Obesity-induced downregulation of miR-192 exacerbates lipopolysaccharide-induced acute lung injury by promoting macrophage activation.

BACKGROUND: Macrophage activation may play a crucial role in the increased susceptibility of obese individuals to acute lung injury (ALI). Dysregulation of miRNA, which is involved in various inflammatory diseases, is often observed in obesity. This study aimed to investigate the role of miR-192 in lipopolysaccharide (LPS)-induced ALI in obese mice and its mechanism of dysregulation in obesity. METHODS: Human lung tissues were obtained from obese patients (BMI ≥ 30.0 kg/m2) and control patients (BMI 18.5-24.9 kg/m2). An obese mouse model was established by feeding a high-fat diet (HFD), followed by intratracheal instillation of LPS to induce ALI. Pulmonary macrophages of obese mice were depleted through intratracheal instillation of clodronate liposomes. The expression of miR-192 was examined in lung tissues, primary alveolar macrophages (AMs), and the mouse alveolar macrophage cell line (MH-S) using RT-qPCR. m6A quantification and RIP assays helped determine the cause of miR-192 dysregulation. miR-192 agomir and antagomir were used to investigate its function in mice and MH-S cells. Bioinformatics and dual-luciferase reporter gene assays were used to explore the downstream targets of miR-192. RESULTS: In obese mice, depletion of macrophages significantly alleviated lung tissue inflammation and injury, regardless of LPS challenge. miR-192 expression in lung tissues and alveolar macrophages was diminished during obesity and further decreased with LPS stimulation. Obesity-induced overexpression of FTO decreased the m6A modification of pri-miR-192, inhibiting the generation of miR-192. In vitro, inhibition of miR-192 enhanced LPS-induced polarization of M1 macrophages and activation of the AKT/ NF-κB inflammatory pathway, while overexpression of miR-192 suppressed these reactions. BIG1 was confirmed as a target gene of miR-192, and its overexpression offset the protective effects of miR-192. In vivo, when miR-192 was overexpressed in obese mice, the activation of pulmonary macrophages and the extent of lung injury were significantly improved upon LPS challenge. CONCLUSIONS: Our study indicates that obesity-induced downregulation of miR-192 expression exacerbates LPS-induced ALI by promoting macrophage activation. Targeting macrophages and miR-192 may provide new therapeutic avenues for obesity-associated ALI.

Impact assessment of vehicle electrification pathways on emissions of CO2 and air pollution in Xi'an, China.

To assess the environmental impact of promoting the use of electric vehicles in road traffic on emissions of CO2 and air pollution in Xi'an, China, both the proportion of electric vehicles and the power generation mix should be considered. Here, vehicle ownership in 2021 served as the baseline scenario, and the vehicle development trend through 2035 was projected. Using emission factor models for fuel vehicles and the electricity generation required for running electric vehicles, this study estimated the related pollutants' emission inventories at 81 corresponding scenarios, in which differing vehicle electrification paths were coupled with power generation mix. Further, the degree to which different vehicle electrification paths impacted the CO2 and air pollutant emissions was also evaluated. The results show that, to achieve the goal of peak carbon emission in the road transport sector in Xi'an by 2030, the penetration rate of electric vehicles must reach at least 40 % in 2035, and the thermal power generation rate should satisfy the necessary coupling conditions. Although reducing the thermal power generation rate could mitigate the environmental problems, we find that electric vehicle development in Xi'an during 2021-2035 would still exacerbate SO2 emissions despite reducing the thermal power generation rate to 10 %. Finally, to avoid exacerbating the adverse effects on public health from vehicle-related pollutants, the penetration rate of electric vehicles should be at least 40 % in 2035, at which time for the 40 %, 50 %, 60 %, and 70 % scenarios, the corresponding thermal power generation rate should not exceed 10 %, 30 %, 50 %, and 60 %. This study systematically analyzed plausible development paths of electric vehicles from the perspectives of peak carbon emissions, air pollution control, and human health, whose findings can serve as a timely and valuable reference for reducing pollution and carbon in the field of road transport.

