ECM stiffness affects cargo sorting into MSC-EVs to regulate their secretion and uptake behaviors.

Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have garnered extensive attention as natural product-based nanomedicines and potential drug delivery vehicles. However, the specific mechanism for regulating MSC-EVs secretion and delivery remains unclear. Here, we demonstrate that extracellular matrix (ECM) stiffness regulates the secretion and delivery of EVs by affecting MSCs' cargo sorting mechanically. Using multi-omics analysis, we found that a decrease in ECM stiffness impeded the sorting of vesicular transport-related proteins and autophagy-related lipids into MSC-EVs, impairing their secretion and subsequent uptake by macrophages. Hence, MSC-EVs with different secretion and uptake behaviors can be produced by changing the stiffness of culture substrates. This study provides new insights into MSC-EV biology and establishes a connection between MSC-EV behaviors and ECM from a biophysical perspective, providing a basis for the rational design of biomedical materials.

Humic substances mediated superior photochemical pollutant conversion on defective TiO2 in environmentally relevant matrices: The key roles of oxygen vacancy in surface interactions, oxidant activation and radical generation.

Ubiquitous humic substances usually exhibit strong interfering effects on target pollutant removal in advanced water purification. This work aims to develop a photochemical conversion system on the nonstoichiometric TiO2 for pollutant removal in environmentally relevant matrices. In this synergistic reaction system, the redox-reactive humic substances and defective oxygen vacancies can serve as the organic electron transfer mediator and the key surface reactive sites, respectively. This system achieves a superior pollutant degradation in real surface water at low oxidant concentrations. Reactive oxygen vacancies on the TiO2 surface and sub-surface are of considerable interest for this photochemical reaction system. By engineering defective oxygen vacancies on high-energy {001} polar facet, the surface and electronic interactions between tailored TiO2 and humic substances are greatly strengthened for the promoted electron transfer and oxidant activation. Rendered by the strong surface affinity and molecular activation, defective oxygen vacancies thermodynamically and dynamically promote reactive chain reactions for free radical formation, including the selective O2 reduction to ·O2- and the H2O2 activation to ·OH. Our findings take new insights into environmental geochemistry, and provide an effective strategy to in-situ boost the humic substances-mediated water purification without secondary pollution. ENVIRONMENTAL IMPLICATION: Humic substances are widely distributed in aquatic environment, thus playing important roles in environmental geochemistry. For example, humic substances can achieve good surface adsorption through electrostatic adsorption, ligand exchange and electronic interactions with typical TiO2 to form reactive ligand-metal charge transfer complexes for pollutant degradation. Inspired by the unique properties of surface and sub-surface oxygen vacancies, the defective TiO2 was designed to refine the humic substances-mediated photochemical reactions. A superior reactivity was measured for pollutant degradation. Our findings provide an effective strategy to boost naturally photochemical decontamination in environmentally relevant matrices.

Sulphate reduction, mixed sulphide- and thiosulphate-driven Autotrophic denitrification, NItrification, and Anammox (SANIA) integrated process for sustainable wastewater treatment.

This study proposes the Sulphate reduction, mixed sulphide- and thiosulphate-driven Autotrophic denitrification, Nitrification, and Anammox integrated (SANIA) process for sustainable treatment of mainstream wastewater after organics capture. Three moving-bed biofilm reactors (MBBRs) were applied for developing sulphate reduction (SR), mixed sulphide- and thiosulphate-driven partial denitrification and Anammox (MSPDA), and NItrification (N), respectively. Typical mainstream wastewater after organics capture (e.g., chemically enhanced primary treatment, CEPT) was synthesized with chemical oxygen demand (COD) of 110 mg/L, sulphate of 50 mg S/L, ammonium of 30 mgN/L. The feasibility of SANIA was investigated with mimic nitrifying effluent supplied in MSPDA-MBBR (Period I), followed by the examination of the applicability of SANIA process with N-MBBR integrated (Period II), under moderate temperatures (25-27 â„ƒ). In Period I, SANIA process was established with both SR- and MSPDA-MBBR continuously operated for over 300 days (no Anammox biomass inoculation). Specifically, in MSPDA-MBBR, high rates of denitratation (2.7 gN/(m2·d)) and Anammox (2.8 gN/(m2·d)) were achieved with Anammox contributing to 81 % of the total inorganic nitrogen removal. In Period II, the integrated SANIA system was continuously operated for over 130 days, achieving up to 90 % of COD, 93 % of ammonium, and 61 % of total inorganic nitrogen (TIN) removal, with effluent concentrations lower than 10 mg COD/L, 3 mg NH4+-N/L, and 13 mg TIN-N/L. The implementation of SANIA can ultimately reduce 75 % and 40 % of organics and aeration energy for biological nitrogen removal. Considering the combination of SANIA with CEPT for carbon capture and sludge digestion/incineration for energy recovery, the new integrated wastewater technology can be a promising strategy for sustainable wastewater treatment.

