Titanium Dioxide Nanoparticles Induce Maternal Preeclampsia-like Syndrome and Adverse Birth Outcomes via Disrupting Placental Function in SD Rats.

The escalating utilization of titanium dioxide nanoparticles (TiO2 NPs) in everyday products has sparked concerns regarding their potential hazards to pregnant females and their offspring. To address these concerns and shed light on their undetermined adverse effects and mechanisms, we established a pregnant rat model to investigate the impacts of TiO2 NPs on both maternal and offspring health and to explore the underlying mechanisms of those impacts. Pregnant rats were orally administered TiO2 NPs at a dose of 5 mg/kg body weight per day from GD5 to GD18 during pregnancy. Maternal body weight, organ weight, and birth outcomes were monitored and recorded. Maternal pathological changes were examined by HE staining and TEM observation. Maternal blood pressure was assessed using a non-invasive blood analyzer, and the urinary protein level was determined using spot urine samples. Our findings revealed that TiO2 NPs triggered various pathological alterations in maternal liver, kidney, and spleen, and induced maternal preeclampsia-like syndrome, as well as leading to growth restriction in the offspring. Further examination unveiled that TiO2 NPs hindered trophoblastic cell invasion into the endometrium via the promotion of autophagy. Consistent hypertension and proteinuria resulted from the destroyed the kidney GBM. In total, an exposure to TiO2 NPs during pregnancy might increase the risk of human preeclampsia through increased maternal arterial pressure and urinary albumin levels, as well as causing fetal growth restriction in the offspring.

Mediating effect of BMI on the relation of dietary patterns and glycemic control inT2DM patients: results from China community-based cross-sectional study.

OBJECTIVE: To analyze the effects of different dietary types on in type 2 diabetes mellitus (T2DM) and determine the mediating effects of Body Mass Index (BMI) on dietary type with Fasting Plasma Glucose (FPG), Glycosylated Hemoglobin (HbA1c) on the associations in T2DM. METHODS: Data of community-based cross-sectional study with 9602 participants including 3623 men and 5979 women were collected from the project 'Comprehensive Research in prevention and Control of Diabetes mellitus (CRPCD)' conducted by Jiangsu Center for Disease Control and Prevention in 2018. The dietary data were collected from a food frequency qualitative questionnaire (FFQ) and dietary patterns were derived through Latent Class Analysis (LCA). Then, Logistics regression analyses were used to evaluate the associations of FPG, HbA1c with different dietary patterns. The BMI (BMI = height/weight2) was used as a moderator to estimate the mediating effect. Mediation analysis was performed using hypothetical variables, the mediation variables, to identify and explain the observed mechanism of association between the independent and dependent variables while the moderation effect was tested with multiple regression analysis with interaction terms. RESULTS: After completing Latent Class Analysis (LCA), the dietary patterns were divided into three categories: TypeI, TypeII, TypeIII. After adjusting for confounding factors such as gender, age, education level, marital status, family income, smoking, drinking, disease course, HDL-C, LDL-C, TC, TG, oral hypoglycemic drugs, insulin therapy, Hypertension, Coronary heart disease, Stroke, Type III were all significantly associated with HbA1c compared to those with Type I (P < 0.05), and the research showed the patients with Type III had High glycemic control rate. Taking type I as the reference level, the 95% Bootstrap confidence intervals of the relative mediating effect of TypeIII on FPG were (-0.039, -0.005), except 0, indicating that the relative mediating effect was significant (αIII = 0.346*, ßIIIFPG = -0.060*). The mediating effect analysis was performed to demonstrate that BMI was used as a moderator to estimate the moderation effect. CONCLUSIONS: Our findings demonstrate that consuming Type III dietary patterns associates with good glycemic control in T2DM and the BMI associations would be playing a two-way effect between diet and FPG in Chinese population with T2DM, indicated that Type III could not only directly affect FPG, but also affect FPG through the mediating effect of BMI.

Fresh fruit consumption, physical activity, and five-year risk of mortality among patients with type 2 diabetes: A prospective follow-up study.

