal waist circumference, the adjusted HRs and 95% CIs of central obesity for mortality were 0.880 (0.832-0.931) in hypertensive participants and 0.918 (0.846-0.996) in normotensive participants. A sensitivity analysis showed similar associations for both hypertensive and normotensive participants. CONCLUSION: Low BMI and WC were associated with a higher risk of all-cause mortality regardless of hypertension status in older Chinese individuals. The lowest risk of death associated with BMI was in the overweight group in normotensive participants and in the obesity group in hypertensive participants.

Human pulmonary artery endothelial cells upregulate ACE2 expression in response to iron-regulatory elements: Potential implications for SARS-CoV-2 infection.

Vascular endothelial cell dysfunction is reported in severe coronavirus disease 2019 disease, however, controversy exists regarding levels of angiotensin-converting enzyme 2 (ACE2) expression, a coreceptor for severe acute respiratory syndrome coronavirus 2, in these cells. We report ACE2 expression and positive regulation by both interleuki-6, hepcidin, and ferroportin knock-down in pulmonary artery endothelial cells with potential implications for viral infection.

Stronger Associations of Body Mass Index and Waist Circumference with Diabetes than Waist-Height Ratio and Triglyceride Glucose Index in the Middle-Aged and Elderly Population: A Retrospective Cohort Study.

Background: It remains controversial whether body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), or triglyceride glucose (TyG) index has a stronger association with diabetes. The aims of the study were to compare the magnitude of associations of four indicators with diabetes risk. Methods: Data collected from annual health examination dataset in the Xinzheng during 2011 and 2019. A total of 41,242 participants aged ≥ 45 years were included in this study. Cox proportional hazard regression models were used to examine associations between the four indicators and diabetes risk. Results: After 205,770 person-years of follow up, diabetes developed in 2,472 subjects. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of diabetes (highest vs reference group) were 1.92 (1.71-2.16) for BMI, 1.99 (1.78-2.23) for WC, 1.65 (1.47-1.86) for WHtR, and 1.66 (1.47-1.87) for TyG, respectively. In addition, the risk of diabetes increased with baseline BMI (HR: 1.30; 95% CI: 1.25, 1.35) and TyG (HR: 1.25; 95% CI: 1.20, 1.30), but the lowest HR was 0.78 (95% CI 0.65-0.92) when WC was approximately 72 cm, and 0.85 (95% CI 0.72-0.99) when WHtR was approximately 0.47 in women. In joint analyses, the highest risk was observed in participants with a high BMI combined with a high WC (HR: 2.26; 95% CI: 1.98, 2.58). Conclusions: In middle-aged and elderly Chinese population, BMI and WC were more strongly associated with diabetes than WHtR or TyG, especially the combined effect of BMI and WC.

Relationship between multimorbidity, disease cluster and all-cause mortality among older adults: a retrospective cohort analysis.

BACKGROUND: Previous studies have evaluated the association of multimorbidity with higher mortality, but epidemiologic data on the association between the disease clusters and all-cause mortality risk are rare. We aimed to examine the relationship between multimorbidity (number/ cluster) and all-cause mortality in Chinese older adults. METHODS: We conducted a population-based study of 50,100 Chinese participants. Multiple logistic regression analysis was used to estimate the impact of long-term conditions (LTCs) on all-cause mortality. RESULTS: The prevalence of multimorbidity was 31.35% and all-cause mortality was 8.01% (50,100 participants). In adjusted models, the odds ratios (ORs) and 95% confidence intervals (CIs) of all-cause mortality risk for those with 1, 2, and ≥ 3 LTCs compared with those with no LTCs was 1.45 (1.32-1.59), 1.72 (1.55-1.90), and 2.15 (1.85-2.50), respectively (Ptrend < 0.001). In the LTCs ≥2 category, the cluster of chronic diseases that included hypertension, diabetes, CHD, COPD, and stroke had the greatest impact on mortality. In the stratified model by age and sex, absolute all-cause mortality was higher among the ≥75 age group with an increasing number of LTCs. However, the relative effect size of the increasing number of LTCs on higher mortality risk was larger among those < 75 years. CONCLUSIONS: The risk of all-cause mortality is increased with the number of multimorbidity among Chinese older adults, particularly disease clusters.

Association of body mass index and waist circumference with high blood pressure in older adults.

