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Background: Hypertension can lead to podocyte damage and subsequent apoptosis, eventually resulting in glomerulosclerosis. Although alleviating podocyte apoptosis has clinical significance for the treatment of hypertensive nephropathy, an effective therapeutic target has not yet been identified. The function of septin4, a proapoptotic protein and an important marker of organ damage, is regulated by post-translational modification. However, the exact role of septin4 in regulating podocyte apoptosis and its connection to hypertensive renal damage remains unclear. Methods: We investigated the function and mechanism of septin4 in hypertensive nephropathy to discover a theoretical basis for targeted treatment. Mouse models including Rosa 26 (Gt(ROSA)26Sor)- SIRT2 (silent mating type information regulation 2 homolog-2)-Flag-TG (transgenic) ( SIRT2 -TG) mice SIRT2 -knockout, and septin4 -K174Q mutant mice, combined with proteomic and acetyl proteomics analysis, followed by multiple molecular biological methodologies, were used to demonstrate mechanisms of SIRT2-mediated deacetylation of septin4-K174 in hypertensive nephropathy. Results: Using transgenic septin4 -K174Q mutant mice treated with the antioxidant Tempol, we found that hyperacetylation of the K174 site of septin4 exacerbates Ang II (angiotensin II)– induced hypertensive renal injury resulting from oxidative stress. Proteomics and Western blotting assays indicated that septin4-K174Q activates the cleaved-PARP1 (poly [ADP-ribose] polymerase family, member 1)-cleaved-caspase3 pathway. In septin4-knockdown human renal podocytes, septin4-K174R, which mimics deacetylation at K174, rescues podocyte apoptosis induced by Ang II. Immunoprecipitation and mass spectrometry analyses identified SIRT2 as a deacetylase that interacts with the septin4 GTPase domain and deacetylates septin4-K174. In Sirt2 -deficient mice and SIRT2-knockdown renal podocytes, septin4-K174 remains hyperacetylated and exacerbates hypertensive renal injury. By contrast, in Rosa26-Sirt2-Flag (SIRT2-TG) mice and SIRT2-knockdown renal podocytes reexpressing wild-type SIRT2, septin4-K174 is hypoacetylated and mitigates hypertensive renal injury. Conclusions: Septin4, when activated through acetylation of K174 (K174Q), promotes hypertensive renal injury. Septin4-K174R, which mimics deacetylation by SIRT2, inhibits the cleaved-PARP1-cleaved-caspase3 pathway. Septin4-K174R acts as a renal protective factor, mitigating Ang II–induced hypertensive renal injury. These findings indicate that septin4-K174 is a potential therapeutic target for the treatment of hypertensive renal injury.

The prevalence of uncontrolled hypertension is high and increasing in low-income and middle-income countries. We tested the effectiveness of a multifaceted intervention for blood pressure control in rural China led by village doctors (community health workers on the front line of primary health care).In this open, cluster randomised trial (China Rural Hypertension Control Project), 326 villages that had a regular village doctor and participated in the China New Rural Cooperative Medical Scheme were randomly assigned (1:1) to either village doctor-led multifaceted intervention or enhanced usual care (control), with stratification by provinces, counties, and townships. We recruited individuals aged 40 years or older with an untreated blood pressure of 140/90 mm Hg or higher (≥130/80 mm Hg among those with a history of cardiovascular disease, diabetes, or chronic kidney disease) or a treated blood pressure of 130/80 mm Hg or higher. In the intervention group, trained village doctors initiated and titrated antihypertensive medications according to a standard protocol with supervision from primary care physicians. Village doctors also conducted health coaching on home blood pressure monitoring, lifestyle changes, and medication adherence. The primary outcome (reported here) was the proportion of patients with a blood pressure of less than 130/80 mm Hg at 18 months. The analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT03527719, and is ongoing.Between May 8 and November 28, 2018, we enrolled 33 995 individuals from 163 intervention and 163 control villages. At 18 months, 8865 (57·0%) of 15 414 patients in the intervention group and 2895 (19·9%) of 14 500 patients in the control group had a blood pressure of less than 130/80 mm Hg, with a group difference of 37·0% (95% CI 34·9 to 39·1%; p0·0001). Mean systolic blood pressure decreased by -26·3 mm Hg (95% CI -27·1 to -25·4) from baseline to 18 months in the intervention group and by -11·8 mm Hg (-12·6 to -11·0) in the control group, with a group difference of -14·5 mm Hg (95% CI -15·7 to -13·3 mm Hg; p0·0001). Mean diastolic blood pressure decreased by -14·6 mm Hg (-15·1 to -14·2) from baseline to 18 months in the intervention group and by -7·5 mm Hg (-7·9 to -7·2) in the control group, with a group difference of -7·1 mm Hg (-7·7 to -6·5 mm Hg; p0·0001). No treatment-related serious adverse events were reported in either group.Compared with enhanced usual care, village doctor-led intervention resulted in statistically significant improvements in blood pressure control among rural residents in China. This feasible, effective, and sustainable implementation strategy could be scaled up in rural China and other low-income and middle-income countries for hypertension control.Ministry of Science and Technology of China.

