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Objectives Cognitive impairment caused by cerebrovascular disease accounts for more than half of vascular dementia. However, neuropsychological tests are limited by their subjectivity. Additional effective approaches to evaluate cognitive impairment in patients with cerebrovascular disease are necessary. Method One hundred and thirty-two patients with cerebrovascular disease were recruited. One hundred participants met the criteria and completed neuropsychological scales. Sixty-nine participants proceeded with polysomnography, and 63 of them had their peripheral blood biomarkers measured. According to Mini-Mental State Examination scores, patients were divided into cognitively impaired and cognitively normal groups. The differences in biomarkers and sleep parameters between the groups were compared, and decision tree models were constructed to evaluate the evaluation ability of these indicators on cognitive decline. Results The integrated decision tree model of sleep parameters yielded an area under curve (AUC) of 0.952 (95% confidence interval [CI]: 0.911–0.993), while that of plasma biomarkers yielded an AUC of 0.872 (95% CI: 0.810–0.935) in the assessment of cognition status. Then the participants were automatically clustered into mild and severe cognitive impairment groups by multiple neuropsychological test results. The integrated plasma biomarker model showed an AUC of 0.928 (95% CI: 0.88–0.977), and the integrated sleep parameter model showed an AUC of 0.851 (95% CI: 0.783–0.919) in the assessment of mild/severe cognitive impairment. Discussion Integrated models which consist of sleep parameters and plasma biomarkers can accurately evaluate dementia status and cognitive impairment in patients with cerebral small vessel disease. This innovative study may facilitate drug development, early screening, clinical diagnosis, and prognosis evaluation of the disease.

Abstract: Alzheimer's disease (AD) is an intricate neurodegenerative disease with chronic and progressive development whose typical neuropathological features encompass senile plaques and neurofibrillary tangles, respectively formed by the extracellular deposition of amyloid-beta (Aβ) and the intracellular accumulation of hyperphosphorylated tau protein in the brain, particularly in limbic and cortical regions. The pathological changes are considered to be caused by the loss of Aβ and tau protein clearance mechanisms under pathological conditions, which leads to an imbalance between the rates of clearance and production. Consequently, the main strategies for treating AD aim to reduce the production of Aβ and hyperphosphorylated tau protein in the brain, inhibit their accumulation, or accelerate their clearance. Although drugs utilizing these therapeutic strategies have been studied successively, their therapeutic effects have generally been less than ideal. Fortunately, recent advances have been made in clearance strategies for these abnormally expressed proteins, including immunotherapies and nanomedicines targeting Aβ or tau, which could represent an important breakthrough for treating AD. Here, we review recent development of the strategies for the removal of abnormal proteins and provide new ideas and methods for treating AD.

The South Qiangtang terrane (SQT), the Tibetan representative of the Cimmerian continent, is bounded in the south by the Bangong-Nujiang suture zone (BNSZ). The BNSZ is geologically manifested by the Mugagangri Group (MG) accretionary complexes developed during northward Meso-Tethyan subduction, whose timing and processes are, however, contentious. Herein, we conducted provenance analysis on the MG trench deposits, via petrography, whole-rock geochemistry and detrital-zircon geochronology. The results reveal a complete picture of provenance evolution during passive- to active-margin transition (from subduction initiation through fringing oceanic-arc, to continental-arc developments) at the SQT margin. In particular, the earliest trench deposits (subunit Trma; ~222 Ma), which contain olistostromes with blocks of oolitic limestone shed from the destructing SQT passive margin, mark the subduction initiation. A second subunit (Trmb; ~210 Ma) has periodically elevated volcanogenic components. Conglomerates of subunit Trmb have abundant basaltic clasts of intra-oceanic arc geochemical affinities, which were likely derived from an intra-oceanic arc fringing the SQT. The youngest subunit (Jmd; ~190 Ma) exhibits enriched ferromagnesian elements and a major youngest detrital-zircon age peak, indicating a continental-arc provenance. Moreover, detrital-zircon age spectra suggest that, at ~210 Ma, the central Qiangtang metamorphic belt became an important source area, and the North Qiangtang terrane (NQT) replaced SQT as the main provenance. This is best explained by that the SQT underthrusted beneath the NQT and was downwarped to form a foreland basin. Our findings confirm that the initial subduction of Meso-Tethys beneath SQT was coeval to other Cimmerian terranes, likely a uniform response to the Paleo-Tethys closure and collision between Eurasia (NQT) and Cimmeria (SQT).

