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Background Outbreaks of severe, acute hepatitis among children have recently attracted global attention. The pathogen causing the outbreak remains unknown, but there is growing evidence that it may be associated with human adenovirus (HAdV). Data sources A review of adenovirus-related clinical studies, epidemiological studies, etiological studies, and case reports was conducted by reviewers independently. Results HAdV can cause a wide variety of clinical symptoms. In the Mainland of China, HAdV infection accounts for 5.8%–13% of patients with acute respiratory infections, and these infections are mainly caused by species B, C, and E of HAdV. For acute conjunctivitis, 39.8%–74.9% of sporadic cases were infected by B and D species of HAdV. Outbreaks of keratoconjunctivitis and pharyngoconjunctival fever related to HAdV infection could be found throughout the country. In pediatric patients with acute gastroenteritis, HAdV-41 was the predominant HAdV type, followed by HAdV species B and C. Several types of HAdV, including HAdV-5, HAdV-7, HAdV-1, and HAdV-2, have previously been reported as potential pathogens associated with HAdV hepatitis in immunocompromised patients. However, few HAdV-related hepatitis cases have been reported in China to date. Conclusions There are no systematic surveillance and clinical studies on HAdV hepatitis in China. Therefore, it is imperative to establish a nationwide HAdV virological surveillance system to collect relevant clinical, epidemiological and virological surveillance data and risk factor information as soon as possible to assess the potential risk of HAdV hepatitis among children.

Infections caused by eukaryotic organisms, such as fungi, are generally more difficult to treat than bacterial infections. With the widespread use of antifungal drugs in humans and plants, resistance and toxicity have emerged. Therefore, it is desirable to develop new antifungal drugs with low toxicity that are not susceptible to the development of resistance. This review presents a summary of the past few years (2017-2021) of research on heterocyclic compounds as antifungal agents for use in humans and plants, focusing on the structure-activity relationships (SAR) of these compounds. This review may provide ideas and information for designing and developing new antifungal drugs with fewer side effects compared with currently available drugs.

Urea electrolysis provides a promising approach for simultaneous energy-saving hydrogen production and wastewater utilization; however, the total reaction rate is severely restricted by the sluggish kinetics of the anodic urea oxidization reaction (UOR). Herein, we report a universal and highly controllable electrochemical defect-engineering approach to enrich the active sites on transition metal oxides toward promoted UOR catalysis. A large number of oxygen vacancies (Vo) were introduced on the surface of a Co3O4 nanowire model-material through negative potential tuning, leading to significantly increased UOR activity of the material. At a potential of 1.34 V vs. RHE, the defect-engineered catalyst delivers an optimal UOR current density of 100 mA cm−2, which is much higher than that (42 mA cm−2) offered by the original Co3O4 catalyst, and outperforms the best reported noble-metal-free UOR catalysts. Experimental results further reveal that the formation of Vo can effectively reduce the charge transport/transfer resistances both inside the nanowires and at the catalyst/electrolyte interface, giving rise to improved UOR activity. These findings suggest the great potential of this electrochemical defect-engineering strategy in the design of defect-enriched catalysts for advanced electrocatalysis.

Hand, foot and mouth disease (HFMD) is a widespread infectious disease that causes a significant disease burden on society. To achieve early intervention and to prevent outbreaks of disease, we propose a novel warning model that can accurately predict the incidence of HFMD.We propose a spatial-temporal graph convolutional network (STGCN) that combines spatial factors for surrounding cities with historical incidence over a certain time period to predict the future occurrence of HFMD in Guangdong and Shandong between 2011 and 2019. The 2011-2018 data served as the training and verification set, while data from 2019 served as the prediction set. Six important parameters were selected and verified in this model and the deviation was displayed by the root mean square error and the mean absolute error.As the first application using a STGCN for disease forecasting, we succeeded in accurately predicting the incidence of HFMD over a 12-week period at the prefecture level, especially for cities of significant concern.This model provides a novel approach for infectious disease prediction and may help health administrative departments implement effective control measures up to 3 months in advance, which may significantly reduce the morbidity associated with HFMD in the future.

