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[This corrects the article DOI: 10.1371/journal.pone.0259299.].

Southern Africa spans nearly 7 million km2 and contains approximately 80% of the world’s savannah elephants (Loxodonta africana) mostly living in isolated protected areas. Here we ask what are the prospects for improving the connections between these populations? We combine 1.2 million telemetry observations from 254 elephants with spatial data on environmental factors and human land use across eight southern African countries. Telemetry data show what natural features limit elephant movement and what human factors, including fencing, further prevent or restrict dispersal. The resulting intersection of geospatial data and elephant presences provides a map of suitable landscapes that are environmentally appropriate for elephants and where humans allow elephants to occupy. We explore the environmental and anthropogenic constraints in detail using five case studies. Lastly, we review all the major potential connections that may remain to connect a fragmented elephant metapopulation and document connections that are no longer feasible.

Accurate maps of species ranges are essential to inform conservation, but time-consuming to produce and update. Given the pace of change of knowledge about species distributions and shifts in ranges under climate change and land use, a need exists for timely mapping approaches that enable batch processing employing widely available data. We develop a systematic approach of batch-processing range maps and derived Area of Habitat maps for terrestrial bird species with published ranges below 125,000 km2 in Central and South America. (Area of Habitat is the habitat available to a species within its range.) We combine existing range maps with the rapidly expanding crowd-sourced eBird data of presences and absences from frequently surveyed locations, plus readily accessible, high resolution satellite data on forest cover and elevation to map the Area of Habitat available to each species. Users can interrogate the maps produced to see details of the observations that contributed to the ranges. Previous estimates of Areas of Habitat were constrained within the published ranges and thus were, by definition, smaller-typically about 30%. This reflects how little habitat within suitable elevation ranges exists within the published ranges. Our results show that on average, Areas of Habitat are 12% larger than published ranges, reflecting the often-considerable extent that eBird records expand the known distributions of species. Interestingly, there are substantial differences between threatened and non-threatened species. Some 40% of Critically Endangered, 43% of Endangered, and 55% of Vulnerable species have Areas of Habitat larger than their published ranges, compared with 31% for Near Threatened and Least Concern species. The important finding for conservation is that threatened species are generally more widespread than previously estimated.

Carvedilol is reported to prevent cancers in humans and animal models. However, a molecular mechanism has yet to be established, and the extent to which other β-blockers are chemopreventive remains relatively unknown. A comparative pharmacological approach was utilized with the expectation that a mechanism of action could be devised. JB6 Cl 41-5a (JB6 P+) murine epidermal cells were used to elucidate the chemopreventative properties of β-blockers, as JB6 P+ cells recapitulate in vivo tumor promotion and chemoprevention. The initial hypothesis was that β-blockers that are GRK/β-arrestin biased agonists, like carvedilol, are chemopreventive. Sixteen β-blockers of different classes, isoproterenol, and HEAT HCl were individually co-administered with epidermal growth factor (EGF) to JB6 P+ cells to examine the chemopreventative properties of each ligand. Cytotoxicity was examined to ensure that the anti-transformation effects of each ligand were not due to cellular growth inhibition. Many of the examined β-blockers suppressed EGF-induced JB6 P+ cell transformation in a non-cytotoxic and concentration-dependent manner. However, the IC50 values are high for the most potent inhibitors (243, 326, and 431 nM for carvedilol, labetalol, and alprenolol, respectively) and there is no correlation between pharmacological properties and inhibition of transformation. Therefore, the role of α1- and β2-adrenergic receptors (AR) was examined by standard competition assays and shRNA targeting β2-ARs, the only β-AR expressed in JB6 P+ cells. The results reveal that pharmacological inhibition of α1- and β2-ARs and genetic knockdown of β2-ARs did not abrogate carvedilol-mediated inhibition of EGF-induced JB6 P+ cell transformation. Furthermore, topical administration of carvedilol protected mice from UV-induced skin damage, while genetic ablation of β2-ARs increased carvedilol-mediated effects. Therefore, the prevailing hypothesis that the chemopreventive property of carvedilol is mediated through β-ARs is not supported by this data.

A photoelectrochemical (PEC) sensor with excellent sensitivity and detection toward copper (II) ions (Cu2+) was developed using a cadmium sulphide-reduced graphene oxide (CdS-rGO) nanocomposite on an indium tin oxide (ITO) surface, with triethanolamine (TEA) used as the sacrificial electron donor. The CdS nanoparticles were initially synthesized via the aerosol-assisted chemical vapor deposition (AACVD) method using cadmium acetate and thiourea as the precursors to Cd2+ and S2-, respectively. Graphene oxide (GO) was then dip-coated onto the CdS electrode and sintered under an argon gas flow (50 mL/min) for the reduction process. The nanostructured CdS was adhered securely to the ITO by a continuous network of rGO that also acted as an avenue to intensify the transfer of electrons from the conduction band of CdS. The photoelectrochemical results indicated that the ITO/CdS-rGO photoelectrode could facilitate broad UV-visible light absorption, which would lead to a higher and steady-state photocurrent response in the presence of TEA in 0.1 M KCl. The photocurrent decreased with an increase in the concentration of Cu2+ ions. The photoelectrode response for Cu2+ ion detection had a linear range of 0.5-120 μM, with a limit of detection (LoD) of 16 nM. The proposed PEC sensor displayed ultra-sensitivity and good selectivity toward Cu2+ ion detection.

The regulation of a series of cellular events requires specific protein-protein interactions, which are usually mediated by modular domains to precisely select a particular sequence from diverse partners. However, most signaling domains can bind to more than one peptide sequence. How do proteins create promiscuity from precision? Moreover, these complex interactions typically occur at the interface of a well-defined secondary structure, α helix and β sheet. However, the molecular recognition primarily controlled by loop architecture is not fully understood. To gain a deep understanding of binding selectivity and promiscuity by the conformation of loops, we chose the forkhead-associated (FHA) domain as our model system. The domain can bind to diverse peptides via various loops but only interact with sequences containing phosphothreonine (pThr). We applied molecular dynamics (MD) simulations for multiple free and bound FHA domains to study the changes in conformations and dynamics. Generally, FHA domains share a similar folding structure whereby the backbone holds the overall geometry and the variety of sidechain atoms of multiple loops creates a binding surface to target a specific partner. FHA domains determine the specificity of pThr by well-organized binding loops, which are rigid to define a phospho recognition site. The broad range of peptide recognition can be attributed to different arrangements of the loop interaction network. The moderate flexibility of the loop conformation can help access or exclude binding partners. Our work provides insights into molecular recognition in terms of binding specificity and promiscuity and helpful clues for further peptide design.

