Micro-interfacial behavior of antibiotic-resistant bacteria and antibiotic resistance genes in the soil environment: A review.

Overutilization and misuse of antibiotics in recent decades markedly intensified the rapid proliferation and diffusion of antibiotic resistance genes (ARGs) within the environment, thereby elevating ARGs to the status of a global public health crisis. Recognizing that soil acts as a critical reservoir for ARGs, environmental researchers have made great progress in exploring the sources, distribution, and spread of ARGs in soil. However, the microscopic state and micro-interfacial behavior of ARGs in soil remains inadequately understood. In this study, we reviewed the micro-interfacial behaviors of antibiotic-resistant bacteria (ARB) in soil and porous media, predominantly including migration-deposition, adsorption, and biofilm formation. Meanwhile, adsorption, proliferation, and degradation were identified as the primary micro-interfacial behaviors of ARGs in the soil, with component of soil serving as significant determinant. Our work contributes to the further comprehension of the microstates and processes of ARB and ARGs in the soil environments and offers a theoretical foundation for managing and mitigating the risks associated with ARG contamination.

Molecular Dynamics Simulation Study of Aluminum-Copper Alloys' Anisotropy under Different Loading Conditions and Different Crystal Orientations.

The commonly used aluminum-copper alloys in industry are mainly rolled plates and extruded or drawn bars. The aluminum-copper alloys' anisotropy generated in the manufacturing process is unfavorable for subsequent applications. Its underlying mechanism shall be interpreted from a microscopic perspective. This paper conducted the loading simulation on Al-4%Cu alloy crystals at the microscopic scale with molecular dynamics technology. Uniaxial tension and compression loading were carried out along three orientations: X-<1¯12>, Y-<11¯1>, and Z-<110>. It analyzes the micro-mechanisms that affect the performance changes of aluminum-copper alloys through the combination of stress-strain curves and different organizational analysis approaches. As shown by the results, the elastic modulus and yield strength are the highest under tension along the <11¯1> direction. Such is the case for the reasons below: The close-packed plane of atoms ensures large atomic binding forces. In addition, the Stair-rod dislocation forms a Lomer-Cottrell dislocation lock, which has a strengthening effect on the material. The elastic modulus and yield strength are the smallest under tension along the <110> direction, and the periodic arrangement of HCP atom stacking faults serves as the main deformation mechanism. This is because the atomic arrangement on the <110> plane is relatively loose, which tends to cause atomic misalignment. When compressed in different directions, the plastic deformation mechanism is mainly dominated by dislocations and stacking faults. When compressed along the <110> direction, it has a relatively high dislocation density and the maximum yield strength. That should be attributed to the facts below. As the atomic arrangement of the <110> plane itself was not dense originally, compression loading would cause an increasingly tighter arrangement. In such a case, the stress could only be released through dislocations. This research aims to provide a reference for optimizing the processing technology and preparation methods of aluminum-copper alloy materials.

Bunyavirus SFTSV nucleoprotein exploits tufm-mediated mitophagy to impair antiviral innate immunity.

Severe fever with thrombocytopenia syndrome is an emerging viral hemorrhagic fever caused by a tick-borne bunyavirus, severe fever with thrombocytopenia syndrome virus (SFTSV), with a high case fatality. We previously found that SFTSV nucleoprotein (NP) induces macroautophagy/autophagy to facilitate virus replication. However, the role of NP in antagonizing host innate immunity remains unclear. Mitophagy, a selected form of autophagy, eliminates damaged mitochondria to maintain mitochondrial homeostasis. Here, we demonstrate that SFTSV NP triggers mitophagy to degrade MAVS (mitochondrial antiviral signaling protein), thereby blocking MAVS-mediated antiviral signaling to escape the host immune response. Mechanistically, SFTSV NP translocates to mitochondria by interacting with TUFM (Tu translation elongation factor, mitochondrial), and mediates mitochondrial sequestration into phagophores through interacting with LC3, thus inducing mitophagy. Notably, the N-terminal LC3-interacting region (LIR) motif of NP is essential for mitophagy induction. Collectively, our results demonstrated that SFTSV NP serves as a novel virulence factor, inducing TUFM-mediated mitophagy to degrade MAVS and evade the host immune response.