In this paper, the model of the rudder electromechanical actuation system is established, and the effect of the pole-zero on the resonance is analyzed. Furthermore, Linear extended state observer (LESO) was designed on the premise of retaining the zero of the linear displacement of the servo actuator. The state and disturbance of the system were observed and compensated, and the active disturbance rejection control (ADRC) law was designed according to the desired poles. Simulation results show that the proposed control strategy can suppress the resonance caused by the system structure and the fluctuation of system performance caused by load disturbance, and obtain the dynamic quality of line and angle feedback. Moreover, the system shows good adaptability and robustness to the variation of parameters and load torque in a large range.

OBJECTIVES: This study aims to evaluate diagnostic performance of radiomic analysis using computed tomography (CT) to identify lymphovascular invasion (LVI) in patients diagnosed with rectal cancer and assess diagnostic performance of different lesion segmentations. METHODS: The study is applied to 169 pre-treatment CT images and the clinical features of patients with rectal cancer. Radiomic features are extracted from two different volumes of interest (VOIs) namely, gross tumor volume and peri-tumor tissue volume. The maximum relevance and the minimum redundancy, and the least absolute shrinkage selection operator based logistic regression analyses are performed to select the optimal feature subset on the training cohort. Then, Rad and Rad-clinical combined models for LVI prediction are built and compared. Finally, the models are externally validated. RESULTS: Eighty-three patients had positive LVI on pathology, while 86 had negative LVI. An optimal multi-mode radiology nomogram for LVI estimation is established. The area under the receiver operating characteristic curves of the Rad and Rad-clinical combined model in the peri-tumor VOI group are significantly higher than those in the tumor VOI group (Rad: peri-tumor vs. tumor: 0.85 vs. 0.68; Rad-clinical: peri-tumor vs. tumor: 0.90 vs 0.82) in the validation cohort. Decision curve analysis shows that the peri-tumor-based Rad-clinical combined model has the best performance in identifying LVI than other models. CONCLUSIONS: CT radiomics model based on peri-tumor volumes improves prediction performance of LVI in rectal cancer compared with the model based on tumor volumes.

The tumor-associated antigen mucin 1 (MUC1) has been pursued as an attractive target for cancer immunotherapy, but the poor immunogenicity of the endogenous antigen hinders the development of vaccines capable of inducing effective anti-MUC1 immunodominant responses. Herein, we prepared synthetic anti-MUC1 vaccines in which the hydrophilic MUC1 antigen was N-terminally conjugated to one or two palmitoyl lipid chains (to form amphiphilic Pam-MUC1 or Pam2 -MUC1). These amphiphilic lipid-tailed MUC1 antigens were self-assembled into liposomes containing the NKT cell agonist αGalCer as an adjuvant. The lipid-conjugated antigens reshaped the physical and morphological properties of liposomal vaccines. Promising results showed that the anti-MUC1 IgG antibody titers induced by the Pam2 -MUC1 vaccine were more than 30- and 190-fold higher than those induced by the Pam-MUC1 vaccine and the MUC1 vaccine without lipid tails, respectively. Similarly, vaccines with the TLR1/2 agonist Pam3 CSK4 as an adjuvant also induced conjugated lipid-dependent immunological responses. Moreover, vaccines with the αGalCer adjuvant induced significantly higher titers of IgG antibodies than vaccines with the Pam3 CSK4 adjuvant. Therefore, the non-covalent assembly of the amphiphilic lipo-MUC1 antigen and the NKT cell agonist αGalCer as a glycolipid adjuvant represent a synthetically simple but immunologically effective approach for the development of anti-MUC1 cancer vaccines.