BACKGROUND AND AIMS: We explored the associations among fruit consumption, physical activity, and their dose-response relationship with all-cause and cardiovascular disease (CVD) mortality in type 2 diabetic patients. METHODS AND RESULTS: We prospectively followed 20,340 community-dwelling type 2 diabetic patients aged 21-94 years. Information on diets and physical activity was collected using standardized questionnaires. All-cause and CVD mortality were assessed. Hazard ratios (HRs) for all-cause mortality were estimated with Cox regression models, and HRs for CVD mortality were derived from a competing risk model. Restricted cubic spline regression was used to analyze dose-response relationships. We identified 1362 deaths during 79,844 person-years. Compared to non-consumption, fruit consumption >42.9 g/d was inversely associated with all-cause mortality (HR 0.76; 95% CI 0.64-0.88), CVD mortality (HR 0.69, 0.51-0.94) and stroke mortality (HR 0.57, 0.36-0.89), but not with heart disease mortality (HR 0.93, 0.56-1.52). The HRs comparing the top vs bottom physical activity quartiles were 0.44 (0.37-0.53) for all-cause mortality, 0.46 (0.33-0.64) for CVD mortality, 0.46 (0.29-0.74) for stroke mortality and 0.51 (0.29-0.88) for heart disease mortality. Lower fruit consumption combined with a lower physical activity level was associated with a greater mortality risk. A nonlinear threshold of 80 g fruit/day was identified; all-cause mortality risk was reduced by approximately 24% at this value. A physical activity threshold of eight metabolic equivalents (MET) h/day was also identified, after which the risk of mortality did not decrease. CONCLUSIONS: Fruit consumption and physical activity may reduce all-cause, CVD, and stroke mortality in type 2 diabetic patients.

Pyrrole-Embedded Linear and Helical Graphene Nanoribbons.

Linear and helical graphene nanoribbons (L-PyGNR and H-PyGNR) bearing electron-rich pyrrole units have been synthesized by using the photochemical cyclodehydrochlorination (CDHC) reaction. The pyrrole units in the polymer backbone make the polymer electron-rich with moderate bandgap values and relatively high HOMO energy levels. The planarization of the pyrrole unit through cyclization yields a bandgap value almost 0.5 eV lower than that measured for polypyrrole. Conductivity values in the thin film up to 0.12 S/cm were measured for the chemically oxidized L-PyGNR (four-point method). Both GNRs showed excellent fluorescence sensing properties for TNT in solution with KSV values up to 6.4 × 106 M-1.

Engineering of exosome-triggered enzyme-powered DNA motors for highly sensitive fluorescence detection of tumor-derived exosomes.

Tumor-derived exosomes containing multiple proteins originating from parent cancer cells have emerged as biomarkers for cancer diagnosis. Herein, we propose a three-dimensional DNA motor-based exosome assay platform for the selective and sensitive detection of exosomes. The DNA motor used gold nanoparticle (GNP) tracks, consisting of fluorescein-labeled substrate strands and aptamer-locked motor strands. Recognition of the target protein on exosomes by its aptamer unlocked the motor strand and triggered the DNA motor process. Powered by restriction endonuclease, the motor strands autonomously walked along the GNP track. Each movement step cleaved one substrate strand and restored one fluorescein molecule. For exosome detection, the proposed method displayed a broad dynamic range acrossing 5 orders of magnitude with the detection limit as low as 8.2 particles/µL in PBS. The method also exhibited good selectivity among different tumor-derived exosomes and performed well in complex biological samples. The capability to profile exosomal surface proteins efficiently endowed our DNA motor great potential for developing a simple and cost-effective device for clinical diagnosis.

Facile Construction of i-Motif DNA-Conjugated Gold Nanostars as Near-Infrared and pH Dual-Responsive Targeted Drug Delivery Systems for Combined Cancer Therapy.

