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1.
Anal Chem ; 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39238086

RESUMO

Tumor cells undergo an epithelial-mesenchymal transition (EMT) accompanied by a reduction in elasticity to initiate metastasis. However, in vivo, tumor cells typically exhibit partial EMT rather than fully EMT. Whether cell mechanics can accurately identify the status of partial EMT, especially the dynamic process, remains unclear. To elucidate the relationship between cell mechanics and partial EMT, we employed scanning ion conductance microscopy (SICM) to analyze the dynamic changes in cell mechanics during the TGFß-induced partial EMT of HCT116 colon cancer cells. Cells undergoing partial EMT, characterized by increased expression of EMT transcription factors, Snai1 and Zeb1, and EMT-related genes, Fn1 and MMP9, while retaining the expression of the epithelial markers E-cadherin (E-cad) and EpCAM, did not exhibit significant changes in cell morphology, suggesting that morphological changes alone were inadequate for identifying partial EMT status. However, cell elasticity markedly decreased in partial EMT cells, and this reduction was reversed with the reversible transition of partial EMT. These findings suggest a strong correlation between cell mechanics and the dynamic process of partial EMT, indicating that cell mechanics could serve as a valuable label-free marker for identifying the status of partial EMT while preserving the physiological characteristics of tumor cells.

2.
Bioorg Chem ; 152: 107758, 2024 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-39216197

RESUMO

GFRS is the conversion product of Panax ginseng Meyer berry after citric acid heat treatment, which is rich in rare ginsenosides. However, the anti-melanin role of GFRS in the regulation of skin pigmentation and its material basis remains unclear. To compare the anti-melanin activity before and after citric acid heat treatment, we determined the effects of GFS and GFRS on tyrosinase activity and melanin lever under α-MSH stimulation and found the potential anti-melanin effect of GFRS. Further, Western blot and immunofluorescence methods were used to reveal the mechanism by which GFRS detects anti-melanin activity by promoting autophagy flux levels. In zebrafish models, GFRS inhibited endogenous melanin and tyrosinase better than arbutin and promoted the accumulation of autophagy levels in vivo. To determine the material basis of the anti-melanin effect of GFRS, HPLC was used to isolate and prepare 12 ginsenosides from GFRS, and their activity evaluation and structure-activity relationship analysis were performed. The results showed that the inhibitory effect of GFRS on melanin was Rg3 > Rg5 > Rk1 > Rd. Molecular docking showed that their docking fraction with mushroom tyrosinase was significantly better than that of arbutin, but the presence of C-20 glycosylation decreased the anti-melanin activity of Rd. To maximize the content of Rg3, Rg5, and Rk1, we optimized the process by using citric acid heat treatment of ginsenoside Rd and found that citric acid heat treatment at 100°C almost completely transformed Rd and obtained a high content of active ingredients. In summary, our data demonstrated that GFRS exerted anti-melanin effects by inducing autophagy. It was further revealed that Rg3, Rg5, and Rk1, as effective active components, could be enriched by the improved process of converting ginsenoside Rd by citric acid heat treatment.

3.
Sci Rep ; 14(1): 17261, 2024 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-39068226

RESUMO

To address the issue of electronic equipment failure inside the instrument compartment due to aerodynamic heating during high-speed flight. Combining the heat transfer characteristics of phase change materials, a new instrument compartment structure was proposed as the research subject based on phase change materials. While studying the heat transfer characteristics of this structure, one-dimensional phase change heat transfer theoretical model was constructed based on the Lightfoot integral equation method, and the corresponding analytical solution was obtained. To explore the temperature change law of the instrument compartment structure and verify the rationality of the theoretical model, the new thermal experiment was carried out for the instrument compartment structure. Compared with the aluminum alloy instrument compartment structure, the experimental results show that the instrument compartment structure design based on phase change materials could effectively reduce the temperature of the structure itself, and the experimental data are in good agreement with the theoretical calculation results, which verified the rationality of the theoretical model and provided a scientific basis for the practical application of phase change materials in instrument compartment structures.