Background and aims The formation of an intranuclear pool of covalently closed circular DNA (cccDNA) in the liver is the main cause of persistent hepatitis B virus (HBV) infection. Here, we established highly sensitive and specific methods to detect cccDNA based on CRISPR-Cas13a technology. Methods We used plasmid-safe ATP-dependent DNase (PSAD) enzymes and HindIII to digest loose circle rcDNA and double-stranded linear DNA, amplify specific HBV cccDNA fragments by rolling circle amplification (RCA) and PCR, and detect the target gene using CRISPR-Cas13a technology. The CRISPR-Cas13a-based assay for the detection of cccDNA was further clinically validated using HBV-related liver tissues, plasma, whole blood and peripheral blood mononuclear cells (PBMCs). Results Based on the sample pretreatment step, the amplification step and the detection step, we established a new CRISPR-Cas13a-based assay for the detection of cccDNA. After the amplification of RCA and PCR, 1 copy/μl HBV cccDNA could be detected by CRISPR/Cas13-assisted fluorescence readout. We used ddPCR, qPCR, RCA-qPCR, PCR-CRISPR and RCA-PCR-CRISPR methods to detect 20, 4, 18, 14 and 29 positive samples in liver tissue samples from 40 HBV-related patients, respectively. HBV cccDNA was almost completely undetected in the 20 blood samples of HBV patients (including plasma, whole blood and PBMCs) by the above 5 methods. Conclusions We developed a novel CRISPR-based assay for the highly sensitive and specific detection of HBV cccDNA, presenting a promising alternative for accurate detection of HBV infection, antiviral therapy evaluation and treatment guidance.

Interconnective sieving pores are fabricated by the hydrolysis of ionic clusters in precursor ion-conductive membranes to provide a versatile strategy for the proton transport-ion selectivity trade-off in vanadium flow batteries.

Single-atom catalysts (SACs) with well-defined active sites provide an efficient route for catalyzing CO2 reduction reaction (CO2RR). Although enormous attention has been focused on metal-Nx moieties, understanding the effect of metal-C coordination and engineering of the hybrid metal-N/C sites have rarely been reported. Herein, we fabricated Co SACs with tunable isolated Co-N5-xCx (x = 1, 2, 3) sites supported on porous carbon frameworks. Benefiting from the difference in electronegativity of the coordinated N and C atoms, the CO Faradaic efficiency (FECO) enhanced considerably from 54 % to 76 % and 92 % at −0.8 V vs. RHE for Co-N4C1, Co-N3C2, and Co-N2C3, respectively. Further density functional theory (DFT) calculations uncover that the increased ratio of Co-C coordination induced electron enrichment of Co atoms and upper-shift the d-band center to near Fermi level, and thus favorably promotes the electron-donating ability of Co centers and strengthens the adsorption of *COOH.

The conversion of CO2 electrocatalytic hydrogenation into energy-rich fuel is considered to be the most effective way to carbon recycle. Nitrogen-doping carbonized ZIF-8 is proposed as carrier of the earth-rich Sn catalyst to overcome the limit of electron transfer and CO2 adsorption capacity of Sn. Hierarchically porous structure of Sn doped carbonized ZIF-8 is controlled by hydrothermal and carbonization conditions, which induces much higher specific surface area than that of the commercial Sn nanoparticle (1003.174 vs. 7.410 m2·g-1). The shift of nitrogen peaks in X-ray Photoelectron Spectroscopy spectra indicates interaction between ZIF-8 and Sn, which induces the shift of electron cloud from Sn to the chemical nitrogen to enhance conductivity and regulate electron transfer from catalyst to CO2. Lower mass transfer resistance and Warburg resistance are investigated through EIS, which significantly improves the catalytic activity for CO2 reduction reaction (CO2RR). Onset potential of the reaction is reduced from -0.74 V to less than -0.54 V vs. RHE. The total Faraday efficiency of HCOOH and CO reaches 68.9 % at -1.14 V vs. RHE, which is much higher than that of the commercial Sn (45.0 %) and some other Sn-based catalyst reported in the literature.

Soil water percolation is an important process required to meet plant water needs, determine soil water storage, and affect soil water quality in riparian buffer strips. However, the effects of plant roots on soil percolation in riparian buffer strips are not totally understood, and contradictory results have been carried out on the effects of the root system on soil percolation rates. This study aimed to investigate soil percolation in natural grasslands and evaluate the relationships between root morphological characteristics and percolation rates. Path analysis was used to provide information on the relative contribution of root characteristics on soil percolation rates. Three mixed grasslands (Imperata cylindrica + Phragmites australis, I. cylindrica + Cynodon dactylon, and I. cylindrica + Juncellus serotinus) were selected in the Yellow River wetland natural reserves of Zhengzhou. Soil percolation rates (initial, average, and steady infiltration rates) were measured by using double-ring methods, and plant root morphological characteristics were analyzed. Soil percolation rates and plant root characteristic parameters of I. cylindrica + P. australis and I. cylindrica + C. dactylon were higher than those of I. cylindrica + J. serotinus. Initial percolation rate of I. cylindrica + P. australis and I. cylindrica + C. dactylon at 0–10 cm depth was 58.06% and 95.55% higher than that of I. cylindrica + J. serotinus, respectively. Percolation rates had a significant positive correlation with root characteristic parameters, and the main factor controlling soil percolation rates was root volume density (RVD). Mixed natural grasslands with more RVD improved soil infiltration and percolation rates.

