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DNA methyltransferase (MTase), modulating the level of genomic DNA methylation, harbors both a pharmacological target for clinical therapy and a potential biomarker for genetic disorders and tumorigenesis. Typical homogeneous electrochemical approaches, employing solution phase probes, have been considered simple, efficient, and economical method, yet these architectures usually require electroactive molecules labeling, rely on weak electrostatic adsorption interaction, and possess low sensitivity. For circumventing the above drawbacks, herein, we devise a ‘plug and play’ microelectrode featuring microminiaturization, rapid response time and enhanced mass transport to quantify MTase activity through monitoring the variation of diffusion current of methylene blue (MB) induced by the less-mobile G-quadruplex framework. By coupling the unique signal-transduction approach with Y-motif-mediated primer-free cyclic signal amplification (YPCSA), the miniaturized biosensor possesses low detection limit (down to 2.5 × 10−4 U mL−1), high specificity, good stability and satisfying reusability, and has been successfully applied to the screening of MTase inhibitors, holding great potential in clinical diagnosis and pharmacological research.

The efficacy of susceptible variants derived from genome-wide association studies (GWAs) optimizing discriminatory accuracy of colorectal cancer (CRC) in Chinese remains unclear. In the present validation study, we assessed 75 recently identified variants from GWAs. A risk predictive model combining 19 variants using the least absolute shrinkage and selection operator (LASSO) statistics offered certain clinical advantages. This model demonstrated an area under the receiver operating characteristic (AUC) of 0.61 during training analysis and yielded robust AUCs from 0.59 to 0.61 during validation analysis in three independent centers. The individuals carrying the highest quartile of risk score revealed over 2-fold risks of CRC (ranging from 2.12 to 2.90) compared with those who presented the lowest quartile of risk score. This genetic model offered the possibility of partitioning risk within the average risk population, which might serve as a first step toward developing individualized CRC prevention strategies in China.

Background Dysphagia is common after stroke. Patients with dysphagia have a higher risk of stroke-associated pneumonia (SAP) and poor outcomes. Early detection of dysphagia is necessary to identify and manage patients at high risk of aspiration. The aim of the study was to assess the impact of the systematic administration of the volume-viscosity swallow test (V-VST) in patients with acute ischaemic stroke. Methods This was a retrospective observational study that enrolled patients with acute ischaemic stroke in two consecutive time periods: pre-V-VST, when the 30-mL water-swallowing test (WST) was systematically administered, and V-VST, when all patients underwent the WST and the V-VST test was systematically administered if the patient failed the WST. Results Two hundred and 42 patients were enrolled. The mean age of the participants was 68.8 ± 10.88 years, 61.2% were male, and the median National Institutes of Health Stroke Scale score was 3 (IQR, 1–6). A total of 147 patients were enrolled during the pre-V-VST period and 95 were enrolled during the V-VST period. There was a significant difference in the occurrence of SAP (21.8% vs. 10.5%, p = 0.024) and the rate of nasogastric tube feeding (25.9% vs. 14.7%, p = 0.040) between the two groups, and no differences were found in the length of hospital stay (p = 0.277) or the total cost of hospitalization (p = 0.846). Conclusions The V-VST was a better clinical screening tool, and it can also provide detailed suggestions regarding dietary modifications to prevent aspiration and SAP.

Herein, an innovative photocathodic enzymatic biosensor is proposed with poly {4,8-bis[5-(2-ethylhexyl)thiophen-2-yl]-benzo[1,2-b:4,5-b']dithiophene-2,6-diyl-alt-3-fluoro-2-[(2-ethylhexyl)carbonyl]thieno[3,4-b]thiophene-4,6-diyl} (PTB7–Th) as donor–acceptor–type photoactive material and three–dimensional (3D) polyaniline hydrogels (PAniHs) as both electron transfer layer and biomolecule carrier. Based on the enhancement effect of PAniHs on the charge separation and electron transfer of PTB7–Th and the competitive consumption of dissolved oxygen (O2) between the xanthine oxidase (XOD)–guanine catalytic reaction and O2–sensitive PTB7–Th/PAniHs, the proposed photocathodic enzymatic biosensor has been demonstrated to detect guanine with the advantages of low limit of detection (0.02 μM), wide linear range (from 0.1 to 80 μM), simple and convenient preparation process, satisfactory stability, and photochemical signal amplification independent of any exogenous electron donor/acceptor or sensitizer. Remarkably, the proposed photocathodic enzymatic biosensor can not only be extended to other aerobic enzymatic bioanalyses, but also pave a horizon for the application of environmentally friendly conductive hydrogel materials in photoelectrochemical bioanalysis.

Herein, for the first time, we engineered click chemistry reaction to trigger a 3D DNA walking machine for ultrasensitive electrochemical detection of copper ion (Cu2+), which provided a convenient access to overcome the shortcomings of poor selectivity and limited amplification efficiency in traditional determination of Cu2+. Click chemistry reaction drove azido-S2 to bind with alkynyl-S1 for the formation of a walker probe on aminated magnetic polystyrene microsphere@gold nanoparticles (PSC@Au), which opened the hairpin-locked DNAzyme. In the presence of magnesium ion (Mg2+), the unlocked DNAzyme was activated to cleave the self-strand at the facing ribonucleotide site, accompanied by the release of product DNA (S3) and the walker probe. Therefore, the walker probe was able to open the adjacent hairpin-locked DNAzyme strand and then be released by DNAzyme cleavage along the PSC@Au-DNAzyme track. Eventually, the liberated single-strand S3 induced catalytic hairpin assembly (CHA) recycling, resulting in t...

