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Strokes are one of the leading causes of death and disability in the world. Previously we have found that conventional protein kinase Cγ (cPKCγ) plays neuroprotective role in ischemic strokes. Further, we found that cPKCγ knockdown increased the level of cleaved (cl)-Caspase-3. However, the precise mechanisms underlying cPKCγ-mediated neuronal death remain unclear. To this end, a model incorporating 1 h oxygen-glucose deprivation/24 h reoxygenation (1 h OGD/24 h R) was established in cortical neurons. We found that cPKCγ knockdown remarkably increased neuronal death after OGD. We also found that cPKCγ knockdown increased the level of cl-Caspase-3 through the upstream initiators Capsases-9 (not Caspase-8/12) in OGD-treated neurons. Overexpression of cPKCγ could decrease neuronal death and cl-Caspase-3 and -9 levels. Moreover, cPKCγ knockdown further reduced the phosphorylation levels of p38 MAPK, p90RSK, and Bad. In addition, the protein levels of Bcl-2 and Bcl-xl were decreased after cPKCγ knockdown, whereas that of Bax was increased. In conclusion, our results suggest that cPKCγ partly alleviates ischemic injury through activating the p38 MAPK-p90RSK-Bad pathway and inhibiting Caspase-9 initiated apoptosis. This may have potential as a therapeutic target for ischemic stroke.

Chemical weathering driven by physical erosion is a natural process that strongly affects chemical and solid matter budgets at the Earth's surface. However, the influence of extreme climatic erosion on chemical weathering dynamics is poorly understood. Badland landscapes formed in highly erodible substrates have the potential to respond to individual events on scales that are rapid enough for direct observation. Here, we assess the geochemical and grain-size composition of suspended sediment and riverine chemistry measurements collected from two catchments during the 2017 Nesat and Haitang typhoons in southwestern (SW) Taiwan. During the typhoons, the Na+ concentration covaried with suspended sediment concentration (SSC), which we attributed to sodium-induced deflocculation. Evaporite weathering at peak rainfall is succeeded by peak silicate weathering at maximum discharge. Overall, our observations suggest that initial weathering of near-surface evaporite enhances the physical erosion of silicate rock during extreme rainfall events.

The biogeography research of orchids through species distribution models (SDMs), a vital tool in the biogeography field, is critical to understanding the fundamental geographic distribution patterns and identifying conservation priorities. The correspondence between species occurrence and environmental information is crucial to the model’s performance. However, ecological preferences unique to different orchid species, such as their life forms, are often overlooked during the modeling process. This oversight can introduce bias and increase model uncertainty. Additionally, human activities, as an important potential predictor, have not been quantified in any orchid SDMs. Taking the Hengduan Mountains as an example, we preprocessed all orchid species’ occurrences based on physiological characteristics. Choosing five spatial factors related to human activities to quantify the interference and enter into models as HI factor. Using different modeling methods (GLM, MaxEnt, and RF) and evaluation indices (AUC, TSS, and Kappa), diverse modeling strategies have been constructed in the study. A double-ranking method has been adopted to select the critical orchid distribution regions. The results showed that classification models based on physiological characteristics significantly improved the model’s accuracy while adding the HI factor had the same effect but the absence of enough significance. Suitability maps indicated that highly heterogeneous mountainous areas were vital for the distribution of orchids in the Hengduan Mountains. Different distribution patterns and critical regions existed between various orchid life forms geographically - terrestrial orchids were dominant in the mountain, and mycoherterophical orchids were primarily located in the north, more influenced by vegetation and temperature. Critical regions of epiphytic orchids were in the south due to a greater dependence on precipitation and temperature. These studies are informative for understanding the orchids’ geographic distribution patterns in the Hengduan Mountains, promoting conservation, and providing references for similar research beyond orchids.

detailed analyses of specific taxonomic groups at finer geographic scales to identify and prioritize biodiversity hotspots is a prominent method for optimizing conservation efforts, especially for the uneven species richness. The ecological suitability prediction and analysis of representative species provide vital references for conservation planning. Yet, in predicting suitability for multi-species or groups by species distribution models (SDMs) under a highly heterogeneous environment, species bias may occur cause of the unequal protection status and the spatial autocorrelation processing of occurrence data. For this, diversity, and protection hotspots were mapped in the south of the Hengduan Mountains, a significant site for global biodiversity. Specifically, creating a network of 1 km2 grid cells spanning the region, counting the orchid species, quantifying the protection value, and classifying attributes by the Jenks. And 5 km and 10 m buffer zone for each grid containing attributes compose the diversity and protection hotspot layers and were compared with the orchid suitability map modeled by SDMs. Results showed that even though there were extensively suitable habitats for orchids, the model results cannot completely cover whole the diversity and protection hotspots at any scale. Based on the map attributes, multi-scenario conservation planning was proposed. This study identifies the critical areas of suitability, diversity, and protection of orchids in this region, providing a meaningful reference for regional biodiversity conservation planning and producing a migrated method for biogeographic analysis in global biodiversity hotspots not just orchids. Besides, the results will supply crucial regional information for global biodiversity conservation.