4.
Natl Sci Rev ; 11(7): nwae196, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39071101

RESUMO

Immune evasion is a pivotal force shaping the evolution of viruses. Nonetheless, the extent to which virus evolution varies among populations with diverse immune backgrounds remains an unsolved mystery. Prior to the widespread SARS-CoV-2 infections in December 2022 and January 2023, the Chinese population possessed a markedly distinct (less potent) immune background due to its low infection rate, compared to countries experiencing multiple infection waves, presenting an unprecedented opportunity to investigate how the virus has evolved under different immune contexts. We compared the mutation spectrum and functional potential of the newly derived mutations that occurred in BA.5.2.48, BF.7.14 and BA.5.2.49-variants prevalent in China-with their counterparts in other countries. We found that the emerging mutations in the receptor-binding-domain region in these lineages were more widely dispersed and evenly distributed across different epitopes. These mutations led to a higher angiotensin-converting enzyme 2 (ACE2) binding affinity and reduced potential for immune evasion compared to their counterparts in other countries. These findings suggest a milder immune pressure and less evident immune imprinting within the Chinese population. Despite the emergence of numerous immune-evading variants in China, none of them outcompeted the original strain until the arrival of the XBB variant, which had stronger immune evasion and subsequently outcompeted all circulating variants. Our findings demonstrated that the continuously changing immune background led to varying evolutionary pressures on SARS-CoV-2. Thus, in addition to viral genome surveillance, immune background surveillance is also imperative for predicting forthcoming mutations and understanding how these variants spread in the population.

5.
Respir Res ; 25(1): 223, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38811936

RESUMO

BACKGROUND: Community-acquired pneumonia (CAP) is a common and serious condition that can be caused by a variety of pathogens. However, much remains unknown about how these pathogens interact with the lower respiratory commensals, and whether any correlation exists between the dysbiosis of the lower respiratory microbiota and disease severity and prognosis. METHODS: We conducted a retrospective cohort study to investigate the composition and dynamics of sputum microbiota in patients diagnosed with CAP. In total, 917 sputum specimens were collected consecutively from 350 CAP inpatients enrolled in six hospitals following admission. The V3-V4 region of the 16 S rRNA gene was then sequenced. RESULTS: The sputum microbiota in 71% of the samples were predominately composed of respiratory commensals. Conversely, 15% of the samples demonstrated dominance by five opportunistic pathogens. Additionally, 5% of the samples exhibited sterility, resembling the composition of negative controls. Compared to non-severe CAP patients, severe cases exhibited a more disrupted sputum microbiota, characterized by the highly dominant presence of potential pathogens, greater deviation from a healthy state, more significant alterations during hospitalization, and sparser bacterial interactions. The sputum microbiota on admission demonstrated a moderate prediction of disease severity (AUC = 0.74). Furthermore, different pathogenic infections were associated with specific microbiota alterations. Acinetobacter and Pseudomonas were more abundant in influenza A infections, with Acinetobacter was also enriched in Klebsiella pneumoniae infections. CONCLUSION: Collectively, our study demonstrated that pneumonia may not consistently correlate with severe dysbiosis of the respiratory microbiota. Instead, the degree of microbiota dysbiosis was correlated with disease severity in CAP patients.


Assuntos
Infecções Comunitárias Adquiridas , Microbiota , Índice de Gravidade de Doença , Escarro , Humanos , Infecções Comunitárias Adquiridas/microbiologia , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/epidemiologia , Masculino , Feminino , Escarro/microbiologia , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Estudos Longitudinais , Estudos de Coortes , Disbiose/microbiologia , Disbiose/diagnóstico , Pneumonia/microbiologia , Pneumonia/diagnóstico , Pneumonia Bacteriana/microbiologia , Pneumonia Bacteriana/diagnóstico , Pneumonia Bacteriana/epidemiologia , Idoso de 80 Anos ou mais , Adulto
6.
Research (Wash D C) ; 7: 0389, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38779486