In the southern Tibetan Plateau, leucogranites are dominantly distributed in the Himalayan orogenic belt with minor occurrences in the southern Lhasa subterrane. In this paper, we report the first Miocene Anglonggangri leucogranites in the northern Lhasa subterrane. This finding provides important constraints on both leucogranite petrogenesis and the tectono-magmatic evolution of the Lhasa terrane. The Anglonggangri leucogranites include biotite-muscovite granite and slightly younger garnet-muscovite granite and pegmatite. Zircon U-Pb and muscovite 40Ar-39Ar dating of these leucogranites yields Miocene ages of 11.1–10.2 Ma. The biotite-muscovite and garnet-muscovite granites are characterized by high SiO2 (72.3–74.4 wt.%) and Al2O3 contents (14.4–15.4 wt.%) and are peraluminous. The biotite-muscovite granite displays geochemical signatures with high Sr/Y (29.2–81.0) and (La/Yb)N (37.5–98.9) ratios, low Y (4.30–7.22 ppm) and Yb contents (0.26–0.47 ppm), low to moderate initial (87Sr/86Sr)i ratios (0.7085–0.7192), and moderate εNd(t) values (−10.17 to −6.94). Furthermore, they also exhibit radiogenic Pb isotope and variable zircon εHf(t) values (−9.6 to +4.4) with Proterozoic Nd (1.1–1.4 Ga) and Hf model ages (0.8–1.7 Ga). By comparison, the garnet-muscovite granite has lower CaO, MgO, TiO2, and total FeO contents and is enriched in Rb (380–466 ppm) and depleted in Sr (24.1–38.5 ppm) and Ba (30.7–58.6 ppm) and further characterized by a significant rare earth element (REE) tetrad effect and non-charge and radius-controlled (CHARAC) trace element behaviors. The garnet-muscovite granite shows a negative Eu anomaly and positive correlations among Sr and Eu, Sr and Ba, and Th and light rare earth elements (LREEs). Pegmatite comprising Nb-Ta oxides and cassiterite occurs in the garnet-muscovite granite. Geochronological and geochemical characteristics of the Anglonggangri leucogranites indicate that the magma of the biotite-muscovite granite was derived from partial melting of amphibolite lower crust contaminated with Proterozoic-Archean upper crustal materials. The garnet-muscovite granite was generated through melt extraction from the biotite-muscovite granite crystal mush. These results confirm that partial melting of the amphibolite lower crust not only occurred in the southern and central Lhasa subterranes but also in the northern Lhasa subterrane.