TG2 participates in pulmonary vascular remodelling by regulating the senescence of pulmonary artery smooth muscle cells.

Pulmonary hypertension (PH) is a severe cardiovascular disease characterised by pulmonary vascular remodelling. The pivotal role of cellular senescence in vascular remodelling has been acknowledged. Transglutaminase type 2 (TG2), a calcium-dependent enzyme, is intricately linked to both cellular senescence and PH. However, the precise mechanisms underlying the involvement of TG2 in PH remain unclear. In this study, we explored the expression of TG2 and the cellular senescence marker p16INK4a in the pulmonary vasculature of mice with PH induced by hypoxia combined with SU5416. Our findings revealed upregulation of both TG2 and p16INK4a expression in the pulmonary vasculature of PH mice. Additionally, a notable increase in TG2 expression was observed in senescent pulmonary artery smooth muscle cells (PASMC). To delve deeper, we employed proteomic sequencing to reveal seven genes associated with cellular senescence, with a subsequent focus on MAPK14. Our investigation revealed that TG2 regulates senescence in PASMC by modulating the phosphorylation levels of MAPK14. Additionally, in the context of hypoxia combined with SU5416, our observations revealed a noteworthy reduction in both pulmonary vascular remodelling and senescent manifestations in smooth muscle-specific TG2 knockout mice compared with their wild-type counterparts. In summary, our findings indicate that TG2 deficiency lowers the senescence levels of PASMC by inhibiting the activity of MAPK14. This inhibition of senescence in the pulmonary vasculature of PH mice helps to decelerate the progression of pulmonary vascular remodelling and consequently hinders the onset and development of PH.

Bunyavirus SFTSV NSs utilizes autophagy to escape the antiviral innate immune response.

Severe fever with thrombocytopenia syndrome virus (SFTSV) nonstructural protein (NSs) is an important viral virulence factor that sequesters multiple antiviral proteins into inclusion bodies to escape the antiviral innate immune response. However, the mechanism of the NSs restricting host innate immunity remains largely elusive. Here, we found that the NSs induced complete macroautophagy/autophagy by interacting with the CCD domain of BECN1, thereby promoting the formation of a BECN1-dependent autophagy initiation complex. Importantly, our data showed that the NSs sequestered antiviral proteins such as TBK1 into autophagic vesicles, and therefore promoted the degradation of TBK1 and other antiviral proteins. In addition, the 8A mutant of NSs reduced the induction of BECN1-dependent autophagy flux and degradation of antiviral immune proteins. In conclusion, our results indicated that SFTSV NSs sequesters antiviral proteins into autophagic vesicles for degradation and to escape antiviral immune responses.

Polymer-DNA Carriers Co-Deliver Photosensitizer and siRNA for Light-Promoted Gene Transfection and Hypoxia-Relieved Photodynamic Therapy.

Photochemical internalization is an efficient strategy relying on photodynamic reactions to promote siRNA endosomal escape for the success of RNA-interference gene regulation, which makes gene-photodynamic combined therapy highly synergistic and efficient. However, it is still desired to explore capable carriers to improve the delivery efficiency of the immiscible siRNA and organic photosensitizers simultaneously. Herein, we employ a micellar nanostructure (PSNA) self-assembled from polymer-DNA molecular chimeras to fulfill this task. PSNA can plentifully load photosensitizers in its hydrophobic core simply by the nanoprecipitation method. Moreover, it can organize siRNA self-assembly by the densely packed DNA shell, which leads to a higher loading capacity than the typical electrostatic condensation method. The experimental results prove that this PSNA carrier can greatly facilitate siRNA escape from the endosome/lysosome and enhance transfection. Accordingly, the PSNA-administrated therapy exhibits a significantly improved anti-tumor efficacy owing to the highly efficient co-delivery capability.

SFTSV nucleoprotein mediates DNA sensor cGAS degradation to suppress cGAS-dependent antiviral responses.