In this study, Cr2O3 and Ni-doped Cr2O3 (Cr2O3: Ni) thin film was deposited on sapphire substrate by pulsed laser deposition. The photoresponse properties of the Au/Cr2O3/Au and Au/Cr2O3: Ni/Au thin film have been investigated. After Ni doping, the photoresponse performance of Cr2O3 film has dramatically enhanced in the wavelength range from 1064 to 365 nm, and the responsivity of Cr2O3 films is increased from 0.357 to 154 μA/W under 365 nm UV light irradiation, i.e. more than 400 times enhancement. Furthermore, the rise/fall times of photodetector is reduced from 32.3 s/12.1 s–9.51 s/9.85 s after Ni doping. The responsivity of Cr2O3: Ni films is higher than c.a.10 μA/W during the whole visible light range. In addition, the photocurrent of Ni-doped Cr2O3 photocathode for water-splitting is enhanced from 0.3 to 19 nA/cm2. The high performance photoresponse properties promote Cr2O3: Ni film as a promising candidate for applications in solar cells and photo electrodes.

Electrochemical CO2 conversion offers a sustainable approach to alleviate the energy crisis but remains a long-standing challenge. Herein, atomically dispersed FeN5 sites anchored on N-doped carbon matrix templated by zeolitic imidazole framework-8 (ZIF-8) are facilely synthesized for efficient catalyzing CO2 reduction. The FeN5 single-atom catalyst (Fe-SA/ZIF) presents the Faradaic efficiency of 98% at −0.7 V vs. RHE and over 95% in a wide potential range from −0.4 to −1.0 V vs. RHE, surpassing most of the reported single-atom catalysts for CO2RR. Further density functional theory (DFT) calculations reveal that the outstanding activity of FeN5 sites mainly originates from the lowered d-band center modulated by the out-of-plane coordinated pyridinic N, which reduces the CO adsorption energy from −1.71 to −1.49 eV compared to FeN4 moieties. Thus, the synergistic effect between FeN4 sites and the coordinated pyridine offers new insight in designing outstanding electrocatalysts for multiple applications.

The diatomic catalysts (DACs) provide a new strategy for efficient catalysis of CO2 reduction reaction (CO2RR) owing to their maximum atomic utility and more flexible active sites. However, it is still challenging to precisely design heteronuclear diatomic active centers and understand the coordination mechanism of binary sites at the atomic level. Herein, a nitrogen-doped carbon matrix with precisely controlled Fe–Cu diatom sites is synthesized through a metal–organic framework. The as-obtained Fe/Cu–N–C catalyst exhibits an excellent CO faradaic efficiency (>95% over a wide potential range of −0.4 to −1.1 V vs. RHE, 99.2% at −0.8 V vs. RHE), a high turnover frequency (5047 h−1 at −1.1 V vs. RHE), and a low overpotential (50 mV), thus outperforming most reported atomically dispersed catalysts. Further density functional theory calculations indicate that the synergy between Fe–Cu diatoms causes rapid charge transfer and effectively adjusts the position of the d-band center, which reduces the energy barriers for *COOH formation and *CO desorption. This work provides a new approach for advancing universal synthesis strategies to construct heteronuclear diatomic catalysts and explore synergistic effects.

BackgroundMother-to-child transmission (MTCT) is the most common propagation mode of hepatitis B virus (HBV) transmission. Exploring the mechanisms of HBV MTCT is the key to protect infant from infection. In this study, we aim to clarify the important role of autophagy complicated in HBV MTCT.MethodsA total of 169 placental samples were collected in this study, includes 144 HBV positive pregnant women and 25 normal pregnant women. In vitro, JEG-3 cells were treated with serum contained different HBV viral loads. Electron microscope was used to observed the number of autophagosome. RT-qPCR and western blotting were used to measure the expression level of autophagy relative genes and proteins respectively. Immunofluorescence was used to analyzed the expression of LC-3 of the frozen section of placental tissue.ResultsAccording to the number of autophagosomes and the expression level of autophagic genes mRNA and protein, autophagy was increased in HBV maternal placenta. Among the control, low viral load, medium viral load and high viral load groups, autophagy was significantly up-regulated with the increase of HBV viral loads. Also, autophagy was increased in the HBeAg positive pregnant women compared with their HBeAg negative counterparts. Also, autophagy in infant-infected group was up-regulated compared with infant-uninfected group. In vitro, choriocarcinoma JEG-3 cells were treated with the different HBV viral loads or different time incubation, the mRNA and protein of autophagy related genes was maximum expression in the medium viral load or treatment in a short period, but decreased in the high viral load treatment or with long-term HBV exposure.ConclusionOur study determines the high levels of viremia could be the cause of both increase autophagy activities and MTCT. Autophagy was significantly up-regulated in pregnant women with high viral load or HBeAg positive, which plays an important part in the HBV MTCT.