To perform achieve fault-tolerant quantum computation, one can use flagged syndrome extraction with fewer ancilla qubits. However, it suffers from long circuit depth if one stabilizer is measured at a time. Previously, Reichardt showed that it is possible to measure multiple stabilizers with at most one shared flag qubit for certain small quantum codes. In this paper, we propose a procedure for general Calderbank-Shor-Steane codes of distance three so that multiple $Z$-stabilizers ($X$-stabilizers) can be fault-tolerantly measured in parallel with one shared flag qubit. We simulate the memory and computation pseudo-thresholds for various code schemes. In particular, our parallel scheme based on Shor's nine-qubit code performs better than known seven- and nine-qubit schemes in the literature.

Single-molecule detection and phasing of A-to-I RNA editing events remain an unresolved problem. Long-read and PCR-free nanopore native RNA sequencing offers a great opportunity for direct RNA editing detection. Here, we develop a neural network model, DeepEdit, that not only recognizes A-to-I editing events in single reads of Oxford Nanopore direct RNA sequencing, but also resolves the phasing of RNA editing events on transcripts. We illustrate the robustness of DeepEdit by applying it to Schizosaccharomyces pombe and Homo sapiens transcriptome data. We anticipate DeepEdit to be a powerful tool for the study of RNA editing from a new perspective.

Models developed using Nanopore direct RNA sequencing data from in vitro synthetic RNA with all adenosine replaced by N6-methyladenosine (m6A) are likely distorted due to superimposed signals from saturated m6A residues. Here, we develop a neural network, DENA, for m6A quantification using the sequencing data of in vivo transcripts from Arabidopsis. DENA identifies 90% of miCLIP-detected m6A sites in Arabidopsis and obtains modification rates in human consistent to those found by SCARLET, demonstrating its robustness across species. We sequence the transcriptome of two additional m6A-deficient Arabidopsis, mtb and fip37-4, using Nanopore and evaluate their single-nucleotide m6A profiles using DENA.

AIM: To explore the expression of cGAS/STING signaling components in Mooren’s ulcer (MU). METHODS: Samples were obtained from ten MU patients, and eight residual corneal-scleral rings of healthy donor corneas for controls. Human corneal epithelial cells (HCECs) were used to evaluate the effect of cGAS/STING signaling pathway. Immunohistochemistry (IHC) and Western blot were used to examine the expression of cGAS, STING, and phosphorylated interferon regulatory factor 3 (p-IRF3) in MU tissues. The expression of interferon-β (IFN-β) and interferon-stimulated genes (ISGs) was quantified by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). RESULTS: The protein levels of cGAS and STING in MU samples were significantly elevated when compared with the healthy controls by Western blot and IHC. After stimulation with cGAMP, real-time PCR and ELISA showed a dramatic increase of IFN-β and ISGs (containing CXCL10, IFIT1, and IL-6) in HCECs. Moreover, HCECs treated with cGAMP was characterized by increased phosphorylation and more nuclear translocation of IRF3. Meanwhile, increased p-IRF3 was observed in MU samples via IHC and Western blot. CONCLUSION: The pronounced expression of cGAS/STING signaling components in the patients with MU and probably contribute to the onset and development of MU.

We propose a highly tunable $$100\%$$ 100 % spin-polarized current generated in a spintronic device based on a Dirac semimetal (DSM) under a magnetic field, which can be achieved merely by controlling electrical parameters, i.e. the gate voltage, the chemical potential in the lead and the coupling strength between the leads and the DSM. These parameters are all related to the special properties of a semimetal. The spin polarized current generated by gate voltage is guaranteed by its semimetallic feature, because of which the density of state vanishes near Dirac nodes. The barrier controlled current results from the different distance of Weyl nodes generated by the Zeeman field. And the coupling strength controlled spin polarized current originates from the surface Fermi arcs. This DSM-based spintronic device is expected to be realized in $$\hbox {Cd}_{3}\hbox {As}_{2}$$ Cd 3 As 2 experimentally.