RESUMO

The gut microbiota undergoes substantial changes in COVID-19 patients; yet, the utility of these alterations as prognostic biomarkers at the time of hospital admission, and its correlation with immunological and hematological parameters, remains unclear. The objective of this study is to investigate the gut microbiota's dynamic change in critically ill patients with COVID-19 and evaluate its predictive capability for clinical outcomes alongside immunological and hematological parameters. In this study, anal swabs were consecutively collected from 192 COVID-19 patients (583 samples) upon hospital admission for metagenome sequencing. Simultaneously, blood samples were obtained to measure the concentrations of 27 cytokines and chemokines, along with hematological and biochemical indicators. Our findings indicate a significant correlation between the composition and dynamics of gut microbiota with disease severity and mortality in COVID-19 patients. Recovered patients exhibited a higher abundance of Veillonella and denser interactions among gut commensal bacteria compared to deceased patients. Furthermore, the abundance of gut commensal bacteria exhibited a negative correlation with the concentration of proinflammatory cytokines and organ damage markers. The gut microbiota upon admission showed moderate prognostic prediction ability with an AUC of 0.78, which was less effective compared to predictions based on immunological and hematological parameters (AUC 0.80 and 0.88, respectively). Noteworthy, the integration of these three datasets yielded a higher predictive accuracy (AUC 0.93). Our findings suggest the gut microbiota as an informative biomarker for COVID-19 prognosis, augmenting existing immune and hematological indicators.

7.
Risk Manag Healthc Policy ; 17: 1039-1052, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38680478

RESUMO

Background: Trust is a major factor affecting patient-physician relationship and healthcare quality. However, there has been a lack of comprehensive study on the extent of and major factors affecting patient trust in healthcare providers of China, the world's largest developing country. The objective of this study is to elucidate the current status of outpatient trust in physicians in China and its influencing factors, providing empirical evidence to enhance doctor-patient trust and improve doctor-patient relationships. Methods: Between December 2017 and January 2018, 28,760 patients seeking care at the outpatient departments of 136 tertiary hospitals were interviewed, where they were asked to rate their trust in physicians. We applied a multilevel logistic regression model to explore the association between patients trust and characteristics of hospitals, physicians and patient characteristics. We conducted a series of sensitivity analysis to check the robustness of our findings. Results: Among 28,760 participants included in this study, 91.54% expressed trust in their physicians, while 7.52% showed moderate trust. Only 0.94% expressly distrusted or strongly distrusted their physicians. Outpatients of hospitals with convenient payment, volunteer guidance and enough seats available in the rest and waiting area showed higher levels of trust. Physicians who had a senior title, showed patience and protection of the patient's privacy were more likely to be trusted by their patients in the outpatient setting. Compared to their female counterparts, male outpatients showed a higher degree of trust. Conclusion: While this study highlights an overall high level of Trust in physicians (TIP) among patients in China's tertiary hospitals, it is found to vary with patient demographic factors as well as provider's attributes. Hospitals with a more keen sense of protecting patients privacy and better meeting patients' need for efficient and caring service provision process appeared to yield a higher level of trust.

8.
Bioinformatics ; 40(3)2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38426352

RESUMO

MOTIVATION: Intra-host variants refer to genetic variations or mutations that occur within an individual host organism. These variants are typically studied in the context of viruses, bacteria, or other pathogens to understand the evolution of pathogens. Moreover, intra-host variants are also explored in the field of tumor biology and mitochondrial biology to characterize somatic mutations and inherited heteroplasmic mutations. Intra-host variants can involve long insertions, deletions, and combinations of different mutation types, which poses challenges in their identification. The performance of current methods in detecting of complex intra-host variants is unknown. RESULTS: First, we simulated a dataset comprising 10 samples with 1869 intra-host variants involving various mutation patterns and benchmarked current variant detection software. The results indicated that though current software can detect most variants with F1-scores between 0.76 and 0.97, their performance in detecting long indels and low frequency variants was limited. Thus, we developed a new software, PySNV, for the detection of complex intra-host variations. On the simulated dataset, PySNV successfully detected 1863 variant cases (F1-score: 0.99) and exhibited the highest Pearson correlation coefficient (PCC: 0.99) to the ground truth in predicting variant frequencies. The results demonstrated that PySNV delivered promising performance even for long indels and low frequency variants, while maintaining computational speed comparable to other methods. Finally, we tested its performance on SARS-CoV-2 replicate sequencing data and found that it reported 21% more variants compared to LoFreq, the best-performing benchmarked software, while showing higher consistency (62% over 54%) within replicates. The discrepancies mostly exist in low-depth regions and low frequency variants. AVAILABILITY AND IMPLEMENTATION: https://github.com/bnuLyndon/PySNV/.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Software , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Mutação , Mutação INDEL , Variação Genética
9.
Environ Pollut ; 348: 123817, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38508366