Alzheimer's disease (AD), one of the progressive neurodegenerative disorders, is characterized by clinical features such as memory loss, acquired skill loss, apraxia, and interpersonal and social communication disorders. The AD hallmarks at the neuropathological level include intracellular neurofibrillary tangles constituted by the hyperphosphorylated tau protein as well as the senile extracellular plaques dominated by the amyloid-β (Aβ) deposits. At present, AD treatment that mainly targeted towards improving symptoms and effective drugs to delay or stop disease progression is lacking. Vaccines and antibody-based therapies are a type of natural, synthetic, and gene recombinant biological product that treat or prevent disease progression by stimulating specific or non-specific immune responses. Compared with traditional targeted drugs, vaccines and antibodybased therapies have better safety and effectiveness and can even maintain the expression and stability of Aβ and Tau proteins in patients for a long time. Logically, vaccines and antibody-based therapies are somewhat different from traditional drugs because these drugs can achieve the therapeutic effect of AD by activating immune cells and regulating the immune system of patients themselves, thereby clearing disease-related proteins and long-term survival. Complete cure is also observed in some patients after receiving the immunotherapy. Currently available vaccines and antibody-based therapies mainly target Aβ and phosphorylated tau proteins. There are 44 vaccines and antibodybased therapies for AD, among which nine drugs are discontinued, three drugs are inactive, eleven drugs are in clinical phase 1, twelve drugs are in clinical phase 2, and seven drugs are in clinical phase 3. Currently, no vaccines and antibody-based therapies have been approved for AD treatment. In this paper, we review and analyse the research progress of vaccines and antibody-based therapies that are used to treat AD.

Early detection, diagnosis and treatment of human immune deficiency virus (HIV) infection is the key to reduce acquired immunodeficiency syndrome (AIDS) mortality. In our research, an innovative surface plasmon resonance (SPR) biosensing strategy has been developed for highly sensitive detection of HIV-related DNA based on entropy-driven strand displacement reactions (ESDRs) and double-layer DNA tetrahedrons (DDTs). ESDRs as enzyme-free and label-free signal amplification circuit can be specifically triggered by target DNA, leading to the cyclic utilization of target DNA and the formation of plentiful double-stranded DNA (dsDNA) products. Subsequently, the dsDNA products bind to the immobilized hairpin capture probes and further combine with DDTs nanostructures. Due to the high efficiency of ESDRs and large molecular weight of DDTs, the SPR response signal was enhanced dramatically. The proposed SPR biosensor could detect target DNA sensitively and specifically in a linear range from 1pM to 150nM with a detection limit of 48fM. In addition, the whole detecting process can be accomplished in 60min with high accuracy and duplicability. In particular, the developed SPR biosensor was successfully used to analyze target DNA in complex biological sample, indicating that the developed strategy is promising for rapid and early clinical diagnosis of HIV infection.

A novel colorimetric biosensing strategy, employing coupling spontaneous cascade catalytic hairpin assembly (CHA) circuits and mismatched hairpin, has been developed successfully for ultrasensitive and specific detection of target microRNA (miRNA). This system is composed of two layers of CHA. While target miRNA exists, the toehold-based assembly of the first-layer hairpins comes into being, followed by the generation of the first-layer CHA products and the cyclic release of the target miRNA. Then the first-layer CHA products can act as initiator for the assembly of the second-layer hairpins to produce the second-layer CHA products, with the first-layer CHA products recovered simultaneously. Finally, the second-layer CHA products can combine with hemin to form G-quadruplex/hemin DNAzyme, a well-known horseradish peroxidase (HRP) mimic, for catalyzing a colorimetric reaction. Under the optimal experimental conditions, the established biosensor can detect target miRNA down to 36.2 fM (S/N = 3) with a linear range from 100 fM to 10 nM, and discriminate target miRNA from mismatched miRNA with high selectivity. It was also applied to test the concentration of miRNA spiked into salmon sperm samples. Therefore, this biosensing strategy may become an alternative tool for the detection of miRNA in biomedical research.

To develop a safe and effective oral vaccine against Helicobacter pylori using its HpaA protein expressed in Lactococcus lactis. The gene encoding HpaA was obtained by PCR and ligated to pNZ8110-lysM following digestion with NaeI + SphI. The recombinant plasmid was transferred into E. coli for multiplication, and then into L. lactis. The recombinant L. lactis was induced to express HpaA, resulting in two products of 29 and 25 kDa, both of which yielded positive immunoreaction with mouse antisera against H. pylori, as confirmed by immunoblot assays. The 29 kDa product constituted 12% of the cell lysates. Oral inoculation with the engineered L. lactis evoked significantly elevated serum IgG level in mice (P