Hepatitis delta virus (HDV) far exceeds our expected level. There remains a lack of reliable quantitative assays for HDV RNA detection. We sought to develop a new method based on digital droplet polymerase chain reaction (ddPCR) for HDV quantitative detection.With plasmid (pMD19T) containing HDV full genome, we determined the method for ddPCR-based HDV RNA quantification. To compare various assays for HDV detection, 30 cases diagnosed with hepatitis D and 14 controls were examined using enzyme-linked immunosorbent assay, reverse-transcriptase PCR (RT-PCR), and ddPCR. A total of 728 hepatitis B virus-related patients, including 182 patients with chronic hepatitis B, 182 with liver cirrhosis, 182 with hepatocellular carcinoma, and 182 with liver failure, were screened for HDV infection.The detection limit of ddPCR for HDV is significantly low, with lower limit of detection and lower limit of quantitation of 0.29 IU/mL (95% confidence interval: 1.93 × 10-3-1.22 IU/mL) and 8.76 IU/mL (95% confidence interval: 1.83-1.03 × 106 IU/mL), respectively. Among the 44 samples, the enzyme-linked immunosorbent assay detected 30 cases positive, ddPCR reported 24 samples, and RT-PCR reported 10 samples positive for HDV RNA. Moreover, the positive rates of anti-HDV were 1.1%, 3.3%, 2.7%, and 7.1% in patients with chronic hepatitis B, liver cirrhosis, hepatocellular carcinoma, and liver failure, respectively; the detection rates of RT-PCR in HDV RNA were 0%, 16.67%, 15.4%, and 20%, respectively. However, the detection rates of ddPCR were 0%, 33.33%, 30.77%, and 60%, respectively.We establish a high sensitivity and specificity quantitative HDV RNA detection method based on ddPCR. Hepatitis B virus-related end-stage liver diseases, especially liver failure, are associated with a remarkably high rate of HDV infection.

The use of Chinese mitten crabs for human consumption is controversial due to their uptake of heavy metals, such as cadmium (Cd). We developed a formula for quantification of benefit and risk assessment (hazard quotient) for the intake of a product containing essential polyunsaturated fatty acids versus heavy metals. A total of 70 samples (2100 individuals) of crabs were collected from 6 representative basins in Jiangsu province to determine Cd levels. Cd levels ranged from 0.028 to 5.015 mg kg−1, and the levels among the basin regions were similar (p > 0.05). To determine the nutritional differences between crabs fed with iced trash fish and formulated feed, we conducted a comparative aquaculture experiment. We simulated the cultivation conditions of crabs in China and found that the nutritional content in the trash fish group (28.724 ± 2.301 mg kg−1) was significantly higher than in the formulated food group (19.278 ± 3.556 mg kg−1; p 0.05). The average hazard quotient of iced trash fish feed culture was 0.023 ± 0.019, compared with the formulated feed culture (0.034 ± 0.028). Formulated feed and iced trash fish produce similar results as culture food for the Chinese mitten crab. In terms of cadmium exposure risk, the appropriate daily consumption of crabs is less than eight. These data can help justify culture using formulated food and the sustainable development of the Chinese mitten crab industry.

Realizing strong laser–matter interaction in a heterostructure consisting of two-dimensional transition metal dichalcogenides (TMDCs) and an optical nanocavity is a potential strategy for novel photonic devices. In this paper, two core-Ω shell nanostructures, Si@WS2 core-Ω shell nanostructure on glass/Si substrates, are briefly introduced. A strong laser–matter interaction occurred in the Si@WS2 core-Ω shell nanostructure when it was excited by femtosecond (fs) laser in the near-infrared-1 region (NIR-1, 650 nm–950 nm), resulting in a resonance coupling between the electric dipole resonance (EDR) of the Si nanosphere (NS) and the exciton resonance of the WS2 nanomembrane (NMB). The generation of resonance coupling regulates the resonant mode of the nanostructure to realize the multi-dimensional nonlinear optical response, which can be utilized in the fields of biological imaging and nanoscale light source.

Background Hepatitis delta virus (HDV) is a satellite RNA virus that relies on hepatitis B virus (HBV) for transmission. HIV/HBV/HDV coinfection or triple infection is common and has a worse prognosis than monoinfection. Objective We aimed to reveal the epidemiological characteristics of HIV/HBV/HDV triple infection in the global population. Methods A systematic literature search in PubMed, Embase, and the Cochrane Library was performed for studies of the prevalence of HIV/HBV/HDV triple infection published from January 1, 1990, to May 31, 2021. The Der Simonian-Laird random effects model was used to calculate the pooled prevalence. Results We included 14 studies with 11,852 participants. The pooled triple infection rate in the global population was 7.4% (877/11,852; 95% CI 0.73%-29.59%). The results of the subgroup analysis showed that the prevalence of triple infection was significantly higher in the Asian population (214/986, 21.4%; 95% CI 7.1%-35.8%), in men (212/5579, 3.8%; 95% CI 2.5%-5.2%), and in men who have sex with men (216/2734, 7.9%; 95% CI 4.3%-11.4%). In addition, compared with people living with HIV, the HIV/HBV/HDV triple infection rate was higher in people with hepatitis B. Conclusions This meta-analysis suggests that the prevalence of HIV/HBV/HDV triple infection in the global population is underestimated, and we should focus more effort on the prevention and control of HIV/HBV/HDV triple infection. Trial Registration PROSPERO CRD42021273949; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=273949