Cyclic GMP-AMP synthase (cGAS) is an important DNA pattern recognition receptor that senses double-stranded DNA derived from invading pathogens or self DNA in cytoplasm, leading to an antiviral interferon response. A tick-borne Bunyavirus, severe fever with thrombocytopenia syndrome virus (SFTSV), is an RNA virus that causes a severe emerging viral hemorrhagic fever in Asia with a high case fatality rate of up to 30%. However, it is unclear whether cGAS interacts with SFTSV infection. In this study, we found that SFTSV infection upregulated cGAS RNA transcription and protein expression, indicating that cGAS is an important innate immune response against SFTSV infection. The mechanism of cGAS recognizing SFTSV is by cGAS interacting with misplaced mitochondrial DNA in the cytoplasm. Depletion of mitochondrial DNA significantly inhibited cGAS activation under SFTSV infection. Strikingly, we found that SFTSV nucleoprotein (N) induced cGAS degradation in a dose-dependent manner. Mechanically, N interacted with the 161-382 domain of cGAS and linked the cGAS to LC3. The cGAS-N-LC3 trimer was targeted to N-induced autophagy, and the cGAS was degraded in autolysosome. Taken together, our study discovered a novel antagonistic mechanism of RNA viruses, SFTSV is able to suppress the cGAS-dependent antiviral innate immune responses through N-hijacking cGAS into N-induced autophagy. Our results indicated that SFTSV N is an important virulence factor of SFTSV in mediating host antiviral immune responses. IMPORTANCE: Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne RNA virus that is widespread in East and Southeast Asian countries with a high fatality rate of up to 30%. Up to now, many cytoplasmic pattern recognition receptors, such as RIG-I, MDA5, and SAFA, have been reported to recognize SFTSV genomic RNA and trigger interferon-dependent antiviral responses. However, current knowledge is not clear whether SFTSV can be recognized by DNA sensor cyclic GMP-AMP synthase (cGAS). Our study demonstrated that cGAS could recognize SFTSV infection via ectopic mitochondrial DNA, and the activated cGAS-stimulator of interferon genes signaling pathway could significantly inhibit SFTSV replication. Importantly, we further uncovered a novel mechanism of SFTSV to inhibit innate immune responses by the degradation of cGAS. cGAS was degraded in N-induced autophagy. Collectively, this study illustrated a novel virulence factor of SFTSV to suppress innate immune responses through autophagy-dependent cGAS degradation.

Trypsin Encapsulation in the Zeolitic Imidazolate Framework for Low-Molecular Weight Protein Analysis with High Selectivity and Efficiency.

Low-molecular weight proteins (LWPs) are important sources of biological information in biomarkers, signaling molecules, and pathology. However, the separation and analysis of LWPs in complex biological samples are challenging, mainly due to their low abundance and the complex sample pretreatment procedure. Herein, trypsin modified by poly(acrylic acid) (PAA) was encapsulated by a zeolitic imidazolate framework (ZIF-L). Mesopores were formed on the ZIF-L with the introduction of PAA. An alternative strategy for separation and pretreatment of LWPs was developed based on the prepared ZIF-L-encapsulated trypsin with adjustable pore size. The mesoporous structure of the prepared materials selectively excluded high-molecular weight proteins from the reaction system, allowing LWPs to enter the pores and react with the internal trypsin, resulting in an improved separation efficiency. The hydrophobicity of the ZIF-L simplified the digestion process by inducing significant structural changes in substrate proteins. In addition, the enzymatic activity was significantly enhanced by the developed encapsulation method that maintained the enzyme conformation, allowed low mass transfer resistance, and possessed a high enzyme-to-substrate ratio. As a result, the ZIF-L-encapsulated trypsin can achieve highly selective separation, valid denaturation, and efficient digestion of LWPs in a short time by simply mixing with substrate proteins, greatly simplifying the separation and pretreatment process of the traditional hydrolysis method. The prepared materials and the developed strategy demonstrated an excellent size-selective assay performance in model protein mixtures, showing great potential in the application of proteomics analysis.

DSYOLO-trash: An attention mechanism-integrated and object tracking algorithm for solid waste detection.