Deep learning image reconstruction algorithms in low-dose radiation abdominal computed tomography: assessment of image quality and lesion diagnostic confidence.

Background: The image quality of computed tomography (CT) can be adversely affected by a low radiation dose, and reconstruction algorithms of an appropriate level may be useful in reducing this impact. Methods: Eight sets of CT images of a phantom were reconstructed with filtered back projection (FBP); adaptive statistical iterative reconstruction-Veo (ASiR-V) at 30% (AV-30), 50% (AV-50), 80% (AV-80), and 100% (AV-100); and deep learning image reconstruction (DLIR) at low (DL-L), medium (DL-M), and high (DL-H) levels. The noise power spectrum (NPS) and task transfer function (TTF) were measured. Thirty consecutive patients underwent low-dose radiation contrast-enhanced abdominal CT scans that were reconstructed using FBP, AV-30, AV-50, AV-80, and AV-100, and three levels of DLIR. The standard deviation (SD), signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) of the hepatic parenchyma and paraspinal muscle were evaluated. Two radiologists assessed the subjective image quality and lesion diagnostic confidence using a 5-point Likert scale. Results: In the phantom study, both a higher DLIR and ASiR-V strength and a higher radiation dose led less noise. The NPS peak and average spatial frequency of the DLIR algorithms were closer to those of FBP, as the tube current increased and declined as the level of ASiR-V and DLIR strengthened. The NPS average spatial frequency of DL-L were higher than those of AISR-V. In clinical studies, AV-30 demonstrated a higher SD and lower SNR and CNR compared to DL-M and DL-H (P<0.05). For qualitative assessment, DL-M produced the highest qualitative image quality scores, with the exception of overall image noise (P<0.05). The NPS peak, average spatial frequency, and SD were the highest and the SNR, CNR, and subjective scores were the lowest with FBP. Conclusions: Compared with FBP and ASiR-V, DLIR provided better image quality and noise texture both in the phantom and clinical studies, and DL-M maintained the best image quality and lesion diagnostic confidence in low-dose radiation abdominal CT.

Quality assessment of rose tea with different drying methods based on physicochemical properties, HS-SPME-GC-MS, and GC-IMS.

The purpose of this study is to compare the physicochemical properties and volatile flavor compounds of rose tea obtained by the methods of normal temperature drying, hot-air drying (HAD), and vacuum freeze-drying (VFD) and to evaluate the quality of rose tea. The physicochemical results showed that the content of ascorbic acid (VC) and the pH value was the highest in rose tea obtained by HAD. The contents of anthocyanin, proanthocyanidins, and total phenols were highest in rose tea obtained by VFD. However, there was no significant difference in total flavonoids between drying methods. The volatile organic compounds (VOCs) in rose tea with different drying methods were analyzed by headspace solid-phase microextraction-gas chromatography-mass spectroscopy (HS-SPME-GC-MS) and HS GC-ion mobility spectroscopy (HS-GC-IMS), and the flavor fingerprint of rose tea was established by principal component analysis (PCA). The concentration of VOCs in rose tea varied greatly with different drying methods. The main flavor compounds of rose tea were alcohols, esters, aldehydes, and terpenoids. HS-GC-IMS was used for the identification of volatile flavor compounds of rose tea, thereby helping to assess the quality of rose tea. In addition, the rose tea samples with different drying methods were well distinguished by PCA. This study deepens the understanding of the physicochemical properties and volatile flavor compounds of rose tea with different drying methods and provides a reference for the identification of rose tea with different drying methods. PRACTICAL APPLICATION: This study deepens the understanding of the physicochemical properties and volatile flavor compounds of rose tea with different drying methods and provides a reference for the identification of rose tea with different drying methods. It also provides an effective theoretical basis for consumers to buy rose tea.

