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RATIONALE: The phenomenon of hypercoagulability has not been previously documented in individuals with Morvan's syndrome, especially in those associated with contactin-associated protein-like receptor 2 (CASPR2). PATIENT CONCERNS: A previously healthy 32-year-old Chinese male was admitted to the hospital with central and peripheral neurologic symptoms. The patient was tested positive for anti-CASPR2 antibodies, and also presented with an activated coagulation state on admission, characterized by a low activated partial thromboplastin time and a high platelet count. With gradual improvement of clinical symptoms, activated partial thromboplastin time, and platelet count returned to normal. Simultaneously, anti-CASPR2 antibody titers significantly decreased and eventually became undetectable. DIAGNOSES: The patient was diagnosed as Morvan's syndrome with positive anti-CASPAR2 antibodies accompanied with hypercoagulable state. INTERVENTIONS: Plasmapheresis was administered to improve the symptoms combined with prednisolone acetate therapy. OUTCOMES: The patient experienced complete resolution of all symptoms during hospitalization and generally recovery after 2 months of discharge. LESSONS: Emphasis should be directed towards hypercoagulability in individuals diagnosed with Morvan's syndrome, particularly those presenting with positive anti-CASPR2 antibodies. Anticoagulant therapy may represent a novel therapeutic approach for individuals afflicted with Morvan's syndrome and exhibiting positivity for anti-CASPR2 antibodies.
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Autoanticorpos , Proteínas de Membrana , Proteínas do Tecido Nervoso , Trombofilia , Humanos , Masculino , Adulto , Trombofilia/imunologia , Trombofilia/tratamento farmacológico , Autoanticorpos/sangue , Autoanticorpos/imunologia , Proteínas de Membrana/imunologia , Proteínas do Tecido Nervoso/imunologia , PlasmafereseRESUMO
Human centromeres have been traditionally very difficult to sequence and assemble owing to their repetitive nature and large size1. As a result, patterns of human centromeric variation and models for their evolution and function remain incomplete, despite centromeres being among the most rapidly mutating regions2,3. Here, using long-read sequencing, we completely sequenced and assembled all centromeres from a second human genome and compared it to the finished reference genome4,5. We find that the two sets of centromeres show at least a 4.1-fold increase in single-nucleotide variation when compared with their unique flanks and vary up to 3-fold in size. Moreover, we find that 45.8% of centromeric sequence cannot be reliably aligned using standard methods owing to the emergence of new α-satellite higher-order repeats (HORs). DNA methylation and CENP-A chromatin immunoprecipitation experiments show that 26% of the centromeres differ in their kinetochore position by >500 kb. To understand evolutionary change, we selected six chromosomes and sequenced and assembled 31 orthologous centromeres from the common chimpanzee, orangutan and macaque genomes. Comparative analyses reveal a nearly complete turnover of α-satellite HORs, with characteristic idiosyncratic changes in α-satellite HORs for each species. Phylogenetic reconstruction of human haplotypes supports limited to no recombination between the short (p) and long (q) arms across centromeres and reveals that novel α-satellite HORs share a monophyletic origin, providing a strategy to estimate the rate of saltatory amplification and mutation of human centromeric DNA.
