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Nowadays, more and more people think education should focus on how students learn rather than how teachers teach. This kind of “student-oriented” education brings about some studies about students’ learning styles. Learning styles play an important role in language learning. This paper reviews some different definitions of learning styles, some factors that are related to learning styles, and several studies about some learning outcomes and academic performances resulting from different learning styles. By analyzing the results from different learning styles, the researcher tries to find out the relationship between learning styles and language learning, which is aimed at helping students learn a foreign language easier and better as well as giving teachers some implications about how to teach students with different learning styles. In this research, the researcher focuses on perceptual learning styles which contain visual, auditory, and tactile learning styles, finding that they all have some effects on language proficiency and influence language learners’ academic performances in different ways. This paper contributes to present some earlier research on learning styles and the acquisition of foreign languages and examine how the two relate.

In this article, a dichromatic plasmonic ELISA CD81 protein sensor is designed for ultrasensitive detection of preeclampsia (PE), which seriously affects pregnant women and fetuses' health, and causes maternal near-misses.

Liver fibrosis is caused by continuous wound healing responses to various harmful stimuli, including viral infection, drugs, alcohol, and autoimmune liver disease. The purpose of this study was to examine the effects of extracts of Periplaneta americana (EPA) in rats with pig serum-induced liver fibrosis to preliminarily assess the antifibrotic effect of EPA.Seventy rats were randomly divided into 7 groups (10 rats in each group): HC, the healthy control group; FC, the fibrotic control group; TL, low-dose EPA treatment group group; TM, medium-dose EPA group; TH, high-dose EPA treatment group; TC1, Panax notoginseng/Salvia mitiorrhiza treatment control group 1; TC2, colchicine treatment control group 2. TC1 and TC2 were used as the positive control to demonstrate the difference between EPA and the effects of other compounds. The liver fibrosis model was induced by intraperitoneal injection of 0.5 mL pig serum twice a week for 13 weeks in all groups except for the HC group. The hepatic fibrosis model was established at the 7th week, and followingly, the corresponding compounds were administered once a day in all groups for 6 weeks. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity was determined in rat blood serum. We also measured liver fibrosis-related serum markers, including hyaluronic acid (HA), mucin layer (LN), type III pre-collagen (PC-III) and type IV collagen (IV-C). Hematoxylin and eosin (HE) and Masson stainings were used to assess liver morphology and determine the stage of fibrosis. Immunohistochemistry was used to detect the protein expression of NF-κB, α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in rat liver tissue.Compared with that of the HC group, the liver tissue of the FC group presented obvious liver damage and collagen deposition. The serum levels of ALT, AST, HA, LN, PC-III and IV-C and the expression of NF-κB, α-SMA, TGF-β1 and TIMP-1 in the FC group were significantly higher than those in the HC group, the EPA treatment groups, the TC1 group and the TC2 group (P0.01). The levels of serum ALT, AST, HA, LN, PC-III and IV-C and the expression of α-SMA, NF-κB, TGF-β1 and TIMP-1 in the TL, TC1 and TC2 groups were significantly higher than those TM and TH groups (P0.05). EPA treatment significantly improved liver function, decreased collagen deposition and reversed the pathological changes related to liver fibrosis.We found that EPA could reduce liver inflammation, suppress liver cell degeneration and necrosis, and reduce the formation of liver fibrous tissue. Its mechanism might be associated with inhibiting the expression of TGF-β1, TIMP-1, NF-κB and α-SMA to block signal transduction pathways in the hepatic fibrosis process. Therefore, EPA, as a traditional Chinese medicine, might be potentially used to prevent and treat hepatic fibrosis in the future. However, further more experiments are necessary to verify its effectiveness and possible signaling pathways.