In essence, cultural and creative design features humanity and culture. The process of how to transform culture into creativity is an essential subject of design education, which, in turn, calls for a new design teaching system. In regard to combining traditional Chinese thinking with modern design experience, the question of how to apply traditional Chinese thinking to design concepts, methods, and education is systematically explored in this research. Firstly, the question of how to transform the philosophy of “Tao, Vessel, Change and Comprehensiveness” in the Book of Changes into “design thinking” in order to establish the learning process of creative design with added value—as well as to set up the teaching model of cultural and creative design under “Tao, Vessel, Change and Comprehensiveness”—is discussed. After this, two cases of the Aboriginal Harvest Festival’s cultural creativity “Dancing Together” candlestick and the animation, cultural, and creative design of the “Wind Lion God” are used in order to examine the effectiveness of the specific design and to verify the feasibility of this teaching model in the development and application of cultural and creative products. The results demonstrate the feasibility of this teaching model, which provides a new systematic approach for the purposes of teaching and practice in the field of cultural and creative design.

The nonlinear behaviour of fibre-reinforced polymer composites (FRPC) in transverse loading is mainly induced by the constituent polymer matrix. The thermoset and thermoplastic matrices are typically rate- and temperature-dependent, complicating the dynamic material characterization process. Under dynamic compression, the microstructure of the FRPC develops local strains and local strain rates whose values can be much higher than those applied at macroscopic level. The correlation between the local (microscopic) values and the measurable (macroscopic) ones still present challenges when applying the strain rate in the range 10−3–103 s−1. This paper presents an in-house uniaxial compression test setup to provide robust stress–strain measurements applying strain rates up to 100 s−1. A semi-crystalline thermoplastic polyetheretherketone (PEEK) and a toughened thermoset epoxy PR520 are assessed and characterized. The thermomechanical response of the polymers is further modelled using an advanced glassy polymer model, naturally capturing the isothermal to adiabatic transition. A micromechanical model of a unidirectional composite undergoing dynamic compression is developed by using both validated polymers as matrices reinforced by carbon fibres (CF) using Representative Volume Element (RVE) models. These RVEs are used to analyse the correlation between the micro- and macroscopic thermomechanical response of the CF/PR520 and CF/PEEK systems investigated at intermediate to high strain rates. Both systems experience an excessive strain localization with local plastic strain about 19% when a macroscopic strain of 3.5% is applied. The comparison of using a thermoplastic and a thermoset as a matrix in composites is discussed with regard to the rate-dependence, the interface debonding and the self-heating effect.

Chemical weathering driven by physical erosion is one of the manifestations of natural processes that strongly affect chemical and solid matter budgets at the Earth’s surface. However, the influence of extreme climatic erosion on chemical weathering dynamics is poorly understood. Badland landscapes formed in highly erodible, homogeneous substrates have the potential to respond to individual events on scales that are rapid enough for direct observation. Here, we assess the geochemical and grain-size composition of suspended sediment and riverine chemistry measurements collected from two catchments during the 2017 Nesat and Haitang typhoons in southwestern Taiwan. During the typhoons, the sodium adsorption ratio covaried with suspended sediment concentration, which we attributed to sodium-induced deflocculation. Evaporite weathering at peak rainfall is succeeded by peak silicate weather at maximum discharge, which dominates the weathering signal of the event. Overall, our observations suggest that initial weathering of near-surface evaporite enhances the physical erosion of silicate rock during extreme rainfall events.

Objectives Cognitive impairment is an important non-motor aspect of Parkinson's disease (PD). Amyloid-β and tau pathologies are well-established in Alzheimer's disease and commonly coexist with synucleinopathy in PD. However, the levels of these biomarkers in the plasma of patients with PD and their relationship with specific cognition domains remain to be clarified. The current study compared the motor severity and neuropsychological assessment of general and specific cognition, with plasma levels of α-synuclein (α-syn), amyloid-β 42 (Aβ42), and total tau (t-tau) in PD subjects. Methods Plasma levels of α-syn, Aβ42, and t-tau were measured in 55 participants with PD through immunomagnetic reduction assay. The evaluation of motor severity and comprehensive neuropsychological assessment was performed in all participants. Results The level of plasma α-syn was negatively correlated with the scores of Unified Parkinson's Disease Rating Scale part III [r = (-.352), p = .008]. The level of plasma t-tau was negatively correlated with the scores of digits recall forwards and digits recall backwards [r = (-.446), p = .001; r = (-.417), p = .002, respectively]. No correlations were found between the levels of α-syn and Aβ42 and any neuropsychological tests. Conclusions This study concluded a lower level of plasma α-syn was correlated with motor dysfunction in PD patients, and a higher level of plasma t-tau was correlated with lower cognitive performance, especially for attention and executive function. These results propose the possibility of using plasma biomarkers to predict specific cognitive performance in PD subjects.