Sensitive and specific detection of HIV-related DNA is of great importance for early accurate diagnosis and therapy of HIV-infected patients. Here, we developed a one-step and rapid fluorescence strategy for HIV-related DNA detection based on strand displacement amplification and a Mg2+-dependent DNAzyme reaction. In the presence of target HIV DNA, it can hybridize with template DNA and activate strand displacement amplification to generate numerous DNAzyme sequences. With the introduction of Mg2+, DNAzyme can be activated to circularly cleave the substrate DNA, which leads to the separation of fluorophore reporters from the quenchers, resulting in the recovery of the fluorescence. Under the optimal experimental conditions, the established biosensing method can detect target DNA down to 61 fM with a linear range from 100 fM to 1 nM, and discriminate target DNA from mismatched DNA perfectly. In addition, the developed biosensing strategy was successfully applied to assay target DNA spiked into human serum samples. With the advantages of fast, easy operation and high-performance, this biosensing strategy might be an alternative tool for clinical diagnosis of HIV infection.

In this paper, a co-designed compact filtering monopole antenna based on the recently developed two-stage split ring resonator (SRR)-inspired high-frequency-selective filter is proposed and demonstrated. The used filter is consisting of two groups of twist-modified SRRs and is inserted in the feeding line of a conventional wide band planar monopole antenna to filter out the unwanted out-of-band antenna gain. The impedance matching and radiation gain of the co-designed filtering antenna are numerically and experimentally demonstrated and a good agreement between them is obtained. The measured results show that such filtering antenna has a 3-dB gain bandwidth of 16.7% centered at 2.4 GHz with peak gain of 2.4 dBi and sharp dropped out-of-band radiation gain feature.

The authors describe an electrochemical strategy for ultrasensitive and specific detection of microRNA (miRNA). It is based on both multicomponent nucleic acid enzyme (MNAzyme) amplification and rolling circle amplification (RCA). In the presence of target miRNAs, partial enzyme A (partzyme A) and partial enzyme B (partzyme B) are assembled to form active MNAzymes. Once formed, the MNAzymes catalyze the cleavage of the hairpin substrates to liberate biotinylated fragments which hybridized with the capture probes immobilized on a gold electrode. The RCA is then initiated to form a product that binds many detection probes. Finally, the amperometric signal (best acquired at a working voltage of 0.22 V vs. Ag/AgCl) is obtained by employing the streptavidinylated alkaline phosphatase as the enzyme. This biosensor has a 1.66 fM detection limit, and a dynamic range that extends from 10 fM to 1 nM. It displays specificity down to single mismatch discrimination of target miRNAs and good reproducibility. It was successfully applied to the determination of miRNA in total RNA samples extracted from human breast adenocarcinoma MCF-7 cells.

The authors describe an electrochemical sensing strategy for highly sensitive and specific detection of target (analyte) DNA based on an amplification scheme mediated by a multicomponent nucleic acid enzyme (MNAzyme). MNAzymes were formed by multicomponent complexes which produce amplified “output” signals in response to specific “input” signal. In the presence of target nucleic acid, multiple partial enzymes (partzymes) oligonucleotides are assembled to form active MNAzymes. These can cleave H0 substrate into two pieces, thereby releasing the activated MNAzyme to undergo an additional cycle of amplification. Here, the two pieces contain a biotin-tagged sequence and a byproduct. The biotin-tagged sequences are specifically captured by the detection probes immobilized on the gold electrode. By employing streptavidinylated alkaline phosphatase as an enzyme label, an electrochemical signal is obtained. The electrode, if operated at a working potential of 0.25 V (vs. Ag/AgCl) in solution of pH 7.5, covers the 100 pM to 0.25 μM DNA concentration range, with a 79 pM detection limit. In our perception, the strategy introduced here has a wider potential in that it may be applied to molecular diagnostics and pathogen detection.