Background: Although abnormal functional activities or connectivities in individuals with autism spectrum disorders (ASD) have been reported, yet, there is still lack of consistent findings of altered functional activities or connectivities and its associated genetic basis for ASD. Methods: Here, we aimed to identify consistent brain functional alterations and the biological genetic mechanisms in children and adults with ASD using a large sample of resting-state functional magnetic resonance imaging data from the Autism Brain Image Data Exchange dataset (ABIDE). Multi-site based meta-analyses were first employed and identified abnormal brain activity, local and global functional connectivities primarily localizing in frontal-temporal-occipital regions and default mode network (DMN) in individuals with ASD. Results: The significant correlations between the aberrant brain regions and clinical phenotypes related to social functions in ASD were found. Importantly, brain-wide transcriptome-neuroimaging spatial association analyses and the follow-up enrichment, tissue-specific expression, and protein-protein interaction analyses were conducted and identified the underlying cellular and molecular mechanisms of ASD. Conclusions: Collectively, our findings link molecular and functional changes in ASD and provide new evidence for neuropathology and a potential precious treatment target for ASD.

Background: Hospitals are an essential part of the health care system. The purpose of this study is to evaluate the equity and service efficiency of health resource allocation in the hospital service system of 31 provinces (municipalities directly under the central government and autonomous regions) in mainland China from 2017 to 2021, and to analyze the influencing factors of hospital service efficiency to provide a reference for rational allocation of hospital health resources and improvement of hospital service efficiency. Methods: Equity of allocation of hospital health resources in mainland China was evaluated in three dimensions using the Gini coefficient and Lorenz curve. Hospital service efficiency was calculated by output-oriented super efficiency slack-based model-data envelopment analysis (SE-SBM-DEA) model and DEA-based Malmquist total factor productivity index (MTFP), and the influencing factors of hospital service efficiency were analyzed by panel data regression. Results: The number of hospitals in mainland China grew from 31056 to 36570 between 2017 and 21st. The equity ranking of the dimensions of hospital health resource allocation was Demographic > Economic > Geographic. However, the curvature of the demographic and economic dimensions is smaller compared to the curvature of the Lorenz curve for the geographic dimension. The demographic dimension has the lowest average Gini coefficient (0.167), followed by the economic (0.295) and the geographical (0.616). The 2017-2021 MTFP results show that none of the DMU efficiency values exceed 1. SE-SBM-DEA results show 15 DMUs in 2021 with total factor productivity above 1. The five-year average efficiency values ranked West (0.851) > East (0.834) > Central (0.673); Five influential factors identified by panel data regression analysis, Among them, X1(The proportion of urban population), X3(The percentage of illiterate population to total aged 15 and over) and X10(The proportion of the volume of medical service in primary medical facilities) have a positive relationship with hospital service efficiency, and X5(The level of per capital outpatient and emergency treatment expenditure) and X8(The proportion of hospital personnel) have a negative relationship with hospital service efficiency. Conclusion: After five years of development, the hospital service system in mainland China has grown significantly in number and size, but there are still differences in the allocation of hospital health resources between the East and the West, and intra-regional differences remain large. The overall level of efficiency in hospital services over the last five years was poor, with the West overtaking the East as the region with the highest five-year average. The regression model verified the effect of some factors on hospital service efficiency, and the effect of disadvantaged groups on hospital service efficiency was not significant (P>0.05).