Stimuli-responsive DNA-based nanostructures have emerged as promising vehicles for intelligent drug delivery. In this study, i-motif DNA-conjugated gold nanostars (GNSs) were fabricated in a facile manner as stimuli-responsive drug delivery systems (denoted as A-GNS/DNA/DOX) for the treatment of cancer via combined chemo-photothermal therapy. The i-motif DNA is sensitive to the environmental pH and can switch from a single-stranded structure to a C-tetrad (i-motif) structure as the environmental pH decreases from neutral (∼7.4) to acidic (<6.0). The loaded drug can then be released along with the conformational changes. To enhance cellular uptake and improve cancer cell selectivity, the aptamer AS1411, which recognizes nucleolins, was employed as a targeting moiety. The A-GNS/DNA/DOX nanocomposites were found to be highly capable of photothermal conversion and exhibited photostability under near-infrared (NIR) irradiation, and the pH and NIR irradiation effectively triggered the drug-release behaviors. In addition, the A-GNS/DNA/DOX nanocomposites exhibited good biocompatibility. The targeting recognition enabled the A-GNS/DNA/DOX to exhibit higher cellular uptake and therapeutic efficiency than the GNS/DNA/DOX. Notably, under NIR irradiation, a synergistic effect between chemotherapy and photothermal therapy can be achieved with the proposed delivery system, which exhibits much higher therapeutic efficiency both in monolayer cancer cells and tumor spheroids as compared with a single therapeutic method. This study highlights the potential of GNS/DNA nanoassemblies for intelligent anticancer drug delivery and combined cancer therapy.

Emerging Bottom-Up Strategies for the Synthesis of Graphene Nanoribbons and Related Structures.

The solution-phase synthesis is one of the most promising strategies for the preparation of well-defined graphene nanoribbons (GNRs) in large scale. To prepare high quality, defect-free GNRs, cycloaromatization reactions need to be very efficient, proceed without side reaction and mild enough to accommodate the presence of various functional groups. In this Minireview, we present the latest synthetic approaches for the synthesis of GNRs and related structures, including alkyne benzannulation, photochemical cyclodehydrohalogenation, Mallory and Pd- and Ni-catalyzed reactions.

Engineering of Porous Silica Coated Gold Nanorods by Surface-Protected Etching and Their Applications in Drug Loading and Combined Cancer Therapy.

Core-shell nanostructures, specifically gold nanorods coated with porous silica (GNR@p-SiO2), were successfully fabricated by surface-protected etching. The nanostructures, photothermal effects, drug loading and drug release behaviors, cellular uptake, and combined chemo-photothermal therapy were investigated. The results showed that the as-prepared GNR@p-SiO2 had a uniform porous silica outer layer. Etching process could be modulated by adjusting the etching time, concentrations of etching agents, and concentrations of protective agents. With doxorubicin (DOX) as the model drug, the drug loading capacity reached 18.9%, which was dependent on the DOX concentrations. The drug release profiles were dual stimulus-responsive to pH and laser irradiation. In addition, the GNR@p-SiO2 nanoparticles were biocompatible and effectively internalized by cancer cells. Compared with chemotherapy or photothermal therapy administered individually, combined chemo-photothermal therapy using GNR@p-SiO2 exhibited higher efficiency in killing cancer cells both in vitro and in vivo. Therefore, surface-protected etching is a powerful method for preparing core-shell nanostructures capped with mesoporous silica for combined cancer chemo-photothermal therapy.

Physical activity, sedentary time and their associations with clustered metabolic risk among people with type 2 diabetes in Jiangsu province: a cross-sectional study.

OBJECTIVE: Investigating the association between total physical activity, physical activity in different domains and sedentary time with clustered metabolic risk in patients with type 2 diabetes from Jiangsu province, China. DESIGN: Interview-based cross-sectional study conducted between December 2013 and January 2014. SETTING: 44 selected townships across two cities, Changshu and Huai'an, in Jiangsu province. PARTICIPANTS: 20 340 participants selected using stratified cluster-randomised sampling and an interviewer-managed questionnaire. METHODS: We constructed clustered metabolic risk by summing sex-specific standardised values of waist circumference, fasting triacylglycerol, fasting plasma glucose, systolic blood pressure and the inverse of blood high-density lipoprotein cholesterol (HDL-cholesterol). Self-reported total physical activity included occupation, commuting and leisure-time physical activity. The un-standardised regression coefficient [B] and its 95% CI were calculated using multivariate linear regression analyses. RESULTS: This study included 17 750 type 2 diabetes patients (aged 21-94 years, 60.3% female). The total (B=-0.080; 95% CI: -0.114 to -0.046), occupational (B=-0.066; 95% CI: -0.101 to- 0.031) and leisure-time physical activity (B=-0.041; 95% CI: -0.075 to -0.007), and sedentary time (B=0.117; 95% CI: 0.083 to 0.151) were associated with clustered metabolic risk. Total physical activity, occupational physical activity and sedentary time were associated with waist circumference, triacylglycerol and HDL-cholesterol, but not with systolic blood pressure. Commuting physical activity and sedentary time were significantly associated with triacylglycerol (B=-0.012; 95% CI: -0.019 to -0.005) and fasting plasma glucose (B=0.008; 95% CI: 0.003 to 0.01), respectively. Leisure-time physical activity was only significantly associated with systolic blood pressure (B=-0.239; 95% CI: -0.542 to- 0.045). CONCLUSIONS: Total, occupational and leisure-time physical activity were inversely associated with clustered metabolic risk, whereas sedentary time increased metabolic risk. Commuting physical activity was inversely associated with triacylglycerol. These findings suggest that increased physical activity in different domains and decreased sedentary time may have protective effects against metabolic risk in type 2 diabetes patients.