Herein a rigid three-dimensional (3D) DNA "nanosafe-box" (DNB) for encapsulation and release of a recognition probe (N3) is designed to construct an electrochemical biosensor with the use of electroactive two-dimensional metal-organic framework (2D MOF) nanosheets as signal tags for ultrasensitive detection of mercury ion (Hg2+). Initially, N3 is locked in the 3D cavity of DNB by blocker DNA. After addition of target Hg2+, exonuclease III (Exo-III) digestion is initiated to the liberate DNA "key" (K); thereby, the free K triggers a strand displacement reaction for exposing the prelocked N3 to successfully ligate dibenzocyclooctyne (DBCO)-tagged anchor via metal-catalyst-free click chemistry, in which amounts of 2D MOF nanosheets containing Co(II) as electron mediator are introduced accompanied by significant electrochemical response. Compared with traditional linear or stem-loop DNA nanostructure, the well-designed 3D DNB possesses remarkably enhanced mechanical rigidity and structural stability, resulting in improved accessibility of probes and increased loading amounts of signal tags. More importantly, by this way of encapsulation and release of recognition probes, the background signal is decreased dramatically, leading to increased sensitivity of the proposed biosensor. Consequently, this electrochemical biosensor exhibits outstanding analytical performance for Hg2+ detection with a low detection limit of 33 fM and dynamic linear range of 0.1 pM to 10 nM. This strategy offers an ingenious method for detection of metal ions and biomarkers, possessing potential applications in environmental tests and clinical diagnosis.

Due to the cost, power requirements and capacity, data are mainly stored off-chip rather than on-chip in embedded systems. The data exchanged between the processor and off-chip memory might be sensitive, security and efficiency of off-chip memory is a major concern in embedded systems. However, existing protection solutions often require significant overhead to achieve adequate protection. This paper proposes a security management method which can guarantee stronger data confidentiality and integrity with a reduced overhead in area, memory footprint, and performance cost. To reduce on-chip memory consumption and latency cost, protection scheduling and storage strategy are carefully studied, then our security management architecture is formed. Afterwards, confidentiality and integrity modules are designed respectively. Data confidentiality is protected through a Binary Additive Stream Cipher-AES-Time Stamp based on circuit and addresses scrambling network of Benes, and data integrity is safeguarded through an integrity checking module based on SHA3-TAH and MSet-XOR-Hash tree. Hardware implementation is designed and synthesized in a 0.18 µm process. The experiment area is about 1.1 mm2 while frequency reaches 563 MHz. The attack complexity is more than 2224 while additional storage consumption is limited in about 26.6%.

In this work, on the basis of a new 2D DNA nanoprobe (DNP) and an enzyme-free-target-recycling amplification, an electrochemical biosensor is developed for the ultrasensitive detection of microRNA-21 (miRNA-21). Herein, two ferrocene-labeled bipedal DNPs, which show small steric hindrance and strong stability, are prepared on the basis of the mechanism of the proximity-ligation assay (PLA), improving the space utilization. In the presence of the target, miRNA-21, and a hairpin DNA strand, the DNP will collapse, and then two ferrocene-labeled DNA strands and the miRNA-21 will be simultaneously released from the electrode surface through toehold-mediated strand-displacement reactions (TSDRs), leading to a decrease in the electrochemical signal and realization of enzyme-free target recycling. As a result, the one input target, miRNA-21, could release 2 N ferrocene-labeled DNA strands, achieving a dramatic decrease in the electrochemical signal. Combining DNPs and enzyme-free target recycling, this proposed biosensor showed a linear dependence with miRNA-21 concentration, ranging from 1.0 fM to 10 nM with a detection limit of 0.31 fM. In addition, it is worth mentioning that this biosensor can be regenerated through incubating with three assistant-DNA strands, realizing the reuse of raw materials. Surprisingly, the elaborated biosensor provides a novel strategy for building controllable DNA nanoprobes for the sensitive detection of various biomarkers.

This paper proposes a multilevel reversible data hiding scheme in encrypted domain by utilizing the controllable redundancy of learning with error public key cryptography. Messages can be embedded into multilevel sub-regions of ciphertext by quantifying the encrypted domain and recoding its redundancy. We recode redundancy based on the characteristics of cipher’s distribution. Extraction and decryption processes are separated by dividing the encrypted domain into multilevel sub-regions and introducing different quantification standards. Original plaintext can be losslessly recovered from the marked ciphertext by using the decryption key; with a specific level data-hiding key, only the message hiding in the corresponding level can be extracted, while plaintext and other messages remain secret. We provide theoretical analysis and experimental results on the feasibility, reversibility, and security of the proposed scheme. The capacity and encryption blow up factor are discussed. The experimental results demonstrate the maximum embedding rate can exceed 0.3000 bpb of ciphertext.

microRNAs (miRNAs) perform various oncogenic or tumor suppressor functions in carcinogenesis. Currently, the underlying mechanisms of miRNAs in osteosarcoma (OS) are poorly understood. In the present study, it is demonstrated that expression of miR-544 was markedly upregulated in OS cells and clinical tissues. Furthermore, overexpression of miR-544 enhanced OS cell proliferation in vitro. Bioinformatics analysis indicated that miR-544 may target the 3'-untranslated region of axis formation inhibitor 2, which was validated using luciferase reporter gene assays. The present study demonstrated a vital role for miR-544 in promoting OS cell proliferation, indicating that it may represent a novel prognostic factor or therapeutic target for OS.