DNA methylation of promoter CpG islands is associated with gene suppression, and its unique genome-wide profiles have been linked to tumor progression. Coupled with high-throughput sequencing technologies, it can now efficiently determine genome-wide methylation profiles in cancer cells. Also, experimental and computational technologies make it possible to find the functional relationship between cancer-specific methylation patterns and their clinicopathological parameters.Cancer methylome system (CMS) is a web-based database application designed for the visualization, comparison and statistical analysis of human cancer-specific DNA methylation. Methylation intensities were obtained from MBDCap-sequencing, pre-processed and stored in the database. 191 patient samples (169 tumor and 22 normal specimen) and 41 breast cancer cell-lines are deposited in the database, comprising about 6.6 billion uniquely mapped sequence reads. This provides comprehensive and genome-wide epigenetic portraits of human breast cancer and endometrial cancer to date. Two views are proposed for users to better understand methylation structure at the genomic level or systemic methylation alteration at the gene level. In addition, a variety of annotation tracks are provided to cover genomic information. CMS includes important analytic functions for interpretation of methylation data, such as the detection of differentially methylated regions, statistical calculation of global methylation intensities, multiple gene sets of biologically significant categories, interactivity with UCSC via custom-track data. We also present examples of discoveries utilizing the framework.CMS provides visualization and analytic functions for cancer methylome datasets. A comprehensive collection of datasets, a variety of embedded analytic functions and extensive applications with biological and translational significance make this system powerful and unique in cancer methylation research. CMS is freely accessible at: http://cbbiweb.uthscsa.edu/KMethylomes/.

One big limitation of computational tools for analyzing ChIP-seq data is that most of them ignore non-unique tags (NUTs) that match the human genome even though NUTs comprise up to 60% of all raw tags in ChIP-seq data. Effectively utilizing these NUTs would increase the sequencing depth and allow a more accurate detection of enriched binding sites, which in turn could lead to more precise and significant biological interpretations. In this study, we have developed a computational tool, LOcating Non-Unique matched Tags (LONUT), to improve the detection of enriched regions from ChIP-seq data. Our LONUT algorithm applies a linear and polynomial regression model to establish an empirical score (ES) formula by considering two influential factors, the distance of NUTs to peaks identified using uniquely matched tags (UMTs) and the enrichment score for those peaks resulting in each NUT being assigned to a unique location on the reference genome. The newly located tags from the set of NUTs are combined with the original UMTs to produce a final set of combined matched tags (CMTs). LONUT was tested on many different datasets representing three different characteristics of biological data types. The detected sites were validated using de novo motif discovery and ChIP-PCR. We demonstrate the specificity and accuracy of LONUT and show that our program not only improves the detection of binding sites for ChIP-seq, but also identifies additional binding sites.

As technological interventions treating acute myocardial infarction (MI) improve, post-ischemic heart failure increasingly threatens patient health. The aim of the current study was to test whether FADD could be a potential target of gene therapy in the treatment of heart failure.Cardiomyocyte-specific FADD knockout mice along with non-transgenic littermates (NLC) were subjected to 30 minutes myocardial ischemia followed by 7 days of reperfusion or 6 weeks of permanent myocardial ischemia via the ligation of left main descending coronary artery. Cardiac function were evaluated by echocardiography and left ventricular (LV) catheterization and cardiomyocyte death was measured by Evans blue-TTC staining, TUNEL staining, and caspase-3, -8, and -9 activities. In vitro, H9C2 cells transfected with ether scramble siRNA or FADD siRNA were stressed with chelerythrin for 30 min and cleaved caspase-3 was assessed.FADD expression was significantly decreased in FADD knockout mice compared to NLC. Ischemia/reperfusion (I/R) upregulated FADD expression in NLC mice, but not in FADD knockout mice at the early time. FADD deletion significantly attenuated I/R-induced cardiac dysfunction, decreased myocardial necrosis, and inhibited cardiomyocyte apoptosis. Furthermore, in 6 weeks long term permanent ischemia model, FADD deletion significantly reduced the infarct size (from 41.20 ± 3.90% in NLC to 26.83 ± 4.17% in FADD deletion), attenuated myocardial remodeling, improved cardiac function and improved survival. In vitro, FADD knockdown significantly reduced chelerythrin-induced the level of cleaved caspase-3.Taken together, our results suggest FADD plays a critical role in post-ischemic heart failure. Inhibition of FADD retards heart failure progression. Our data supports the further investigation of FADD as a potential target for genetic manipulation in the treatment of heart failure.

The transcriptional response driven by Hypoxia-inducible factor (HIF) is central to the adaptation to oxygen restriction. Despite recent characterization of genome-wide HIF DNA binding locations and hypoxia-regulated transcripts in different cell types, the molecular bases of HIF target selection remain unresolved. Herein, we combined multi-level experimental data and computational predictions to identify sequence motifs that may contribute to HIF target selectivity. We obtained a core set of bona fide HIF binding regions by integrating multiple HIF1 DNA binding and hypoxia expression profiling datasets. This core set exhibits evolutionarily conserved binding regions and is enriched in functional responses to hypoxia. Computational prediction of enriched transcription factor binding sites identified sequence motifs corresponding to several stress-responsive transcription factors, such as activator protein 1 (AP1), cAMP response element-binding (CREB), or CCAAT-enhancer binding protein (CEBP). Experimental validations on HIF-regulated promoters suggest a functional role of the identified motifs in modulating HIF-mediated transcription. Accordingly, transcriptional targets of these factors are over-represented in a sorted list of hypoxia-regulated genes. Altogether, our results implicate cooperativity among stress-responsive transcription factors in fine-tuning the HIF transcriptional response.