Urinary Creatinine Concentrations and Its Explanatory Variables in General Chinese Population: Implications for Creatinine Limits and Creatinine Adjustment.

Objective: The study aimed to analyze the applicability of the World Health Organization's exclusionary guidelines for Urinary creatinine (Ucr) in the general Chinese population, and to identify Ucr related factors. Methods: We conduct a cross-sectional study using baseline data from 21,167 participants in the China National Human Biomonitoring Program. Mixed linear models and restricted cubic splines (RCS) were used to analyze the associations between explanatory variables and Ucr concentration. Results: The geometric mean and median concentrations of Ucr in the general Chinese population were 0.90 g/L and 1.01 g/L, respectively. And 9.36% samples were outside 0.3-3.0 g/L, including 7.83% below the lower limit and 1.53% above the upper limit. Middle age, male, obesity, smoking, higher frequency of red meat consumption and chronic kidney disease were associated significantly with higher concentrations of Ucr. Results of the RCS showed Ucr was positively and linearly associated with body mass index, inversely and linearly associated with systolic blood pressure, diastolic blood pressure, triglycerides level, and glomerular filtration rate, and were non-linearly associated with triiodothyronine. Conclusion: The age- and gender-specific cut-off values of Ucr that determine the validity of urine samples in the general Chinese population were recommended. To avoid introducing bias into epidemiologic associations, the potential predictors of Ucr observed in the current study should be considered when using Ucr to adjust for variations in urine dilution.

Progress on aptamer-based SERS sensors for food safety and quality assessment: methodology, current applications and future trends.

It is well known that food safety has aroused extensive attentions from governments to researchers and to food industries. As a versatile technology based on molecular interactions, aptamer sensors which could specifically identify a wide range of food contaminants have been extensively studied in recent years. Surface-enhanced Raman spectroscopy integrated aptamer combines the advantages of both technologies, not only in the ability to specifically identify a wide range of food contaminants, but also in the ultra-high sensitivity, simplicity, portable and speed. To provide beneficial insights into the evaluation techniques in the field of food safety, we offer a comprehensive review on the design strategies for aptamer-SERS sensors in different scenarios, including non-nucleic acid amplification methods ("on/off" mode, sandwich mode, competition model and catalytic model) and nucleic acid amplification methods (hybridization chain reaction, rolling circle amplification, catalytic hairpin assembly). Meanwhile, a special attention is paid to the application of aptamer-SERS sensors in biological (foodborne pathogenic, bacteria and mycotoxins) and chemical contamination (drug residues, metal ions, and food additives) of food matrix. Finally, the challenges and prospects of developing reliable aptamer-SERS sensors for food safety were discussed, which are expected to offer a strong guidance for further development and extended applications.

Carrier Free O2 -Economizer for Photodynamic Therapy Against Hypoxic Tumor by Inhibiting Cell Respiration.

Abnormal tumor metabolism causes the hypoxic microenvironment, which greatly limits the efficacy of photodynamic therapy (PDT). In this work, a strategy of metabolic reprogramming is proposed to economize O2 for enhanced PDT against hypoxic tumors. The carrier-free O2 -economizer (designated as LonCe) is prepared based on the metabolic antitumor drug of Lonidamine (Lon) and the photosensitizer of chlorin e6 (Ce6). By virtue of intermolecular interactions, Lon and Ce6 self-assemble into nanosized LonCe with favorable stability and high drug contents. Compared with Ce6, LonCe exhibits an improved cellular uptake and photodynamic property for tumor treatment. Moreover, LonCe is capable of inhibiting cell metabolism and mitochondrial respiration to remit the tumor hypoxia, which would promote reactive oxygen species (ROS) production and elevate the PDT efficacy on tumor suppression. In vivo experiments indicate that intravenously injected LonCe prefers to accumulate at the tumor site for highly efficient PDT regardless of the hypoxic environment. Besides, the self-delivery LonCe is fabricated without any carriers, which avoids the excipients induced system toxicity and immunogenicity in vivo. This carrier-free nanomedicine with cell respiratory inhibition mechanism would expedite the development and clinical translation of photodynamic nanoplatforms in tumor treatment.