In this paper, the design of the electromagnetic soft surfaces realized by metal strips loaded with C-shaped slots is demonstrated having good suppression of electromagnetic coupling in bet...

Electrochemical aptasensors have been wildly used in the detection and quantification of protein biomarkers, but their practical applications are limited by inefficient signal amplification and laborious and time-consuming probe surface-immobilization procedure. Here, we combine the homogeneous electrochemical aptasensor with the CRISPR/Cas12a strategy to overcome such limitations. The binding-induced DNA strand displacement (BIDSD) strategy is designed to transform thrombin-aptamer interaction into nucleic acid output, which further triggers the rolling circle amplification (RCA) to regulate the deoxyribonuclease activity of CRISPR/Cas12a. Based on the difference in affinity of graphene to single-stranded DNA and double-stranded DNA, this electrochemical aptasensor is free of probe surface-immobilization procedure, which greatly simplifies operation steps and facilitates its flexibility. By integrating BIDSD with two amplification strategies of RCA and CRISPR/Cas12a, this electrochemical aptasensor achieves specific and sensitive detection of thrombin with a calculated limit of detection of 1.26 fM, which provides a paradigm for the sensitive detection of protein biomarker.

The results of a commissioning experiment on the SILEX-Ⅱ laser facility (formerly known as CAEP-PW) are reported. SILEX-Ⅱ is a complete optical parametric chirped-pulse amplification laser facility. The peak power reached about 1 PW in a 30 fs pulse duration during the experiment. The laser contrast was better than 1010 at 20 ps ahead of the main pulse. In the basic laser foil target interaction, a set of experimental data were collected, including spatially resolved x-ray emission, the image of the coherent transition radiation, the harmonic spectra in the direction of reflection, the energy spectra and beam profile of accelerated protons, hot-electron spectra, and transmitted laser energy fraction and spatial distribution. The experimental results show that the laser intensity reached 5 × 1020 W/cm2 within a 5.8 µm focus (FWHM). Significant laser transmission did not occur when the thickness of the CH foil was equal to or greater than 50 nm. The maximum energy of the accelerated protons in the target normal direction was roughly unchanged when the target thickness varied between 50 nm and 15 µm. The maximum proton energy via the target normal sheath field acceleration mechanism was about 21 MeV. We expect the on-target laser intensity to reach 1022 W/cm2 in the near future, after optimization of the laser focus and upgrade of the laser power to 3 PW.

The East Kunlun Orogen in the Northern Qinghai–Tibet Plateau is an ideal region in which to investigate net crustal growth through a process of syn-collisional felsic magmatism. In this paper, we report zircon U–Pb geochronology, whole-rock geochemistry, and multiple isotope data from the Nan’getan quartz diorite porphyrites and syenogranites in the East Kunlun Orogen. Zircon U–Pb ages indicate that the quartz diorite porphyrites and syenogranites were synchronously emplaced at ∼240 Ma. The syenogranites are characterized by a high SiO2 (77.4–79.2 wt%) and differentiation index (DI = 95), and marked depletion in Sr, Ba and Eu, thereby indicating that they are highly fractionated I-type granitoids. These rocks yielded zircon eHf(t) of −4.8 to +3.0 and Hf crustal model ages ( T DM c -Hf) of 1565–1075 Ma. The quartz diorite porphyrites are characterized by a high MgO of 4.19–6.37 wt% and Mg# of 59–61. These porphyrites have varying whole-rock eNd(t) (−13.2 to −10.8), (206Pb/204Pb) 240Ma of 18.325–18.511, (207Pb/204Pb)240Ma of 15.608–15.630, (208Pb/204Pb)240Ma of 38.167–38.614, and δ18OSMOW of 12.5‰–13.7‰. These signatures indicate that the Nan’getan syenogranites were most likely generated by an extensive differentiation of mixed parental magmas with both mantle-derived melt and crustal melt triggered by intrusion or underplating by mantle-derived basaltic magma. The Nan’getan Mg-rich diorites were likely derived from magma mixing between melts of ancient lower crustal materials and melts of an enriched mantle source that was metasomatized by fluids during ascent. In combination with the presence of the regional angular unconformity and the contemporaneous collisional metamorphism, the ∼240 Ma magmatism in the East Kunlun Orogen is inferred to have occurred in a compressional setting from subduction to syn-collision. The Nan’getan granitoids may have recorded the onset of collision between the Bayan Har–Songpan Ganze and East Kunlun terrane and net continental crust growth at ∼240 Ma.