Based on density functional theory and density functional perturbation theory calculations, we systematically investigate the vibration responses of monolayer $1H\text{\ensuremath{-}}{\mathrm{MoTe}}_{2}$ to equibiaxial strains. It is found that, at the $\mathrm{\ensuremath{\Gamma}}$ point, the frequency shift of Raman-active modes $({E}^{\ensuremath{'}},$ ${A}_{1}^{\ensuremath{'}},$ and ${E}^{\ensuremath{''}})$ and infrared-active modes $({A}_{2}^{\ensuremath{''}}$ and ${E}^{\ensuremath{'}})$ show domelike shapes; that is, their frequencies decrease monotonically under tensile strains but first increase and then decrease rapidly under compressive strains. The frequency-shift behaviors are revealed to come from vibration responses to both bond stretching and bond-angle bending in strained $1H\text{\ensuremath{-}}{\mathrm{MoTe}}_{2}$. At the $K$ point, a special acoustic mode becomes soft because its frequency drops to zero at a compressive strain of $\ensuremath{-}11.27%$. We find that electron occupancies in Mo ${d}_{{z}^{2}}$, Te ${p}_{x}$, and Te ${p}_{y}$ orbitals weaken the vibration mode at $K$, which exhibits the in-plane vibration of Mo atoms and out-of-plane vibration of Te atoms. On the other hand, compressive strains enhance the Fermi surface nesting and abruptly soften the vibration frequency for one acoustic mode at $K$. Our results point out a way to detect the strain status of monolayer $1H\text{\ensuremath{-}}{\mathrm{MoTe}}_{2}$ by measuring the vibration frequencies.

Direct aminolysis of selenoester in aqueous media was investigated as a glycopeptide ligation strategy. This strategy allows the peptide and glycopeptide ligation to proceed smoothly (even with hindered amino acids) without the need of cysteine residue, N-terminal thiol auxiliary or coupling additive, and to afford the corresponding amide products in excellent yields. No epimerization was observed during ligation reations. In this work, the selenoester of unprotected glycopeptide was readily prepared, and the direct aminolysis of glycopeptide selenoester was successfully applied to synthesize MUC1 mucin sequence efficiently.

Objective: We evaluated the protective effects of berberine (BBR) combined with ginsenoside Rb1 (G-Rb1) on high-fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) in rats and futher investigated the underlying mechanisms. Methods: Rats were fed an HFD for 6 weeks and then randomly divided into four groups and treated with BBR (50 mg/kg), G-Rb1 (100 mg/kg), BBR (50 mg/kg)+G-Rb1 (100 mg/kg), or fenofibrate (40 mg/kg). Histological examination of liver tissue was performed. In human hepatocellular carcinoma cells HepG2, protein expression of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase was detected by western blotting, and the mRNA expression of carnitine palmitoyl transferase 1 and 3-hydroxy-3-methyl glutaryl coenzyme A reductase was detected by quantitative PCR. Pharmacokinetic assessments included analysis of bioavailability of BBR and G-Rb1 in vivo and G-Rb1 metabolism by intestinal bacteria in vitro. Results: Compared to the single-use group, BBR combined with G-Rb1 significantly ameliorated hepatic fat accumulation in HFD-induced obese rats, as demonstrated by reduced hepatic triglyceride content, and histological evaluation of liver sections. Activation of hepatic AMPK and phosphorylation of acetyl-CoA carboxylase were significantly elevated in hepatocytes treated with both BBR and G-Rb1. Consistent with the activation of AMPK, the mRNA expression of carnitine palmitoyl transferase 1 was stimulated, while the mRNA expression of 3-hydroxy-3-methyl glutaryl coenzyme A reductase was suppressed. Pharmacokinetic analysis revealed that BBR increased the bioavailability of G-Rb1 in Sprague-Dawley rats. Additionally, BBR prevented degradation of G-Rb1 in fecal solution in vitro. Conclusion: BBR combined with G-Rb1 improved NAFLD through the AMPK signaling pathway, and BBR enhanced G-Rb1 bioavailability via promoting the intestinal absorption of G-Rb1. This combination may be a useful therapeutic agent for NAFLD.