Distribution, ecological risk assessment and source identification of pollutants in soils of different land-use types in degraded wetlands.

BACKGROUND: Urbanization and global warming are generating ecological degradation and land pattern alteration problems in natural wetlands. These changes are greatly affecting the ecological services of wetlands. Therefore, there is an urgent need to explore the relationship between pollutants and land-use type for wetland restoration purposes. Zaozhadian Lake is a freshwater wetland in the North China Plain, which is facing degradation and land-use types changes. An experiment for analyzing soil pollutants was conducted in three land-use types of farmland, lake, and ditch in the Zaozhadian Lake. The aims of this study were to identify the distribution, pollution degree, and sources of pollutants in different land-use types, and to explore the influence of land-use type changes on contamination. METHODS: In this study, surface sediments (0-10 cm) of three land types (farmland, lake, and ditch) in Zaozhadian Lake were collected, and heavy metals (Cu, Ni, Zn, Pb, Cd, Cr, Hg), As, total nitrogen (TN), total phosphorus (TP) and organic matter (OM) were determined. Kriging interpolation was used to visualize the pollutants distribution. The pollution degree of TN and TP was evaluated by the Nemerow pollution index. The pollution of heavy metals and As was evaluated by the geological accumulation index (Igeo ) and the potential ecological risk index (RI). Then, dual hierarchical clustering analysis and the principal component analysis were performed to further analyze the impact of land type changes on pollutants. RESULTS: The heavy metal contents in the farmland were higher than other areas, while the TN (3.71 ± 1.03 g kg-1) and OM (57.17 ± 15.16 g kg-1) in lake sediments were higher than that in other regions. Farmland, lake, and ditches had low ecological risks, with RI values of 84.21, 71.34, and 50.78, respectively. The primary heavy metal pollutants are Pb, Cu, and Ni. Furthermore, Cu, As, Ni, Pb, and Zn were primarily derived from agriculture pollution, the source of Cd was the industrial pollution, and Cr mainly originated from natural sources. Nutrients primarily came from the decomposition of aquatic animals, plants, and human-related activities. When the lake area was converted into farmland, the heavy metal concentrations in the soils increased and the TN and OM decreased. Based on the results, this study put forward key strategies including the adjustment of the land-use type and restriction of the entry of pollutants into the wetland ecosystems in the Zaozhadian Lake. More attention should be paid to the impact of land-use type change on pollutants in wetlands.

Organophosphate esters in children and adolescents in Liuzhou city, China: concentrations, exposure assessment, and predictors.

Dermal contact with dust is commonly considered an important pathway of exposure to organophosphate esters (OPEs), but the importance of OPE uptake from diet is unclear. Herein, we used hand wipes to estimate OPE exposure from indoor dust and examined whether urinary OPE metabolite concentrations were influenced by sociodemographic characteristics, OPE amount in hand wipes, and dietary factors. OPEs were measured in urine and hand wipes from 6 to 18-year-old children and adolescents (n=929) in Liuzhou, China. Sociodemographic and dietary factors were obtained from questionnaire. Six OPE metabolites were detected in >70% of the urine samples, and seven OPEs were detected in >50% of the hand wipes. Estimated daily intakes (EDIs) were calculated using urinary OPE metabolites to investigate the total daily intake of OPEs, in which 0.36-10.1% of the total intake was attributed to the exposure from dermal absorption. In multivariate linear regression models, sex, age, and maternal education were significant predictors of urinary OPE metabolite concentrations. Urinary diphenyl phosphate (DPHP) is positively associated with its parent compounds 2-ethylhexyl-diphenyl phosphate (EHDPP) and triphenyl phosphate (TPHP) in hand wipes. High versus low vegetable intake was associated with a 23.7% higher DPHP (95% confidence interval (CI): 0.51%, 52.1%). Barreled water drinking was associated with a 30.4% (95% CI: 11.8%, 52.0%) increase in bis(1-chloro-2-propyl) 1-hydroxy-2-propyl phosphate (BCIPHIPP) compared to tap water drinking. Our results suggested the widespread exposure to OPEs in children and adolescents. In addition to dermal absorption, dietary intake may be an important exposure source of certain OPEs.