Herein, we construct an ingenious spatially localized amplification reaction (SLAR) by colocalizing the entropy-driven reaction (EDR) in a nanometer space, which greatly accelerates target conversion and realizes the sensitive detection of microRNA-21 (miRNA-21). A large number of EDR complex are hybridized with the prefabricated DNA scaffold via a DNA self-assembly strategy to form the SLAR nanoprobe. Target miRNA-21 triggers interval EDR along the long DNA scaffold, resulting in fluorescence recovery with high signal gain because of the fast release of reporter. Compared with reactions with diffusible components, spatial arrangement of all components of EDR on a nanoscale scaffold can increase the local concentration of reactants, accelerating the interaction between adjacent components, and can also avoid the influence of stochastic diffusion to reduce the unintentional binding interaction between further separated components. Therefore, this SLAR assay displayed an excellent analytical performance for miRNA-21 detection with a detection limit of 6 pM and showed good specificity in distinguishing miRNA-21 from similar miRNAs. In addition, the proposed assay has been experimentally demonstrated for estimation of miRNA-21 in MCF-7 and HeLa cells lysates, which exhibited great promise in the sensitive detection of biomarkers in early diagnosis.

Objectives Olfactory bulbectomy (OB) induced behaviors, hypercortisolism, inflammation and neurotrophin dysfunctions are similar to those observed in depressed patients. Omega (n)-3 polyunsaturated fatty acids (PUFAs) can effectively treat depression via anti-inflammatory and neuroprotective effects. However, n-3 PUFA purities, caloric contents, and ratios in different diets often cause contradictive results. This study used Fat-1 mice, which can convert n-6 to n-3 PUFAs in the brain, to study the effect of n-3 PUFAs on OB-induced behaviors and related changes. Methods Fat-1 and wild-type littermates were fed safflower oil for 3 months. Behaviors were tested on day 21 after surgery. Monoamine neurotransmitters were measured by HPLC. Macrophage activity was measured by MTT assay. Astrocyte phenotypes A1 S100β, A2 BDNF and cholesterol level were measured by ELISA and total cholesterol assay kits respectively. PUFA profile and membrane fluidity were detected by GC and DPH fluorescence probe respectively. Results OB significantly induced animal hyperactivity and spatial memory impairment, while decreased sucrose consumption and social contact with decreased 5-HT turnover, increased the macrophage activity and S100β/BDNF ratio. Meanwhile, n-3/n-6 PUFAs ratio and total cholesterol level were reduced in OB mice. Whereas, OB-induced behavioral changes were attenuated, which were associated with increasing 5-HT turnover, decrease macrophage activity, restored S100β/BDNF and n-3/n-6 PUFAs ratios, and total cholesterol concentrations in Fat-1 mice. Conclusion The present study for the first time demonstrated that endogenous n-3 PUFAs attenuated OB-induced depression-like behaviors and spatial memory impairment through modulating serotonergic and immune function, balancing the astrocyte A1/A2 phenotypes, and normalizing PUFAs profile and membrane function.

DNAzyme and G-quadruplex are purposed as universal recognition elements to achieve multi-functional signal amplification and readout, showing great potential in the design of biosensors and nanodevices. Herein, the single-stranded DNA (ssDNA) opens the dumbbell-shaped hairpin probes, the generated double-stranded DNA (dsDNA) is constructed as a nanobridge, and the released G-rich sequence is folded into a G-quadruplex village. The fluorescence of crystal violet/G-quadruplex complex villages is enhanced by the dsDNA nanobridge connections. Under the excitation wavelength of 580 nm, the fluorescence emission intensity at 624 nm exhibits a good linearity with the concentration of crystal violet (CV) in the range of 10–250 nM, which can be used for sensitive detection of CV. Additionally, combined with Pb2+-dependent DNAzyme, a platform for quantitative detection of Pb2+ is established. In the concentration range of 5 nM – 25 μM, the fluorescence signal increases with the increase of Pb2+ concentration. The quantitative detection limit of Pb2+ by this method is 5 nM, and it possesses good selectivity and recovery for Pb2+ in a variety of water samples. More importantly, the platform can sensitively detect various metal ions by changing the DNAzyme sequence. It has potential application in the field of environmental monitoring.