Rattle-Type Gold Nanorods/Porous-SiO2 Nanocomposites as Near-Infrared Light-Activated Drug Delivery Systems for Cancer Combined Chemo-Photothermal Therapy.

Rattle-type nanostructures with movable cores, porous shells, and hollow interiors have become attractive nanoplatforms in the field of nanomedicine, especially for targeted and stimuli-responsive drug delivery. In this work, rattle-type gold nanorods@void@porous-SiO2 (GVPS) nanocomposites were fabricated facilely using the surface-protecting etching method and exhibited high photothermal conversion efficiency. Taking advantage of the porous shell and hollow interior, the nanocomposites have abundant space for drug loading and successfully improved the drug loading capacity up to ∼19.6%. To construct a multifunctional drug delivery system, GVPS was further functionalized with polyethylene glycol (PEG) and cyclic RGD peptides to improve biocompatibility as well as selectivity toward the targeted cancer cells. Besides, to achieve precise regulation and near-infrared laser activation of the drug release, a phase-changing material, 1-tetradecanol (1-TD, Tm: 39 °C), was employed as gatekeepers in this system. After incubation with an αVß3 integrin receptor-overexpressed cell line, the as-prepared GVPSPR-DOX/TD nanocomposites exhibited great performances in combined photothermal therapy and chemotherapy. It is worth noting that the combined therapy showed superior efficiency in cancer cell killing to chemotherapy or photothermal therapy alone.

Mesoporous silica-coated gold nanostars with drug payload for combined chemo-photothermal cancer therapy.

Combined chemo-photothermal therapy is attracting increasing attention in the treatment of cancers. In this work, PEGylated mesoporous SiO2-coated gold nanostars (GNS@mSiO2-PEG) were synthesised without using the cytotoxic surfactant cetyltrimethylammonium bromide as the template. Mesoporous nanostructures were obtained by poly(vinylpyrrolidone) protection of the outer silica shell and NaOH etching of the inner shell. GNS@mSiO2-PEG exhibited good dispersity in medium and excellent photothermal effects. Loading capacity for the anticancer drug doxorubicin (DOX) was ∼17.9%, and the drug release profile was pH- and light-responsive. In vitro studies revealed that the as-prepared nanocomposites featured good biocompatibility. Furthermore, the nanocomposites were readily internalised by cancer cells, and a combined chemo-photothermal therapy assay revealed that DOX-loaded GNS@mSiO2-PEG have a higher therapeutic efficiency than individual therapies, demonstrating suitable synergistic effects.

Preparation of Dimpled Polystyrene-Silica Colloidal Nanocomposite Particles.

Preparation of polymer-silica colloidal nanocomposite particles with concave shape is challenging and seldom reported. This paper presents a novel and facile method to prepare dimpled polymer-silica nanocomposite particles with a thin silica shell through the judicious combination of alcoholic dispersion polymerization and the decane evaporation method. Submicrometer-sized polystyrene-silica (PS-SiO2) nanocomposite particles were first prepared by dispersion polymerization of styrene in methanol in the presence of a methanolic silica sol, and then dimpled PS-SiO2 particles were prepared by heating the near-spherical PS-SiO2 particles dispersed in methanol/water media in the presence of decane and subsequent cooling. The effects of different heat treatment parameters, such as methanol/water ratio, stirring temperature, and stirring rate on the formation of the nanocomposite particles were investigated. Optimization of the heating conditions allowed ∼100% of dimpled particles to be achieved with one dimple on each particle. Moreover, calcination of the dimpled PS-SiO2 nanocomposite particles led to the formation of hollow dimpled particles with a thin silica shell. This method is expected to enrich the shapes of polymer-silica nanocomposite particles.