Biological monitoring and health assessment of 21 metal(loid)s in children and adolescents in Liuzhou City, Southwest China.

Exposure to metal(loid)s is associated with adverse effects on human health, especially for children and adolescents. This study was designed to evaluate metal(loid)s exposure in 2050 children and adolescents aged 6-18 years from Liuzhou City, Southwest China. The detection rates of 21 elements were all above 99%. We found that age was an important predictor for most elements, and that children exhibited more exposure than adolescents, expect for strontium (p < 0.05). Interestingly, urinary levels were higher in girls for 13 of our study elements. Multiple regression models also showed that dietary habits also affected the distribution of elements. Moreover, we estimated exposure risk by generating the hazard quotient (HQ) for single metal and the hazard index (HI) for the co-occurrence of metals. The HQ of cadmium was > 1 at the P95 value and that the risk of the mixed effect of cadmium, mercury, and thallium was not negligible, and indicated that the associated risk was of concern. Our results provide basic data on the reference values of urinary metal(loid) levels and an assessment of health risks for children and adolescents that reside in industrial areas.

Spatio-temporal analysis of the coupling relationship between urbanization and eco-environment in backward regions of China.

The strategy of the Silk Road Economic Belt in China has promoted the urban development of the backward regions in the west, but it might also cause serious eco-environmental concerns. Studying the coupling relationship between urbanization and the eco-environment (UEE) is essential to promote the sustainable development in backward regions. This study developed a combined method of coupling coordination degree (CCD) model, linear regression, and gray relational analysis (GRA) model to investigate the spatio-temporal coupling relationship and the influencing factors between UEE in Ningxia Hui Autonomous Region (NHAR), a typical backward region along the Silk Road Economic Belt. Results show that (1) the economic urbanization and eco-environmental pressure made the largest contribution to the system of urbanization and eco-environment, respectively. (2) The overall CCD in NHAR showed a linear upward trend from 2001 to 2018, while the CCD of each district presented significant spatial difference. The CCDs in the more developed northern regions were generally higher than those in southern mountainous regions. (3) Furthermore, population factors were the main mechanism imposing stress on the eco-environment, and the factors of eco-environmental status had higher restrictive effect on urban development in NHAR. This study could provide theoretical basis for investigating the interaction between UEE in backward regions, which might enable policymakers to formulate targeted sustainable development plans.

An optimized method for the induction and purification of mouse bone marrow dendritic cells.

Dendritic cells (DCs) play an essential role in the initiation of adaptive immune responses, but they are rare in all organs. The traditional methods used to increase the yield and purity of DCs are the early removal of granulocyte culture medium and the isolation of high-purity DCs by magnetic-activated cell sorting (MACS). This study provides a more rapid and economical optimization method to obtain more high-purity DCs. (i) We harvested 18% more bone marrow (BM) cells by using forceps to crack the epiphysis instead of cutting it with scissors during BM cell extraction. (ii) When the cells in the culture medium that is discarded on day 3 in the traditional method were centrifuged and then added back to the petri dish, the DC yield on day 5 increased by 61%. (iii) On the third day, the addition of fresh medium and the retention of the original medium rather than discarding it increased the number of DCs harvested on the fifth day by 137%. (i-iii) The improved method cost an average of 74% less than the conventional method and yielded the same number and function of cells. (iv) The initial number of BM cells was increased by 15% in 4-week-old mice compared with 8-week-old mice. (v) The Percoll density centrifugation (PDS) method was used to purify DCs on day 6 after induction, and the purity of the DCs was greater than 90%, which showed no significant difference from the MACS method. However, the yield of the PDS method increased by 21%. In addition, the PDS method has a lower cost, with an average purification cost of 4 CNY ($0.58) compared with 648 CNY ($93.25) for MACS, reducing the cost by 99%. Therefore, high-purity and high-yield DCs can be rapidly obtained through a five-step improvement in the process of BM cell extraction, induction and purification.