Background: NKTCL is an aggressive and heterogenous type of non-Hodgkin's lymphoma that is characterized by malignant proliferation of cytotoxic natural killer (NK) or T cells and is associated with Epstein-Barr virus (EBV). Previous studies have shown that NKTCL tumors variably express CD38. Thus daratumumab (DARA), a human IgGκ monoclonal antibody targeting CD38 with direct on-tumor and immunomodulatory mechanism of action, was hypothesized to be a novel therapeutic option for patients with relapsed or refractory (R/R) NKTCL. The open-label, single-arm, multicenter, phase 2 study NKT2001 (NCT02927925) assessed the safety and efficacy of DARA in patients with R/R NKTCL, with an overall response rate of 25% and a 55 day median duration of response (DOR). Baseline serum EBV and CD38 expression levels did not show a clear correlation with clinical response. One NKTCL patient whose tumors did not express CD38 responded to treatment, suggesting that the immunomodulatory activities of DARA may be sufficient to confer clinical benefit. To understand the suboptimal response rate and short DOR, we interrogated the environmental, viral, and immune profile of NKTCL patients from NKT2001 in the context of DARA anti-tumor activity. Methods: CD38 expression was assessed by immunohistochemistry. Patient immune landscapes were assessed by cytometry by time-of-flight (CyTOF), multi-parameter flow cytometry (MPFC), clonal sequencing, and serum EBV level measurements. Results: Based on CyTOF and MPFC, high levels of baseline naive CD38- B cells with low percentage of CD38+ B cell populations (including transitional B, plasmablast, and plasma cells) were found to be significantly correlated with clinical response. However, subsequent B and T cell receptor sequencing did not detect clear relationships between pre-existing or treatment-emergent EBV-related B or T cell clones with clinical response. CyTOF analyses demonstrated a reduction of CD38+ NK cells, NK T cells, myeloid-derived suppressor cells (MDSCs), and regulatory T cells (Tregs) with DARA treatment. Nevertheless, persisting NK and NK T cells maintained cell surface markers indicative of functionality. Total Tregs and MDSCs levels did not change despite diminished CD38 expression, suggesting that DARA did not reverse the immune suppression mediated by Tregs or MDSCs. In contrast, there was a trend towards a decrease in CD4/CD8 ratio from baseline in responders but not in nonresponders, suggesting modulation of the immune environment is crucial for DARA anti-tumor activities in NKTCL. Conclusion: These results demonstrate that DARA can lead to clinical response in patients with NKTCL by modulating the immune environment. Citation Format: Tianyuan Zhou, Min Qing, Yann Abraham, Tatiana Perova, Cheryl Sweeney, Maria Krevvata. Understanding the anti-tumor activities of daratumumab in natural killer/T cell lymphoma (NKTCL) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1023.

Zircon LA-MC-ICP-MS U–Pb geochronology, major and trace element geochemistry, and Sr–Nd–Pb–Hf isotope analysis were performed on the Paleoproterozoic mafic dykes from the Wulashan area to investigate their petrogenesis and tectonic implications. The mafic dykes are diabase porphyries with a dominant mineral assemblage of plagioclase and clinopyroxene. Zircon U–Pb isotopic data yield weighted mean 207Pb/206Pb ages of 1769 ± 12 and 1770 ± 5 Ma for the NEE–EW trending and the N–S trending mafic dykes, respectively. Geochemically, these rocks belong to medium-K or high-K calc-alkaline series with K2O + Na2O contents of 3.39 to 5.28 wt.%. They show low MgO contents (3.92–4.63 wt.%) and Mg# values (32–37) and high contents of TiO2 (2.38–3.23 wt.%) and FeOt (13.60–15.29 wt.%). The dykes exhibit right-declined REE patterns, with (La/Yb)N of 4.63–9.35 and LREE/HREE of 5.02–7.92, and are characterized by enrichment in Rb, Ba, K, La, and Ce but depletion in Nb, Ta, Th, U, and Sr. Particularly, the NEE–EW trending samples display pronounced positive Ti anomalies, whereas the N–S trending samples exhibit negative P anomalies. All of the studied mafic dykes display similar Nd–Pb–Hf isotopic compositions with eNd(t) ranging from −3.41 to −1.49, (206Pb/204Pb)i of 15.0010 to 16.6626, (207Pb/204Pb)i of 15.2192 to 15.3468, (208Pb/204Pb)i of 35.0147 to 37.2389, and zircon eHf(t) values varying from −2.8 to 3.8. Geochemical modeling reveals that the NEE–EW and N–S trending mafic dykes were derived from 8% to 10% and 2%–4% partial melting of a common mantle source with ∼2% garnet. During emplacement, the parental mafic magma of the NEE–EW trending dykes experienced fractionation of clinopyroxene and accumulation of Ti–Fe oxides, whereas the N–S trending ones experienced fractionation of olivine and apatite. The selective enrichment of LILEs and LREEs, together with negative eNd(t) values and EMI-like Pb isotopic compositions, suggests that the dykes were derived from the partial melting of subcontinental lithospheric mantle metasomatized by slab-derived fluids. Furthermore, the marked depletion in Th and U and decoupled Nd–Hf isotopes indicate the incorporation of continental crustal components into the mantle prior to partial melting. Based on the geochemical features and previous regional geological data, we propose an extensional tectonic setting for the formation of the mafic dykes from the Wulashan area, possibly related to the post-orogenic setting following the collision between the Yinshan and Ordos Blocks.

This research examines the level of pre-exposure prophylaxis (PrEP) self-efficacy among HIV-negative men who have sex with men (MSM) in China and identifies the influencing factors associated with the level of PrEP self-efficacy in terms of social-demographic characteristics and social psychological factors. The data were gathered from a baseline assessment of a longitudinal randomized controlled intervention trial. From April 2013 to March 2015, nonprobability sampling was used to recruit HIV-negative MSM at Chongqing, Guangxi, Xinjiang, and Sichuan in west China. A total of 1884 HIV-negative MSM were analyzed. Chi-square test and nonparametric rank sum test were used for univariate analysis. Multivariable linear regression analysis was used to discuss the factors that influence the level of PrEP self-efficacy. Overall levels of PrEP self-efficacy were low, and five factors were found to effect PrEP self-efficacy: age, residence, AIDS-related knowledge, PrEP-related motivation, and anxiety. Age and anxiety score were negatively related to PrEP self-efficacy. The higher the age and anxiety score, the lower the PrEP self-efficacy. AIDS-related knowledge and PrEP-related motivation were actively related to PrEP self-efficacy. The higher the knowledge and motivation score, the higher the PrEP self-efficacy. In addition, the PrEP self-efficacy level of MSM in rural areas is lower than that in urban areas. The lower level of self-efficacy in the MSM population needs to be improved. Pertinent interventions should be taken to promote the self-efficacy of PrEP in MSM, to enhance their willingness to take medicine, improve their medication adherence, and thus reduce HIV infection among MSM.