Due to the development of the Internet of Things (IoT), physically unclonable function (PUF) has also been developed. In this study, aluminum nitride (AlN)-based complementary resistive switches (CRSs) with three different orientations were fabricated. We observed that the resistance values of the (100)-orientation and (002)-orientation AlN-based devices in the high resistance state (HRS) were very messy. This feature is quite appropriate for PUF, because PUF must be unique and unpredictable. In addition, we also verified the prerequisite ( $\vert {V}_{\text {reset}}\vert > \vert {V}_{\text {set}}\vert $ /2) for fabricating CRS using bipolar resistive switches (BRSs) through experiments. This prerequisite can be used to predict the suitability of CRS devices for manufacturing. We believe this work could help in determining the preferable AlN orientation for PUF applications.

BackgroundMotoric cognitive risk (MCR) syndrome is a conceptual construct that combines slow gait speed with subjective cognitive complaints and has been shown to be associated with an increased risk of developing dementia. However, the relationships between the pathology of Alzheimer’s disease (AD) and MCR syndrome remain uncertain. Therefore, the purpose of this study was to determine the levels of plasma AD biomarkers (Aβ42 and total tau) and their relationships with cognition in individuals with MCR.Materials and methodsThis was a cross-sectional pilot study that enrolled 25 individuals with normal cognition (NC), 27 with MCR, and 16 with AD. Plasma Aβ42 and total tau (t-tau) levels were measured using immunomagnetic reduction (IMR) assays. A comprehensive neuropsychological assessment was also performed.ResultsThe levels of plasma t-tau proteins did not differ significantly between the MCR and AD groups, but that of plasma t-tau was significantly increased in the MCR and AD groups, compared to the NC group. Visuospatial performance was significantly lower in the MCR group than in the NC group. The levels of plasma t-tau correlated significantly with the Montreal Cognitive Assessment (MoCA) and Boston naming test scores in the MCR group.ConclusionIn this pilot study, we found significantly increased plasma t-tau proteins in the MCR and AD groups, compared with the NC group. The plasma t-tau levels were also significantly correlated with the cognitive function of older adults with MCR. These results implied that MCR and AD may share similar pathology. However, these findings need further confirmation in longitudinal studies.

This study aims to explore the mechanism of Tianhe Zhuifeng Ointment in treating rheumatoid arthritis(RA) with syndrome of internal obstruction and cold-dampness and the compatibility characteristics based on thequot;disease-syndrome-formulaquot; association network. A gene set associated with the clinical symptoms of RA was collected from Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine v2.0(TCMIP v2.0). The different expression gene set of RA with syndrome of internal obstruction and cold-dampness was screened out by transcriptomic expression profile detection and bioinformatics data mining of the comparison of RA patients with syndrome of internal obstruction and cold-dampness and healthy volunteers. The chemical composition information of 35 Chinese medicines from Tianhe Zhuifeng Ointment was collected from TCMIP v2.0 and Traditional Chinese Medicine Bank(TCMBank). The candidate targets were predicted based on the similarity principle of compounds structure. The interactive network ofquot;related gene of RA with syndrome of internal obstruction and cold-dampness-candidate target of Tianhe Zhuifeng Ointmentquot; was constructed. The core network targets were screened out by topological characteristics of calculating network, and the functional exploration was carried out based on Kyoto Encyclopedia of Genes and Genomes(KEGG) and Reactome Pathway Database. The compatibility mechanisms of various efficacy groups of Tianhe Zhuifeng Ointment were further explored. The results showed that the candidate targets of Tianhe Zhuifeng Ointment were mainly involved into the modules ofquot;immune-inflammationquot; regulation, nervous system function, cell function, and substance and energy metabolism, etc. The mechanisms of various efficacy groups emphasized on different aspects. The group of dispelling wind and removing dampness-dredging channels and activating collaterals, the group of extinguishing wind and stopping convulsions, and the group of pungent analgesia regulatedquot;immune-inflammationquot; system by warming meridians and dissipating cold. The group of activating blood and resolving stasis and the group of strengthening sinews and bones regulatedquot;immune-inflammationquot; system by activating blood and dredging channels. The group of dispelling wind and removing dampness-dredging channels and activating collaterals, the group of extinguishing wind and stopping convulsions, the group of activating blood and resolving stasis, the group of strengthening sinews and bones, and the group of clearing heat and draining water affected the nervous system by invigorating Qi-blood and benefiting spirit. The group of dispelling wind and removing dampness-dredging channels and activating collaterals and the group of extinguishing wind and stopping convulsions regulated cell function and substance and energy metabolism by dispelling wind and eliminating cold-dampness. The group of activating blood and resolving stasis and the group of strengthening sinews and bones regulated the cell function and substance and energy metabolism by activating blood and strengthening sinews and bones. The results showed that Tianhe Zhuifeng Ointment exerted the comprehensive efficacy of dispelling wind, removing dampness, activating blood, removing stasis, warming meridians, dredging channels, and strengthening sinews and bones through adjusting the imbalance ofquot;immune-inflammationquot;, regulating nervous system, cell function, and interfering with substance and energy metabolism, thus improving the syndrome of internal obstruction and cold-dampness. The findings of this study laid foundations for clarifying the therapeutic characteristics and clinical orientation of Tianhe Zhuifeng Ointment.