RESUMO

Microplastic is an emerging pollutant and a technical fossil in Anthropocene sediments. Typhoon frequency and intensity have increased due to climate change, which has a major effect on the distribution patterns of microplastics. It is still unknown, though, how the topography of the peninsula affects the reconstruction of the distribution of microplastic in typhoons. Due to frequent typhoons, the Leizhou Peninsula (LZP) in the north part of the South China Sea is an ideal place to study the impact of topographic variations on microplastic distribution during typhoon events. This study investigated microplastics ranging in size from 50 µm to 5 mm in sediment. Microscopic inspection and µ-FTIR tests were used to identify microplastic characteristics from offshore surface sediments before and after typhoons. The average microplastic abundance in offshore sediments decreased from 18 ± 17 items/kg to 15 ± 15 items/kg after typhoons. Results show that typhoons only increase the microplastic abundance in topographically protected areas along the northeast coast of LZP, with no significant difference observed in other regions. The influence of typhoon on the morphological characteristics of microplastics in sediments is more pronounced and widespread, as evidenced by a shift in the predominant shape of microplastics from fibers to fragments and a decrease in size accompanied by an increased abundance within the 100 µm-1 mm fraction. The color of microplastics remained similar before and after typhoons, and the polymer composition of microplastics became more uniform. The alteration of microplastic morphology may be attributed to the enhancement of wave intensity induced by typhoons. This study enhances the comprehension of typhoon-induced impacts on pollutant redistribution, specifically microplastics, thereby providing essential empirical evidence and theoretical foundations for pollution regulation.


Assuntos
Tempestades Ciclônicas , Poluentes Químicos da Água , Microplásticos , Plásticos , Poluentes Químicos da Água/análise , Sedimentos Geológicos , Monitoramento Ambiental/métodos , China
10.
iScience ; 27(2): 108983, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38357660

RESUMO

Rhizosphere dwelling microorganism such as Bacillus spp. are helpful for crop growth. However, these functions are adversely affected by long-term synthetic fertilizer application. We developed a modified CRISPR/Cas9 system using non-specific single-guide RNAs to disrupt the genome-wide cis-acting catabolite-responsive elements (cres) in a wild-type Bacillus pumilus strain, which conferred dual plant-benefit properties. Most of the mutations occurred around imperfectly matched cis-acting elements (cre-like sites) in genes that are mainly involved in carbon and secondary metabolism pathways. The comparative metabolomics and transcriptome results revealed that carbon is likely transferred to some pigments, such as riboflavin, carotenoid, and lycopene, or non-ribosomal peptides, such as siderophore, surfactin, myxochelin, and bacilysin, through the pentose phosphate and amino acid metabolism pathways. Collectively, these findings suggested that the mutation of global cre-like sequences in the genome might alter carbon flow, thereby allowing beneficial biological interactions between the rhizobacteria and plants.

11.
Sci Total Environ ; 919: 170938, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38354795

RESUMO

Stratigraphic determination of the Anthropocene, the "Great Acceleration", requires more key globally synchronous stratigraphic markers which reflect the significant human impacts on Earth. Lacustrine sediment magnetic characteristics are of considerable importance in Anthropocene studies because they respond sensitively to environmental changes. There are many shallow lakes in the Songnen Plain (SNP) in northeast China, which are conducive to obtaining Anthropocene sedimentary records. This study explored magnetic materials in lacustrine sediment responses to environmental evolution impact by human activities on the SNP by measuring magnetic parameters in dated sediment cores from 5 shallow lakes in the SNP, northeast China. The results revealed that detrital magnetite and hematite dominated the magnetic minerals in lake sediments. The persistently low value of magnetic susceptibility might be caused by the low content of natural ferrimagnetic minerals in Quaternary fluvial deposits and humus-rich black soil in the catchment, and the loss of magnetic materials during the transport process. In Lake Longjiangpao (LJP), the magnetic concentrations significantly responded to regional precipitation, whereas in the other 4 lakes in the center of the plain, the parameters tended to reflect complex human activities. However, the isothermal remanent magnetization ratio (S-300), which is indicative of the ratio of hematite to magnetite, exhibited relatively consistent variations in the 5 studied lakes. After 1950, the "Great Acceleration", the increase of S-300 indicated a relative proportion of magnetite in sediments, and was positively correlated with the growth of human-activity proxies (Gross Domestic Product (GDP) and population). Thus, this proxy can be regarded as a useful indicator of the beginning of the Anthropocene in the studied region. This study provides new insights into the estimation of local human activities in history and possible evidence for the global definition of the Anthropocene.