To solve the maneuvering decision problem in air combat of unmanned combat aircraft vehicles (UCAVs), in this paper, an autonomous maneuver decision method is proposed for a UCAV based on deep reinforcement learning. Firstly, the UCAV flight maneuver model and maneuver library of both opposing sides are established. Then, considering the different state transition effects of various actions when the pitch angles of the UCAVs are different, the 10 state variables including the pitch angle, are taken as the state space. Combined with the air combat situation threat assessment index model, a two-layer reward mechanism combining internal reward and sparse reward is designed as the evaluation basis of reinforcement learning. Then, the neural network model of the full connection layer is built according to an Asynchronous Advantage Actor–Critic (A3C) algorithm. In the way of multi-threading, our UCAV keeps interactively learning with the environment to train the model and gradually learns the optimal air combat maneuver countermeasure strategy, and guides our UCAV to conduct action selection. The algorithm reduces the correlation between samples through multi-threading asynchronous learning. Finally, the effectiveness and feasibility of the method are verified in three different air combat scenarios.

Using Monte Carlo simulation and experiment, this study shows that the self-attenuation correction factors (SACFs) for identical samples measured with different detectors are not equal. The Geant4 toolkit is used to study and the following conclusions are drawn: compared with the unattenuated case, when γ-rays with different energies are attenuated by the matrix and container, the distribution of γ-rays on the surface of the entrance window of the detector is distorted. As a consequence, the SACF should be modified to account for both the self-attenuation of the sample, and the corresponding changes in detector efficiency as a result of the changes in the spatial distribution and to the energy spectra caused by the self-attenuation of the source matrix. This paper demonstrates that within certain energy ranges, and for a certain range of detectors, the required SACF modifications are not negligible. Detector parameters should therefore be considered and included when calculating the SACF.

The electrode, as one of the most critical components in a proton exchange membrane water electrolysis (PEMWE) cell for hydrogen production, has a significant impact on cell performance. Electrodes that are fabricated via various techniques may exhibit different morphologies or properties, which might change the kinetics and resistances of the PEMWE. In this study, we have successfully fabricated several electrodes by different techniques, and the effects of electrode coating methods (ultrasonic spray, blade coating, and rod coating), hot press, and decal transfer processes are comprehensively investigated. The performance differences between various electrodes are due to kinetic or high frequency resistance changes, while the influences are not significant, with the biggest deviation of about 26 mV at 2.0 A cm−2. In addition, the effects of catalyst ink compositions, including ionomer to catalyst ratio (0.1 to 0.3), water to alcohol ratio (1:1 to 3:1), and catalyst weight percentage (10% to 30%), are also studied, and the electrodes’ performance variations are less than 10 mV at 2.0 A cm−2. The results show that the PEMWE electrode has superior compatibility and redundancy, which demonstrates the high flexibility of the electrode and its applicability for large-scale manufacturing.

Background & Aims The prevalence of hepatitis delt virus (HDV) far exceeds our expected level, there remains a lack of reliable quantitative assays for HDV RNA detection. We sought to develop a new method based on digital droplet PCR (ddPCR) for HDV RNA quantitative detection. Methods With plasmid (pMD19T) containing HDV full-genome, we determined the method for ddPCR-based HDV RNA quantification. To compare various assays for HDV detection, 30 cases diagnosed hepatitis D and 14 controls were examined by ELISA, RT-PCR and ddPCR. 728 HBV-related patients including 182 chronic hepatitis B (CHB), 182 liver cirrhosis (LC), 182 hepatocellular carcinoma (HCC) and 182 liver failure (LF) were screened for HDV infection. Results The limit of detection of ddPCR for HDV is significantly low, which lower limit of detection (LLoD) and lower limit of quantitation (LLoQ) to be 5.51 copies/reaction (95% CI: 1.15–6.4*105) and 0.18 copies/reaction (95% CI: 0.0012151- 0.76436), respectively. Among the 44 samples, ELISA detected 30 cases positive for anti-HDV, ddPCR reported 24 samples and RT-PCR reported 10 samples positive for HDV RNA. Moreover, the positive rates of anti-HDV IgG were 1.1%, 3.3%, 2.7% and 7.1% in patients with CHB, LC, HCC, and LF; the detection rates of RT-PCR in HDV RNA were 0%, 16.67%, 15.4% and 20%, however, the detection rates of ddPCR were 0%, 33.33%, 30.77% and 60%. Conclusion We establish a high sensitivity and high specificity quantitative HDV RNA detection method based on ddPCR compared to RT-PCR. HBV-related end-stage liver disease, especially liver failure, are associated with a remarkably high rate of HDV infection.

Since the discovery of exosomes, their potential diagnostic value has been the focus of considerable research. However, the lack of a rapid and simple technique for the quantitative analysis of exosomes greatly limits the application of exosomes in clinical research. In this study, we describe a newly developed one-step chemiluminescence immunoassay for the rapid quantitative analysis of exosomes from biofluids. Our new technique, named ExoNANO, adopts a double-antibody sandwich strategy using anti-CD63 antibody-conjugated superparamagnetic iron oxide particles (SIOPs) and acridinium ester (ACE)-labeled anti-CD9 antibodies. SIOPs have narrow size distribution and high magnetic susceptibility, and ACE has excellent chemiluminescent properties such as low background signal and no need for a catalyst. We demonstrated that ExoNANO allows the quantitative analysis of exosomes in the range of 2.92 ×105 to 2.80×108 particles/μL, with a limit of detection of 2.63×105 particles/μL. Using ExoNANO, we quantified exosomes in cell culture medium and clinical biofluids such as serum, saliva, ascitic fluid, and cerebrospinal fluid. We believe that ExoNANO might pave the way for the rapid isolation and quantitative analysis of exosomes for routine clinical applications.