The Leqingla and Xin'gaguo deposits are two representative skarn Pb–Zn polymetallic deposits of the Gangdese Pb–Zn polymetallic belt, Tibet, China. LA-ICP-MS zircon U–Pb dating of the mineralization-related biotite granites from both the Leqingla and Xin'gaguo deposits yielded weighted mean ages of 60.8 Ma and 56.5 Ma, respectively, which can be inferred as their mineralization ages. The Leqingla biotite granite is characterized by high Al 2 O 3 , total Fe, Na 2 O, and low K 2 O. In comparison, the Xin'gaguo biotite granite is characterized by relative higher K 2 O but lower Al 2 O 3 , total Fe, and Na 2 O. Geochemical and mineralogical characteristics indicate that the Leqingla and Xin'gaguo biotite granites are calc-alkaline I-type granite and High K calc-alkaline I-type granite, respectively. Both the Leqingla and Xin'gaguo biotite granites are enrichment in LREE and LILEs and depletion in HFSEs, and they were formed at the India–Asia collision stage. δ 18 O and δD values for the Leqingla and Xin'gaguo deposits are −8.8‰ to 5.3‰ and −140.4‰ to −90.1‰, −4.5‰ to 7.0‰ and −117.3‰ to −81.0‰, respectively, indicating magma fluids mixed with meteoric water in ore-forming fluids. δ 34 S values (−11.6‰ to −0.3‰) of ore sulfides from the Leqingla deposit show characteristics of biogenetic sulfur isotope compositions, suggesting sulfur for the Leqingla deposit were sourced from wall rocks of the Mengla and Luobadui Formation, which are rich in organic materials. δ 34 S values of ore sulfides from the Xin'gaguo deposits show bimodal distribution (−5.0‰ to −1.6‰ and 1.6–2.1‰), indicating sulfur in the Xin'gaguo deposit were derived from both wall rocks and magma. In the Leqingla deposit, most ore sulfides have the similar Pb isotopic compositions with that of the mineralization-related biotite granite, suggesting the biotite granite supplied most of the ore-forming metals. Pb isotopic compositions of ore sulfides and Hf isotopic compositions of biotite granite show that the majority of ore-forming metals are derived from mantle components of partial melting of the Neo-Tethys Ocean slab, with some upper crust materials of the Lhasa terrane. Pb isotopic compositions of ore sulfides from the Xin'gaguo deposit are similar to that of the Leqingla deposit, indicating they have the similar sources of ore-forming metals.

This Letter proposes a circularly polarised (CP) monopole antenna with filtering function, which is achieved by integrating a miniaturised coupled filter based on the bent-loop resonators. The circular-polarisation is obtained by using the falcate-shaped patch as the radiation part, and the existence of the coupled filter in the feeding line would not affect the CP radiation performances. Both numerical simulation and experimental demonstration are performed for the designed CP filtering antenna, and good agreements are obtained. The designed antenna with dimension of 70 × 75 mm2 exhibits good frequency selective performances for the return loss, gain and axial ratio at 2.45 GHz with measured impedance matching bandwidth (|S 11| < 10 dB) of 0.23 GHz. Such CP filtering antenna is a good candidate for the emerging application area, e.g. wearable biotelemetric devices.

In this paper, two co-designed linear and circular polarized compact filtering monopole antennas based on the recently developed miniaturized coupled filter, namely the two-stage split ring resonator (SRR)-inspired high-frequency-selective filter, are proposed and demonstrated. The used filter is consisting of two groups of twist-modified SRRS and is inserted in the feeding line of the conventional wide band planar monopole antennas to filter out the unwanted out-of-band antenna gain. The measured results show that such filtering antennas have sharp dropped out-of-band radiation gain feature. These filtering antennas is suitable for the Internet of Things devices application.