12.
Pest Manag Sci ; 80(2): 837-845, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37794292

RESUMO

BACKGROUND: Assessment of the risk of pesticide inhalation in populations around farmland is necessary because inhalation is one of the ways in which pesticides can risk human health. This study aimed to identify the inhalation risk of difenoconazole on humans by using dose-response and exposure assessments. RESULTS: In the field simulation application, respiratory exposure in populations around farmland ranged from 71 to 430 ng/m3 . Using response surface methodology, the maximum bioaccessibility of difenoconazole in three simulated lung fluids was 35.33% in Gamble's solution (GS), 34.12% in artificial lysosomal fluid (ALF), and 42.06% in simulated interstitial lung fluid (SLF). Taking the proliferation activity of the A549 cell model as the endpoint, the benchmark dose limit and benchmark dose of difenoconazole on A549 cells were 16.36 and 5.60 mg/kg, respectively. The margin of exposure to difenoconazole in GS, ALF and SLF were, respectively, 8.66 × 105 to 5.28 × 106 , 8.97 × 105 to 5.47 × 106 and 7.28 × 105 to 4.44 × 106 . CONCLUSION: The risk assessment results indicate that under all circumstances, applying difenoconazole is safe for populations around farmland. However, a fan-shaped nozzle, suspension concentrate and greater inhalation height increase the risk of inhalation. © 2023 Society of Chemical Industry.


Assuntos
Dioxolanos , Exposição por Inalação , Material Particulado , Triazóis , Humanos , Material Particulado/análise , Exposição por Inalação/análise , Medição de Risco , Atmosfera
13.
Cell Host Microbe ; 32(1): 25-34.e5, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38029742

RESUMO

Emerging SARS-CoV-2 sub-lineages like XBB.1.5, XBB.1.16, EG.5, HK.3 (FLip), and XBB.2.3 and the variant BA.2.86 have recently been identified. Understanding the efficacy of current vaccines on these emerging variants is critical. We evaluate the serum neutralization activities of participants who received COVID-19 inactivated vaccine (CoronaVac), those who received the recently approved tetravalent protein vaccine (SCTV01E), or those who had contracted a breakthrough infection with BA.5/BF.7/XBB virus. Neutralization profiles against a broad panel of 30 sub-lineages reveal that BQ.1.1, CH.1.1, and all the XBB sub-lineages exhibit heightened resistance to neutralization compared to previous variants. However, despite their extra mutations, BA.2.86 and the emerging XBB sub-lineages do not demonstrate significantly increased resistance to neutralization over XBB.1.5. Encouragingly, the SCTV01E booster consistently induces higher neutralizing titers against all these variants than breakthrough infection does. Cellular immunity assays also show that the SCTV01E booster elicits a higher frequency of virus-specific memory B cells. Our findings support the development of multivalent vaccines to combat future variants.