BACKGROUND: The relationship between obesity and prevalent high blood pressure in older adults has predominantly been estimated using categorical measures of body mass index (BMI) and waist circumference (WC), masking the shape of the dose-response relationship. We aimed to examine the precise relationship of BMI, WC with high blood pressure and to assess the appropriate level of BMI and WC for high blood pressure. METHODS: We examined data for 126,123 individuals in Xinzheng city aged ≥60 years from a population based study from January to December 2019. Logistic regression and restricted cubic spline models were applied to assess the relationship and the appropriate level of BMI and WC for high blood pressure. An additive interaction analysis was used to test synergistic effects between a higher BMI and WC for high blood pressure. RESULTS: The full-adjusted odds ratios (ORs) with 95% confidence intervals (CIs) of an increase of 1 kg/m2 in BMI and 1 cm in WC for high blood pressure were 1.084 (1.080-1.087) and 1.026(1.024-1.027), respectively. Multivariable adjusted restricted cubic spline analyses showed the nonlinear relationships of BMI and WC with high blood pressure in both men and women (all P < 0.001). The risk of high blood pressure increased steeply with increasing BMI from ≥25 kg/m2 and WC ≥ 88 cm or 86 cm for males and females, respectively. And we observed a significant additive interaction between a higher BMI and WC such that the prevalence of high blood pressure was significantly enhanced. CONCLUSION: These findings suggest increased high blood pressure prevalence in the older adults with increased BMI and WC. BMI ≤ 25 kg/m2 and WC ≤ 88 cm or 86 cm for males and females may be the best suggestion with regard to primary prevention of high blood pressure in older adults.

Identification of a Prognostic Signature Model with Tumor Microenvironment for predicting Disease-free Survival after Radical Prostatectomy.

Background: The tumor microenvironment (TME) and immune checkpoint inhibitors have been shown to promote active immune responses through different mechanisms. We attempted to identify the important prognostic genes and prognostic characteristics related to TME in prostate cancer (PCa). Methods: The gene transcriptome profiles and clinical information of PCa patients were obtained from The Cancer Genome Atlas (TCGA) database, and the immune and stromal scores were calculated by the ESTIMATE algorithm. We evaluated the prognostic value of the risk score (RS) model based on univariate Cox analysis and least absolute shrinkage and selection operation (LASSO) Cox regression analysis and established a nomogram to predict disease-free survival (DFS) in PCa patients. The GSE70768 dataset was utilized for external validation. Twenty-two subsets of tumor-infiltrating immune cells were analyzed using the CIBERSORT algorithm. Results: In this study, the patients with higher immune/stromal scores were associated with a worse DFS, higher Gleason score, and higher pathological T stage. Based on the immune and stromal scores, 515 differentially expressed genes (DEGs) were identified. The univariate Cox and LASSO Cox regression models were employed to select 18 DEGs from 515 DEGs and construct an RS model. The DFS of the high-RS group was significantly lower than that of the low-RS group (P<0.001). The AUCs for the 1-year, 3-year and 5-year DFS rates in the RS model were 0.890, 0.877 and 0.841, respectively. A nomogram of DFS was established based on the RS and Gleason score, and the AUCs for the 1-year, 3-year and 5-year DFS rates in the nomogram were 0.907, 0.893, and 0.872, respectively. These results were further validated in the GSE70768 dataset. In addition, the proportion of Tregs was determined to be higher in high-RS patients (P<0.05), and the expression levels of five immune checkpoints (CTLA-4, PD-1, LAG-3, TIM-3 and TIGIT) were observed to be higher in high-RS patients (P<0.05). Conclusions: Our study established and validated an 18-gene prognostic signature model associated with TME, which might serve as a prognosis stratification tool to predict DFS in PCa patients after radical prostatectomy.

Trajectories of body mass index (BMI) and hypertension risk among middle-aged and elderly Chinese people.

This study aimed to identify heterogeneity in BMI trajectories and evaluate the impact of BMI trajectories on the risk of hypertension in middle-aged and elderly Chinese people. After data screening, 28, 706 residents' e-health records from 2010 to 2018, including basic personal information, lifestyle and health, were finally included in this population-based longitudinal study. By latent class growth modeling, we identified 12 BMI trajectories: "underweight-increase I (A1)" and "underweight-increase II (A2)"; "normal weight-stable (B1)", "normal weight-decrease (B2)", "normal weight-increase I (B3)" and "normal weight-increase II (B4)"; "overweight-stable (C1)", "overweight-decrease (C2)" and "overweight-increase (C3)"; and "obese-stable I (D1)", "obese-decrease (D2)" and "obese-stable II (D3)". By Cox proportional hazards models, we found that the risk of hypertension in the BMI stable group was lower than that in the BMI increasing trajectory group and higher than that in the BMI decreasing group. For the underweight and normal weight groups, the risk of hypertension was related not only to the magnitude of BMI growth, but also to the rate of growth. For overweight and obesity groups, the risk of hypertension was higher in the high-level stable BMI group than in the low-level stable BMI group. Therefore, for underweight and normal weight people, weight growth and growth rate should be controlled; for overweight and obese people, health education or targeted weight loss exercise should be taken to reduce weight as much as possible to prevent hypertension.