Herein, a p-n quenching photoelectrochemical (PEC) biosensor is constructed for the ultrasensitive detection of miRNA-21 which the SnO2/CdCO3/CdS ternary composite nanomaterial is used as a signal indicator and the Y-type DNA structure stabilized p-type CuS quantum dot (QD) is employed as a signal quencher. Constructing the cascade energy level structure by using three photosensitive materials, in which stannic oxide (SnO2) is used as the photoactive material and cadmium sulfide (CdS) and cadmium carbonate (CdCO3) are served as the sensitizers. The prepared SnO2/CdCO3/CdS cascade co-sensitization structure with significantly improved photocurrent signal can inhibit the recombination of photogenerated electrons and holes, thereby dramatically enhancing the initial photocurrent response. Amounts of single strands DNA (assistant DNA) are output via the exponential strand displacement amplification (E-SDA) when miRNA-21 is present. The output assistant DNA can stabilize the CuS QD by forming stable Y-type DNA nanostructure on the surface of SnO2/CdCO3/CdS modified electrode. Therefore, the PEC signal of SnO2/CdCO3/CdS ternary composite nanomaterial is greatly quenched, because of the competitive consumption of exciting light energy and electron donors, as well as the steric effect of Y-type DNA structure. The linear range of the biosensor is from 10 fM to 1 μM with the detection limit down to 3.25 fM.

Based on the 7-nitro-1,2,3-benzoxadiazole (NBD) unit, many fluorescent probes have been developed for the differential detection of biothiols. Among them, however, the use of fluorescent probes for rapid simultaneous identification of biothiols in vivo has been rarely reported. In this work, a simple fluorescent probe (NC-NBD) is rationally designed and developed according to the different reactivity of biothiols, which can simultaneously distinguish homocysteine (Hcy), cysteine (Cys), and glutathione (GSH) by adjusting two different fluorescence signals (green and yellow). The probe NC-NBD can discriminatively detect biothiols using two fluorescence channels with fast response (120–360 s), which is suitable for real-time monitoring of biothiols in biological systems. As expected, the probe NC-NBD with excellent performance is able to determine the levels of Cys/Hcy and GSH in human serum samples, and therefore has potential applications in biological specimens. The robust probe shows low toxicity and high sensitivity when applied to living cells, and successfully achieves rapid sequence distinguishing of biothiols and intracellular imaging by using two different fluorescence signals. The probe can provide an effective tool for the real-time monitoring of intracellular biothiols.

Both organic and inorganic phosphates play important roles in biological activities. Considering the conventional methods are not very useful for identifying them from their analogues, the sensor array strategy has emerged in recent years, which is able to distinguish chemical species with similar structure or chemical properties. We propose a fluorescence sensor array based on two 3d-4f metal-organic frameworks (MOFs) by recording their direct one-step fluorescence changes with the addition of various phosphates. With the introduction of d-metal ions in the sensor unit synthesis process, two 3d-4f MOFs display higher sensitivity and noticeable fluorescence differences to five phosphates than the homometallic MOFs. Phosphates show diverse affinities to sensor units, forming the basis of differential sensing. The signals are much easier to collect, enabling the sensor array to simply accomplish the identification. Through statistical analysis, the sensor array is proved to be excellent in discriminating individual phosphate and mixture. Discrimination of five phosphates is successfully performed in serum samples to illustrate the practicability of the sensor array. This work presents an efficient and reliable approach for simultaneous detection of different phosphates, which can be extended to devise other array-based sensing methods.