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Centrômero , Evolução Molecular , Variação Genética , Animais , Humanos , Centrômero/genética , Centrômero/metabolismo , Proteína Centromérica A/metabolismo , Metilação de DNA/genética , DNA Satélite/genética , Cinetocoros/metabolismo , Macaca/genética , Pan troglodytes/genética , Polimorfismo de Nucleotídeo Único/genética , Pongo/genética , Masculino , Feminino , Padrões de Referência , Imunoprecipitação da Cromatina , Haplótipos , Mutação , Amplificação de Genes , Alinhamento de Sequência , Cromatina/genética , Cromatina/metabolismo , Especificidade da EspécieRESUMO
The crab-eating macaques ( Macaca fascicularis ) and rhesus macaques ( M. mulatta ) are widely studied nonhuman primates in biomedical and evolutionary research. Despite their significance, the current understanding of the complex genomic structure in macaques and the differences between species requires substantial improvement. Here, we present a complete genome assembly of a crab-eating macaque and 20 haplotype-resolved macaque assemblies to investigate the complex regions and major genomic differences between species. Segmental duplication in macaques is â¼42% lower, while centromeres are â¼3.7 times longer than those in humans. The characterization of â¼2 Mbp fixed genetic variants and â¼240 Mbp complex loci highlights potential associations with metabolic differences between the two macaque species (e.g., CYP2C76 and EHBP1L1 ). Additionally, hundreds of alternative splicing differences show post-transcriptional regulation divergence between these two species (e.g., PNPO ). We also characterize 91 large-scale genomic differences between macaques and humans at a single-base-pair resolution and highlight their impact on gene regulation in primate evolution (e.g., FOLH1 and PIEZO2 ). Finally, population genetics recapitulates macaque speciation and selective sweeps, highlighting potential genetic basis of reproduction and tail phenotype differences (e.g., STAB1 , SEMA3F , and HOXD13 ). In summary, the integrated analysis of genetic variation and population genetics in macaques greatly enhances our comprehension of lineage-specific phenotypes, adaptation, and primate evolution, thereby improving their biomedical applications in human diseases.
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We sequenced and assembled using multiple long-read sequencing technologies the genomes of chimpanzee, bonobo, gorilla, orangutan, gibbon, macaque, owl monkey, and marmoset. We identified 1,338,997 lineage-specific fixed structural variants (SVs) disrupting 1,561 protein-coding genes and 136,932 regulatory elements, including the most complete set of human-specific fixed differences. We estimate that 819.47 Mbp or â¼27% of the genome has been affected by SVs across primate evolution. We identify 1,607 structurally divergent regions wherein recurrent structural variation contributes to creating SV hotspots where genes are recurrently lost (e.g., CARD, C4, and OLAH gene families) and additional lineage-specific genes are generated (e.g., CKAP2, VPS36, ACBD7, and NEK5 paralogs), becoming targets of rapid chromosomal diversification and positive selection (e.g., RGPD gene family). High-fidelity long-read sequencing has made these dynamic regions of the genome accessible for sequence-level analyses within and between primate species.
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Genoma , Primatas , Animais , Humanos , Sequência de Bases , Primatas/classificação , Primatas/genética , Evolução Biológica , Análise de Sequência de DNA , Variação Estrutural do GenomaRESUMO
Understanding gene expression variations between species is pivotal for deciphering the evolutionary diversity in phenotypes. Rhesus macaques ( Macaca mulatta, MMU) and crab-eating macaques ( M. fascicularis, MFA) serve as crucial nonhuman primate biomedical models with different phenotypes. To date, however, large-scale comparative transcriptome research between these two species has not yet been fully explored. Here, we conducted systematic comparisons utilizing newly sequenced RNA-seq data from 84 samples (41 MFA samples and 43 MMU samples) encompassing 14 common tissues. Our findings revealed a small fraction of genes (3.7%) with differential expression between the two species, as well as 36.5% of genes with tissue-specific expression in both macaques. Comparison of gene expression between macaques and humans indicated that 22.6% of orthologous genes displayed differential expression in at least two tissues. Moreover, 19.41% of genes that overlapped with macaque-specific structural variants showed differential expression between humans and macaques. Of these, the FAM220A gene exhibited elevated expression in humans compared to macaques due to lineage-specific duplication. In summary, this study presents a large-scale transcriptomic comparison between MMU and MFA and between macaques and humans. The discovery of gene expression variations not only enhances the biomedical utility of macaque models but also contributes to the wider field of primate genomics.