Plasma membrane targeted photodynamic O2 economizer for hypoxic tumor therapy.

The development of photodynamic therapy (PDT) is severely limited by short half-life of singlet oxygen (1O2) and the hypoxic microenvironment. In this work, a plasma membrane targeted photodynamic O2 economizer (designated as P-POE) is developed to improve the subcellular delivery of photosensitizers and alleviate the tumor hypoxia for enhanced PDT effect. After self-assembly into nanomicelles, P-POE has a relatively high stability and a favorable photochemical performance, which are conducive to boosting the 1O2 production. Besides, the plasma membrane anchoring of P-POE contributes to enhancing the preferential retention and cellular accumulation of photosensitizers on tumor tissues and cells. More importantly, P-POE-induced mitochondrial respiratory depression is demonstrated to reduce the O2 consumption of tumor cells to relieve the hypoxia. Consequently, P-POE still exhibits a robust PDT effect against hypoxic tumors, which greatly inhibits the proliferation of breast cancer with low adverse reactions. This innovative combination of subcellular targeting and hypoxic alleviation would advance the development of individualized drug delivery systems for photodynamic therapy against hypoxic tumors.

Fabrication of a Novel, Cost-Effective Double-Sided Indium Tin Oxide-Based Nanoribbon Electrode and Its Application of Acute Toxicity Detection in Water.

Microelectrode plays a crucial role in developing a rapid biosensor for detecting toxicity in water. In this study, a nanoribbon electrode (NRE) with amplified microelectrode signal was successfully prepared by electrodepositing 2-allylphenol on a double-sided indium tin oxide glass. The NRE provided a simple mean for obtaining large steady-state current response. Its advantages were discussed by contrasting the toxicity detection of 3,5-dichlorophenol (DCP) with single microelectrode, microelectrode array, and millimeter electrode as working electrodes in which potassium ferricyanide (K3[Fe(CN)6]) was adopted as a mediator, and Escherichia coli was selected as bioreceptor. At a constant potential of 450 mV, the current reached a steady state within 10 s. The biosensor was constructed using the NRE as working electrode, and its feasibility was verified by determining the toxicity of DCP. A 50% inhibitory concentration (IC50) of 3.01 mg/L was obtained by analyzing the current responses of different concentrations of DCP within 1 h. These results exhibited that the proposed method based on the as-prepared NRE was a rapid, sensitive, and cost-effective way for toxicity detection in water.

Post-hoc assessment of the immunogenicity of three antibodies reveals distinct immune stimulatory mechanisms.

Biologics have the potential to induce an immune response when used therapeutically. A number of in vitro assays are currently used preclinically to predict the risk of immunogenicity, but the validation of these preclinical tools suffers from the relatively small number of accessible immunogenic molecules and the limited understanding of the mechanisms underlying the immunogenicity of biologics. Here, we present the post-hoc analysis of three monoclonal antibodies with high immunogenicity in the clinic. Two of the three antibodies elicited a CD4 T cell proliferative response in multiple donors in a peripheral blood mononuclear cell assay, but required different experimental conditions to induce these responses. The third antibody did not trigger any T cell response in this assay. These distinct capacities to promote CD4 T cell responses in vitro were mirrored by different capacities to stimulate innate immune cells. Only one of the three antibodies was capable of inducing human dendritic cell (DC) maturation; the second antibody promoted monocyte activation while the third one did not induce any innate cell activation in vitro. All three antibodies exhibited a moderate to high internalization by human DCs and MHC-associated peptide proteomics analysis revealed the presence of potential T cell epitopes that were confirmed by a T-cell proliferation assay. Collectively, these findings highlight the existence of distinct immune stimulatory mechanisms for immunogenic antibodies. These findings have implications for the preclinical immunogenicity risk assessment of biologics.