The dynamic response and the failure of the different composite structures subjected to impulsive loadings are performed experimentally with metallic foam projectile. The composite lattice core based sandwich structure is reinforced with polyurethane foam and shows a significant improvement in impulsive mitigation. The effects of core and loading intensity are carried out to identify and quantify the dynamic response, failure mode, and energy absorption efficiency of the composite structures. The results show that the foam filled lattice sandwich has an outperformed deflection resistance and remains better intact due to the loading transferring and weak effect of localization of the out-of-plane deflection. Although the energy absorption efficiency per unit mass of the lattice/foam sandwich is lower, the energy absorption capacity of the structure is confirmed to have been improved significantly, and the difference in the efficiency decreases noticeably with the increasing impulsive intensities. Both the sandwich structures have superior performance of impulsive resistance in comparison with the composite laminate.

Endoplasmic reticulum stress (ER stress) just like a double-edged sword depending on different conditions in the development of multiple hepatic diseases. But the molecular mechanisms of functional conversion during ER stress have not been fully elucidated. In this study, we aim to illustrate the role of PPARα and the subtle mechanism in the functional conversion of ER stress. Tunicamycin (TM) and thapsigargin (TG), as ER stress inducers, were used to induce ER stress in AML12 cells. During the ER stress, qRT-PCR and immunoblotting was used to measure the expression levels of GRP78 and CHOP which show a gradually increasing trend, while PPARα and autophagy was significantly activated in the early stage but was inhibited in the late stage. Moreover, PPARα inhibition by siRNA promoted cell injury in the mild-ER stress and PPARα activation by WY-14643 reduced cell apoptosis in the serious ER stress. In the mild-ER stress with PPARα knocked down, activation of autophagy by rapamycin significantly improved cell survival, in the serious ER stress with PPARα activation, inhibition of autophagy by 3-MA aggravate cell injury. In addition, in the mild-ER stress with PPARα knocked down, CHOP knocked down by siRNA reduced cell apoptosis, in the serious ER stress activated PPARα, CHOP over-expression mediated by lentiviral vector contributed to serious cell injury. Furthermore, C57BL/6 mice was used to induce ER stress with TM intraperitoneal injection, PPARα and autophagy was upregulated in the mild-ER stress while downregulated in the serious ER stress, measured by qRT-PCR and immunoblotting, further confirmed the finding in vitro. Our results firstly demonstrated that PPARα is a key molecule in the functional conversion of ER stress: protective effects in the mild ER stress was mediated by PPARα-autophagy pathway and destructive effects in the serious ER stress was mediated by PPARα-CHOP pathway.

ObjectivesThe health-related quality of life (HRQoL) and utilities of patients with chronic hepatitis B (CHB) virus infection, including compensated cirrhosis (CC), decompensated cirrhosis (DC) and different stages of hepatocellular carcinoma (HCC), have not been well described in China. This study aimed to evaluate HRQoL and utilities and provide parameters for the economic evaluation of CHB-related diseases.MethodsWe conducted a multicentre cross-sectional and study to measure the HRQoL of patients with CHB, CC, DC and HCC using the Chinese short form (SF) 36 health survey V.2. The utilities were extracted based on the SF-six dimension scoring model. Multivariable regression analyses identified the effects on HRQoL.ResultsA total of 1071 patients (639 with CHB, 125 with CC, 85 with DC and 222 with HCC) were invited to complete the questionnaire. Physical HRQoL was not impaired in the CHB stage, while mental HRQoL was significantly impaired. Physical composite summary scores have a more significant decrease than mental composite summary scores at the advanced stages (CC, DC and HCC). The utility scores of CHB only, CC, DC and HCC were 0.773, 0.750, 0.683 and 0.640, respectively. The utility scores in the early, middle and terminal stages of HCC were 0.656, 0.635 and 0.615, respectively.ConclusionSlowing the progress of CHB-related diseases and providing psychological support early are the key points to improving the quality of life with the diseases. The utility values estimated in this study can provide a vital instrument for cost-effectiveness studies on CHB-related diseases.

The composite lattice sandwich structures with crushable foam core have exhibited outstanding potential in lightweight structures for underwater blast resistance. In this paper, the dynamic failure, energy absorption and associated mechanisms of the composite sandwich structures against the underwater impulsive loading are investigated experimentally and numerically. The underwater impulsive resistance of the composite lattice sandwich and the foam-reinforcement composite lattice sandwich are estimated by considering the varying impulsive intensities. With the reinforcement of the foam, the energy absorption capacity experiences a nearly 6 times of increase under the quasi-static compression. Although the influence on the deformed profile is limited, the effect of the impulsive intensity is fairly confirmed to have significant influences on the failure modes and energy absorption mechanisms of the sandwich structures. The impulsive resistance of the foam reinforced lattice sandwich structure is superior to the unreinforced counterpart in terms of the deflection resistance and structural integrity. The loading dispersion distribution, crushing, and cracking of the foam make the former optimize the energy absorption mechanism by highlighting the sacrifice of the front facesheet and decrease the back facesheet deflection. With the same areal mass with the lattice sandwich, the composite laminate exhibits inferior impulsive resistance to both the sandwich plates.