Assuntos
Infecções Irruptivas , Vacinas contra COVID-19 , COVID-19 , Imunização Secundária , Humanos , COVID-19/prevenção & controle , SARS-CoV-2/genética , Anticorpos Neutralizantes , Anticorpos Antivirais
14.
NPJ Biofilms Microbiomes ; 9(1): 98, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38086914

RESUMO

Bifidobacteria are key gut commensals that confer various health benefits and are commonly used as probiotics. However, little is known about the population-level variation in gut bifidobacterial composition and its affecting factors. Therefore, we analyzed Bifidobacterium species with amplicon sequencing of the groEL gene on fecal samples of 1674 healthy individuals, who belonged to eight ethnic groups and resided in 60 counties/cities of 28 provinces across China. We found that the composition of the bifidobacterial community was associated with geographical factors, demographic characteristics, staple food type, and urbanization. First, geography, which reflects a mixed effect of other variables, explained the largest variation in the bifidobacterial profile. Second, middle adolescence (age 14-17) and age 30 were two key change points in the bifidobacterial community development, and a bifidobacterial community resembling that of adults occurred in middle adolescence, which is much later than the maturation of the whole gut microbial community at approximately age 3. Third, each ethnicity showed a distinct bifidobacterial profile, and the remarkable amount of unknown Bifidobacterium species in the Tibetan gut suggested undiscovered biodiversity. Fourth, wheat as the main staple food promoted the flourish of B. adolescentis and B. longum. Fifth, alpha diversity of the bifidobacterial community decreased with urbanization. Collectively, our findings provide insight into the environmental and host factors that shape the human gut bifidobacterial community, which is fundamental for precision probiotics.


Assuntos
Bifidobacterium , Probióticos , Adulto , Humanos , Adolescente , Pré-Escolar , Bifidobacterium/genética , Etnicidade , Fezes/microbiologia , Geografia
15.
Brief Bioinform ; 24(6)2023 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-37779249

RESUMO

To contain infectious diseases, it is crucial to determine the origin and transmission routes of the pathogen, as well as how the virus evolves. With the development of genome sequencing technology, genome epidemiology has emerged as a powerful approach for investigating the source and transmission of pathogens. In this study, we first presented the rationale for genomic tracing of SARS-CoV-2 and the challenges we currently face. Identifying the most genetically similar reference sequence to the query sequence is a critical step in genome tracing, typically achieved using either a phylogenetic tree or a sequence similarity search. However, these methods become inefficient or computationally prohibitive when dealing with tens of millions of sequences in the reference database, as we encountered during the COVID-19 pandemic. To address this challenge, we developed a novel genomic tracing algorithm capable of processing 6 million SARS-CoV-2 sequences in less than a minute. Instead of constructing a giant phylogenetic tree, we devised a weighted scoring system based on mutation characteristics to quantify sequences similarity. The developed method demonstrated superior performance compared to previous methods. Additionally, an online platform was developed to facilitate genomic tracing and visualization of the spatiotemporal distribution of sequences. The method will be a valuable addition to standard epidemiological investigations, enabling more efficient genomic tracing. Furthermore, the computational framework can be easily adapted to other pathogens, paving the way for routine genomic tracing of infectious diseases.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/epidemiologia , COVID-19/genética , Filogenia , Pandemias , Genoma Viral , Genômica/métodos
16.
Nat Ecol Evol ; 7(9): 1457-1466, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37443189

RESUMO

Mutations in the SARS-CoV-2 genome could confer resistance to pre-existing antibodies and/or increased transmissibility. The recently emerged Omicron subvariants exhibit a strong tendency for immune evasion, suggesting adaptive evolution. However, because previous studies have been limited to specific lineages or subsets of mutations, the overall evolutionary trajectory of SARS-CoV-2 and the underlying driving forces are still not fully understood. Here we analysed all open-access SARS-CoV-2 genomes (up to November 2022) and correlated the mutation incidence and fitness changes with the impacts of mutations on immune evasion and ACE2 binding affinity. Our results show that the Omicron lineage had an accelerated mutation rate in the RBD region, while the mutation incidence in other genomic regions did not change dramatically over time. Mutations in the RBD region exhibited a lineage-specific pattern and tended to become more aggregated over time, and the mutation incidence was positively correlated with the strength of antibody pressure. Additionally, mutation incidence was positively correlated with changes in ACE2 binding affinity, but with a lower correlation coefficient than with immune evasion. In contrast, the effect of mutations on fitness was more closely correlated with changes in ACE2 binding affinity than with immune evasion. Our findings suggest that immune evasion and ACE2 binding affinity play significant and diverse roles in the evolution of SARS-CoV-2.