This study developed a predictive model for cognitive degeneration in patients with Parkinson’s disease (PD) using a machine learning method. The clinical data, plasma biomarkers, and neuropsychological test results of patients with PD were collected and utilized as model predictors. Machine learning methods comprising support vector machines (SVMs) and principal component analysis (PCA) were applied to obtain a cognitive classification model. Using 32 comprehensive predictive parameters, the PCA-SVM classifier reached 92.3% accuracy and 0.929 area under the receiver operating characteristic curve (AUC). Furthermore, the accuracy could be increased to 100% and the AUC to 1.0 in a PCA-SVM model using only 13 carefully chosen features.

A new orchid species, Hemipilia avisoides, is described from Songpan County, Sichuan Province, China. Morphologically, it is most similar to H. occidensichuanensis (≡ Ponerorchis limprichtii), but H. avisoides can be easily distinguished by its pendulous lateral lip lobes, the oblong middle lip lobe that is smaller than lateral lobes, the dorsal sepal that is concave at each side of central vein below middle, floral bracts that are always shorter than ovary, the leaf that is appressed to substrate and is adaxially green with white and parallel veins, and the solitary sheath at the base of stem. Floral morphology of H. avisoides is also presented by utilizing in vivo micro-CT scanning and 3D visualization.

Both bench and bedside investigations have challenged the supportive role of Hedgehog (Hh) activity in the progression of colorectal cancers, thus raising a critical need to further deeply determine the contribution of Hh to the growth of colorectal cancer. Combining multiple complementary means, including in vitro and in vivo inflammatory colorectal cancer models, and pathological analysis of clinical colorectal cancer patients samples. We report that colorectal cancer cells hijack prostaglandin E2 (PGE2) to non-canonically promote Hh transcriptional factor Gli activity and Gli-dependent proliferation of colorectal cancer cells in a Smo-independent manner. Mechanistically, PGE2 activates c-Jun N-terminal kinase (JNK), which in turn enables Gli2 to evade ubiquitin-proteasomal degradation by phosphorylating Gli2 at Thr1546. This study not only presents evidence for understanding the contribution of Hh to colorectal cancers, but also provides a novel molecular portrait underlying how PGE2-activated JNK fine-tunes the evasion of Gli2 from ubiquitin-proteasomal degradation. Therefore, it proposes a rationale for the future evaluation of chemopreventive and selective therapeutic strategies for colorectal cancers by targeting PGE2-JNK-Gli signaling route.

Objective Knee osteoarthritis (KOA) is prevalent in middle-aged and elderly people. This condition negatively affects the quality of life of patients. Although non-steroidal anti-inflammatory drugs (NSAIDs) are often used to relieve symptoms associated with KOA, it is associated with many side effects. Acupuncture and moxibustion therapies have been applied in the treatment of KOA. However, the efficacy of various acupuncture and moxibustion treatments has not been compared. Methods Randomized controlled trials (RCTs) on the application of acupuncture and moxibustion in the treatment of KOA were searched in English databases and Chinese databases. Data were retrieved from establishment of the database to September 2020. Data analysis was performed using Stata14.0 and GeMTC 0.14.3 softwares. Results A total of 40 RCTs involving 3215 patients with KOA were retrieved. Network meta-analysis revealed that the fire needle was superior to western medicine, electro-acupuncture, conventional acupuncture, warm needle and sham acupuncture; warm needle was better than conventional acupuncture and western medicine whereas electro-acupuncture was better than conventional acupuncture in improving pain scores in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Moreover, we found that fire needle and warm needle more effectively improved WOMAC stiffness scores than western medicine and sham moxibustion, whereas electro-acupuncture was superior to western medicine and sham moxibustion in improving WOMAC stiffness scores. Further analysis revealed that fire needle, warm needle and electro-acupuncture were more effective in improving WOMAC joint function scores than conventional acupuncture and western medicine. The fire needle was superior to conventional acupuncture and sham acupuncture, whereas electro-acupuncture was better than western medicine, conventional acupuncture and sham acupuncture in improving visual analogue scale scores. Conclusion This study shows that fire needle is superior to warm needle and electro-acupuncture, whereas warm needle and electro-acupuncture are better than conventional acupuncture, western medicine, sham moxibustion and sham acupuncture.