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Genômica , Transcriptoma , Humanos , Animais , Macaca mulatta/genética , Macaca fascicularis/genética , Perfilação da Expressão Gênica/veterináriaRESUMO
BACKGROUND: Limited evidence exists on the relationship between vitamin D status and mortality in depressed patients. METHODS: This study investigates serum 25-hydroxyvitamin D [25(OH)D] concentrations in 8417 adults with depression among the National Health and Nutrition Examination Survey (NHANES, 2005-2018). Mortality outcomes were assessed through National Death Index records up to December 31, 2019. Cox proportional risk models estimated risk ratios (HR) and 95 % confidence intervals (CI) for all-cause, cardiovascular disease (CVD), and cancer mortality. Restricted cubic spline analyses explored the nonlinear association of serum 25(OH)D levels with mortality, using the likelihood ratio test for nonlinearity. RESULTS: The weighted mean serum 25(OH)D level was 66.40 nmol/L (95 % CI: 65.8, 67.0), with 36.3 % having deficient vitamin D (<50 nmol/L [20 ng/mL]). Over an average 7.16-year follow-up, 935 deaths were documented, including 296 CVD deaths and 191 cancer deaths. Higher serum 25(OH)D levels were associated with reduced all-cause mortality (HRs 0.55-1.00, p trend = 0.006) and cancer-specific mortality (HRs 0.36-1.00, p trend = 0.015) after multivariate adjustment. The relationship between serum 25(OH)D and all-cause mortality exhibited a nonlinear pattern (P for nonlinearity <0.001), with a 34 % lower risk for each unit increase in natural log-transformed 25(OH)D levels. Significant interactions were observed with age, antidepressant use, and diabetes status. CONCLUSIONS: Higher serum 25(OH)D levels were associated with decreased all-cause and cancer-specific mortality in depressed adults, particularly among younger individuals and those using antidepressants or without diabetes. Further research is essential to understand mechanisms and interventions related to vitamin D in depression.
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Doenças Cardiovasculares , Diabetes Mellitus , Neoplasias , Deficiência de Vitamina D , Vitamina D/análogos & derivados , Adulto , Humanos , Estudos de Coortes , Causas de Morte , Inquéritos Nutricionais , Depressão , Vitaminas , Neoplasias/complicações , Fatores de RiscoRESUMO
Topological associating domains (TADs) are self-interacting genomic units crucial for shaping gene regulation patterns. Despite their importance, the extent of their evolutionary conservation and its functional implications remain largely unknown. In this study, we generate Hi-C and ChIP-seq data and compare TAD organization across four primate and four rodent species and characterize the genetic and epigenetic properties of TAD boundaries in correspondence to their evolutionary conservation. We find 14% of all human TAD boundaries to be shared among all eight species (ultraconserved), while 15% are human-specific. Ultraconserved TAD boundaries have stronger insulation strength, CTCF binding, and enrichment of older retrotransposons compared to species-specific boundaries. CRISPR-Cas9 knockouts of an ultraconserved boundary in a mouse model lead to tissue-specific gene expression changes and morphological phenotypes. Deletion of a human-specific boundary near the autism-related AUTS2 gene results in the upregulation of this gene in neurons. Overall, our study provides pertinent TAD boundary evolutionary conservation annotations and showcases the functional importance of TAD evolution.
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Genoma , Genômica , Animais , Camundongos , Humanos , Regulação da Expressão Gênica , Epigenômica , Sequenciamento de Cromatina por Imunoprecipitação , Cromatina , Mamíferos/genéticaRESUMO
Structural variations have emerged as an important driving force for genome evolution and phenotypic variation in various organisms, yet their contributions to genetic diversity and adaptation in domesticated animals remain largely unknown. Here we constructed a pangenome based on 250 sequenced individuals from 32 pig breeds in Eurasia and systematically characterized coding sequence presence/absence variations (PAVs) within pigs. We identified 308.3-Mb nonreference sequences and 3438 novel genes absent from the current reference genome. Gene PAV analysis showed that 16.8% of the genes in the pangene catalog undergo PAV. A number of newly identified dispensable genes showed close associations with adaptation. For instance, several novel swine leukocyte antigen (SLA) genes discovered in nonreference sequences potentially participate in immune responses to productive and respiratory syndrome virus (PRRSV) infection. We delineated previously unidentified features of the pig mobilome that contained 490,480 transposable element insertion polymorphisms (TIPs) resulting from recent mobilization of 970 TE families, and investigated their population dynamics along with influences on population differentiation and gene expression. In addition, several candidate adaptive TE insertions were detected to be co-opted into genes responsible for responses to hypoxia, skeletal development, regulation of heart contraction, and neuronal cell development, likely contributing to local adaptation of Tibetan wild boars. These findings enhance our understanding on hidden layers of the genetic diversity in pigs and provide novel insights into the role of SVs in the evolutionary adaptation of mammals.