High-resolution magnetic resonance imaging-based radiomic features aid in selecting endovascular candidates among patients with cerebral venous sinus thrombosis.

OBJECTIVES: Cerebral venous sinus thrombosis (CVST) can cause sinus obstruction and stenosis, with potentially fatal consequences. High-resolution magnetic resonance imaging (HRMRI) can diagnose CVST qualitatively, although quantitative screening methods are lacking for patients refractory to anticoagulation therapy and who may benefit from endovascular treatment (EVT). Thus, in this study, we used radiomic features (RFs) extracted from HRMRI to build machine learning models to predict response to drug therapy and determine the appropriateness of EVT. MATERIALS AND METHODS: RFs were extracted from three-dimensional T1-weighted motion-sensitized driven equilibrium (MSDE), T2-weighted MSDE, T1-contrast, and T1-contrast MSDE sequences to build radiomic signatures and support vector machine (SVM) models for predicting the efficacy of standard drug therapy and the necessity of EVT. RESULTS: We retrospectively included 53 patients with CVST in a prospective cohort study, among whom 14 underwent EVT after standard drug therapy failed. Thirteen RFs were selected to construct the RF signature and CVST-SVM models. In the validation dataset, the sensitivity, specificity, and area under the curve performance for the RF signature model were 0.833, 0.937, and 0.977, respectively. The radiomic score was correlated with days from symptom onset, history of dyslipidemia, smoking, fibrin degradation product, and D-dimer levels. The sensitivity, specificity, and area under the curve for the CVST-SVM model in the validation set were 0.917, 0.969, and 0.992, respectively. CONCLUSIONS: The CVST-SVM model trained with RFs extracted from HRMRI outperformed the RF signature model and could aid physicians in predicting patient responses to drug treatment and identifying those who may require EVT.

Reductive inactivation of the hemiaminal pharmacophore for resistance against tetrahydroisoquinoline antibiotics.

Antibiotic resistance is becoming one of the major crises, among which hydrolysis reaction is widely employed by bacteria to destroy the reactive pharmacophore. Correspondingly, antibiotic producer has canonically co-evolved this approach with the biosynthetic capability for self-resistance. Here we discover a self-defense strategy featuring with reductive inactivation of hemiaminal pharmacophore by short-chain dehydrogenases/reductases (SDRs) NapW and homW, which are integrated with the naphthyridinomycin biosynthetic pathway. We determine the crystal structure of NapW·NADPH complex and propose a catalytic mechanism by molecular dynamics simulation analysis. Additionally, a similar detoxification strategy is identified in the biosynthesis of saframycin A, another member of tetrahydroisoquinoline (THIQ) antibiotics. Remarkably, similar SDRs are widely spread in bacteria and able to inactive other THIQ members including the clinical anticancer drug, ET-743. These findings not only fill in the missing intracellular events of temporal-spatial shielding mode for cryptic self-resistance during THIQs biosynthesis, but also exhibit a sophisticated damage-control in secondary metabolism and general immunity toward this family of antibiotics.

Prescribing Silver Chirality with DNA Origami.