In a global context, the production of urban solid waste significantly varies with changes in living standards. This trend exhibits diversity across different countries and regions, reflecting shifts in lifestyles as well as varying needs and challenges in waste management strategies. However, current standards of waste recycling are too complex for the general public to follow. In this study, we propose a model called DSYOLO-Trash to identify solid waste by integrating the dual attention mechanisms convolutional block attention module (CBAM) and Contextual Transformer Networks(CotNet), which significantly enhance its ability to mine channel-related and spatial attention features while optimizing the learning process. We apply the deep simple online and realtime tracking (DeepSORT) object tracking algorithm to solid waste detection for the first time in the literature to enable the real-time identification and tracking of waste. We also develop a multi-label dataset of mixed solid waste, called MMTrash, to realistically simulate actual scenarios of waste classification. Our proposed DSYOLO-Trash delivered superior performance to classical detection algorithms on both the MMTrash and the TrashNet datasets. Our system combines the improved you only look once(YOLO) algorithm with DeepSORT technology by using industrial cameras and PLC-controlled robotic arms to intelligently sort waste. The work here constitutes an important contribution to intelligent waste management and the sustainable development of cities.

Identifying metabolic dysfunction-associated steatotic liver disease in patients with hypertension and pre-hypertension: An interpretable machine learning approach.

Objective: Metabolic dysfunction-associated steatotic liver disease (MASLD) is one of the most prevalent liver diseases and is associated with pre-hypertension and hypertension. Our research aims to develop interpretable machine learning (ML) models to accurately identify MASLD in hypertensive and pre-hypertensive populations. Methods: The dataset for 4722 hypertensive and pre-hypertensive patients is from subjects in the NAGALA study. Six ML models, including the decision tree, K-nearest neighbor, gradient boosting, naive Bayes, support vector machine, and random forest (RF) models, were used in this study. The optimal model was constructed according to the performances of models evaluated by K-fold cross-validation (k = 5), the area under the receiver operating characteristic curve (AUC), average precision (AP), accuracy, sensitivity, specificity, and F1. Shapley additive explanation (SHAP) values were employed for both global and local interpretation of the model results. Results: The prevalence of MASLD in hypertensive and pre-hypertensive patients was 44.3% (362 cases) and 28.3% (1107 cases), respectively. The RF model outperformed the other five models with an AUC of 0.889, AP of 0.800, accuracy of 0.819, sensitivity of 0.816, specificity of 0.821, and F1 of 0.729. According to the SHAP analysis, the top five important features were alanine aminotransferase, body mass index, waist circumference, high-density lipoprotein cholesterol, and total cholesterol. Further analysis of the feature selection in the RF model revealed that incorporating all features leads to optimal model performance. Conclusions: ML algorithms, especially RF algorithm, improve the accuracy of MASLD identification, and the global and local interpretation of the RF model results enables us to intuitively understand how various features affect the chances of MASLD in patients with hypertension and pre-hypertension.

Nonlinear relationship between untraditional lipid parameters and the risk of prediabetes: a large retrospective study based on Chinese adults.

BACKGROUND: Abnormal lipid metabolism poses a risk for prediabetes. However, research on lipid parameters used to predict the risk of prediabetes is scarce, and the significance of traditional and untraditional lipid parameters remains unexplored in prediabetes. This study aimed to comprehensively evaluate the association between 12 lipid parameters and prediabetes and their diagnostic value. METHODS: This cross-sectional study included data from 100,309 Chinese adults with normal baseline blood glucose levels. New onset of prediabetes was the outcome of concern. Untraditional lipid parameters were derived from traditional lipid parameters. Multivariate logistic regression and smooth curve fitting were used to examine the nonlinear relationship between lipid parameters and prediabetes. A two-piecewise linear regression model was used to identify the critical points of lipid parameters influencing the risk of prediabetes. The areas under the receiver operating characteristic curve estimated the predictive value of the lipid parameters. RESULTS: A total of 12,352 participants (12.31%) were newly diagnosed with prediabetes. Following adjustments for confounding covariables, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol were negatively correlated with prediabetes risk. Conversely, total cholesterol, triglyceride (TG), lipoprotein combine index (LCI), atherogenic index of plasma (AIP), non-HDL-C, atherogenic coefficient, Castelli's index-I, remnant cholesterol (RC), and RC/HDL-C ratio displayed positive correlations. In younger adults, females, individuals with a family history of diabetes, and non-obese individuals, LCI, TG, and AIP exhibited higher predictive values for the onset of prediabetes compared to other lipid profiles. CONCLUSION: Nonlinear associations were observed between untraditional lipid parameters and the risk of prediabetes. The predictive value of untraditional lipid parameters for prediabetes surpassed that of traditional lipid parameters, with LCI emerging as the most effective predictor for prediabetes.