The Bangpu porphyry Mo–Cu deposit is a representative Mo-dominated deposit besides the Sharang porphyry Mo deposit in the Gangdese metallogenic belt. The Mo–Cu mineralization has a close relationship with the monzogranite porphyry and diorite porphyrite. We identify three stages during the ore formation: a pre-ore stage, a main-ore stage with Mo–Cu deposited dominantly, and a post-ore stage. In this study, He–Ar, H–O, S and Pb isotopic compositions of the Bangpu deposit were determined. Based on these determinations, integrated isotope geochemistry studies were performed to constrain the possible sources of the ore-forming fluids and metals. The 3He/4He and 40Ar/36Ar ratios of fluid inclusions exhibit a range of 0.12209–0.36370 Ra and 275.6–346.1, respectively. The 4He and 40Ar concentrations vary from 1.51 to 3.57 (10−7 cm3 STP g−1) and 0.49 to 9.31 (10−7 cm3 STP g−1), respectively. He–Ar isotopic compositions suggest dominantly crustal-derived fluid with minor amount of meteoric water in the main ore stage. The δ18Ofluid and δDfluid values vary from −1.3‰ to 3.9‰ and −140.5‰ to −73.7‰, respectively, indicating that magma fluids mixed with meteoric water. The average δ34S value of the sulfides (0.3‰) in the main-ore stage is close to the ore-forming porphyries, indicating a magmatic source. The lead isotopic components of ore sulfides exhibit restricted ranges with 206Pb/204Pb, 207Pb/204Pb, and 208Pb/204Pb ratios of 18.450–18.728, 15.602–5.672, and 38.715–39.211, respectively and μ values in the range of and 9.46–9.58, indicating ore-forming metals of primarily an upper crust source with a small amount of mantle materials. Compared to the Bangpu deposit, the ore metals derived from mantle are even greater in the Jiama and Qulong deposits, which leads to Cu being the dominant mineralization in the Jiama and Qulong deposit.

The Longmala and Mengya’a deposits are two representative skarn Pb–Zn deposits of the Nyainqentanglha Pb–Zn–(Cu–Mo–Ag) polymetallic belt in the Gangdese region, Tibet, China. Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) zircon U–Pb dating of the mineralization-related biotite monzogranite from the Longmala deposit yielded a weighted mean age of 55.7 Ma, which can be interpreted as the emplacement age of the pluton. Re–Os dating of three molybdenite samples from the Longmala deposit yielded model ages of 51.8–54.3 Ma, with a weighted mean age of 53.3 Ma, which is interpreted as the mineralization age of the deposit and overlaps the age of the causative intrusion. The Re–Os dating of four molybdenite samples from the Mengya’a deposit yielded model ages of 60.4–65.8 Ma, with a weighted mean age of 63.6 Ma, which represents the mineralization age of this deposit. Our new precise age data for these two deposits are consistent with the existing ages of ca. 65–51 Ma for other skarn pol...

Sedimentological and geochronological studies along a north–south traverse across the Bangong-Nujiang suture zone (BNSZ) in Gaize, Tibet provide evidence for a Late Triassic–Jurassic accretionary wedge accreted to the south margin of Qiangtang. This wedge, preserved as the Mugagangri Group (MG), records evidence for the northward subduction of the Bangong-Nujiang Ocean (BNO) beneath Qiangtang. The MG strata comprise two coarser intervals (lower olistostromes and upper conglomerates) intercalated within sandy turbidites, which are consistent with timing and forearc stratigraphy during subduction initiation predicted by geodynamic modelling. Following the model, the northward subduction of the BNO beneath Qiangtang and subsequent arc-magmatism are inferred to have begun, respectively, at ca. 220 Ma and ca. 210 Ma, with respect to depositional ages constrained by youngest detrital-zircon ages. The initiation of arc-magmatism is also supported by provenance transition reflected by sandstone detrital modes and age patterns of detrital zircons. Previously, evidence for an incipient arc was lacking, but the timing of Late Triassic BNO subduction and related arc-magmatism is coincident with an important Late Triassic magmatic event in central Qiangtang that probably represents the ‘missing’ arc. Other Qiangtang events, such as exhumation of the Qiangtang metamorphic belt as a source area, and development of the Late Triassic Nadigangri deposits and bimodal volcanism, are more easily explained in the tectonic context of early northward subduction of the BNO beneath Qiangtang, beginning at about 220 Ma.