Objective Previous studies mainly reported the clinical characteristics of novel coronavirus 2019 (COVID-19) infections, but the research on clinical characteristics and treatment outcomes of COVID-19 patients with stroke is still rare. Methods A multi-center retrospective study was conducted at 11 hospitals in 4 provinces of China, and COVID-19 patients with stroke were enrolled from February 24 to May 4, 2020. We analyzed epidemiological, demographic, and clinical characteristics of cases as well as the laboratory test results, treatment regimens and outcomes, and the clinical characteristics and therapeutic outcomes were compared between severe and nonsevere patients, and by age group, respectively. Results A total of 27 patients [mean age: 66.41 (SD 12.1) years] were enrolled. Among them, 9 (33.3%) were severe patients and 18 (66.7%) were nonsevere patients; 17 (63.0%) were female; 19 (70.4%) were aged 60 years and above. The most common symptoms were fever [19 (70.4%)], fatigue [12 (44.4%)] and cough [11 (40.7%)], respectively. Abnormal laboratory findings of COVID-19 patients with stroke included high levels of C-reactive protein [19 (73.1%)], D-dimer [14 (58.3%)], blood glucose [14 (53.8%)], fibrinogen [13 (50.0%)], and decreased lymphocytes [12 (44.4%)]. Comparing to nonsevere cases with stroke, severe patients with stroke were likely to be older, susceptible to receiving oxygen inhalation, and had more complications (p < 0.05). In addition, there were significant differences in lymphocytes, neutrophils, lactate dehydrogenase, C-reactive protein, creatine kinase between the severe cases and nonsevere cases (p < 0.05). The older patients had a decreased platelet count and elevated fibrinogen, compared with the younger (p < 0.05). All patients (100%) received antiviral treatment, 12 (44.4%) received antibiotics treatment, 26 (96.3%) received Traditional Chinese Medicine (Lung cleansing & detoxifying decoction), and oxygen inhalation was in 18 (66.7%). The median duration of hospitalization was 16 days. By May 4, 2020, a total of 26 (96.3%) patients were cured and discharged, and 1 (3.7%) patients died. Conclusion COVID-19 patients with stroke had poor indicators of coagulation system, and severe and older patients might have a higher risk of complications and unfavorable coagulation system. However, the overall treatment outcome is favorable., Graphical abstract Image, graphical abstract

Ionic liquid (IL) has attracted wide attention as a pretreating solvent for efficient utilization of lignocellulosic biomass. However, IL is known to severely inactivate the cellulases. In this study, the relative activity of Paenibacillus sp. LLZ1 cellulases (PCs) was analyzed in the presence of 1-ethyl-3-methylimidazolium diethylphosphate ([Emim]DEP) with respect to carboxymethylcellulose (CMC), filter paper (FP), and microcrystalline cellulose (MCC). With increasing [Emim]DEP concentration, PCs were differentially inhibited depending on the substrate. Subsequently, the kinetic parameters Km and Vmax were analyzed. A significant increase in the Km indicated that [Emim]DEP exerted a negative impact on the affinity of the enzyme on the substrate MCC. Comparatively, the Vmax was influenced only slightly. Further study on the relative MCCase activity with different substrate content showed that PCs were less inhibited at higher substrate concentration. Finally, sodium dodecyl sulfate polyacrylamide gel elec...

The newly discovered and large ca. 99 Ma Gaosongshan gold deposit is located in the Lesser Hinggan (or Xinggan) Range to the west of the Jiamusi Massif. The deposit is located at the border of the Great Hinggan Range–Mongolian Orogen with the Circum-Pacific tectonic belt and has a resource of ~ 22 t @ 6.3 g/t Au. Gaosongshan is classified as an adularia–sericite epithermal deposit associated with the large tensional Shaqihe Fault and has a low-sulfide content with a high concentration of gold hosted by pure chalcedonic quartz, which makes the deposit both unique and economically important in the area. Early Cretaceous volcanic rocks host the deposit as well as other gold deposits in the region. The mineralization at Gaosongshan includes Au, Ag, Mo, Sb, As, Pb and Hg. Stable isotope studies of fluid inclusions associated with the mineralization suggest that the mineralizing fluid had a meteoric origin (D V-SMOW : − 129 to − 111‰; 18 O fluid : 7.9 to 13.8‰). Fluid inclusion thermography indicates that the mineralized fluid was between 150° and 310 °C and had a low salinity (0.7–3.71 wt.% NaCl), low density (0.48–0.94 g/cm 3 ), shallow metallogenic depth (430–1270 m), and a large amount of reducing gaseous components (CH 4 , C 2 H 6 , CO, N 2 , and CO 2 ). The presence of large quantities of flaky quartz, adularia, gas-rich fluid inclusions, low-sulfide minerals and pure gold-bearing chalcedonic quartz suggests that fluid boiling was the principal mechanism for the gold precipitation. Sulfur isotopic data (δ 34 S: ~ − 2.4 to 2.9‰) indicate a deep magmatic origin for the mineralization, and the Pb isotopes ( 206 Pb/ 204 Pb: 18.14–18.46; 207 Pb/ 204 Pb: 15.51–15.57; 208 Pb/ 204 Pb: 38.01–38.40) also indicate that the metallogenic source of the deposit contained a significant mantle component. The mineralizing fluid interacted with a Late Paleozoic (ca. 260–253 Ma) substrate and ca. 141–91 Ma volcanic host rocks. The geological and geochemical characteristics of the deposit, and the Tuanjiegou, Dongan, Sandaowanzi and other large gold deposits represent an Early Cretaceous (114–80 Ma) epithermal mineralizing events in the Lesser Hinggan Range. The belt is controlled by the volcanic Sunwu–Jiayin Basin formed in a back-arc extensional setting along an active continental margin in East China, and the gold deposits in the belt have the same genesis as porphyritic Au(–Cu) deposits along the continental margin in eastern Jilin and Heilongjiang provinces. It is here proposed that the mineralization in both regions is related to the subduction of the Paleo-Pacific plate.