Dual-functionalized two-dimensional metal-organic framework composite with highly hydrophilicity for effective enrichment of glycopeptides.

Protein glycosylation research is currently focused on the development of various functionalized materials that can effectively enrich the levels of glycopeptides in samples. However, most of these materials possess limited glycopeptide-specific recognition sites because of large steric hindrance, unsuitable mass transfer kinetics, and relatively low surface areas. Herein, a highly hydrophilic two-dimensional (2-D) metal-organic framework (MOF) nanosheet modified with glutathione (GSH) and l-cysteine (l-Cys) (denoted as Zr-Fc MOF@Au@GC) has been synthesized for efficient glycopeptide enrichment. Using this composite material, 39 and 44 glycopeptides from horseradish peroxidase (HRP) and human serum immunoglobulin G (IgG) digests were detected, respectively, which represents a higher efficiency for glycopeptide enrichment from model glycoprotein digests than has been previously reported. The material Zr-Fc MOF@Au@GC exhibited ultra-high sensitivity (0.1 fmol/µL), excellent selectivity (weight ratio of HRP tryptic digest to bovine serum albumin (BSA) tryptic digest = 1:2000), good binding capacity (200 mg/g), satisfactory reusability, and long-term storage capacity. In addition, 655 glycopeptides corresponding to 366 glycoproteins were identified from human serum samples. To the best of our knowledge, this is the largest number of glycoproteins detected in human serum samples to date. These results indicated that Zr-Fc MOF@Au@GC has the potential to be used for the enrichment of glycopeptides in biological samples and the analysis of protein glycosylation.

De Ritis Ratio is Associated with Contrast-Associated Acute Kidney Injury Prediction and Long-Term Clinical Outcomes in Patients Undergoing Emergency Percutaneous Coronary Intervention.

Contrast-associated acute kidney injury (CA-AKI) is a familiar complication following percutaneous coronary intervention (PCI). The present study evaluated the predictive value of the De Ritis ratio for CA-AKI and its association with long-term clinical outcomes in patients undergoing emergency PCI. Overall, 546 patients were included in this study. The De Ritis ratio was calculated by aspartate aminotransferase/alanine aminotransferase activity. The De Ritis ratios in the CA-AKI patients were significantly higher than the non-CA-AKI patients [3.74 (2.32, 4.90) vs 1.61 (1.02, 2.53); P < .001]. The De Ritis ratio was an independent risk factor for CA-AKI [odds ratio, 2.243; 95% confidence interval (CI), 1.823-2.759; P < .001]. The area under the ROC curve was .813 (95% CI, .763-.862; P < .001), and the sensitivity and specificity were 67.0% and 82.4%, respectively, when the optimum cut-off value was 2.97. Furthermore, patients in the high De Ritis ratio group (≥1.76) had a significantly greater incidence of primary endpoints [26.7% (73/273) vs 13.2% (36/273); P < .001], and the high De Ritis ratio was an independent predictor for primary endpoints (hazard ratio, 1.888, 95% CI, 1.235-2.887; P = .003). In conclusion, the De Ritis Ratio is associated with CA-AKI prediction and long-term clinical outcomes in patients undergoing emergency PCI.

Natural Mediterranean Spotted Fever Foci, Qingdao, China.

We sequenced DNA from spleens of rodents captured in rural areas of Qingdao, East China, during 2013-2015. We found 1 Apodemus agrarius mouse infected with Rickettsia conorii, indicating a natural Mediterranean spotted fever foci exists in East China and that the range of R. conorii could be expanding.

The effects of salinity changes on anammox performance: The response rule and tolerance mechanism.