Assuntos
COVID-19 , Evasão da Resposta Imune , Humanos , Enzima de Conversão de Angiotensina 2 , Mutação , SARS-CoV-2/genética
17.
Inorg Chem ; 62(19): 7324-7332, 2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-37130306

RESUMO

Negative temperature coefficient (NTC) thermistors feature higher sensitivities and faster response speeds and thereby have particular applications in many fields. However, current NTC thermistors are mostly based on inorganic ceramic materials, which show obvious drawbacks in material synthesis, property modulation, and flexible film fabrication. Herein, we report, for the first time, the promising application of an inorganic-organic hybrid NTC thermistor. A new lead-free hybrid iodo bismuthate [1,1',1″-(benzene-1,3,5-triyl)tris(3-methyl-1H-imidazol-3-ium)]Bi2I9 [denoted as (Me3TMP)Bi2I9] was synthesized by a "double-free" strategy. (Me3TMP)Bi2I9 features a lead-free binuclear bismuth iodine anion charge compensated by a "classic hydrogen-bond-free" cation. (Me3TMP)Bi2I9 exhibits remarkable stability in water and UV light irradiation and shows the largest temperature sensitivity coefficient among all reported NTC materials. Theoretical calculation and detailed structural analysis disclose that the seriously distorted (BiI6) octahedra are responsible for the intriguing NTC effect for (Me3TMP)Bi2I9.

19.
MedComm (2020) ; 4(1): e208, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36744219

RESUMO

The recent pandemic of variants of concern (VOC) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlights the need for innovative anti-SARS-CoV-2 approaches in addition to vaccines and antiviral therapeutics. Here, we demonstrate that a CRISPR-Cas13-based strategy against SARS-CoV-2 can effectively degrade viral RNA. First, we conducted a cytological infection experiment, screened CRISPR-associated RNAs (crRNAs) targeting conserved regions of viruses, and used an in vitro system to validate functional crRNAs. Reprogrammed Cas13d effectors targeting NSP13, NSP14, and nucleocapsid transcripts achieved >99% silencing efficiency in human cells which are infected with coronavirus 2, including the emerging variants in the last 2 years, B.1, B.1.1.7 (Alpha), D614G B.1.351 (Beta), and B.1.617 (Delta). Furthermore, we conducted bioinformatics data analysis. We collected the sequence information of COVID-19 and its variants from China, and phylogenetic analysis revealed that these crRNA oligos could target almost 100% of the SARS-CoV family, including the emerging new variant, Omicron. The reprogrammed Cas13d exhibited high specificity, efficiency, and rapid deployment properties; therefore, it is promising for antiviral drug development. This system could possibly be used to protect against unexpected SARS-CoV-2 variants carrying multiple mutations.

20.
Micromachines (Basel) ; 14(1)2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36677278

RESUMO

Accurately recognizing the hardness and type of different objects by tactile sensors is of great significance in human-machine interaction. In this paper, a novel porous graphene flexible tactile sensor array with great performance is designed and fabricated, and it is mounted on a two-finger mechanical actuator. This is used to detect various tactile sequence features from different objects by slightly squeezing them by 2 mm. A Residual Network (ResNet) model, with excellent adaptivity and feature extraction ability, is constructed to realize the recognition of 4 hardness categories and 12 object types, based on the tactile time sequence signals collected by the novel sensor array; the average accuracies of hardness and type recognition are 100% and 99.7%, respectively. To further verify the classification ability of the ResNet model for the tactile feature information detected by the sensor array, the Multilayer Perceptron (MLP), LeNet, Multi-Channel Deep Convolutional Neural Network (MCDCNN), and ENCODER models are built based on the same dataset used for the ResNet model. The average recognition accuracies of the 4hardness categories, based on those four models, are 93.6%, 98.3%, 93.3%, and 98.1%. Meanwhile, the average recognition accuracies of the 12 object types, based on the four models, are 94.7%, 98.9%, 85.0%, and 96.4%. All of the results demonstrate that the novel porous graphene tactile sensor array has excellent perceptual performance and the ResNet model can very effectively and precisely complete the hardness and type recognition of objects for the flexible tactile sensor array.

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