It is now established that, as compared to normal cells, the cancer cell genome has an overall inverse distribution of DNA methylation ("methylome"), i.e., predominant hypomethylation and localized hypermethylation, within "CpG islands" (CGIs). Moreover, although cancer cells have reduced methylation "fidelity" and genomic instability, accurate maintenance of aberrant methylomes that underlie malignant phenotypes remains necessary. However, the mechanism(s) of cancer methylome maintenance remains largely unknown. Here, we assessed CGI methylation patterns propagated over 1, 3, and 5 divisions of A2780 ovarian cancer cells, concurrent with exposure to the DNA cross-linking chemotherapeutic cisplatin, and observed cell generation-successive increases in total hyper- and hypo-methylated CGIs. Empirical bayesian modeling revealed five distinct modes of methylation propagation: (1) heritable (i.e., unchanged) high-methylation (1186 probe loci in CGI microarray); (2) heritable (i.e., unchanged) low-methylation (286 loci); (3) stochastic hypermethylation (i.e., progressively increased, 243 loci); (4) stochastic hypomethylation (i.e., progressively decreased, 247 loci); and (5) considerable "random" methylation (582 loci). These results support a "stochastic model" of DNA methylation equilibrium deriving from the efficiency of two distinct processes, methylation maintenance and de novo methylation. A role for cis-regulatory elements in methylation fidelity was also demonstrated by highly significant (p

Deregulation of the transforming growth factor-β (TGFβ) signaling pathway in epithelial ovarian cancer has been reported, but the precise mechanism underlying disrupted TGFβ signaling in the disease remains unclear. We performed chromatin immunoprecipitation followed by sequencing (ChIP-seq) to investigate genome-wide screening of TGFβ-induced SMAD4 binding in epithelial ovarian cancer. Following TGFβ stimulation of the A2780 epithelial ovarian cancer cell line, we identified 2,362 SMAD4 binding loci and 318 differentially expressed SMAD4 target genes. Comprehensive examination of SMAD4-bound loci, revealed four distinct binding patterns: 1) Basal; 2) Shift; 3) Stimulated Only; 4) Unstimulated Only. TGFβ stimulated SMAD4-bound loci were primarily classified as either Stimulated only (74%) or Shift (25%), indicating that TGFβ-stimulation alters SMAD4 binding patterns in epithelial ovarian cancer cells. Furthermore, based on gene regulatory network analysis, we determined that the TGFβ-induced, SMAD4-dependent regulatory network was strikingly different in ovarian cancer compared to normal cells. Importantly, the TGFβ/SMAD4 target genes identified in the A2780 epithelial ovarian cancer cell line were predictive of patient survival, based on in silico mining of publically available patient data bases. In conclusion, our data highlight the utility of next generation sequencing technology to identify genome-wide SMAD4 target genes in epithelial ovarian cancer and link aberrant TGFβ/SMAD signaling to ovarian tumorigenesis. Furthermore, the identified SMAD4 binding loci, combined with gene expression profiling and in silico data mining of patient cohorts, may provide a powerful approach to determine potential gene signatures with biological and future translational research in ovarian and other cancers.

Methyl-CpG binding domain protein sequencing (MBD-seq) is widely used to survey DNA methylation patterns. However, the optimal experimental parameters for MBD-seq remain unclear and the data analysis remains challenging. In this study, we generated high depth MBD-seq data in MCF-7 cell and developed a bi-asymmetric-Laplace model (BALM) to perform data analysis. We found that optimal efficiency of MBD-seq experiments was achieved by sequencing ∼100 million unique mapped tags from a combination of 500 mM and 1000 mM salt concentration elution in MCF-7 cells. Clonal bisulfite sequencing results showed that the methylation status of each CpG dinucleotides in the tested regions was accurately detected with high resolution using the proposed model. These results demonstrated the combination of MBD-seq and BALM could serve as a useful tool to investigate DNA methylome due to its low cost, high specificity, efficiency and resolution.

MicroRNAs are small non-coding RNAs involved in post-transcriptional regulation of gene expression. Due to the poor annotation of primary microRNA (pri-microRNA) transcripts, the precise location of promoter regions driving expression of many microRNA genes is enigmatic. This deficiency hinders our understanding of microRNA-mediated regulatory networks. In this study, we develop a computational approach to identify the promoter region and transcription start site (TSS) of pri-microRNAs actively transcribed using genome-wide RNA Polymerase II (RPol II) binding patterns derived from ChIP-seq data. Based upon the assumption that the distribution of RPol II binding patterns around the TSS of microRNA and protein coding genes are similar, we designed a statistical model to mimic RPol II binding patterns around the TSS of highly expressed, well-annotated promoter regions of protein coding genes. We used this model to systematically scan the regions upstream of all intergenic microRNAs for RPol II binding patterns similar to those of TSS from protein coding genes. We validated our findings by examining the conservation, CpG content, and activating histone marks in the identified promoter regions. We applied our model to assess changes in microRNA transcription in steroid hormone-treated breast cancer cells. The results demonstrate many microRNA genes have lost hormone-dependent regulation in tamoxifen-resistant breast cancer cells. MicroRNA promoter identification based upon RPol II binding patterns provides important temporal and spatial measurements regarding the initiation of transcription, and therefore allows comparison of transcription activities between different conditions, such as normal and disease states.

Alterations in DNA methylation in cancer include global hypomethylation and gene-specific hypermethylation. It is not clear whether these two epigenetic errors are mechanistically linked or occur independently. This study was performed to determine the relationship between DNA hypomethylation, hypermethylation and microsatellite instability in cancer.We examined 61 cancer cell lines and 60 colorectal carcinomas and their adjacent tissues using LINE-1 bisulfite-PCR as a surrogate for global demethylation. Colorectal carcinomas with sporadic microsatellite instability (MSI), most of which are due to a CpG island methylation phenotype (CIMP) and associated MLH1 promoter methylation, showed in average no difference in LINE-1 methylation between normal adjacent and cancer tissues. Interestingly, some tumor samples in this group showed increase in LINE-1 methylation. In contrast, MSI-showed a significant decrease in LINE-1 methylation between normal adjacent and cancer tissues (P