Some wastewaters contain high concentrations of ammonia coexisting with large amounts of salt, which might negatively affect the anaerobic ammonium oxidation (anammox) process. In this study, the performance of the anammox process under different saline conditions was investigated using an upflow anaerobic sludge bed-anammox system. After long-term operating for 275 days, the results indicated that the nitrogen removal efficiency remained high under the 0-40 g NaCl/L, and low salinity (15 g NaCl/L) substantially promoted specific anammox activity. Affected by the saline environment, the appearance, color, and shape of sludge notably changed, and the amount of extracellular polymeric substances gradually increased with increasing salinity, which might be one of the reasons for the strong salt tolerance of the system. Chloroflexi and Planctomycetes were the dominant strains under long-term salinity, and Brocadiaceae_g_ unclassified exhibited halophilic characteristics. The redundancy analysis results showed that the concentration of influent NH4 + -N and salinity were the main environmental factors affecting the microbial community of the system. PRACTITIONER POINTS: Provides data to support the maximum value for salinity wastewater treatment with anammox processes' tolerance of 40 g NaCl/L. EPS changes may be responsible for the response to salinity challenges and provide direction for high salinity wastewater treatment. Brocadiaceae_g_ unclassified exhibited a halophilic quality. And it can be focused on to improve treatment efficiency.

Neutralizing antibodies and cellular immune response after two doses of inactivated SARS-CoV-2 vaccine in China.

BACKGROUND: As of 2022, inactivated SARS-CoV-2 vaccines had been used in more than 91 countries. However, limited real world information was available on the immune responses of the inactivated SARS-CoV-2 vaccine. METHODS: We used SARS-CoV-2 pseudovirues to determine the neutralizing antibodies (NAbs) to wild type and several global variants and utilized enzyme-linked immunosorbent assay to investigate IFN-γ-secreting T-cell responses to SARS-CoV-2 among 240 vaccinated individuals after two doses of inactivated vaccine in China. RESULTS: A majority of the vaccinated (>90%) developed robust NAbs and T-cell responses to SARS-CoV-2 in the first two months after the second dose. After six months, only 37.0% and 44.0% of vaccinees had NAbs and T-cell immunity to SARS-CoV-2, respectively. Immune serum retained most of its neutralizing potency against the Alpha and Iota variants, but lost significant neutralizing potency against the Beta, Kappa, Delta, and Omicron variants. Only 40% of vaccine-sera retained low-level neutralization activities to Omicron, with a 14.7-fold decrease compared to the wild type. CONCLUSION: The inactivated SARS-CoV-2 vaccine stimulated robust NAbs and T-cell immune responses in the first two months after the second dose but the immune effect dropped rapidly, highlighing that a third dose or additional booster immunizations may be required to boost immunity against SARS-CoV-2.

The Association of Serum AIM2 Level with the Prediction and Short-Term Prognosis of Coronary Artery Disease.

Objective: Coronary artery disease (CAD), one of the commonest cardiovascular diseases, has high morbidity and mortality. Absent in melanoma 2 (AIM2) is involved in atherosclerosis, and no clinical trials have explored the association between AIM2 and CAD. Therefore, this study was aimed at evaluating the predictive and short-term prognostic value of AIM2 for CAD. Methods: 279 patients who underwent coronary angiography were enrolled in this study. The AIM2 level was detected from the serum of collected artery blood samples. The association of serum AIM2 level with the prediction and short-term prognosis of CAD was further assessed. Results: The serum AIM2 level of the CAD group was significantly higher than the control group (5.5 ± 2.1 vs. 3.7 ± 1.7; p < 0.001). AIM2 was demonstrated to be the risk factor of CAD [odds ratio, 1.589; 95% confidence interval (CI), 1.346-1.876; p < 0.001]. The area under the receiver operating characteristic (ROC) curve of 0.738 showed the diagnostic value of AIM2 in CAD. Additionally, AIM2 was an independent predictor of major adverse cardiovascular events (hazard ratio, 1.453; 95% CI, 1.086-1.945; p = 0.012), and CAD patients with high AIM2 levels (>4.9 ng/mL) had a markedly lower survival rate (log-rank p = 0.040). Conclusions: The serum AIM2 level > 4.9 ng/mL can predict CAD to a certain extent. AIM2 might be an independent predictor of its short-term poor prognosis.

High efficiency and related mechanism of Au(RC) nanoclusters on disaggregating Aß fibrils.