Metal nanostructures of chiral geometry interacting with light via surface plasmon resonances can produce tailorable optical activity with their structural alterations. However, bottom-up fabrication of arbitrary chiral metal nanostructures with precise size and morphology remains a synthetic challenge. Here we develop a DNA origami-enabled aqueous solution metallization strategy to prescribe the chirality of silver nanostructures in three dimensions. We find that diamine silver(I) complexes coordinate with the bases of prescribed single-stranded protruding clustered DNA (pcDNA) on DNA origami via synergetic interactions including coordination, hydrogen bonds, and ion-π interaction, which induce site-specific pcDNA condensation and local enrichment of silver precursors that lowers the activation energy for nucleation. Using tubular DNA origami-based metallization, we obtain helical silver patterns up to a micrometer in length with well-defined chirality and pitches. We further demonstrate tailorable plasmonic optical activity of metallized chiral silver nanostructures. This method opens new pathways to synthesize programmable inorganic materials with arbitrary morphology and chirality.

Antimony tin oxide/lead selenide composite as efficient counter electrode material for quantum dot-sensitized solar cells.

Antimony tin oxide (ATO)/lead selenide (PbSe) composite was rationally designed and fabricated on fluorine doped tin oxide glass (FTO) for using as counter electrode (CE) of quantum dot sensitized solar cells (QDSSCs). The electrocatalytic activity of the CE is deeply investigated in the polysulfide electrolyte by employing the Tafel, electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) of the symmetrical cells. The results confirm that the ATO/PbSe CE has better electrocatalytic activity and stability than that of PbSe CE obtained by pulse voltage electrodeposition (PVD). The enhanced electrocatalytic performance of ATO/PbSe CE can be attributed to its high specific surface area, excellent permeability, conductivity and interface connectivity, which provide more electrocatalytic active sites for the reduction of polysulfide species, as well as fast channels for ions diffusion and electron transport. As a result, the CdS QDSSCs and CdS/CdSe co-sensitized QDSSCs assembled by the ATO/PbSe CE exhibits better power conversion efficiency (η) of 1.72% and 5.59%, respectively than that of PbSe CE obtained by PVD. Furthermore, photovoltaic property of the ATO/PbSe CE in CdS/CdSe co-sensitized QDSSCs keeps stable for over 200 min. This present work provides a simple and effective strategy for the construction of high-performance CE materials of QDSSCs.

Features of a simvastatin-loaded multi-layered co-electrospun barrier membrane for guided bone regeneration.

A novel tri-layer membrane consisting of polycaprolactone (PCL) fibrous sheets and structured nanofibers with a gelatin (Gt) shell and a simvastatin-containing PCL core (PCL-Gt/PCL-simvastatin membrane) was prepared. The soft external layer comprised of Gt/PCL-simvastatin, the external layer of PCL and the middle layer of both microfilaments, interwoven together. The membrane was designed to promote osteoinduction and act as a barrier against cells but not against water and molecules in order to promote guided bone regeneration. The structure of the membrane was characterized by scanning electronic microscopy. The in vitro release rates of simvastatin over 32 days were determined by high-performance liquid chromatography. For in vitro biological assays, bone marrow mesenchymal stem cells and human fibroblasts were cultured on the different surfaces of the membrane. Cell adhesion, proliferation, distribution, and differentiation were examined. For in vivo testing, cranial defects were created in rabbits to assess the amount of new bone formed for each membrane. The results revealed that membranes with multi-layered structures showed good cell viability and effective osteoinductive and barrier properties. These results suggest that the novel multi-layered PCL-Gt/PCL-simvastatin membranes have great potential for bone tissue engineering.

Toward Smart Information Processing with Synthetic DNA Molecules.

DNA, a biological macromolecule, is a naturally evolved information material. From the structural point of view, an individual DNA strand can be considered as a chain of data with its bases working as single units. For decades, due to the high biochemical stability, large information storage capacity, and high recognition specificity, DNA has been recognized as an attractive material for information processing. Especially, the chemical synthesis strategies and DNA sequencing techniques have been rapidly developed recently, further enabling encoding information with synthetic DNA molecules. Herein, recent progresses are summarized on information processing based on synthetic DNA molecules from three aspects including information storage, computation, and encryption, and proposed the challenges and future development directions.