It is now established that, as compared to normal cells, the cancer cell genome has an overall inverse distribution of DNA methylation ("methylome"), i.e., predominant hypomethylation and localized hypermethylation, within "CpG islands" (CGIs). Moreover, although cancer cells have reduced methylation "fidelity" and genomic instability, accurate maintenance of aberrant methylomes that underlie malignant phenotypes remains necessary. However, the mechanism(s) of cancer methylome maintenance remains largely unknown. Here, we assessed CGI methylation patterns propagated over 1, 3, and 5 divisions of A2780 ovarian cancer cells, concurrent with exposure to the DNA cross-linking chemotherapeutic cisplatin, and observed cell generation-successive increases in total hyper- and hypo-methylated CGIs. Empirical Bayesian modeling revealed five distinct modes of methylation propagation: (1) heritable (i.e., unchanged) high- methylation (1186 probe loci in CGI microarray); (2) heritable (i.e., unchanged) low-methylation (286 loci); (3) stochastic hypermethylation (i.e., progressively increased, 243 loci); (4) stochastic hypomethylation (i.e., progressively decreased, 247 loci); and (5) considerable "random" methylation (582 loci). These results support a "stochastic model" of DNA methylation equilibrium deriving from the efficiency of two distinct processes, methylation maintenance and de novo methylation. A role for cis-regulatory elements in methylation fidelity was also demonstrated by highly significant (p<2.2x10-5) enrichment of transcription factor binding sites in CGI probe loci showing heritably high (118 elements) and low (47 elements) methylation, and also in loci demonstrating stochastic hyper-(30 elements) and hypo-(31 elements) methylation. Notably, loci having "random" methylation heritability displayed nearly no enrichment. These results demonstrate an influence of cis-regulatory elements on the nonrandom propagation of both strictly heritable and stochastically heritable CGIs. [ABSTRACT FROM AUTHOR]

Objective: (-)-Epicatechin (EC) is an active ingredient of Fagopyrum dibtrys (D. Don) Hara and can regulate lung cancer progression. However, the specific regulatory mechanism is poorly understood. This study explored the specific mechanism of EC in the treatment of lung cancer., Methods: H460 cells were injected subcutaneously into the left dorsal sides of nude mice to establish an animal model of lung cancer. H460 and H1299 cells and nude mice were treated with different concentrations of EC. The expression levels of related proteins were detected by Western blotting. Cell proliferation, migration, and invasion were detected by CCK-8, colony formation, and Transwell assays. Flow cytometry was used to detect the Ca2+ level in lung cancer cells. Immunohistochemistry was used to detect the expression of Ki-67 in tumor tissues., Results: This study revealed that ferroptosis in lung cancer cells was inhibited during lung cancer development. EC treatment promotes ferroptosis, inhibits the proliferation, migration and invasion of lung cancer cells, and inhibits the formation of tumors in vivo. Ferroptosis inhibitors (Fer-1) weaken the effects of EC on lung cancer cells, whereas a ferroptosis inducer (erastin) further promotes the effects of EC. In addition, endoplasmic reticulum (ER) stress is involved in the EC-induced ferroptosis of lung cancer cells, and treatment with GSK, an inhibitor of the ER stress protein PERK, can reverse the effect of EC., Conclusion: EC therapy activates the PERK-eIF2α-ATF4 signaling pathway to increase ER stress, thereby promoting ferroptosis in lung cancer cells and inhibiting the occurrence and development of lung cancer. Our research suggests that EC may become a drug candidate for treating lung cancer., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lv et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Adenosine to inosine (A-to-I) RNA editing by ADAR1 has been implicated in maintaining self-tolerance, preventing autoimmunity, and mediating antiviral immunity. Foreign viral double-stranded RNA triggers rapid interferon response and activates ADAR1 in the host immune system. Emerging data points to a role of ADAR1 A-to-I editing in the inflammatory response associated with severe COVID-19 disease. We identify A-to-I editing events within human whole transcriptome data from SARS-CoV-2 infected individuals, non-infected individuals, and individuals with other viral illnesses from nasopharyngeal swabs. High levels of RNA editing in host cells are associated with low SARS-CoV-2 viral load (p = 9.27 E-06), suggesting an inhibitory effect of ADAR1 on viral infection. Additionally, we find differentially expressed genes associated with RNA-modifications and interferon response. Single cell RNA-sequencing analysis of SARS-CoV-2 infected nasopharyngeal swabs reveals that cytotoxic CD8 T cells upregulate ADAR1 in COVID-19 positive samples (p = 0.0269). We further reveal ADAR1 expression increases with CD4 and CD8 T cell activation, and knockdown of ADAR1 leads to apoptosis and aberrant IL-2 secretion. Together, our data suggests A-to-I RNA editing is required to maintain healthy homeostasis of activated T cells to combat SARS-CoV-2 infection., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Digital technologies can bring about fundamental changes in corporate processes, which may result in a shift from process innovation to digital process innovation. However, owing to resource constraints and various stakeholders, digital process implementation is extremely challenging for firms. Based on stakeholder theory, this study explores whether and how stakeholder pressure for digitalization can facilitate corporate digital process innovation and unravels the mediating effect of routine reconfiguration and the moderating effect of strategic flexibility. The findings from a survey of 351 firms prove that stakeholder pressure for digitalization can facilitate corporate digital process innovation via routine reconfiguration. Moreover, this study finds that increased strategic flexibility can strengthen the positive mediating effect of routine reconfiguration. The findings contribute to the deep understanding of digital process innovation and offer a boundary condition for the effectiveness of stakeholder pressure., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Jin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: To analyze the causal relationship between 486 human serum metabolites and the active tuberculosis (ATB) in European population., Methods: In this study, the causal relationship between human serum metabolites and the ATB was analyzed by integrating the genome-wide association study (GWAS). The 486 human serum metabolites were used as the exposure variable, three different ATB GWAS databases in the European population were set as outcome variables, and single nucleotide polymorphisms were used as instrumental variables for Mendelian Randomization. The inverse variance weighting was estimated causality, the MR-Egger intercept to estimate horizontal pleiotropy, and the combined effects of metabolites were also considered in the meta-analysis. Furthermore, the web-based MetaboAnalyst 6.0 was engaged for enrichment pathway analysis, while R (version 4.3.2) software and Review Manager 5.3 were employed for statistical analysis., Results: A total of 21, 17, and 19 metabolites strongly associated with ATB were found in the three databases after preliminary screening (P < 0.05). The intersecting metabolites across these databases included tryptophan, betaine, 1-linoleoylglycerol (1-monolinolein) (1-LG), 1-eicosatrienoylglycerophosphocholine, and oleoylcarnitine. Among them, betaine (I2 = 24%, P = 0.27) and 1-LG (I2 = 0%, P = 0.62) showed the lowest heterogeneity among the different ATB databases. In addition, the metabolic pathways of phosphatidylethanolamine biosynthesis (P = 0.0068), methionine metabolism (P = 0.0089), betaine metabolism (P = 0.0205) and oxidation of branched-chain fatty acids (P = 0.0309) were also associated with ATB., Conclusion: Betaine and 1-LG may be biomarkers or auxiliary diagnostic tools for ATB. They may provide new guidance for medical practice in the early diagnosis and surveillance of ATB. In addition, by interfering with phosphatidylethanolamine biosynthesis, methionine metabolism, betaine metabolism, oxidation of branched-chain fatty acids, and other pathways, it is helpful to develop new anti-tuberculosis drugs and explore the virulence or pathogenesis of ATB at a deeper level, providing an effective reference for future studies., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Xian et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