Bio-Inspired Protein-Based Nanoformulations for Cancer Theranostics.

Over the past decade, more interests have been aroused in engineering protein-based nanoformulations for cancer treatment. This excitement originates from the success of FDA approved Abraxane (Albumin-based paclitaxel nanoparticles) in 2005. The new generation of biocompatible endogenous protein-based nanoformulations is currently constructed through delivering cancer therapeutic and diagnostic agents simultaneously, as named potential theranostics. Protein nanoformulations are commonly incorporated with dyes, contrast agents, drug payloads or inorganic nanoclusters, serving as imaging-guided combinatorial cancer therapeutics. Employing the nature identity of proteins, the theranostics, escape the clearance by reticuloendothelial cells and have a long blood circulation time. The nanoscale sizet allows them to be penetrated deeply into tumor tissues. In addition, stimuli release and targeted molecules are incorporated to improve the delivery efficiency. The ongoing advancement of protein-based nanoformulations for cancer theranostics in recent 5 years is reviewed in this paper. Fine-designed nanoformulations based on albumin, ferritin, gelatin, and transferrin are highlighted from the literature. Finally, the current challenges are identified in translating protein-based nanoformulations from laboratory to clinical trials.

Toward Thiophene-Annulated Graphene Nanoribbons.

Narrow thiophene-edged graphene nanoribbons (GNRs) were prepared from polychlorinated thiophene-containing poly(p-phenylene)s using the photochemical, metal-free cyclodehydrochlorination (CDHC) reaction. 1 H NMR and Raman spectroscopy confirmed the structures of the GNRs. The regioselectivity of the CDHC reaction allows the preparation of both laterally symmetrical and unsymmetrical GNRs and, consequently, the modulation of their optical and electronic properties.

Relationship between serum uric acid and ischemic stroke in a large type 2 diabetes population in China: A cross-sectional study.

OBJECTIVE: To investigate the relationship of serum UA and ischemic stroke in type 2 diabetes patients in China. METHOD: We examined the above relationship using the data of the project "Comprehensive Research on the Prevention and Control of the Diabetes" (CRPCD) study. A total of 19,442 participants were enrolled in the cross-sectional study. The enrolled participants were divided into quintiles of the serum UA levels with cut off values for two age groups (<60 versus ≥60years). Binary logistic regression analyses were used to evaluate whether the levels of serum UA were independently associated with ischemic stroke in type 2 diabetes. RESULTS: The serum UA levels were significantly higher in the participants with age≥60years than those with age<60years (P=0.000). In the age group of <60years, the odds ratio for ischemic stroke with type 2 diabetes in quintile 5 over quintile 1 was 2.420 (95% CI, 1.566-3.470) in the unadjusted model and 1.765 (95% CI, 1.097-2.840) after controlling potential confounders. However, the reverse results were observed in the age group of ≥60years. The odds ratio in quintile 4 over quintile 1 in model 3 and model 4 were 0.767 (95% CI, 0.630-0.934) and 0.782 (95% CI, 0.640-0.957). CONCLUSION: Our results indicated that serum UA levels were independently positively associated with ischemic stroke in patients aged <60years, but the association was U-shaped in patients aged ≥60years.

Helically Coiled Graphene Nanoribbons.

Graphene is a zero-gap, semiconducting 2D material that exhibits outstanding charge-transport properties. One way to open a band gap and make graphene useful as a semiconducting material is to confine the electron delocalization in one dimension through the preparation of graphene nanoribbons (GNR). Although several methods have been reported so far, solution-phase, bottom-up synthesis is the most promising in terms of structural precision and large-scale production. Herein, we report the synthesis of a well-defined, helically coiled GNR from a polychlorinated poly(m-phenylene) through a regioselective photochemical cyclodehydrochlorination (CDHC) reaction. The structure of the helical GNR was confirmed by 1 H NMR, FT-IR, XPS, TEM, and Raman spectroscopy. This Riemann surface-like GNR has a band gap of 2.15 eV and is highly emissive in the visible region, both in solution and the solid state.