The coupling between chemical weathering (including silicate, carbonate and pyrite weathering) and physical erosion is of high interest in active mountain belts. Participation of pyrite weathering which, results in CO2 emission to the atmosphere, also is of great research attention. Nevertheless, the responses of the (de-)couplings to landslide and typhoon are unclear. We used records of riverine TDS (total dissolved solids) and TSS (total suspended solids) with high-frequency sampling during typhoons to estimate chemical denudation rates of silicate (CDRsil), carbonate (CDRcarb), pyrite (CDRpyrite) and physical denudation rates (PDR) in two adjacent catchments, eastern Taiwan. Results show that the CDRsil in the two catchments is approx. 10-fold higher than the global mean, whereas the CDRcarb, CDRpyrite and PDR are over 15-fold higher than the global averages. Landslides likely elevate carbonate and sulfate dissolution, and streamflow is a kinetic control on the CDRs. Among CDRs, CDRsil remains constant with various landslides and typhoons. Yet, CDRcarb and CDRpyrite rapidly respond to typhoons and then contribute more CO2 emission. In sum, landslides expose fresh minerals to enhance chemical weathering; typhoons, which transport the dissolved solids within a short time and prompt new rainwater for weathering, are also dominant agents. We demonstrate the importance of dynamic partitioning of sulfuric and carbonic acid on silicate weathering for quantitative estimation of weathering-associated CO2 budget in active mountain belts.

APOBEC3A (A3A) is a cytidine deaminase involved in innate immune response and is able to catalyze deamination on both DNA and RNA substrates. It was used in creating the CRISPR-mediated base editor, but has since been held back due to its dual activities. On the other hand, it has been a challenge to separate A3A's dual activities in order to enable it for single-base RNA editors. Here we developed the reporter system for C-to-U RNA editing and employed rational design for mutagenesis to differentiate deaminase activities on RNA and DNA substrates to obtain an RNA-specific editase. Generation and examination of 23 previous A3A mutants showed their deamination activity on RNA was mostly abolished when their activity on DNA was impaired, with the exception of mutant N57Q that displayed an inverse change. We designed new mutations on Loops 1 and 7 based on A3A's crystal structure and found mutants H29R and Y132G had differential effects on catalytic activity on RNA and DNA substrates. In order to engineer an A3A with RNA-specific deaminase activity, we combined Y132G with mutations in Loop 1 or helix 6 by rational design. Two multipoint mutants, Y132G/K30R and Y132G/G188A/R189A/L190A, were successful in retaining high deaminase activity on RNA substrate while eliminating deaminase activity on DNA. We, for the first time, created novel human A3A variants with RNA-specific cytidine deaminase activity, providing insight into A3A's mechanism on substrate recognition and a new addition of a toolset to the creation of a RNA-specific C-to-U base editor.

To explore the autoimmune response and outcome in the central nervous system (CNS) at the onset of viral infection and correlation between autoantibodies and viruses.MethodsA retrospective observational study was conducted in 121 patients (2016–2021) with a CNS viral infection confirmed via cerebrospinal fluid (CSF) next-generation sequencing (cohort A). Their clinical information was analysed and CSF samples were screened for autoantibodies against monkey cerebellum by tissue-based assay. In situ hybridisation was used to detect Epstein-Barr virus (EBV) in brain tissue of 8 patients with glial fibrillar acidic protein (GFAP)-IgG and nasopharyngeal carcinoma tissue of 2 patients with GFAP-IgG as control (cohort B).ResultsAmong cohort A (male:female=79:42; median age: 42 (14–78) years old), 61 (50.4%) participants had detectable autoantibodies in CSF. Compared with other viruses, EBV increased the odds of having GFAP-IgG (OR 18.22, 95% CI 6.54 to 50.77, pp=0.003), more meningitis (26/61 (42.6%) vs 12/60 (20.0%), p=0.007) and higher follow-up modified Rankin Scale scores (1 (0–6) vs 0 (0–3), p=0.037) compared with antibody-negative patients. A Kaplan-Meier analysis revealed that autoantibody-positive patients experienced significantly worse outcomes (p=0.031).ConclusionsAutoimmune responses are found at the onset of viral encephalitis. EBV in the CNS increases the risk for autoimmunity to GFAP.