To investigate a novel approach for establishing the transverse pedicle angle (TPA) of the lower lumbar spine using preoperative digital radiography (DR). Computed Tomography (CT) datasets of the lower lumbar were reconstructed using MIMICS 17.0 software and then imported into 3-matic software for surgical simulation and anatomical parameter measurement. A mathematical algorithm of TPA based on the Pythagorean theorem was established, and all obtained data were analyzed by SPSS software. The CT dataset from 66 samples was reconstructed as a digital model of the lower lumbar vertebrae (L3-L5), and the AP length/estimated lateral length for L3 between the right and left sides was statistically significant (P = 0.015, P = 0.005). The AP length of the right for L4 was smaller than that of the left after a paired t test was executed (P = 0.006). Both the width of the pedicle and the length of the pedicle (P2C1) were consistent with TPA (L3

This paper presents a novel approach to addressing the challenges associated with energy storage capacity allocation in high-permeability wind and solar distribution networks. The proposed method is a two-phase distributed robust energy storage capacity allocation method, which aims to regulate the stochasticity and volatility of net energy output. Firstly, an energy storage capacity allocation model is established, which considers energy storage's investment and operation costs to minimize the total cost. Then, a two-stage distributed robust energy storage capacity allocation model is established with the confidence set of uncertainty probability distribution constrained by 1-norm and ∞-norm. Finally, a Column and Constraint Generation (C&CG) algorithm is used to solve the problem. The validity of the proposed energy storage capacity allocation model is confirmed by examining different wind and solar penetration levels. Furthermore, the model's superiority is demonstrated by comparing it with deterministic and robust models., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Delirium, a common occurrence in clinical work, can be divided into three subtypes according to Diagnostic and Statistical Manual of Mental Disorders, 5 th Edition (DSM-5). Each subtype has its special significance and focus. As the primary caregivers and observer of delirious patients, nurses should be able to quickly and accurately indentify each subtype. Therefore, it is necessary to clarify nurses' assessment ability of delirium subtypes. However, there is currently no suitable questionnaire available for investigating nurses' assessment ability of delirium subtypes., Objective: To develop a scientifically validated questionnaire for assessing nursing assessment ability of delirium subtypes based on Knowledge-Attitude-Practice(KAP) Model., Methods: The questionnaire was conducted from October 2021 to February 2022 to assess the KAP status of nurses the regarding delirium subtype. A two-round Delphi Method was employed to revise the draft questionnaire, ensuring the importance and rationality of each item. Ten experts specializing in critically ill patients, clinical nursing, and nursing management were invited from seven provinces in China for the Delphi process. Additionally, we validated the reliability and validity of the questionnaire., Results: The return rate in the first and second rounds were 83% and 100%, respectively. The individual authority coefficients for the two rounds of correspondence ranged from 0.787 to 0.987, while the overall authority coefficient of experts was 0.866. Kendall's coefficient of coordination for the importance scores were found to be 0.192 and 0.156, respectively, whereas those for rationality scores were calculated as 0.149 and 0.141, respectively. Notably, all mean values of importance and rationality scores in the two rounds were exceeded a threshold of 4.10 across both rounds of assessment with coefficient variations (CV) ranging from 0.00 to 0.19 for importance ratings and 0.00 to 0.16 for rationality ratings, both of which were <0.25. Experts proposed modifications to eleven items while introducing four new ones into consideration during this process; thus ensuring that reliability and validity standards were met by the final questionnaire design which consists of a total of thirty-seven items distributed across four dimensions: delirium subtype-related knowledge, assessment attitude, assessment practice, and knowledge source-thereby establishing its clinical relevance as a reliable scientific instrument., Conclusion: The development process is both scientific and theoretical, encompassing reliable expert correspondence results and a diverse range of question formats. As thus, effectively captures the current landscape of delirium subtypes assessment among clinical nurses from multiple perspectives, including knowledge level and source, attitude, assessment behavior, and assessment barriers. It offers comprehensive and detailed insights., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zhou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The global cold chain logistics market is witnessing a significant upswing, driven by the rising demand for perishable food products and increasing shipment volumes worldwide. Technological advancements are leading to a more intelligent and digitally enabled cold chain logistics system. However, the high loss rate of fresh agricultural products in China poses a significant threat to the country's food security. Therefore, it is imperative to explore innovative solutions, such as blockchain, to address the challenges of traditional cold chain logistics. In this paper, inspired by the prospect theory and evolutionary game theory, we propose an evolutionary game model to analyze the behavioral strategies of the tripartite of n-level cold chain participants, consumers, and government. Using MATLAB software, the numerical simulation of the game path of this tripartite theory is conducted, and the influence of variable parameters on the evolutionary process and outcomes of the system is analyzed. The results the following: (1) The development of an effective cold chain supply chain system can be divided into three stages, and blockchain technology plays a pivotal role in creating a seamless cold chain environment. The cost of blockchain adoption, government rewards, as well as penalties can significantly influence the behavioral choices of the three stakeholders. (2) The behavior of individual cold chain participants has a strong negative externality, which can impact the behavior of others. We also find that the larger the scale of the cold chain, the lower the probability of default by the participants. (3) The government's adoption of blockchain technology and the implementation of effective incentive policies can foster the successful development of the cold chain blockchain infrastructure. Our research contributes to the theoretical understanding of cold chain logistics decision making and policy creation for the tripartite stakeholders, including cold chain participants, consumers, and government. Our findings can serve as a valuable reference for scientific decision making and policy formulation to encourage the development of a robust cold chain supply chain system., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Bai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Thoracic aortic aneurysm (TAA) occurs due to pathological aortal dilation, and both individuals with normal tricuspid aortic valves (TAV) or abnormal bicuspid aortic valves (BAV), the latter being a congenital condition, are at risk. However, some differences are present between TAA/BAV and TAA/TAV with respect to their pathophysiological processes and molecular mechanisms, but their exact nature is still mostly unknown. Therefore, it is necessary to elucidate TAA developmental differences among BAV vs. TAV patients., Methods: Publically-available gene expression datasets, aortic tissue derived from TAA/BAV and TAA/TAV individuals, were analyzed by weighted gene co-expression network analysis (WGCNA) to identify gene modules associated with those conditions. Gene Ontology (GO) enrichment analysis was performed on those modules to identify the enriched genes within those modules, which were verified by Gene Set Variation Analysis (GSVA) on a dataset derived from aortic smooth muscle cell gene expression between TAA/TAV and TAV/BAV patients. Immune cell infiltration patterns were then analyzed by CIBERSORT, and a protein-protein interaction (PPI) network was constructed based on WGCNA and enrichment analysis results to identify hub genes, followed by validation via stepwise regression analysis. Three