Development of a FRET-Based Assay for Analysis of mAbs Internalization and Processing by Dendritic Cells in Preclinical Immunogenicity Risk Assessment.

Treatment-emergent antidrug antibodies (TE-ADA) pose a major challenge to the development of biotherapeutics. The antidrug antibody responses are highly orchestrated and involve many types of immune cells and biological processes. Biological drug internalization and processing by antigen-presenting cells (APCs) are two initial and critical steps in the cascade of events leading to T cell-dependent ADA production. The assays thus far described in literature to evaluate immunogenicity potential/risk as a function of APC activity mainly focus on internalization of labeled drug candidates in vitro. Herein, we describe a high-throughput Förster Resonance Energy Transfer (FRET)-based assay for assessing both internalization and processing using CD14+ monocyte-derived dendritic cells (DCs) as APCs. Antigen-binding fragment F(ab')2 against IgG fragment crystallizable gamma (Fcγ) was labeled with the activatable FRET pair TAMRA-QSY7 as a universal probe for antibodies and proteins with a fragment crystallizable (Fc) domain. The assay was qualified using six mAbs of known clinical immunogenicity and one IgG1 isotype antibody using Design of Experiment (DoE). Correlation analysis of internalization and clinical immunogenicity data showed that this FRET-based internalization assay was able to detect clinically immunogenic antibodies. This method provides a tool for analyzing/screening the immunogenicity risk of biological candidates by assessing one of the critical components of the ADA formation process within the broader context of an immunogenicity risk assessment strategy.

Self-Delivery Nanomedicine for O2-Economized Photodynamic Tumor Therapy.

Tumor hypoxia is the Achilles heel of oxygen-dependent photodynamic therapy (PDT), and tremendous challenges are confronted to reverse the tumor hypoxia. In this work, an oxidative phosphorylation inhibitor of atovaquone (ATO) and a photosensitizer of chlorine e6 (Ce6)-based self-delivery nanomedicine (designated as ACSN) were prepared via π-π stacking and hydrophobic interaction for O2-economized PDT against hypoxic tumors. Specifically, carrier-free ACSN exhibited an extremely high drug loading rate and avoided the excipient-induced systemic toxicity. Moreover, ACSN not only dramatically improved the solubility and stability of ATO and Ce6 but also enhanced the cellular internalization and intratumoral permeability. Abundant investigations confirmed that ACSN effectively suppressed the oxygen consumption to reverse the tumor hypoxia by inhibiting mitochondrial respiration. Benefiting from the synergistic mechanism, an enhanced PDT effect of ACSN was observed on the inhibition of tumor growth. This self-delivery system for oxygen-economized PDT might be a potential appealing clinical strategy for tumor eradication.

A respiration substrate-less isolation method for acute toxicity assessment.

Respiration substrate (RS)-less isolation method was developed for enhancing the sensitivity of acute toxicity assessment of heavy metal ions. RS was removed from the first step of previous isolation method, which was an effective strategy for improving acute toxicity assessment. 50% inhibiting concentration (IC50) values of Cu2+, Cd2+, Zn2+, Hg2+ and Ni2+ were 0.39 mg L-1, 5.99 mg L-1, 3.99 mg L-1, 0.23 mg L-1 and 5.74 mg L-1, respectively. Beyond that, the complicacy of organic toxicants assessments was investigated by choosing 3,5-dichlorophenol (DCP) as model toxicant. Biofilm sensor, morphology method and suspended microbes-based methods including one-pot method, RS-isolation method, RS-less isolation method, RS-less isolation method with added potassium ferricyanide (+F), were compared. The sensitivity to DCP can be ranked as morphology method > suspended microbes-based methods > biofilm method. The difference of the present results implicated that the methodological interference, leading in different detection mechanisms of these methods. The relative investigations can provide theoretical guidance for developing comprehensive detection methods of pollutants.