[Analysis on the status of health literacy and its influencing factors among residents aged 15-69 years old in Haidian District of Beijing City in 2018].

OBJECTIVE: To understand the status of health literacy and its influencing factors among the residents in Haidian District of Beijing, and to provide references for targeted health education intervention. METHODS: A multi-staged probability proportionate to size sampling(PPS) sampling method was used to collect 7034 residents that aged 15-69 years old in Haidian District in 2018. RESULTS: The standardized rate of health literacy among the residents of Haidian District was 28. 56%. The standardized health literacy rate of basic health knowledge and concept literacy, health lifestyle and behavior literacy, basic health skill were 35. 79%, 30. 90% and 36. 39%, respectively. The standardized health literacy rate of 6 health literacy issues from high to low were safety and first aid(66. 39%), scientific health perspectives(51. 24%), infectious diseases prevention and treatment(39. 78%), health information(30. 25%), chronic disease control and prevention(13. 33%), and basic medical care(11. 23%), respectively. The result of multiple logistic regression showed that aged between 30-39 years old, female, high school education and above, the teacher, medical and government staff, staff of other institutions, staff of other enterprises, other employees and the annual income of the family>45000 RMB were protective factors for health literacy. Aged between 50-69 years old was risk factor for health literacy. CONCLUSION: The level of health literacy in Haidian District was low. Various forms of intervention activities should be carried out to improve the residents' health literacy, especially focused on health lifestyle and behavior literacy, chronic disease control and prevention and basic medical care.

Constructing Microbial Hosts for the Production of Benzoheterocyclic Derivatives.

Natural products containing benzoheterocyclic skeletons are widely found in plants and exhibit various pharmacological activities. To address the current limited availability of these compounds, we herein demonstrate the production of benzopyran, furanocoumarins, and pyranocoumarins in Streptomyces xiamenensis by employing prenyltransferases and two substrate-promiscuous enzymes, XimD and XimE. To avoid the degradation in S. xiamenensis, furanocoumarins and pyranocoumarins were also successfully produced in Escherichia coli. The production of linear furanocoumarins (marmesin) and angular pyranocoumarins (decursinol) reached 3.6 and 3.7 mg/L in shake flasks, respectively. To the best of our knowledge, this is the first report of the microbial production of the plant metabolites furanocoumarins and pyranocoumarins. Our study complements the missing link in the biosynthesis of pyranocoumarins by leveraging the catalytic promiscuity of microbial enzymes.

The Smartphone-Assisted Intervention Improved Perception of Nutritional Status among Middle School Students.

Misperception of nutritional status is common and hinders the progress of childhood obesity prevention. This study aimed to examine the effectiveness of a smartphone-assisted intervention to improve student and parental perception of students' nutritional status (underweight, normal weight, overweight, obese). We conducted a parallel-group controlled trial with a non-randomized design in three junior middle schools of Beijing, China in 2019. One school was allocated to the intervention group and two schools to the control group. A total of 573 students (aged 13.1 ± 0.4 years) participated in the trial. The 3-month intervention included three components: health education sessions for students and parents, regular monitoring of students' weight, and the provision of feedback via a smartphone application. Schools in the control group continued their usual practice. Primary outcomes included the student and parental accurate perception of students' nutritional status. The percentage of students' accurate perception of their own nutritional status in the intervention group increased from 49.0% to 59.2% from baseline to three months, whereas it decreased from 64.1% to 58.1% in the control group; the adjusted odds ratio (OR) between the two groups was 1.71 (95% confidence interval (CI): 1.13, 2.59). The intervention did not significantly improve parental perception of students' nutritional status (p > 0.05). The study findings provided a brief approach for improving perception of nutritional status among middle school students.

Effect of scrubbing by NaClO backwashing on membrane fouling in anammox MBR.