As a central work in medical knowledge graph construction, relation extraction has gained extensive attention in the fields of natural language processing and artificial intelligence. Conventional works on relation extraction share a common assumption: a sentence can express a relation of an entity pair only if both entities appear in this sentence. Under this assumption, plenty of informative sentences are precluded. In this paper, we break the assumption and propose a new relation extraction model that incorporates article structure information, which not only provide additional information, but also allows extracting long distance relations. We apply the model to online medical relation extraction and demonstrate its advantage over conventional models.

The Chinese mitten crab (Eriocheir Sinensis) is a popular aquatic product in China. However, these crabs accumulate heavy metals from the ecosystem. The occurrence, source, and risk assessment of heavy metals in crabs from the main production area in China were investigated. The abundance of the metals in crabs was Mn >> As > Se > Ni > Cr > Cd > Pb> Hg. Each metal was present at a level less than the national standard (A standard for the limits of contaminants in food from China). Agricultural activities, industrial discharges, and urban sewage were the three main sources of heavy metals accumulation in Chinese mitten crab. Based on an assessment of the target hazard quotient (THQ), arsenic is the most harmful heavy metal in the crabs. In addition, mercury and lead also pose risks. The results indicate that the estimated daily intake (EDI) of mitten crabs in China would not pose a high dietary risk. (THQ

Multiscale hybrid method is reported to enhance thermal ablative and insulative properties of lightweight ablative materials in high temperature oxidation extreme environment. A novel lightweight hybrid carbon-quartz fiber fabric reinforced phenolic-silica (C-QF/PSi) aerogel nanocomposite was fabricated through impregnation using C-QF hybrid needled felt as three-dimensional reinforcement and PSi hybrid aerogel as matrix. The prepared aerogel nanocomposite perfectly inherits their nanoporous microstructure and fascinating properties, resulting in remarkable high compressive strength (5.96–17.01 MPa), low thermal conductivity (~0.112 W/(mK)). In particular, good thermal ablative and insulative properties in oxy-acetylene oxidizing flame (linear ablation rate as low as 0.017 mm/s and internal temperature peaks below 100 °C at 80 mm in-depth position when the surface temperature exceeds 2000 °C). From mentioned above, this lightweight composite presents huge application prospects in thermal protection and heat insulation field, especially in aerospace industry.

Although considerable progress has been achieved by Cu nanoparticles for catalyzing CO2 reduction reaction (CO2RR), Cu single atom catalysts (Cu SACs) are generally suffered from inferior performance to that of widely investigated Fe, Co, Ni SACs. This phenomenon mainly ascribes to the lack of effective geometry and electronic engineering of copper active center from an atomic level. Herein, highly exposed atomically dispersed Cu-Nx (x denotes Cu–N coordination number) sites anchored on 3D porous carbon matrix are successfully synthesized through facile one step thermal activation, and Cu-N4 sites exhibit boosted activity and selectivity compared to its nearly inert Cu-N3 counterparts. Aided by density functional theory (DFT) calculations, the edge-hosted Cu-N4 moieties are revealed as key active sites for efficient CO generation via optimized local coordination environment and electronic properties, which strongly interact with *COOH intermediate and facilitate the desorption of *CO. As a result, Cu-N4 catalyst achieves high CO Faradaic efficiency (FECO) of over 90% from −0.6 to −1.1 V vs. RHE with a maximum value of 98%, surpassing the previously reported Cu SACs for CO2-to-CO conversion. This work provides new insight into proper Cu SACs design and fundamental mechanism understanding to boost CO2RR.

Quasi-static and dynamic compressive tests are undertaken on the polyurethane (PU) foam and fumed silica reinforced polyurethane (PU/SiO2) foam experimentally. The ceramic microspheres with varying mass fractions are adopted to mix with the PU/SiO2 foam to fabricate the composite particle-reinforced foams. The effects of strain rate and particle mass fraction are discussed to identify and quantify the compressive response, energy-absorbing characteristic, and the associated mechanisms of the composite foams. The results show the initial collapse strength and plateau stress of the foams are improved significantly by reinforcing with the ceramic microsphere within 60 wt% at quasi-static compression. The rate sensitivity is observed on all the foams, but in different patterns due to the influence of ceramic microsphere. The compressive response affected by ceramic microsphere can be attributed to the particle cluster effect and stress wave propagation. Together with the deformation, the compressive characteristic experiences non-monotonic change from the low to high strain rates. The specific energy absorption (SEA) of the foam with 41 wt% ceramic microsphere show the largest magnitude at quasi-static compression. With the increasing strain rate, the ceramic reinforced foam exhibits superior energy absorption efficiency at high strain rates to that of the pure foams.