Background General practitioners (GP) are the gatekeepers of residents' health, and 2021 is the 10th year of the establishment of the GP system in China. This study aims to assess the equity and trends of GP allocation in China from 2012–2021, summarize the efforts and progress of GPs in China during the decade, and predict the development trend of GPs in mainland China in the next five years to provide a reference for regional health planning and rational allocation of GPs in China. Methods Data from 2012 to 2021 on GPs in 22 provinces, 5 autonomous regions, and 4 municipalities directly under the central government in mainland China (excluding Hong Kong, Macao, and Taiwan) are collected by us. Gini coefficient, Lorenz curve and health resource agglomeration degree (HRAD) were used to analyze the equity of the allocation of GPs in China from different dimensions, and a Grey forecasting model was used to forecast the number of GPs in 2022–2026. Results The number of GPs in mainland China increased from 109,794 to 434,868 from 2012–2021, with 3.08 GPs per 10,000 people. The Gini coefficient of GPs allocation by population in China decreased from 0.312 to 0.147 from 2012–2021, while the Gini coefficient of geographic dimension remained between 0.7 ~ 0.75. Compared with the degree of curvature of the Lorentz curve in the geographic dimension, the degree of curvature of the population and economic dimension were smaller. In 2021, the HRAD in the Eastern region was 4.618, and the Central region was 1.493, with different degrees of imbalance among regions, and the HRAD/PAD in the Eastern, Central and Western regions were 1.196, 0.880 and 0.821, respectively. GPs in the Eastern region is still concentrated, while the Central and Western regions were at a similar level, and GPs were more scarce. The Grey forecasting model predicts that the number of GPs in mainland China will reach about 720,000 in 2026, and the number of GPs per 10,000 people will reach 4.9. Conclusion After a decade of development, the number of GPs in China has increased significantly. It has reached the goal of the GP system when it was first established. However, the equity of the geographical dimension, both in terms of Gini coefficient and HRAD, has great differences between different regions, and at a low level. The Western region has the problem of insufficient GP allocation in both population and geographical dimension. In the future, the number of GPs in China will continue to grow rapidly with the support of policies. The "2030" goal, proposed in 2018, is expected to be achieved by 2026. But due to certain factors (such as COVID-19), the actual situation may be different from the predicted results.

As one of the fundamental characteristics of blockchain networks, consensus mechanism has attracted tremendous interests from both the academics and industries. Recently, more attention has been paid to the consensus mechanism with fair multi-miners participation. However, most of them are fixed-miners based and one-by-one block creation, and thus offering opportunities for attackers to launch DoS attack against the fixed miners or manipulate the blocks creation by bribing the fixed miners. Additionally, one-by-one block creation may result in vast transactions waiting to be confirmed, especially in a large scale of blockchain network. In this paper, we propose a novel consensus mechanism called proof-of-negotiation (PoN). With negotiation rules, trust management is introduced to evaluate the trustworthiness of miners, and thus achieving the random-honest miners selection for a round of block creation. To further improve the efficiency of PoN in creating blocks, parallel multi-blocks creation can be implemented synchronously or asynchronously by dividing the miner team as k groups. Meanwhile, a distributed blocks storage scheme is designed with a map function to alleviate the storage volume caused by massive blocks creation. Simulation results show that PoN is more effective than traditional consensus mechanism in one-by-one block creation and more efficient in creating blocks.

BackgroundColorectal cancer (CRC) ranks as the second-leading cause of cancer-related death worldwide with metastases being the main cause of cancer-related death. Here, we investigated the genomic and transcriptomic alterations in matching adjacent normal tissues, primary tumors, and metastatic tumors of CRC patients.MethodsWe performed whole genome sequencing (WGS), multi-region whole exome sequencing (WES), simultaneous single-cell RNA-Seq, and single-cell targeted cDNA Sanger sequencing on matching adjacent normal tissues, primary tumors, and metastatic tumors from 12 metastatic colorectal cancer patients (n=84 for genomes,n=81 for exomes,n=9120 for single cells). Patient-derived tumor organoids were used to estimate the anti-tumor effects of a PPAR inhibitor, and self-renewal and differentiation ability of stem cell-like tumor cells.ResultsWe found that the PPAR signaling pathway was prevalently and aberrantly activated in CRC tumors. Blocking of PPAR pathway both suppressed the growth and promoted the apoptosis of CRC organoids in vitro, indicating that aberrant activation of the PPAR signaling pathway plays a critical role in CRC tumorigenesis. Using matched samples from the same patient, distinct origins of the metastasized tumors between lymph node and liver were revealed, which was further verified by both copy number variation and mitochondrial mutation profiles at single-cell resolution. By combining single-cell RNA-Seq and single-cell point mutation identification by targeted cDNA Sanger sequencing, we revealed important phenotypic differences between cancer cells with and without critical point mutations (KRASandTP53) in the same patient in vivo at single-cell resolution.ConclusionsOur data provides deep insights into how driver mutations interfere with the transcriptomic state of cancer cells in vivo at a single-cell resolution. Our findings offer novel knowledge on metastatic mechanisms as well as potential markers and therapeutic targets for CRC diagnosis and therapy. The high-precision single-cell RNA-seq dataset of matched adjacent normal tissues, primary tumors, and metastases from CRCs may serve as a rich resource for further studies.