NaClO based chemically enhanced backwash (CEB) is often administered to maintain membrane permeability during the operation of MBR. However, the effect and working mechanism of NaClO concentrations in CEB were rarely investigated. The current investigation examined the changes in membrane resistance, permeate production and membrane morphology with or without CEB in an anammox MBR to reveal the scrubbing effect of different NaClO concentrations (0-596 mg/L). Good cleaning effect indicated by membrane fouling rate of 1.98-2.26 kPa/day and membrane permeate production of 80-88 L was observed when NaClO concentration of 149-596 mg/L was used. The best cleaning effect was observed when 298 mg/L of NaClO was used. To explore the mechanism of CEB action, backwashing foulants were also analyzed. Insoluble EPS transformed into soluble forms like S-EPS or SMP after the sludge was exposed to NaClO. The NaClO based CEB removed 112-675 mg of polysaccharide (PS)/m2 in foulants at NaClO concentration of 149-596 mg/L, which was significantly higher than the value obtained by pure water (35 mg PS/m2). The possible mechanisms behind the detachment of soluble PS seemed as oxidation and sterilization by NaClO. The current investigation provides useful guidelines on NaClO concentrations applied during CEB for anammox MBR.

The application of aged refuse in nitrification biofilter: Process performance and characterization.

High adsorption capacity, good biocompatibility and low cost are highly demanded for biofilter used in ammonium-rich wastewater treatment. In this study, we used SEM, BET, XRD and 16S rRNA to document the evidence for good performance in adsorption and biodegradation in aged refuse. Parallel experiment between raw and inert refuse showed ammonium adsorption occurred at the initial week, with the highest ammonium removal efficiency of 90.36%, but saturated during the subsequent long-term operation. Meanwhile, over 6months' operation of an aged refuse biofilter was conducted to confirm that nitrification was the main pathway of ammonium conversion. The maximum nitrogen loading rate could reach up to as high as 1.28kg/m3/d, with ammonium removal efficiency at 99%. Further, high nitrifier biodiversity were detected with 'Nitrosomonas' and 'Nitrospira' in domination in the refuse. However, Nitrospira would outcompete Nitrosomonas under the oxygen limiting condition and resulted in the failure of partial nitrification. The physicochemical and biological analysis show that biodegradation is the main ammonium conversion pathway, which is the critical finding of this work. This investigation would help to accelerate the application of the aged refuse process in ammonium-rich wastewater treatment.

A hospital-associated measles outbreak in health workers in Beijing: Implications for measles elimination in China, 2018.

BACKGROUND: Since the National Action Plan for Measles Elimination 2006-2012 was released in 2006, China has entered into an era of accelerated measles elimination. Despite substantial decline, measles outbreak continued to occur mainly in a non-targeted population, in particular health workers due to occupational exposure. We investigated a measles outbreak in a Chinese medicine hospital, Beijing, in March 2018. METHODS: Descriptive analysis was performed on epidemiology of the outbreak, clinical and laboratory evaluations, vaccination status of cases, and public health response. A case-control study was also conducted to identify the associated risk factors for measles. RESULTS: From March 13, 2018, through March 27, 2018, a total of 11 measles cases in health workers were reported in Hospital X, Beijing. The median age of cases was 26 years (range, 21-53) and 4 (36.4%) were male. Of the 11 cases, ten had not been vaccinated or had unknown vaccination status; two occurred in emergency departments. No inpatients became infected, 141 (83.9%) of whom in affected departments were 55 years of age or older. The outbreak was confirmed by laboratory testing; the virus strain was genotype H1. The response activities included isolation of cases, and enhanced health surveillance of health workers and inpatients, particularly in affected departments. A total of 2234 doses of measles-containing vaccines (MCVs) were administered, covering 93.3% of susceptible health workers, in addition to 973 doses to the susceptible individuals in household and community. Lack of documentation of MCV vaccination before the outbreak was identified as a risk factor for measles (odd ratio: 3.333, 95% confidence interval: 1.295-8.621). CONCLUSIONS: High coverage of outbreak response immunization activities contributed largely to limit the spread of measles and might provide an indirect protection for inpatients. 2-Dose measles-containing vaccination of personnel in healthcare settings is warranted to prevent potential nosocomial transmission of measles.

To establish a talent pool for global health in China: from political will to action.