signatures most strongly associated with TAA/TAV were confirmed by receiver operating characteristic (ROC) and decision curve analyses (DCA) between prior-established training and testing gene sets., Results: WGCNA delineated 2 gene modules being associated with TAA/TAV vs. TAA/BAV; both were enriched for immune-associated genes, such as those relating to immune responses, etc., under enrichment analysis. TAA/TAV and TAA/BAV tissues also had differing infiltrating immune cell proportions, particularly with respect to dendritic, mast and CD4 memory T cells. Identified three signatures, CD86, integrin beta 2 (ITGB2) and alpha M (ITGAM), as yielding the strongest associations with TAA/TAV onset, which was verified by areas under the curve (AUC) at levels approximating 0.8 or above under ROC analysis, indicating their predictive value for TAA/TAV onset. However, we did not examine possible confounding variables, so there are many alternative explanations for this association., Conclusions: TAA/TAV pathogenesis was found to be more associated with immune-related gene expression compared to TAA/BAV, and the identification of three strongly-associated genes could facilitate their usage as future biomarkers for diagnosing the likelihood of TAA/TAV onset vs. TAA/BAV, as well as for developing future treatments., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Ginseng, a valuable Chinese medicinal herb, is renowned worldwide for its effectiveness in alleviating certain conditions and promoting overall health. In this study, we performed weighted gene co-expression network analysis (WGCNA) on the accumulation of essential saponins under the influence of 13 essential environmental factors (including air temperature, air bottom temperature, surface mean temperature, soil temperature, surface shortwave radiation, soil moisture, soil water content, rainfall, total precipitation, elevation, soil type, soil pH, and soil water potential). We identified a total of 40 transcript modules associated with typical environmental factors and the accumulation of essential saponins. Among these, 18 modules were closely related to the influence of typical environmental factors, whereas 22 modules were closely related to the accumulation of essential saponins. These results were verified by examining the transcriptome, saponin contents, environmental factor information and the published data and revealed the regulatory basis of saponin accumulation at the transcriptome level under the influence of essential environmental factors. We proposed a working model of saponin accumulation mediated by the transcriptional regulatory network that is affected by typical environmental factors. An isomorphic white-box neural network was constructed based on this model and the predicted results of the white-box neural network correlated with saponin accumulation. The effectiveness of our correlation-directed graph in predicting saponin contents was verified by bioinformatics analysis based on results obtained in this study and transcripts known to affect the biosynthesis of saponin Rb1. The directed graph represents a useful tool for manipulating saponin biosynthesis while considering the influence of essential environmental factors in ginseng and other medicinal plants., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Continuous tillage cultivation positioning trials can provide the basis for maintaining soil health, improving resource utilization efficiency and crop productivity, and achieving sustainable agricultural development. In this study, changes in soil stability and water-holding capacity characteristics were measured under different tillage cultivations from a multi-year microscopic perspective and analyzed to evaluate selected key indicators. Continuous monitoring of rainfall utilization efficiency and yield was carried out for five years. Here, we discuss the role of conservation tillage in buffering and stabilizing rainfall precipitation pattern on the fluctuation and uncertainty of soil water retention and water supply capacity and soil quality. The study was carried out on dryland areas of the Loess Plateau in northern China with eight tillage systems established in 2016: no-tillage (NT); no-tillage and straw (NTS); subsoiling (SU); subsoiling and straw (SUS); rotary tillage (RT); rotary tillage and straw (RTS); conventional tillage (CT); and conventional tillage and straw (CTS). All treatments were applied in conjunction with continuous cropping for five years. The evaluated soil parameters were mean weight diameter (MWD), geometric mean diameter (GMD), >0.25 mm aggregate content (R0.25) of water-stable aggregates (WSAs), soil moisture characteristic curve (SMCC), specific soil water capacity (Cθ), soil organic matter (SOM), rainfall utilization efficiency (RUE), and maize yields for five consecutive years. The MWD, GMD, and R0.25 of SUS were 27.38%, 17.57%, and 7.68% more than CTS (control), respectively. Overall, SOM, average annual RUE, and average annual yields increased by 14.64%, 11.89%, and 9.59%, respectively, compared with 2016. Our results strongly suggest that conservation tillage can considerably improve these characterization indicators. SUS was more effective than CTS in the 0-40 cm soil layer at hedging against drought in the area, stabilizing crop production, and achieving sustainable agricultural development., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Deng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Computed tomography (CT) is a non-invasive examination tool that is widely used in medicine. In this study, we explored its value in visualizing and quantifying coconut., Materials and Methods: Twelve coconuts were scanned using CT for three months. Axial CT images of the coconuts were obtained using a dual-source CT scanner. In postprocessing process, various three-dimensional models were created by volume rendering (VR), and the plane sections of different angles were obtained through multiplanar reformation (MPR). The morphological parameters and the CT values of the exocarp, mesocarp, endocarp, embryo, bud, solid endosperm, liquid endosperm, and coconut apple were measured. The analysis of variances was used for temporal repeated measures and linear and non-linear regressions were used to analyze the relationship between the data., Results: The MPR images and VR models provide excellent visualization of the different structures of the coconut. The statistical results showed that the weight of coconut and liquid endosperm volume decreased significantly during the three months, while the CT value of coconut apple decreased slightly. We observed a complete germination of a coconut, its data showed a significant negative correlation between the CT value of the bud and the liquid endosperm volume (y = -2.6955x + 244.91; R2 = 0.9859), and a strong positive correlation between the height and CT value of the bud (y = 1.9576 ln(x) -2.1655; R2 = 0.9691)., Conclusion: CT technology can be used for visualization and quantitative analysis of the internal structure of the coconut, and some morphological changes and composition changes of the coconut during the germination process were observed during the three-month experiment. Therefore, CT is a potential tool for analyzing coconuts., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Lin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Studies have shown the indicative role of handgrip strength in health. However, there is limited evidence revealing its potential effect on death events among middle-aged and older adults in China. We aimed to prospectively evaluate if lower handgrip strength is associated with the event of death. Among 17,167 middle-aged and older adults between age 45 to 96, handgrip strength was collected by a handheld dynamometer in a Chinese longitudinal study of aging trend (CHARLS) 2011-2018. Using Cox proportional hazard models with exposures, we assessed the association between handgrip strength and death events. Elevated handgrip strength values were independently associated with the decreased death risk. These results illustrate that lower handgrip strength is an independent indicator of death risks among middle-aged and older Chinese, which highlights the significance of related intercessions. The median values of five levels of handgrip strength in the entire cohort were 16.5,23,28,33,42kg at baseline. A linear association existed between the handgrip strength values and the risk of all-cause death within 34.2kg. Handgrip strength can serve as an independent indicator for death risks., Competing Interests: The authors have declared that no competing interests exist.