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Cruzamento , Genoma , Humanos , Animais , Suínos , Variação Genética , MamíferosRESUMO
We completely sequenced and assembled all centromeres from a second human genome and used two reference sets to benchmark genetic, epigenetic, and evolutionary variation within centromeres from a diversity panel of humans and apes. We find that centromere single-nucleotide variation can increase by up to 4.1-fold relative to other genomic regions, with the caveat that up to 45.8% of centromeric sequence, on average, cannot be reliably aligned with current methods due to the emergence of new α-satellite higher-order repeat (HOR) structures and two to threefold differences in the length of the centromeres. The extent to which this occurs differs depending on the chromosome and haplotype. Comparing the two sets of complete human centromeres, we find that eight harbor distinctly different α-satellite HOR array structures and four contain novel α-satellite HOR variants in high abundance. DNA methylation and CENP-A chromatin immunoprecipitation experiments show that 26% of the centromeres differ in their kinetochore position by at least 500 kbp-a property not readily associated with novel α-satellite HORs. To understand evolutionary change, we selected six chromosomes and sequenced and assembled 31 orthologous centromeres from the common chimpanzee, orangutan, and macaque genomes. Comparative analyses reveal nearly complete turnover of α-satellite HORs, but with idiosyncratic changes in structure characteristic to each species. Phylogenetic reconstruction of human haplotypes supports limited to no recombination between the p- and q-arms of human chromosomes and reveals that novel α-satellite HORs share a monophyletic origin, providing a strategy to estimate the rate of saltatory amplification and mutation of human centromeric DNA.
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BACKGROUND: The first telomere-to-telomere (T2T) human genome assembly (T2T-CHM13) release is a milestone in human genomics. The T2T-CHM13 genome assembly extends our understanding of telomeres, centromeres, segmental duplication, and other complex regions. The current human genome reference (GRCh38) has been widely used in various human genomic studies. However, the large-scale genomic differences between these two important genome assemblies are not characterized in detail yet. RESULTS: Here, in addition to the previously reported "non-syntenic" regions, we find 67 additional large-scale discrepant regions and precisely categorize them into four structural types with a newly developed website tool called SynPlotter. The discrepant regions (~ 21.6 Mbp) excluding telomeric and centromeric regions are highly structurally polymorphic in humans, where the deletions or duplications are likely associated with various human diseases, such as immune and neurodevelopmental disorders. The analyses of a newly identified discrepant region-the KLRC gene cluster-show that the depletion of KLRC2 by a single-deletion event is associated with natural killer cell differentiation in ~ 20% of humans. Meanwhile, the rapid amino acid replacements observed within KLRC3 are probably a result of natural selection in primate evolution. CONCLUSION: Our study provides a foundation for understanding the large-scale structural genomic differences between the two crucial human reference genomes, and is thereby important for future human genomics studies.
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Genoma Humano , Genômica , Animais , Humanos , Duplicações Segmentares Genômicas , Família Multigênica , Centrômero/genética , Subfamília C de Receptores Semelhantes a Lectina de Células NK/genéticaRESUMO
A novel statistical ink drop displacement (IDD) printer model for the direct binary search (DBS) halftoning algorithm is proposed. It is intended primarily for pagewide inkjet printers that exhibit dot displacement errors. The tabular approach in the literature predicts the gray value of a printed pixel based on the halftone pattern in some neighborhood of that pixel. However, memory retrieval time and the complexity of memory requirements hamper its feasibility in printers that have a very large number of nozzles and produce ink drops that affect a large neighborhood. To avoid this problem, our IDD model embodies dot displacements by moving each perceived ink drop in the image from its nominal location to its actual location, rather than manipulating the average gray values. This enables DBS to directly compute the appearance of the final printout without retrieving values from a table. In so doing, the memory issue is eliminated and the computation efficiency is enhanced. The deterministic cost function of DBS is replaced by the expectation over the ensemble of the displacements for the proposed model such that the statistical behavior of the ink drops is accounted for. Experimental results show significant improvement in the quality of the printed image over the original DBS. Besides, the image quality obtained by the proposed approach appears to be slightly better than that obtained by the tabular approach.