Background Single-cell RNA sequencing (scRNA-seq) is the most widely used technique to obtain gene expression profiles from complex tissues. Cell subsets and developmental states are often identified via differential gene expression patterns. Most of the single-cell tools utilized highly variable genes to annotate cell subsets and states. However, we have discovered that a group of genes, which sensitively respond to environmental stimuli with high coefficients of variation (CV), might impose overwhelming influences on the cell type annotation. Result In this research, we developed a method, based on the CV-rank and Shannon entropy, to identify these noise genes, and termed them as “sensitive genes”. To validate the reliability of our methods, we applied our tools in 11 single-cell data sets from different human tissues. The results showed that most of the sensitive genes were enriched pathways related to cellular stress response. Furthermore, we noticed that the unsupervised result was closer to the ground-truth cell labels, after removing the sensitive genes detected by our tools. Conclusion Our study revealed the prevalence of stochastic gene expression patterns in most types of cells, compared the differences among cell marker genes, housekeeping genes (HK genes), and sensitive genes, demonstrated the similarities of functions of sensitive genes in various scRNA-seq data sets, and improved the results of unsupervised clustering towards the ground-truth labels. We hope our method would provide new insights into the reduction of data noise in scRNA-seq data analysis and contribute to the development of better scRNA-seq unsupervised clustering algorithms in the future.

In this work, porous La1−xBaxFeO3 (x = 0.01, 0.02, 0.03, 0.04 and 0.05) microspheres of the orthorhombic perovskite phase were prepared by an environment-friendly one-step hydrothermal method with a series of characterization of the six sensing nanomaterials. Characterization results show that their grain size is between 21.2 and 23.2 nm, and the grain growth is inhibited with the increase in Ba-doping concentration. The samples are all spherical with a diameter of about 10 μm, and the surface is very rough. By the gas sensing study of the samples, the results show that the La1−xBaxFeO3 sensor exhibits a fairly high response to the ethanol gas. In particular, the La1−xBaxFeO3 microspheres with a Ba-doping concentration of 2 mol% showed not only a significant improvement in sensitivity but also a rather rapid response recovery time compared to the undoped samples, demonstrating the superiority as an ethanol sensing nanomaterial. More importantly, the optimum operating temperature of La0.98Ba0.02FeO3 is only 200 °C, while that of the pure LaFeO3 is 260 °C. The Ba-doped porous microspheres prepared are a high-performance sensing material capable of rapid and accurate detection of ethanol.

Mild cognitive impairment (MCI) is considered an intermediate state between normal aging and early dementia. Fear of falling (FOF) could be considered a risk indicator for falls and quality of life in individuals with MCI. Our objective was to explore factors associated with FOF in those with MCI due to Alzheimer’s disease (AD-MCI) and mild cognitive impairment in Parkinson’s disease (PD-MCI). Seventy-one participants were separated into two groups, AD-MCI (n = 37) and PD-MCI (n = 34), based on the disease diagnosis. FOF was assessed using the Activities-specific Balance Confidence scale. The neuropsychological assessment and gait assessment were also measured. FOF was significantly correlated with global cognitive function, attention and working memory, executive function, Tinetti assessment scale scores, gait speed, and stride length in the AD-MCI group. Moreover, attention and working memory were the most important factors contributing to FOF. In the PD-MCI group, FOF was significantly correlated with gait speed, and time up and go subtask performance. Furthermore, turn-to-walk was the most important factor contributing to FOF. We noted that FOF in different types of MCI was determined by different factors. Therapies that aim to lower FOF in AD-MCI and PD-MCI populations may address attention and working memory and turn-to-walk, respectively.