In the context of global warming, although the coordinated development of tourism has led to regional economic growth, the high energy consumption-driven effects of such development have also led to environmental degradation. This research combines the undesired output of the Super-SBM model and social network analysis methods to determine the eco-efficiency of provincial tourism in China from 2010-2019 and analyzes its spatial correlation characteristics as well as its influencing factors. The aim of the project is to improve China's regional tourism eco-efficiency and promote cross-regional tourism correlation. The results show that (1) the mean value of provincial tourism eco-efficiency in China is maintained at 0.405~0.612, with an overall fluctuating upward trend. The tourism eco-efficiency of eastern China is higher than that of central, western and northeastern China, but the latter three regions have not formed a stable spatial distribution pattern. (2) The spatial network of provincial tourism eco-efficiency in China is multithreaded, dense and diversified. Throughout the network, affiliations are becoming closer, and network structure robustness is gradually improving, although the "hierarchical" spatial network structure remains. In individual networks, Jiangsu, Guangdong and Shandong provinces in eastern China have higher centrality degrees, closeness centrality and betweenness centrality than other provinces, which means they are dominant in the network. Hainan Province, also located in eastern China, has not yet built a "bridge" for tourism factor circulation. In the core-periphery model, the core-periphery areas of China's provincial tourism eco-efficiency are distributed in clusters, and the number of "core members" has increased. (3) The economic development level, information technology development level, and tourism technology level collectively drive the development and evolution of China's provincial tourism eco-efficiency spatial network., Competing Interests: We confirm that neither the manuscript nor any parts of its content are currently under consideration or published in another journal.

Automatic operations of multi-functional and time-lapse live-cell imaging are necessary for the biomedical science community to study active, multi-faceted, and long-term biological phenomena. To achieve automatic control, most existing solutions often require the purchase of extra software programs and hardware that rely on the manufacturers' own specifications. However, these software programs are usually non-user-programmable and unaffordable for many laboratories. To address this unmet need, we have developed a novel open-source software program, titled Automatic Multi-functional Integration Program (AMFIP), as a new Java-based and hardware-independent system that provides proven advantages over existing alternatives to the scientific community. Without extra hardware, AMFIP enables the functional synchronization of the μManager software platform, the Nikon NIS-Elements platform, and other 3rd party software to achieve automatic operations of most commercially available microscopy systems, including but not limited to those from Nikon. AMFIP provides a user-friendly and programmable graphical user interface (GUI), opening the door to expanding the customizability for myriad hardware and software systems according to user-specific experimental requirements and environments. To validate the intended purposes of developing AMFIP, we applied it to elucidate the question whether single cells, prior to their full spreading, can sense and respond to a soft solid substrate, and if so, how does the interaction depend on the cell spreading time and the stiffness of the substrate. Using a CRISPR/Cas9-engineered human epithelial Beas2B (B2B) cell line that expresses mNeonGreen2-tagged mechanosensitive Yes-associated protein (YAP), we show that single B2B cells develop distinct substrate-stiffness-dependent YAP expressions within 10 hours at most on the substrate, suggesting that cells are able to sense, distinguish, and respond to mechanical cues prior to the establishment of full cell spreading. In summary, AMFIP provides a reliable, open-source, and cost-free solution that has the validated long-term utility to satisfy the need of automatic imaging operations in the scientific community., Competing Interests: The authors have declared that no competing interests exist.

A service can be an intangible commodity in which no physical goods are transferred from the seller to the buyer. However, traditional trading platforms have many limitations in trading services due to dishonest buyers and brokers. In this paper, we propose a service trading ecosystem based on blockchain, named STEB, which combines blockchain, smart contract, encryption, and digital authentication techniques for service trading. In addition, a dual-chain architecture, which contains two types of blockchains, namely TraChain and SerChain, and a hierarchical encryption scheme of the data on the chain, are proposed to ensure the integrity of transaction data and fine-grained privacy protection of users. Furthermore, we describe a new set of smart contracts to ensure safe transactions for the entire service trading. Security analysis and simulation results confirm that the proposed STEB can achieve more efficient contract execution and enhance service transaction privacy., Competing Interests: The authors have declared that no competing interests exist.