The ceramic particle reinforced foam-filled carbon fiber reinforced composites sandwich unit cell subjected to quasi-static and dynamic compressions are studied experimentally. The weight fraction of the ceramic particle is discussed to analyze its effect on the failure and energy absorption of the composite cells. The results show that the failure modes and energy absorption mechanisms of the cell are influenced significantly by the strain rate and ceramic particle reinforcement effects. The cluster of the particle makes the strut experience node failure under impulsive loadings, not the strut buckling and fracture shown at other cells. The mechanical property, especially the plateau stress, is enhanced noticeably as the foam is reinforced with the higher weight fraction of ceramic particles. The filling foams improve the impact resistance of the cells by transmitting less impulses and absorbing more energy. With a higher energy absorption efficiency, the foam-filled cell with higher weight fraction of ceramic particle has the highest energy absorption capacity under the quasi-static compression. Under the impulsive loading, the increasing ceramic particles can reduce the transmitted impulse, but cannot absorb additional energy.

The aggregate behaviors of users can collectively encode deep semantic information about the objects with which they interact. In this paper, we demonstrate novel ways in which the synthesis of these data can illuminate the terrain of users’ environment and support them in their decision making and wayfinding. A novel application of recurrent neural networks and skip-gram models, approaches popularized by their application to modeling language, are brought to bear on student university enrollment sequences to create vector representations of courses and map out traversals across them. We present demonstrations of how scrutability from these neural networks can be gained and how the combination of these techniques can be seen as an evolution of content tagging and a means for a recommender to balance user preferences inferred from data with those explicitly specified. From validation of the models to the development of a UI, we discuss additional requisite functionality informed by the results of a usability study leading to the ultimate deployment of the system at a university.

Background: Although exosomes are potential diagnostic and therapeutic biomarkers for diverse diseases, efficient and sensitive technologies for exosomes isolation and detection are still lacking. Methods: In this study, we construct a microfluidic system (ExoNANO) for exosomes separation using CD63 antibody conjugated nano-sized superparamagnetic iron oxide particles (SIOP) and microfluidic isolation column. Further, a chemiluminescence immunoassay (CLIA) strategy was established for exosomal protein detection. Findings: Results show that microfluidic ExoNANO reveals high isolation efficiency (94%) and allows quantitative analysis of exosomes in the range of 2.92×105 to 2.80×108 particles/μL with a limit of detection (LOD) of 2.63×105 particles/μL from as little as 1μL serum sample. Using microfluidic ExoNANO, we quantified exosomes in serum, cell culture media (CM), saliva, ascitic fluid and cerebrospinal fluid (CSF) samples. Interpretation: We developed microfluidic ExoNANO, which could pave the way for routine, rapid isolation and quantitative analysis of exosomes in clinical application. Funding Statement: This study was supported by grant from the National Natural Science Foundation of China (Grant nos. 81271917, 81802571), Natural Science Foundation of Zhejiang province (Grant nos. LY14H200002, LY15H200002 and LY16H160023). Declaration of Interests: The authors declare: "There does not exist any conficts of interest." Ethics Approval Statement: Serum samples of healthy individuals and cerebrospinal fluid, ascitic fluid, and saliva samples were obtained from the Second Affiliated Hospital of Zhejiang University School of Medicine. Research protocols were approved by the Ethical Committees for Clinical Research of supporting institutions, and all patients provided written informed consent for the use of their samples for experimentation.

In this research, fan-shaped ZnMoO4 is deposited on flower-like ZnCo2O4 nanowire arrays by two-step hydrothermal method. ZnCo2O4 nanowire is synthesized first and used as the backbone to support ZnMoO4. The flower-like ZnCo2O4 nanowire arrays are fully overspread by ZnMoO4. And this unique structure shows a high capacitance of 1506 F g−1 when used as electrode for supercapacitor at a current density of 1 A g−1 and a good cycling ability (5000 cycles).

During natural fermentation processes, a characteristic microbial community structure (MCS) is naturally formed, and it is interesting to know about its batch-batch stability. This issue was explored in a traditional semi-solid-state fermentation process of huyumei, a Chinese broad bean paste product. The results showed that this MCS mainly contained four aerobic Bacillus species (8 log CFU per g), including B. subtilis, B. amyloliquefaciens, B. methylotrophicus, and B. tequilensis, and the facultative anaerobe B. cereus with a low concentration (4 log CFU per g), besides a very small amount of the yeast Zygosaccharomyces rouxii (2 log CFU per g). The dynamic change of the MCS in the brine fermentation process showed that the abundance of dominant species varied within a small range, and in the beginning of process the growth of lactic acid bacteria was inhibited and Staphylococcus spp. lost its viability. Also, the MCS and its dynamic change were proved to be highly reproducible among seven batches of fermentation. Therefore, the MCS naturally and stably forms between different batches of the traditional semi-solid-state fermentation of huyumei.Revealing microbial community structure and its batch-batch stability is helpful for understanding the mechanisms of community formation and flavour production in a traditional fermentation. This issue in a traditional semi-solid-state fermentation of huyumei broad bean paste was firstly explored. This fermentation process was revealed to be dominated by a high concentration of four aerobic species of Bacillus, a low concentration of B. cereus and a small amount of Zygosaccharomyces rouxii. Lactic acid bacteria and Staphylococcus spp. lost its viability at the beginning of fermentation. Such the community structure was proved to be highly reproducible among seven batches.