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Interpretação de Imagem Assistida por Computador , Tinta , Interpretação de Imagem Assistida por Computador/métodos , Aumento da Imagem/métodos , Algoritmos , Modelos EstatísticosRESUMO
The hybrid technology of CO2 capture-mineral carbonation (CCMC) using alkaline streams has emerged in recent years. However, thus far, there has been no comprehensive study revealing the mechanisms of the simultaneous CCMC process regarding the choice of amine types and sensitivity of parameters. Combining with the analysis of multistep reaction mechanisms for different amines, we investigated a representative from each category in CCMC using calcium chloride to simulate the alkaline resource after leaching, i.e., primary (ethanolamine, MEA), secondary (diisopropanolamine, DIPA), tertiary (diethylethanolamine, DEAE), and triamine (diethylenetriamine, DETA), respectively. In the adsorption step, increasing the amine concentration beyond 2 mol/L reduced the absorption efficiency of DEAE due to the hydration mechanism, motivating a rational choice of concentration. In CCMC sections, when the amine concentration increased, only DEAE exhibited an increased carbonation efficiency of up to 100%, while DETA showed the lowest conversion. The carbonation of DEAE demonstrated the least sensitivity to temperature. The crystal transformation experiments suggested that over time, the produced vaterite could completely transform to calcite or aragonite, except those from DETA. Thus, with rationally chosen conditions, DEAE was demonstrated ideal for CCMC. These findings obtained in this work provided a theoretical foundation for designing future CCMC processes.
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Aminas , Dióxido de Carbono , Dióxido de Carbono/química , DEET , Minerais , Carbonatos , Carbonato de Cálcio/químicaRESUMO
BACKGROUND: Duchenne muscular dystrophy (DMD) is an X-linked, incurable, degenerative neuromuscular disease that is exacerbated by secondary inflammation. N6-methyladenosine (m6A), the most common base modification of RNA, has pleiotropic immunomodulatory effects in many diseases. However, the role of m6A modification in the immune microenvironment of DMD remains elusive. METHODS: Our study retrospectively analyzed the expression data of 56 muscle tissues from DMD patients and 26 from non-muscular dystrophy individuals. Based on single sample gene set enrichment analysis, immune cells infiltration was identified and the result was validated by flow cytometry analysis and immunohistochemical staining. Then, we described the features of genetic variation in 26 m6A regulators and explored their relationship with the immune mircoenvironment of DMD patients through a series of bioinformatical analysis. At last, we determined subtypes of DMD patients by unsupervised clustering analysis and characterized the molecular and immune characteristics in different subgroups. RESULTS: DMD patients have a sophisticated immune microenvironment that is significantly different from non-DMD controls. Numerous m6A regulators were aberrantly expressed in the muscle tissues of DMD and inversely related to most muscle-infiltrating immune cell types and immune response-related signaling pathways. A diagnostic model involving seven m6A regulators was established using LASSO. Furthermore, we determined three m6A modification patterns (cluster A/B/C) with distinct immune microenvironmental characteristics. CONCLUSION: In summary, our study demonstrated that m6A regulators are intimately linked to the immune microenvironment of muscle tissues in DMD. These findings may facilitate a better understanding of the immunomodulatory mechanisms in DMD and provide novel strategies for the treatment.