Urea electrolysis enables simultaneous energy-saving hydrogen production and wastewater purification at a small thermodynamic potential of 0.37 V; however, the total energy-utilization efficiency is still substantially restricted by the sluggish kinetics of the urea oxidization reaction (UOR) at the anode. In this work, an electrochemical tuning strategy has been employed to obtain a Ni (III)-enriched catalyst by starting from NiMoO4∙xH2O nanorod arrays. It has been found that the electrochemical tuning not only modifies the valency state of Ni but also causes a dramatic change in stoichiometry and microstructure of the material, leading to significantly improved activities for UOR under alkaline conditions. Notably, the obtained catalyst delivers a current density of 100 mA cm−2 for UOR at the potential of only 1.36 V vs RHE, which surpasses the best-reported values for UOR catalysis at the same applied potential, demonstrating the great promise of the electrochemical tuning strategy in rational modifications of material towards promoted electrocatalysis.

H-related defects have been investigated in Ga-doped ZnO thin films deposited by RF magnetron sputtering at room temperature in Ar+H2 ambient. When the flow ratio of H2/(Ar+H2) increases from 0 to 4%, the resistivity significantly decreases from 1·94 × 10−2 to 5·69 × 10−4 Ω cm. X-ray diffraction and X-ray photoelectron spectroscopy results show that it should not be ascribed to the films’ crystalline quality, the chemical states and substitutional situation of Ga and Zn. It is suggested that there are a large number of acceptors in the films, the major role of H is to passivate the acceptors but H-donors themselves do not play a significant role. These acceptor-like defects are located at grain boundaries (dangling bonds) and in bulk (VZn and/or GaZn–VZn). Post-growth annealing experiment and optical transmittance results exhibit that the passivated acceptors are mainly at grain boundaries rather than in bulk.

To identify measles vaccine failures in Tianjin, China using a measles virus IgG avidity assay.The China Information System for Disease Control and Prevention (CISDCP) was used to collect information about measles cases and blood specimens in Tianjin from 2013 to 2015. Measlesspecific IgM and IgG antibodies were detected using Enzyme-Linked Immunosorbent Assay (ELISA). Avidity testing for measles IgG was performed using a commercial enzyme immunoassay (EIA).A total of 284 confirmed measles cases were identified. Of this total, 262 (92.25%) were in patients aged ⪖ 20 years. High avidity was exhibited in 172 (60.56%) cases, while 80 (28.17%) cases demonstrated low avidity. High avidity was detected in only 21.43% of cases in patients aged1 year. The proportion of high avidity increased with age, and was significantly higher in patients aged 30-39 years at 70.07% (χ2 = 17.27, P = 0.002). Of the 52 measles cases in patients with a history of vaccinations, 41 (78.85%) cases showed high avidity, indicating secondary vaccine failures (SVF). In these vaccinations, there was no significant difference (P0.05) in clinical severity between high avidity and low avidity cases. However, regardless of vaccination status, clinical severity was significantly lower in high avidity cases (P0.001) than in low avidity cases. The percentages of positive measles IgM results in high avidity and low avidity cases were 66.28% and 91.25%, respectively. Geometric Mean Concentration (GMC) was significantly lower in high avidity cases at 33.73 U/mL, compared to 166.07 U/mL in low avidity cases.Low clinical severity and inconclusive IgM antibody results are more likely in high avidity measles cases. Measles cases were more common in adults. Therefore, a further dose of vaccines should be recommended for 30-39 years in Tianjin..