Economic variations in patterns of care and outcomes of patients receiving invasive mechanical ventilation in China: a national cross-sectional survey.

BACKGROUND: Ventilation practice may be affected by economic variations, which might result in different outcomes to mechanically ventilated patients. We aimed to investigate the important effect of economic variations in patients with mechanical ventilation (MV) in China. METHODS: We carried out a national prospective multicentre cross-sectional observational study over 1 month of all patients receiving invasive MV for more than 24 hours in 20 intensive care units (ICUs), including patient characteristics, practice of MV, weaning modalities and outcomes, including probability of weaning and survival. Based on the 2012 World Bank classification of counties, patients were divided into high-income and middle-income groups according to gross domestic product per capita in their province of origin. RESULTS: Of the 483 patients enrolled, 291 (60.2%) were from high-income provinces and 192 (39.8%) were from middle-income provinces. Tidal volume, peak pressure, plateau and driving pressure were significantly lower, and the proportion of patients receiving protective ventilation (71.1% vs. 59.9%, P=0.014) was significantly higher in the high-income group than in the middle-income group. The probability of weaning within 28 days was significantly greater in the high-income group than in the middle-income group (P=0.046). Patients in the high-income group had significantly higher median numbers of ventilator-free days within 14 and 28 days than those in the middle-income group (P<0.05). Although the patients did not differ in terms of their demographics, survival within 28 days was significantly higher in the high-income group than in the middle-income group (P=0.025). Driving pressure, positive end-expiratory pressure and spontaneous breathing trial were independently associated with hospital mortality. CONCLUSIONS: Important economic differences exist in the management of MV and patient outcomes. Higher income is associated with a higher proportion of protective ventilation, lower driving pressure, shorter weaning and better survival in mechanically ventilated patients in China.

Clinical and economic impact of goal-directed fluid therapy during elective gastrointestinal surgery.

BACKGROUND: Several randomized controlled trials suggest that goal-directed fluid therapy (GDFT) may result in improved postoperative outcomes. The aim of this study was to assess the clinical and financial impact of the real-life implementation of intraoperative GDFT in patients undergoing elective gastrointestinal surgery in a Chinese tertiary medical center. METHODS: This Quality Improvement Program (QIP) study comprised three phases of 5, 1, and 5 months, respectively. During the first phase, we retrospectively collected perioperative data from patients who received standard intraoperative fluid management from January to May 2016. Then a 1-month training period allowed the clinical staff to become familiar with the GDFT protocol. After the training phase, GDFT was used from July to November 2016. In the GDFT group, stroke volume (SV) was continuously monitored and optimized towards the plateau of the Frank-Starling curve. The primary outcome measure was postoperative morbidity (the proportion of patients with one or more complications within 30 days after surgery). Secondary outcomes were total hospital cost, postoperative length of hospital stay, and 30-day mortality. RESULTS: Data from 200 patients before (control group) and 201 patients after the implementation of GDFT (GDFT group) were collected and compared. There was no significant difference in demographics and surgical procedures between the two groups. Postoperative morbidity was significantly lower in the GDFT group than in the control group (30.8% vs. 44.0%, p = 0.006). No significant differences were observed for mean total hospital cost (76,793 RMB vs. 74,444 RMB; p = 0.430), median postoperative length of hospital stay (10 days vs. 10 days; p = 0.104), and 30-day mortality (1% vs. 0.5%; p = 0.565). CONCLUSION: In patients undergoing gastrointestinal surgery, the implementation of a GDFT protocol was associated with a reduction in postoperative morbidity without increasing costs. TRIAL REGISTRATION: clinicaltrials.gov, NCT02507557. Registered 13 July 2015.