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Distrofia Muscular de Duchenne , Humanos , Análise por Conglomerados , Citometria de Fluxo , Imunomodulação , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/imunologia , Estudos RetrospectivosRESUMO
Since the release of the complete human genome, the priority of human genomic study has now been shifting towards closing gaps in ethnic diversity. Here, we present a fully phased and well-annotated diploid human genome from a Han Chinese male individual (CN1), in which the assemblies of both haploids achieve the telomere-to-telomere (T2T) level. Comparison of this diploid genome with the CHM13 haploid T2T genome revealed significant variations in the centromere. Outside the centromere, we discovered 11,413 structural variations, including numerous novel ones. We also detected thousands of CN1 alleles that have accumulated high substitution rates and a few that have been under positive selection in the East Asian population. Further, we found that CN1 outperforms CHM13 as a reference genome in mapping and variant calling for the East Asian population owing to the distinct structural variants of the two references. Comparison of SNP calling for a large cohort of 8869 Chinese genomes using CN1 and CHM13 as reference respectively showed that the reference bias profoundly impacts rare SNP calling, with nearly 2 million rare SNPs miss-called with different reference genomes. Finally, applying the CN1 as a reference, we discovered 5.80 Mb and 4.21 Mb putative introgression sequences from Neanderthal and Denisovan, respectively, including many East Asian specific ones undetected using CHM13 as the reference. Our analyses reveal the advances of using CN1 as a reference for population genomic studies and paleo-genomic studies. This complete genome will serve as an alternative reference for future genomic studies on the East Asian population.
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Diploide , População do Leste Asiático , Genoma Humano , Telômero , Humanos , Masculino , Povo Asiático/genética , População do Leste Asiático/etnologia , População do Leste Asiático/genética , Genoma Humano/genética , Genômica , Telômero/genéticaRESUMO
The common marmoset ( Callithrix jacchus) has emerged as a valuable nonhuman primate model in biomedical research with the recent release of high-quality reference genome assemblies. Epileptic marmosets have been independently reported in two Asian primate research centers. Nevertheless, the population genetics within these primate centers and the specific genetic variants associated with epilepsy in marmosets have not yet been elucidated. Here, we characterized the genetic relationships and risk variants for epilepsy in 41 samples from two epileptic marmoset pedigrees using whole-genome sequencing. We identified 14â¯558â¯184 single nucleotide polymorphisms (SNPs) from the 41 samples and found higher chimerism levels in blood samples than in fingernail samples. Genetic analysis showed fourth-degree of relatedness among marmosets at the primate centers. In addition, SNP and copy number variation (CNV) analyses suggested that the WW domain-containing oxidoreductase ( WWOX) and Tyrosine-protein phosphatase nonreceptor type 21 ( PTPN21) genes may be associated with epilepsy in marmosets. Notably, KCTD18-like gene deletion was more common in epileptic marmosets than control marmosets. This study provides valuable population genomic resources for marmosets in two Asian primate centers. Genetic analyses identified a reasonable breeding strategy for genetic diversity maintenance in the two centers, while the case-control study revealed potential risk genes/variants associated with epilepsy in marmosets.
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Callithrix , Epilepsia , Animais , Callithrix/genética , Estudos de Casos e Controles , Variações do Número de Cópias de DNA , Genética Populacional , Epilepsia/veterináriaRESUMO
This paper aims to explore how to promote green technology innovation (GTI) among new energy vehicle (NEV) manufacturers and the strategic changes among the government, manufacturers, and consumers. From the perspective of evolutionary game theory, a tripartite evolutionary game model is established to analyze the influence of key factors on the tripartite strategies in the context of the government's willingness to subsidize gradually decreases. The main findings are as follows: (1) government subsidies provided to manufacturers better promote their willingness to participate in GTI. The relationship between government subsidies and GTI is not linear, and the government cannot blindly increase the level of subsidies. (2) The willingness of NEV manufacturers to engage in GTI is influenced by price and consumer purchase preferences. The higher the price of new energy vehicle using green technology (NEVG) is not better, and lowering the price of NEVGs can promote manufacturers' participation in GTI and consumers' purchase of NEVGs. (3) Increasing the mileage of NEVGs and consumers' green consumption preferences will effectively increase consumers' willingness to purchase. Accordingly, this study suggests that to enhance manufacturers' participation in GTI, the government should increase subsidies and encourage green consumption among consumers. In addition, manufacturers should focus on improving the mileage of NEVGs and reducing their prices to make them more accessible to consumers.