Summary Many cancer vaccines are not successful in clinical trials, mainly due to the challenges associated with breaking immune tolerance. Herein, we report a new strategy using an adjuvant-protein-antigen (three-in-one protein conjugates with built-in adjuvant) as an anticancer vaccine, in which both the adjuvant (small-molecule TLR7 agonist) and tumor-associated antigen (mucin 1, MUC1) are covalently conjugated to the same carrier protein (BSA). It is shown that the protein conjugates with built-in adjuvant can increase adjuvant's stimulation, prevent adjuvant's systemic toxicities, facilitate the codelivery of adjuvants and antigens, and enhance humoral and cellular immune responses. The IgG antibody titers elicited by the self-adjuvanting three-in-one protein conjugates were significantly higher than those elicited by the vaccine mixed with TLR7 agonist (more than 15-fold) or other traditional adjuvants. Importantly, the potent immune responses against cancer cells suggest that this new vaccine construct is an effective strategy for the personalized antitumor immunotherapy., Graphical Abstract, Highlights • Adjuvant-protein-antigen protein conjugates act as new cancer vaccine strategy • Built-in adjuvant of TLR7 agonist can reduce toxicities and enhance immune stimulations • Three-in-one protein conjugates boost potent immune responses against cancer cells, Conjugate; Biochemistry; Immunology

Hand, foot, and mouth disease (HFMD) is a common infectious disease in childhood caused by an enterovirus (EV), and which is principally seen in children under 5 years of age. To promote diagnostic awareness and effective treatments, to further standardize and strengthen the clinical management and to reduce the mortality of HFMD, the guidelines for diagnosis and treatment have been developed. National Health Commission of China assembled an expert committee for a revision of the guidelines. The committee included 33 members who are specialized in diagnosis and treatment of HFMD. Early recognition of severe cases is utmost important in diagnosis and treatment of patients with HFMD. The key to diagnosis and treatment of severe cases lies in the timely and accurate recognition of stages 2 and 3 of HFMD, in order to stop progression to stage 4. Clinicians should particularly pay attention to those EV-A71 cases in children aged less than 3 years, and those with disease duration less than 3 days. The following indicators should alert the clinician of possible deterioration and impending critical disease: (1) persistent hyperthermia; (2) involvement of nervous system; (3) worsening respiratory rate and rhythm; (4) circulatory dysfunction; (5) elevated peripheral WBC count; (6) elevated blood glucose and (7) elevated blood lactic acid. For treatment, most mild cases can be treated as outpatients. Patients should be isolated to avoid cross-infection. Intense treatment modalities should be given for those severe cases. The guidelines can provide systematic guidance on the diagnosis and management of HFMD.

Knowledge of an enterovirus genome sequence is very important in epidemiological investigation to identify transmission patterns and ascertain the extent of an outbreak. The MinION sequencer is increasingly used to sequence various viral pathogens in many clinical situations because of its long reads, portability, real-time accessibility of sequenced data, and very low initial costs. However, information is lacking on MinION sequencing of enterovirus genomes.In this proof-of-concept study using Enterovirus 71 (EV71) and Coxsackievirus A16 (CA16) strains as examples, we established an amplicon-based whole genome sequencing method using MinION. We explored the accuracy, minimum sequencing time, discrimination and high-throughput sequencing ability of MinION, and compared its performance with Sanger sequencing.Within the first minute (min) of sequencing, the accuracy of MinION was 98.5% for the single EV71 strain and 94.12%-97.33% for 10 genetically-related CA16 strains. In as little as 14 min, 99% identity was reached for the single EV71 strain, and in 17 min (on average), 99% identity was achieved for 10 CA16 strains in a single run.MinION is suitable for whole genome sequencing of enteroviruses with sufficient accuracy and fine discrimination and has the potential as a fast, reliable and convenient method for routine use.