The medicinal mushroom Ganoderma lucidum is traditionally used for treating multiple diseases, including cancer. This study examined skin cancer preventive activity of a commercial product containing spore and fruiting body in 30:8 ratio (GLSF). Extracts of GLSF and spore component (GLS) were prepared using artificial gastrointestinal juice and examined on JB6 cells. GLSF and GLS dose-dependently inhibited epidermal growth factor-induced JB6 transformation at non-toxic concentrations. SKH-1 mice which were fed with diets containing GLSF (1.25%), GLS (0.99%) or the fruiting body (GLF) (0.26%) were exposed to chronic low-dose ultraviolet (UV) radiation to assess their effects on skin carcinogenesis. GLSF, but not GLS or GLF, reduced skin tumor incidence and multiplicity. In non-tumor skin tissues of mice, GLSF attenuated UV-induced epidermal thickening, expression of Ki-67, COX-2 and NF-κB, while in tumor tissues, GLSF increased expression of CD8 and Granzyme B. To examine the effects of GLSF on UV-induced immunosuppression, mice which were fed with GLSF were evaluated for the contact hypersensitivity (CHS) response to dinitrofluorobenzene (DNFB). GLSF significantly reversed UV-mediated suppression of DNFB-induced CHS by increasing CD8+ and decreasing CD4+ and FoxP3+ T-cells in mouse ears. Therefore, GLSF prevents skin cancer probably via attenuating UV-induced immunosuppression., Competing Interests: The authors have declared that no competing interests exist.

Background: The prevalence of anxiety and depression in pregnant women has significantly increased after the spread of COVID-19 throughout the world. We carried out this meta-analysis to reveal the information about risk factors for depression and anxiety in pregnant women during the COVID-19 pandemic., Methods: We searched the PubMed, Embase and CNKI (China National Knowledge Infrastructure) databases for all articles. The odds ratio (OR) corresponding to the 95% confidence interval (95% CI) was used to assess the risk factors for mental health. The statistical heterogeneity among studies was assessed with the Q-test and I2 statistics., Results: We collected 17 studies including 15,050 pregnant women during the COVID-19 pandemic. Our results found that factors including decrease in the perception of general support and difficulties in household finances have damage effects on anxiety, and factors including undereducated, unemployed during pregnancy, with a chronic physical illness before pregnancy, decrease in the perception of general support, difficulties in household finances, disobey the isolation rules, and smoking during pregnancy have increased risk of depression., Conclusion: Our meta-analysis revealed some risk factors for mental health in pregnant women during COVID-19 pandemic. Mental health interventions in pregnant women may involve targeted methods individually., Competing Interests: The authors have declared that no competing interests exist.

This paper reports a plasma reactive oxygen species (ROS) method for decontamination of PPE (N95 respirators and gowns) using a surface DBD source to meet the increased need of PPE due to the COVID-19 pandemic. A system is presented consisting of a mobile trailer (35 m3) along with several Dielectric barrier discharge sources installed for generating a plasma ROS level to achieve viral decontamination. The plasma ROS treated respirators were evaluated at the CDC NPPTL, and additional PPE specimens and material functionality testing were performed at Texas A&M. The effects of decontamination on the performance of respirators were tested using a modified version of the NIOSH Standard Test Procedure TEB-APR-STP-0059 to determine particulate filtration efficiency. The treated Prestige Ameritech and BYD brand N95 respirators show filtration efficiencies greater than 95% and maintain their integrity. The overall mechanical and functionality tests for plasma ROS treated PPE show no significant variations., Competing Interests: The authors have declared that no competing interests exist.

With the growth of the economy, the number of automobiles on the road is fast growing, resulting in substantial environmental pollution from exhaust gas emissions. In the automobile factory, some improvements have been achieved by constructing devices to degrade automobile exhaust. However, although most of the vehicle exhaust emissions have met the national standards, the exhaust gas is superimposed at the same time period due to the increasing traffic volume, making the exhaust emissions seriously reduce the air quality. Therefore, the scholars in the road field began to study new road materials to degrade vehicle exhaust, which has gradually become one of the effective ways to reduce automobile exhaust. Photocatalyst materials have been widely concerned because of their ability to oxidize harmful gases by solar photocatalysis. Yet, the effect has been not satisfactory because of the small light response range of photocatalyst material, which restricts the catalytic effect. In this study, this paper attempts to use Fe3+ to modify the TiO2, which is one of the main photocatalytic materials, to expand the range of light reaction band and to improve the degradation effect of automobile exhaust. The degradation effects of ordinary TiO2 and modified TiO2 on automobile exhaust were compared by test system in the laboratory. The results show that the modified TiO2 can effectively improve the performance of vehicle exhaust degradation. Moreover, the molecular dynamics method was used to establish the channel model of TiO2, and the dynamic process of automobile exhaust diffusion and absorption was simulated. The diffusion law and adsorption process of different types of automobile exhaust gas such as NO, CO, and CO2 in the TiO2 channel were analyzed from the molecular scale through the radial concentration distribution and adsorption energy., Competing Interests: The authors have declared that no competing interests exist.

The Longshi Scale, a visual-based scale, is reliable and valid in activity assessment, but lacks cutoff definition corresponding to classical scales such as the modified Rankin Scale and Barthel Index. Therefore, this study aimed to investigate the relationships of the Longshi Scale with the modified Rankin Scale and Barthel Index and optimize cutoff scores of these scales in stroke outcomes assessment. This is a cross-sectional study. Stroke patients were measured concurrently by the Longshi scale, modified Rankin Scale and Barthel Index. Kruskal-Wallis test and Spearman correlation analysis were used to analyze the differences and associations among the three scales. The receiver operating characteristic curve was performed to determine the optimal cutoff scores. A total of 5475 stroke patients (67.3% ischemic) were included in this study. There are close relationships of the Longshi Scale with adjusted modified Rankin Scale and Barthel Index (r = -0.861, 0.922; p<0.001, <0.001; respectively). The activity levels assessed by adjusted modified Rankin Scale and Barthel Index among different Longshi scale grades were significantly different (χ2:4217.27, 4676.55; p<0.001, <0.001; respectively). The optimal cutoff scores were adjusted modified Rankin Scale 4, 3, 3, 3, 2 for Longshi scale grade 2 to 6 (sensitivity%: 96.12, 70.24, 89.10, 96.80, 86.23, specificity%: 72.72, 98.29, 93.81, 79.82, 92.89, respectively), and Barthel Index 15, 45, 60, 75, 80 for Longshi scale grade 2 to 6 (sensitivity%: 92.54, 89.28, 91.32, 90.30, 95.65, specificity%: 95.48, 89.51, 94.02, 90.41, 90.62, respectively). In conclusion, the classification of Longshi Scale is consistent with those of modified Rankin Scale and Barthel Index. We recommend the Longshi Scale as an effective supplement for modified Rankin Scale and Barthel Index in assessing the outcome in acute stroke patients., Competing Interests: The authors have declared that no competing interests exist.