As an essential form of material migration on the surface of the earth, soil erosion is one of the primary causes of soil fertility reduction and environmental degradation. Quantifying soil erosion rate is the precondition and foundation for regional soil erosion control. The Pu isotopes produced by atmospheric nuclear tests have a long half-life after settling into the soil and could be easily adsorbed by clay minerals and organic matter. In recent years, Pu isotopes have become principal trace elements in the quantitative studies of soil erosion rate, especially with the development of mass spectrometry technique. The measurement time of Pu isotopes has been shortened, and the sensitivity of Pu isotopes has been improved, both of which help improve the radionuclide tracing technology for soil erosion. Here, we summarized the distribution characteristics as well as the adsorption and migration behavior of Pu isotopes in soil. We described the basic principles for the application of Pu isotopes in tracing soil erosion, and elaborated the research progress concerning relevant applications. Moreover, we compared the applicability of Pu isotope and土壤侵蚀是地球表面物质迁移的重要形式,也是造成土壤肥力下降和生态环境退化的重要诱因之一,对土壤侵蚀速率的定量研究是进行区域土壤侵蚀治理的前提和基础。大气核试验产生的Pu同位素具有较长的半衰期,其沉降到土壤中易被土壤中的黏土矿物和有机质吸附,近年来被认为是定量研究土壤侵蚀速率的重要示踪元素,尤其是质谱技术的发展,缩短了Pu同位素的测量时间并提高了其测量灵敏度,大力推动了土壤侵蚀核素示踪技术的发展。本文在梳理已有相关研究的基础上,总结土壤中Pu同位素的分布特征及吸附与迁移行为,阐述了应用Pu同位素示踪土壤侵蚀的基本原理和应用研究进展,并对Pu同位素和

Materials with interactions between the topology and magnetism are triggering increasing interest. We constructed a two-dimensional (2D) van der Waals heterostructure germanene/Mn

By taking advantage of benzylidene succinimides as a new class of 3C synthons, a highly diastereo- and enantioselective tandem Mannich reaction/transamidation has been established by reacting them with cyclic trifluoromethyl N-acyl ketimines. Using a Cinchona alkaloid-derived squaramide as the catalyst, the tandem reaction proceeded smoothly under mild conditions and afforded a range of F3C-containing chiral polycyclic dihydroquinazolinones with excellent results (up to 99% yield, all cases >20 : 1 dr, up to 99% ee).

Background Motoric cognitive risk syndrome (MCR) is defined by slow gait speed combined with subjective cognitive complaint. MCR is a predementia syndrome, similar to mild cognitive impairment (MCI). However, there is currently no study comparing the differences in cognitive performance and physical function between these two types of cognitive impairment. Thus, the aim of this study is to compare cognitive performance and physical function in individuals with MCR versus MCI. Methods A total of 77 participants, free of dementia, were recruited from the neurological outpatient clinic of a medical center in Taiwan. Participants were separated into 2 groups, MCR (n = 33) and MCI (n = 44) groups, based on definition criteria from previous studies. The priority was to assign a diagnosis of MCR first, followed by MCI. Hence, “pure” MCI had no overlap with MCR syndrome. Cognitive performance, including executive function, attention, working memory, episode memory, visuospatial function, and language, were measured. Physical functions such as activities in daily living, the Tinetti Assessment Scale, and the Timed Up and Go test were also measured. Results Executive function, attention, working memory, episodic memory and language were all significantly lower in the MCR group than the MCI group. Abilities related to physical function, including those measured by the Tinetti Assessment Scale and the Timed Up and Go test, were significantly lower in the MCR group than the MCI group. Conclusions We noted that cognitive performance and physical function were lower in MCR individuals than MCI but without MCR syndrome. However, the conclusions were based on the enrollment procedure of participants prioritizes the MCR syndrome. Because of the overlap of MCR and MCI, future studies should use different enrollment strategies to further clarify the status of these two populations.

Objective To summarize the characteristics of non ⁃ motor symptoms of Meige's syndrome（MS）, including depression and sleep disorders, and to explore the effect of deep brain stimulation (DBS) on these non⁃motor symptoms. Methods Twelve patients with MS treated with DBS were recruited from February to May 2019 in Department of Neurosurgery in Peking University People's Hospital. The Self ⁃ Rating Depression Scale (SDS) and Pittsburgh Sleep Quality Index (PQSI) were used to assess the depression and sleep disorders before surgery and 3, 6 and 12 months after surgery. Results Before surgery, 9 (9/12) patients had different degrees of depression and sleep disorders. At 3 months after surgery, 8 (8/12) patients had different degrees of depression and 9 (9/12) had different degrees of sleep disorders. At 6 months after surgery, 8 (8/12) patients had different degrees of depression and 9 (9/12) had different degrees of sleep disorders. At 12 months after surgery, 6 (6/12) patients had different degrees of depression and 10 (10/12) had different degrees of sleep disorders. There was no significant difference in the proportion of depression (χ2 = 3.102, P = 0.376) and sleep disorders (χ2 = 2.598, P = 0.458) before and after DBS. Conclusions Depression and sleep disorders are common in patients with MS, and there is no significant improvement after DBS. DOI：10.3969/j.issn.1672⁃6731.2020.12.008