Nanocapsules engineered from polyhedral ZIF-8 templates for bone-targeted hydrophobic drug delivery.

A novel bone-targeted delivery systems based on nanocapsules was developed utilizing a Zeolitic Imidazolate Framework (ZIF-8) as a template and catechol-modified gelatin as wall material. A targeting ligand was facilely conjugated on the surface of nanocapsules. Simvastatin was encapsulated within the nanocapsules with a loading of 37.9%. Hydroxyapatite binding and in vivo biodistribution of the drug-loaded nanocapsules were investigated.

Hydrogen peroxide-responsive micelles self-assembled from a peroxalate ester-containing triblock copolymer.

A novel ABA triblock copolymer by using peroxalate esters as linkages was synthesized. In water, this amphiphilic copolymer self-assembled into micelles which were used as drug delivery carriers. When stimulated with hydrogen peroxide, the micelles disassembled to release drugs since the responsive peroxalate ester linkages would be cleaved after the reaction with hydrogen peroxide.

High prevalence of HIV among men who have sex with men in Zhejiang, China: a respondent-driven sampling survey.

OBJECTIVES: To examine the prevalence of HIV and risk behaviours among men who have sex with men (MSM) and to explore the feasibility of using respondent-driven sampling in this population in order to conduct customised interventions among MSM in the future. DESIGN: Cross-sectional study. SETTING: Zhejiang, China. PARTICIPANTS: 1316 MSM. PRIMARY AND SECONDARY OUTCOME MEASURES: HIV prevalence rates and factors associated with HIV infection; sociodemographic and behavioural information of participants, syphilis prevalence rates. RESULTS: The adjusted prevalence of HIV and syphilis were 13.8% and 11.4%, respectively. Multivariate analysis showed that higher educational level, support treatment of HIV, negative syphilis are protective factors of HIV infection. MSM who had heterosexual behaviour before and whose primary sexual partner was HIV-positive were less likely to be infected with HIV compared with their counterparts, while frequency of sexual behaviour with primary sexual partner was positively associated with HIV infection. CONCLUSIONS: This survey confirmed a high HIV prevalence among MSM in Zhejiang province. MSM are extremely vulnerable to HIV infection and comprehensive interventions are urgently needed to slow the spread of HIV among MSM.

Verification of the correlation between progression-free survival and overall survival considering magnitudes of survival post- progression in the treatment of four types of cancer.

BACKGROUND: With development and application of new and effective anti-cancer drugs, the median survival post-progression (SPP) is often prolonged, and the role of the median SPP on surrogacy performance should be considered. To evaluate the impact of the median SPP on the correlation between progression-free survival (PFS) and overall survival (OS), we performed simulations for treatment of four types of cancer, advanced gastric cancer (AGC), metastatic colorectal cancer (MCC), glioblastoma (GBM), and advanced non-small-cell lung cancer (ANSCLC). MATERIALS AND METHODS: The effects of the median SPP on the statistical properties of OS and the correlation between PFS and OS were assessed. Further, comparisons were made between the surrogacy performance based on real data from meta-analyses and simulation results with similar scenarios. RESULTS: The probability of a significant gain in OS and HR for OS was decreased by an increase of the SPP/ OS ratio or by a decrease of observed treatment benefit for PFS. Similarly, for each of the four types of cancer, the correlation between PFS and OS was reduced as the median SPP increased from 2 to 12 months. Except for ANSCLC, for which the median SPP was equal to the true value, the simulated correlation between PFS and OS was consistent with the values derived from meta-analyses for the other three kinds of cancer. Further, for these three types of cancer, when the median SPP was controlled at a designated level (i.e., < 4 months for AGC, < 12 months for MCC, and <6 months for GBM), the correlation between PFS and OS was strong; and the power of OS reached 34.9% at the minimum. CONCLUSIONS: PFS is an acceptable surrogate endpoint for OS under the condition of controlling SPPs for AGC, MCC, and GBM at their limit levels; a similar conclusion cannot be made for ANSCLC.