Socioeconomic and Demographic Factors for Spousal Resemblance in Obesity Status in China.

INTRODUCTION: The purposes of this study were to explore the resemblance in the weight status within couples with different family contextual factors and analyze the influence of the level of overweight or obesity of a spouse on that of the other spouse. METHODS: The data were from the sixth National Health Service Survey of Henan Province in 2018. After screening, 7432 eligible couples were finally included. Socioeconomic and demographic factors were compared by the χ2 test or nonparametric test. The difference in the body mass index (BMI) of spouses was assessed by a t-test. The Pearson correlation coefficient and kappa value were used as indicators of consistency in weight status. A logistic regression analysis was used to further explore the effect of a spouse's level of overweight/obesity on that of the other spouse. RESULTS: The results show that the prevalence of overweight/obesity in couples aged 20 or older is 33.76%. The Pearson correlation coefficient of the BMI within couples was 0.102 (95% CI: 0.076-0.120). The kappa coefficients suggested a low resemblance in the weight status within couples (k = 0.049, 95% CI: 0.031-0.069). Besides, the influence of the overweight/obesity status of the wives on that of the husbands (odds ratio (OR) = 1.411, 95% CI: 1.309-1.521) was slightly higher than that of the husbands on that of the wives (OR = 1.404, 95% CI: 1.302-1.514). CONCLUSIONS: We found that there was a moderate but significant resemblance in the body weight status between spouses, especially elderly couples with a low education level in rural areas. Health education activities for couple interventions can have a good effect of intervention.

Shenlian Extract Against Myocardial Injury Induced by Ischemia Through the Regulation of NF-κB/IκB Signaling Axis.

Ischemic heart disease (IHD), caused predominantly by atherosclerosis, is a leading cause of global mortality. Our previous studies showed that Shenlian extract (SL) could prevent the formation of atherosclerosis and enhance the stability of atherosclerotic plaques. To further investigate the protective effects of SL on myocardial ischemic injury and its possible mechanisms, anesthetized dogs, ex vivo rat hearts, and H9c2 cardiomyocytes were used as models. The results showed that SL had a significant protective effect on the anesthetized dog ligating coronary artery model, reduced the degree of myocardial ischemia (Σ-ST), and reduced the scope of myocardial ischemia (N-ST). Meanwhile, SL alleviated ischemic reperfusion damage in ex vivo rat hearts with improved LVEDP and ± dp/dtmax values of the left ventricle. SL reduced the pathological changes of LDH, IL-1ß, MDA, and NO contents, all of which are related to the expression of NF-κB. Further analysis by Bio-Plex array and signal pathway blocker revealed that the phosphorylation of IκB was a key factor for SL to inhibit myocardial ischemic injury, and the regulation of SL on IκB was primarily related to degradation of the IκB protein. These results provided dependable evidence that SL could protect against myocardial ischemic injury through the NF-κB signaling pathway.

Decomposition of Composite Electric Field in a Three-Phase D-Dot Voltage Transducer Measuring System.

In line with the wider application of non-contact voltage transducers in the engineering field, transducers are required to have better performance for different measuring environments. In the present study, the D-dot voltage transducer is further improved based on previous research in order to meet the requirements for long-distance measurement of electric transmission lines. When measuring three-phase electric transmission lines, problems such as synchronous data collection and composite electric field need to be resolved. A decomposition method is proposed with respect to the superimposed electric field generated between neighboring phases. The charge simulation method is utilized to deduce the decomposition equation of the composite electric field and the validity of the proposed method is verified by simulation calculation software. With the deduced equation as the algorithm foundation, this paper improves hardware circuits, establishes a measuring system and constructs an experimental platform for examination. Under experimental conditions, a 10 kV electric transmission line was tested for steady-state errors, and the measuring results of the transducer and the high-voltage detection head were compared. Ansoft Maxwell Stimulation Software was adopted to obtain the electric field intensity in different positions under transmission lines; its values and the measuring values of the transducer were also compared. Experimental results show that the three-phase transducer is characterized by a relatively good synchronization for data measurement, measuring results with high precision, and an error ratio within a prescribed limit. Therefore, the proposed three-phase transducer can be broadly applied and popularized in the engineering field.