Revealing the disaggregating mechanism of amyloids fibrils under nanomaterials action is a key issue for their successful future use in therapy of neurodegenerative and overall amyloid-related diseases. Herein a gold nanocluster stabilized by Arg-Cys dipeptide (Au(RC)NCs) was synthesized to investigate its disaggregation activity toward Aß fibrils by using Thioflavin-T (ThT) fluorescence assay and atomic force microscopy. It was demonstrated that Au(RC)NCs is very effective in disaggregating preformed Aß fibrils, and characterized by the ultra-low apparent completely disaggregation concentration at the dose of 10 µg·mL-1. A possible disaggregation mechanism based on Au(RC)NCs triggering the disassembly of Aß fibrils into a dynamic equilibrium was proposed. The introduction of Au(RC)NCs with appropriate dose (5 µg·mL-1) can trigger the disassemble process of mature Aß fibrils into a critical state, at this very moment, if there is no more nano-disassembler, destruction of old Aß fibrils and formation of new Aß fibrils are thus in permanent dynamic equilibrium; in contrast, if there is more nano-disassembler (>10 µg·mL-1), the dynamic equilibrium prefer to shift to the direction of Aß further disassembly. Moreover, Au(RC)NCs with dosage over 10 µg·mL-1 exhibited superb protection effect against Aß-induced cytotoxicity in cell experiments. This study not only proposed a possible disassembly mechanism of amyloids fibrils under nanomaterials action, but also provide Au(RC)NCs as a promising high-effective nano-disassembler to disassemble unwanted amyloid aggregates.

Applying the Moving Epidemic Method to Establish the Influenza Epidemic Thresholds and Intensity Levels for Age-Specific Groups in Hubei Province, China.

BACKGROUND: School-aged children were reported to act as the main transmitter during influenza epidemic seasons. It is vital to set up an early detection method to help with the vaccination program in such a high-risk population. However, most relative studies only focused on the general population. Our study aims to describe the influenza epidemiology characteristics in Hubei Province and to introduce the moving epidemic method to establish the epidemic thresholds for age-specific groups. METHODS: We divided the whole population into pre-school, school-aged and adult groups. The virology data from 2010/2011 to 2017/2018 were applied to the moving epidemic method to establish the epidemic thresholds for the general population and age-specific groups for the detection of influenza in 2018/2019. The performances of the model were compared by the cross-validation process. RESULTS: The epidemic threshold for school-aged children in the 2018/2019 season was 15.42%. The epidemic thresholds for influenza A virus subtypes H1N1 and H3N2 and influenza B were determined as 5.68%, 6.12% and 10.48%, respectively. The median start weeks of the school-aged children were similar to the general population. The cross-validation process showed that the sensitivity of the model established with school-aged children was higher than those established with the other age groups in total influenza, H1N1 and influenza B, while it was only lower than the general population group in H3N2. CONCLUSIONS: This study proved the feasibility of applying the moving epidemic method in Hubei Province. Additional influenza surveillance and vaccination strategies should be well-organized for school-aged children to reduce the disease burden of influenza in China.

Light-Harvesting Fluorescent Spherical Nucleic Acids Self-Assembled from a DNA-Grafted Conjugated Polymer for Amplified Detection of Nucleic Acids.

The ultralow concentration of nucleic acids in complex biological samples requires fluorescence probes with high specificity and sensitivity. Herein, a new kind of spherical nucleic acids (SNAs) is developed by using fluorescent π-conjugated polymers (FCPs) as a light-harvesting antenna to enhance the signal transduction of nucleic acid detection. Specifically, amphiphilic DNA-grafted FCPs are synthesized and self-assemble into FCP-SNA structures. Tuning the hydrophobicity of the graft copolymer can adjust the size and light-harvesting capability of the FCP-SNAs. We observe that more efficient signal amplification occurs in larger FCP-SNAs, as more chromophores are involved, and the energy transfer can go beyond the Förster radius. Accordingly, the optimized FCP-SNA shows an antenna effect of up to 37-fold signal amplification and the limit of detection down to 1.7 pM in microRNA detection. Consequently, the FCP-SNA is applied to amplified in situ nucleic acid detecting and imaging at the single-cell level.