Using optical microscopy、impact and tensile test,Study the effects of different quenching and tempering temperature on the microstructure and mechanical properties of the steel 20SiMn2MoVA.The results showed that, at the test temperature range,with the rise of quenching temperature the tensile strength of steel 20SiMn2MoVA declining, Low-temperature impact energy along with the quenching temperature rise was increasing. After quenching at 920°Cand tempering at different temperatures, with increasing tempering temperature, the tensile strength of the material showed a declining trend, impact toughness values were rising trend has decreased, 220°Ctempered impact toughness appear peak. Below 300°C tempering is tempered martensite and a small amount of residual austenite; More than 300°C tempering, residual austenite begins to decompose, carbide separeated out, 400°Ctempering is tempered flexor s body. Test material at 920°Cafter quenching and tempering 220°C, has good strength and toughness, specific properties: tensile strength 1506 MPa and temperature impact toughness Akv 35.6J.

Heat self-generated CO2 technique is proposed, which is focused on the problems of recovery difficulty, poor effect steam soaking and so on for heavy oil reservoirs. This technology is combining of steam flooding and gas flooding and so on. Its main mechanism is the application of steam heating blowing agent to generate a large volume of gases (including CO2, NH3, etc) in the formation. While some of these gases acting with the oil to reduce the oil viscosity, some form miscible flooding to reduce water interfacial tension, so as to achieve the purpose of enhancing oil recovery. An optimized selection of the heat blowing agents was performed. By comparison the difference before and after the reaction of blowing agent solution, the increase of alkaline is occurred after the reaction, and is helpful to reduce oil viscosity and lower interfacial tension, etc. Studies indicate that heat-generating CO2 flooding technology can get a maximum viscosity reduction rate of 76.7%, oil-water interfacial tension decreased by 54.77%, further improve oil recovery by 4.17% based on the steam drive, which shows a technical advantage toward conventional EOR method. The field experiments indicate that the technique can greatly improve the oil production, which will provide a powerful technical supporting for the efficient development of heavy oil.

Quantum-behaved particle swarm optimization (QPSO) has shown excellent performance in solving optimization problems which inspired by analysis from particle swarm optimization (PSO) and quantum mechanics. In QPSO, the only parameter contraction-expansion coefficientβis vital to the performance of algorithm. This paper employs Q-Learning strategy and presents a novel parameter control method to improve QPSO performance. Then the empirical studies on a suite of well-known benchmark functions are to be performed to test performance. Finally, a further performance comparison between the proposed algorithm and other parameter control methods of QPSO are listed and the simulation results show the efficiency of the proposed QPSO with novel adaptive strategies.

A bi-layer mathematical model of nodal analysis under the condition of separate layer injection-production has been set up on the study of inflow performance relationship between injectors and producers, horizontal flow, vertical flow, choke flow etc., according to nodal analysis principle. In theory, this method can be used to determine reasonable working system of injectors and producers, and can be optimized the allocation and injection allocation, and can also be made water flooding regime in its optimum condition.

Critical rainfall is one of the most important parameters of prediction, forecasting and early warning on mountain torrents disasters with important meanings for preventing mountain torrents disasters. In this paper, the measured rainfall method was taken to calculate the critical rainfall in typical regions based on the rainfall data of typical regional meteorological stations. Then, the Inverse Distance Weighting spatial interpolation method and Ordinary Kriging Interpolation method are taken based on the typical regional critical rainfall to get the critical rainfall distribution map of Sichuan Province. The critical rainfall distribution maps, which obtained from the two kinds of interpolation methods, both have universality and operability. Among them, the critical rainfall distribution map mapped by the Ordinary Kriging Interpolation method was more consistent with the practical situation.

In order to improve precision, outdated measurement method, complicated structure and weak anti-jam ability in liquid level measurement, a set of liquid level system was designed with the core of high-precision laser displacement sensor. The system adopted non-contact laser trigonometric survey method and powerful virtual instrument techniques. It could conduct online and real-time measurement to infinitesimal displacement on liquid level with high speed and precision. Through measurement experiment, its accuracy and practical applicability is verified.