To develop a safe and effective oral vaccine against Helicobacter pylori using its HpaA protein expressed in Lactococcus lactis.The gene encoding HpaA was obtained by PCR and ligated to pNZ8110-lysM following digestion with NaeI + SphI. The recombinant plasmid was transferred into E. coli for multiplication, and then into L. lactis. The recombinant L. lactis was induced to express HpaA, resulting in two products of 29 and 25 kDa, both of which yielded positive immunoreaction with mouse antisera against H. pylori, as confirmed by immunoblot assays. The 29 kDa product constituted 12% of the cell lysates. Oral inoculation with the engineered L. lactis evoked significantly elevated serum IgG level in mice (P 0.05).A novel engineered L. lactis strain was developed that efficiently produces whole HpaA protein with desired antigenicity and potent immunogenicity. It provides a basis for approaches to L. lactis-delivered anti-H. pylori vaccination.

Research on the Internet of Things (IoT) has been a hot spot in recent years. Resource authentication and management in IoT is a most important and challenging problem and is far to be solved. In this paper, we propose an effective distributed hierarchical IoT resource authentication and management model based on the key technologies of distributed hash table, Chord Ring and public key infrastructure. By using the exceptional advantage of search and Research on the Internet of Things (IoT) has been a hot spot in recent years. Resource authentication and management in IoT is a most important and challenging problem and is far to be solved. In this paper, we propose an effective distributed hierarchical IoT resource authentication and management model based on the key technologies of distributed hash table, Chord Ring and public key infrastructure. By using the exceptional advantage of search and query ability of the above technologies, the proposed model owns enhanced security and improved efficiency. Simulation results show that the proposed model can mutually authenticate the IoT end entities each other in more short time compared to other existing approaches. query ability of the above technologies, the proposed model owns enhanced security and improved efficiency. Simulation results show that the proposed model can mutually authenticate the IoT end entities each other in more short time compared to other existing approaches.

DNA methyltransferase (MTase) activity assay and its inhibitor screening are important for the diagnosis and treatment of methylation-related diseases. Herein, a label-free and highly sensitive biosensing method based on entropy-driven reaction and toehold-initiated rolling circle amplification (TIRCA) was developed for DNA MTase activity detection and inhibitor screening. Briefly, in the presence of MTase, the triple-stranded complex (TSC) could be methylated to avoid cleaving by MboI endonuclease. The complete TSC was able to initiate downstream entropy-driven reaction and TIRCA to produce G-quadruplex that can bind with Thioflavin T (ThT) to output fluorescent signal. Under the optimal experimental conditions, the established biosensing strategy could detect Dam MTase down to 0.06 U/mL with a linear range from 0.1 U/mL to 40 U/mL. Importantly, the signal-to-noise (S/N) of this biosensing strategy was extremely high. This strategy could discriminate target Dam MTase from another two MTases efficiently. Moreover, this developed biosensing method was applied to screen DNA MTase inhibitors. Therefore, we anticipate this unique strategy will serve as an alternative tool to detect DNA MTase activity and screen its inhibitors in clinical diagnosis and therapeutics.

This paper studies the asymptotical stability for a class of neural networks (NNs) with time-varying delay. Under weaker assumptions on the activation functions, by defining a more general type of Lyapunov functionals and using a delay decomposition method and employing a new convex combination technique, a new less conservative stability criterion are established to guarantee the global asymptotical stability of the discussed NNs. The obtained conditions are dependent on the upper bound of the delay, and are expressed in terms of linear matrix inequalities (LMIs). A numerical example is given to illustrate the effectiveness and the less conservatism of the proposed conditions.