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Teoria dos Jogos , Indústrias , Tecnologia , Custos e Análise de Custo , Comportamento do Consumidor , Governo , ChinaRESUMO
Background: Depression, a serious public health disorder, is increasingly prevalent worldwide. An association between alkaline phosphatase (ALP) and neurological disorders has been reported. However, data on ALP and depression risk are scarce, which warrants attention. Methods: We assessed the association between ALP and risk of depression in adults from the 2007-2014 National Health and Nutrition Examination Survey (NHANES). Depression was assessed using the Patient Health Questionnaire-9. Univariate and multivariate logistic regression were used to assess the association between ALP and risk of depression, and subgroup analyses were also performed. Results: A total of 17,485 participants were included. The prevalence of depression was 9.3% (1,631/17,485) and ALP was significantly associated with the risk of depression when ALP was a categorical variable (quadratic or categorized by 79 U/L) in a multivariate logistic regression model after adjusting for confounding factors (≥79 U/L vs. <79 U/L, adjusted OR, 1.15; 95%CI, 1.02-1.29). Each 1-unit increase in ALP (log2) was associated with a 20% increase in depression prevalence (adjusted OR, 1.20; 95%CI, 1.06-1.36) when ALP was used as a continuous variable. Subgroup analysis showed that ALP was positively associated with the risk of depression with different characteristics. Conclusion: Our findings suggest that higher alkaline phosphatase levels, even within the normal range, are significantly associated with a higher risk of depression in US adults. Such findings require further prospective studies to provide more evidence.
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Background: Lung cancer (LC) is the most common cancer. Using data from The Cancer Genome Atlas (TCGA), we analyzed the functional roles of M1 macrophage status in LC patients. Methods: Clinical and transcriptome data of LC patients were obtained from the TCGA dataset. We identified M1 macrophage-related genes in LC patients and investigated the underlying molecular mechanisms of these genes in LC patients. After performing a least absolute shrinkage and selection operator (LASSO) Cox regression analysis, the LC patients were divided into two subtypes, and the underlying mechanism of the association between them was further explored. A comparison of immune infiltration was conducted between the two subtypes. Based on gene set enrichment analysis (GSEA), the key regulators associated with subtypes were further explored. Results: M1 macrophage-related genes were identified using TCGA data, and these genes might be related to the activation of the immune response and cytokine-mediated signaling pathways in LC. A seven M1 macrophage-related gene signature (including STAT1, TAP1, UBE2L6, TAP2, CXCR6, PSMB8 and CD2) was identified in LC using LASSO Cox regression analysis. Two subtypes (low risk and high risk) of LC patients were created based on the seven M1 macrophage-related gene signature. Univariate and multivariate survival analyses further confirmed that the subtype classification was an effective independent prognostic factor. Moreover, the two subtypes were correlated with immune infiltration, and GSEA revealed that the pathways of tumor cell proliferation and immune-related biological processes (BPs) might play an important role in LC in the high-risk group and low-risk group, respectively. Conclusions: M1 macrophage-related subtypes of LC were identified and were closely associated with immune infiltration. The gene signature involved in M1 macrophage-related genes could help make a distinction and predict prognosis for LC patients.
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Slack resources and organizational learning are key elements in building organizational resilience. This paper constructs an impact model of organizational resilience and investigates the impact of slack resources on organizational resilience using data from Chinese-listed companies, as well as verifying the moderating effect of organizational dual learning through hierarchical analysis. The findings show that: Firstly, both absorbed slack resources and unabsorbed slack resources promote organizational resilience. Secondly, organizational learning has a moderating effect on the relationship between slack resources and organizational resilience, where organizational exploitative learning positively moderates the relationship between unabsorbed slack resources and organizational resilience, while organizational exploitative learning negatively moderates the relationship between absorbed slack resources and organizational resilience. Accordingly, organizations should pay attention to the composition of slack resources and the coordination between slack resources and organizational dual learning in order to improve organizational resilience.