Recently, China has played a more and more important role in global health, mainly by improving health outcomes of its own population nationwide and participating international health activities. In addition, China has participated in a dozen of international organizations, which all contained health domains, particularly the Belt and Road Initiative with an ambitious goal to improve health of the people in the countries alongside closely partnered with the World Health Organization. All these highlight the need of human resource for global health at the national level. The National Health and Family Planning Commission translated this political will into action - that a talent pool candidate for global health will be established in China. The establishment of the talent pool would be of great significance for China's engagement in global health activities. However, much work, such as training, collaboration, and innovation, etc., remains to be done in the future. Based on the successful practice, China can share lessons learned to other countries.

Epidemiology of varicella in Haidian district, Beijing, China-2007-2015.

BACKGROUND: 1-Dose varicella vaccination was recommended for children in Beijing before November 2012. To further control school-based outbreaks and decrease incidence, a 2-dose vaccination was implemented in 2013. We described the varicella epidemiology and assessed impact of the 2-dose vaccination in Haidian district, Beijing, 2007-2015. METHODS: We examined the estimated incidence and disease characteristics of varicella during 2007-2015 and obtained the 1-dose vaccination coverage for children born during 2005-2013. Number of vaccine doses given was used to indirectly reflect the second-dose vaccination coverage. Overall and age-specific estimated incidences were compared between 2007-2012 and 2013-2015. RESULTS: A total of 23,497 cases were reported during 2007-2015. Of the 23,497 cases, 13,440 (57.20%) were male, and 68.40% were <20years of age and 70.02% were students and children in kindergarten. The estimated incidence increased from 82 cases per 100,000 population in 2007 to 104 in 2011, before substantially decreasing from 86 in 2012 to 56 in 2015. The median age increased from 14years in 2007 to 18years in 2015. The 1-dose varicella coverage for children at ≥2years of age gradually increased from 74.21% in 2007 to 90.06% in 2015. Compared with 2007-2012, two-fold average vaccine doses were given during 2013-2015, and the overall estimated incidence declined by 34.4%, particularly in children aged 5-9years, with a significantly declined trend in children aged 1-9years and older adolescents aged 15-19years and non-significantly declined trend in adults aged ≥20years, but a significant increasing trend in infants. CONCLUSIONS: The overall incidence of varicella has decreased substantially in Haidian district since 2013, with largest decline in children aged 5-9years. The 2-dose varicella vaccination might not lead to increase in incidence in adults. Long-term surveillance is needed to fully evaluate the long-term impact of the 2-dose varicella vaccination.

Increased Expression of P-Glycoprotein Is Associated With Chlorpyrifos Resistance in the German Cockroach (Blattodea: Blattellidae).

A principal method for control of the German cockroach, Blattella germanica (L.), is the broad-spectrum organophosphorus insecticide, chlorpyrifos (O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphorothioate); however, extensive and repeated application has resulted in the development of resistance to chlorpyrifos in this insect. Evidence suggests that ATP-binding cassette protein transporters, including P-glycoprotein, are involved in insecticide resistance. However, little is known of the role of P-glycoprotein in insecticide resistance in the German cockroach. Here, we developed a chlorpyrifos-resistant strain of German cockroach and investigated the relationship between P-glycoprotein and chlorpyrifos resistance using toxicity assays; inhibition studies with two P-glycoprotein inhibitors, verapamil and quinine; P-glycoprotein-ATPase activity assays; and western blotting analysis. After 23 generations of selection from susceptible strain cockroaches, we obtained animals with high resistance to chlorpyrifos. When P-glycoprotein-ATPase activity was inhibited by verapamil and quinine, we observed enhanced susceptibility to chlorpyrifos in both control and chlorpyrifos-resistant cockroaches. No significant alterations of P-glycoprotein expression or ATPase activity were observed in cockroaches acutely exposed to LD50 doses of chlorpyrifos for 24 h, while P-glycoprotein expression and ATPase activity were clearly elevated in the chlorpyrifos-resistant cockroach strain. Thus, we conclude that P-glycoprotein is associated with chlorpyrifos resistance in the German cockroach and that elevated levels of P-glycoprotein expression and ATPase activity may be an important mechanism of chlorpyrifos resistance in the German cockroach.