In this work, it came up a hydrophilic and stable nitronyl nitroxide monoradical 4-methacryloyloxy-2,2,6,6-tetramethylpiperidine 1-oxyl freeradical (MATMP) as new monomer of polymerization for DNA detection. The detection limit was over 1,000,000 times lower than 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) derivatives as electrochemical labels alone. Within this approach, a single biomolecule can be converted into the strong electrochemical signal, therefore lung cancer DNA can be detected at low concentration. For the first step, the HS-PNA probe was fixed on the surface of the Au electrode. After the target DNA was captured by complementary base pairing, 4-cyano-4-(phenylcarbonothioylthio) pentanoic acid (CPAD), chain transfer agent of RAFT polymerization, was bonded to target DNA as reaction via coordination bond of Zr

Background RNA splicing defects are emerging molecular hallmarks of cancer. The gene encoding splicing factor RNA binding motif protein 10 (RBM10) has been found frequently mutated in various types of cancer, particularly lung adenocarcinoma (LUAD), but how RBM10 affects cancer pathogenesis remains to be determined. Moreover, the functional roles and clinical significance of RBM10 mutation-associated splicing events in LUAD are largely unknown. Methods RBM10 mutations and their functional impacts were examined in LUAD patients from a Chinese patient cohort and The Cancer Genome Atlas (TCGA). Alternative splicing (AS) changes induced by RBM10 mutations in LUAD were identified by RNA sequencing and correlated with patient survival. Functions of RBM10 and the splice variants of eukaryotic translation initiation factor 4H containing or lacking exon 5 (EIF4H-L and EIF4H-S respectively) in LUAD development and progression were examined by cellular phenotypic assays and xenograft tumour formation. Findings RBM10 mutations in LUAD generally lead to loss-of-function and cause extensive alterations in splicing events that can serve as prognostic predictors. RBM10 suppresses LUADprogression largely by regulating alternative splicing of EIF4H exon 5. Loss of RBM10 in LUAD enhances the expression of EIF4H-L in LUAD. EIF4H-L, but not EIF4H-S, is critical for LUAD cell proliferation, survival and tumourigenesis. Interpretation Our study demonstrates a new molecular mechanism underlying RBM10 suppressive functions in lung cancer and the therapeutic value of RBM10-regulated AS events, providing important mechanistic and translational insights into splicing defects in cancer.

SummaryBy circumventing cellular heterogeneity, single cell omics have now been widely utilized for cell typing in human tissues, culminating with the undertaking of human cell atlas aimed at characterizing all human cell types. However, more important are the probing of gene regulatory networks, underlying chromatin architecture and critical transcription factors for each cell type. Here we report the Genomic Architecture of Cells in Tissues (GeACT), a comprehensive genomic data base that collectively address the above needs with the goal of understanding the functional genome in action. GeACT was made possible by our novel single-cell RNA-seq (MALBAC-DT) and ATAC-seq (METATAC) methods of high detectability and precision. We exemplified GeACT by first studying representative organs in human mid-gestation fetus. In particular, correlated gene modules (CGMs) are observed and found to be cell-type-dependent. We linked gene expression profiles to the underlying chromatin states, and found the key transcription factors for representative CGMs.HighlightsGenomic Architecture of Cells in Tissues (GeACT) data for human mid-gestation fetusDetermining correlated gene modules (CGMs) in different cell types by MALBAC-DTMeasuring chromatin open regions in single cells with high detectability by METATACIntegrating transcriptomics and chromatin accessibility to reveal key TFs for a CGM