The age, petrogenesis and geodynamic implication of Xiaomiaogou granite porphyry dykes in the northern margin of the North China Craton were investigated using geochronology, geochemistry and Sr–Nd–Pb–Hf isotopic data. LA-MC-ICP-MS zircon U–Pb dating yielded the concordant 206Pb/238U weighted mean age of 350.4 ± 1.4 Ma for the dykes, suggesting they were the productions of the Early Carboniferous magmatism in the northern margin of the North China Craton. The granite porphyries display the pronounced A-type affinities: apart from higher zircon saturation temperature, they are high-K calc-alkaline and metaluminous, with high concentrations of K2O + Na2O varying from 7.93 to 8.55 wt.%, incompatible elements (e.g. Zr, Y, Nb and Ce), REEs and 10 000 Ga/Al ratios but less obvious LREE and HREE fractionation. With the lower initial 87Sr/86Sr ratios (0.7055 to 0.7070), negative values of eNd(t) (−7.1 to −4.9) and eHf(t) (−11.2 to −8.0) and old Nd (1505 to 1681 Ma) and Hf (1861 to 2061 Ma) model ages, all the rocks exhibit the similar geochemical compositions to the melts obtained in experimental studies by dehydration melting of meta-basalts, implying a lower continental crust origin. However, the high Mg# values (47.53 to 53.60) and subcontinental lithospheric mantle-like eNd(t), eHf(t) and Pb isotopic compositions ((206Pb/204Pb)i = 17.296–17.766, (207Pb/204Pb)i = 15.460–15.490 and (208Pb/204Pb)i = 37.097–37.568) indicate the involvement of melts from subcontinental lithospheric mantle. Combined with the special features of mafic microgranular enclaves occurring within the granite porphyries, mixing of the lower crust and subcontinental lithospheric mantle of the North China Craton is proposed for the genesis of granite porphyry dykes in this study. During the hybrid magma ascending, pronounced fractional crystallization and crustal assimilation may have also occurred. Based on geochemical criteria, the Xiaomiaogou granite porphyries can be classified into A1 group. Characterized by the compositional features of anorogenic granites, an intraplate setting is envisaged for the formation of Xiaomiaogou granite porphyry dykes. Such a tectonic environment may be related to the northward drift of the North China Craton during rifting away from East Gondwana. Copyright © 2016 John Wiley & Sons, Ltd.

The East Kunlun Orogen in the Northern Qinghai–Tibet Plateau is an ideal region to investigate the geodynamic processes of magmatism related to the closure of the Paleo-Tethys Ocean. Here, we report petrology, zircon U–Pb geochronology, whole-rock geochemistry and multiple isotope data from granodiorites and the associated dioritic enclaves in a dominant Nan'getan granitoid in the East Kunlun Orogen. Zircon U–Pb ages indicate that the host granodiorites and dioritic enclaves were synchronously emplaced at ~ 243 Ma. The granodiorites are medium- to high-K calc-alkaline, metaluminous (A/CNK = 0.93–0.98), with high Al 2 O 3 content (15.28%–16.10%), Mg # (47–49), very low Sr/Y ratios (127–217), high abundances of incompatible elements (Y = 3.87–8.36 ppm, Nb = 3.04–5.71 ppm, Th = 3.04–5.71 ppm), low ( 87 Sr/ 86 Sr) i (0.7050–0.7079), negative whole-rock e Nd (t) (− 8.2 to − 5.8), ( 206 Pb/ 204 Pb) 243Ma of 18.520 to 18.772, ( 207 Pb/ 204 Pb) 243Ma of 15.611 to 15.650, ( 208 Pb/ 204 Pb) 243Ma of 38.227 to 38.528, δ 18 O SMOW = 6.8‰–9.1‰, e Hf (t) of − 1.2 to + 2.4. The dioritic enclaves (SiO 2 = 51.08%–56.29%) have Mg # values of 48–51, with negative Eu anomalies (δEu = 0.59–0.79), low ( 87 Sr/ 86 Sr) i (0.7058–0.7080), negative whole-rock e Nd (t) (− 8.2 to − 5.8), ( 206 Pb/ 204 Pb) 243Ma of 18.376 to 18.809, ( 207 Pb/ 204 Pb) 243Ma of 15.606 to 15.661, ( 208 Pb/ 204 Pb) 243Ma of 38.244 to 38.540, δ 18 O SMOW = 5.6‰–10.0‰, e Hf (t) of − 3.5 to + 1.7. These isotopic features of arc-type rocks from the East Kunlun suggest that the parental magmas of the Nan'getan granodiorites and the dioritic enclaves originated from an enriched lithospheric mantle. The Nan'getan granitoids might have recorded the northward subduction of the Paleo-Tethys ocean lithosphere following the initial collision of the Bayan Har–Songpan Ganzi–East Kunlun terrane and the closure of the Paleo-Tethys Ocean at ~ 243 Ma.

In this study, a mesh stiffness model of spur gear drives considering the tooth corrosion effect, which is based on Ishikawa model, is proposed. The fidelity of mesh stiffness based on the proposed model is checked by comparing the result with a benchmark result from the reference and the effect of the tooth corrosion on mesh stiffness is analyzed. The prediction indicates mesh stiffness is insensitive to the tooth corrosion, but this conclusion has a signification for assessing the stability of inherent properties of a spur gear drive when the tooth corrosion is produced.