The development of entry inhibitors is an emerging approach to the inhibition of influenza virus. In our previous research, oleanolic acid (OA) was discovered as a mild influenza hemagglutinin (HA) inhibitor. Herein, as a further study, we report the preparation of a series of OA-saccharide conjugates via the CuAAC reaction, and the anti-influenza activity of these compounds was evaluated in vitro. Among them, compound 11b, an OA-glucose conjugate, showed a significantly increased anti-influenza activity with an IC50 of 5.47 μM, and no obvious cytotoxic effect on MDCK cells was observed at 100 μM. Hemagglutination inhibition assay and docking experiment indicated that 11b might interfere with influenza virus infection by acting on HA protein. Broad-spectrum anti-influenza experiments showed 11b to be robustly potent against 5 different strains, including influenza A and B viruses, with IC50 values at the low-micromole level. Overall, this finding further extends the utility of OA-saccharide conjugates in anti-influenza virus drug design.

The recent reports of resistance in Plasmodium falciparum to artemisinin derivatives and their partner drugs demand intensive studies toward understanding the molecular mechanisms of resistance. In this study, we examined the in vitro susceptibility of 63 P. falciparum field isolates collected from the China-Myanmar border area to chloroquine (CQ) and piperaquine (PPQ). Parasite isolates remained highly resistant to CQ, with the geometric mean 50% inhibitory concentration (IC 50 ) of 252.7 nM and a range of 51.9 to 1,052.0 nM. In comparison, these parasites had a geometric mean IC 50 of 28.4 nM for PPQ, with a fairly wide range of 5.3 to 132.0 nM, suggesting that certain parasite isolates displayed relatively high levels of resistance to PPQ. Interestingly, within the 4 years of study, the parasites exhibited a continuous decline in susceptibilities to both CQ and PPQ, and there was a significant correlation between responses to CQ and PPQ (Pearson correlation coefficient = 0.79, P < 0.0001). Consistent with the CQ-resistant phenotype, all parasites carried the pfcrt K76T mutation, and most parasites had the CVIET type that is prevalent in Southeast Asia. In contrast, pfmdr1 mutations were relatively rare, and no gene amplification was detected. Only the pfmdr1 N1042D mutation was associated with resistance to CQ. For the pfmrp1 gene, four substitutions reached relatively high prevalence of >22%, and the I876V mutation was associated with reduced sensitivity to CQ. However, we could not establish a link between PPQ responses and the polymorphisms in the three genes associated with quinoline drug resistance.

We evaluated the dynamics of parasite populations during in vitro culture adaptation in 15 mixed Plasmodium falciparum infections, which were collected from a hypoendemic area near the China–Myanmar border. Allele types at the msp1 block 2 in the initial clinical samples and during subsequent culture were quantified weekly using a quantitative PCR method. All mixed infections carried two allele types based on the msp1 genotyping result. We also genotyped several polymorphic sites in the dhfr, dhps and mdr1 genes on day 0 and day 28, which showed that most of the common sites analyzed were monomorphic. Two of the three clinical samples mixed at dhps 581 remained stable while one changed to wild-type during the culture. During in vitro culture, we observed a gradual loss of parasite populations with 10 of the 15 mixed infections becoming monoclonal by day 28 based on the msp1 allele type. In most cases, the more abundant msp1 allele types in the clinical blood samples at the beginning of culture became the sole or predominant allele types on day 28. These results suggest that some parasites may have growth advantages and the loss of parasite populations during culture adaptation of mixed infections may lead to biased results when comparing the phenotypes such as drug sensitivity of the culture-adapted parasites.