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1.
Cell ; 185(13): 2265-2278.e14, 2022 06 23.
Article in English | MEDLINE | ID: mdl-35568034

ABSTRACT

Breakthrough infections by SARS-CoV-2 variants become the global challenge for pandemic control. Previously, we developed the protein subunit vaccine ZF2001 based on the dimeric receptor-binding domain (RBD) of prototype SARS-CoV-2. Here, we developed a chimeric RBD-dimer vaccine approach to adapt SARS-CoV-2 variants. A prototype-Beta chimeric RBD-dimer was first designed to adapt the resistant Beta variant. Compared with its homotypic forms, the chimeric vaccine elicited broader sera neutralization of variants and conferred better protection in mice. The protection of the chimeric vaccine was further verified in macaques. This approach was generalized to develop Delta-Omicron chimeric RBD-dimer to adapt the currently prevalent variants. Again, the chimeric vaccine elicited broader sera neutralization of SARS-CoV-2 variants and conferred better protection against challenge by either Delta or Omicron SARS-CoV-2 in mice. The chimeric approach is applicable for rapid updating of immunogens, and our data supported the use of variant-adapted multivalent vaccine against circulating and emerging variants.


Subject(s)
COVID-19 , Vaccines , Animals , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Mice , SARS-CoV-2/genetics
2.
Cell ; 185(10): 1728-1744.e16, 2022 05 12.
Article in English | MEDLINE | ID: mdl-35460644

ABSTRACT

As the emerging variants of SARS-CoV-2 continue to drive the worldwide pandemic, there is a constant demand for vaccines that offer more effective and broad-spectrum protection. Here, we report a circular RNA (circRNA) vaccine that elicited potent neutralizing antibodies and T cell responses by expressing the trimeric RBD of the spike protein, providing robust protection against SARS-CoV-2 in both mice and rhesus macaques. Notably, the circRNA vaccine enabled higher and more durable antigen production than the 1mΨ-modified mRNA vaccine and elicited a higher proportion of neutralizing antibodies and distinct Th1-skewed immune responses. Importantly, we found that the circRNARBD-Omicron vaccine induced effective neutralizing antibodies against the Omicron but not the Delta variant. In contrast, the circRNARBD-Delta vaccine protected against both Delta and Omicron or functioned as a booster after two doses of either native- or Delta-specific vaccination, making it a favorable choice against the current variants of concern (VOCs) of SARS-CoV-2.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Macaca mulatta , Mice , RNA, Circular/genetics , SARS-CoV-2/genetics , Vaccines, Synthetic/genetics , mRNA Vaccines
3.
Nature ; 586(7830): 572-577, 2020 10.
Article in English | MEDLINE | ID: mdl-32726802

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a respiratory disease called coronavirus disease 2019 (COVID-19), the spread of which has led to a pandemic. An effective preventive vaccine against this virus is urgently needed. As an essential step during infection, SARS-CoV-2 uses the receptor-binding domain (RBD) of the spike protein to engage with the receptor angiotensin-converting enzyme 2 (ACE2) on host cells1,2. Here we show that a recombinant vaccine that comprises residues 319-545 of the RBD of the spike protein induces a potent functional antibody response in immunized mice, rabbits and non-human primates (Macaca mulatta) as early as 7 or 14 days after the injection of a single vaccine dose. The sera from the immunized animals blocked the binding of the RBD to ACE2, which is expressed on the cell surface, and neutralized infection with a SARS-CoV-2 pseudovirus and live SARS-CoV-2 in vitro. Notably, vaccination also provided protection in non-human primates to an in vivo challenge with SARS-CoV-2. We found increased levels of RBD-specific antibodies in the sera of patients with COVID-19. We show that several immune pathways and CD4 T lymphocytes are involved in the induction of the vaccine antibody response. Our findings highlight the importance of the RBD domain in the design of SARS-CoV-2 vaccines and provide a rationale for the development of a protective vaccine through the induction of antibodies against the RBD domain.


Subject(s)
Antibodies, Viral/immunology , Betacoronavirus/immunology , Coronavirus Infections/immunology , Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/immunology , Pneumonia, Viral/prevention & control , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology , Viral Vaccines/immunology , Animals , Antibodies, Neutralizing/immunology , COVID-19 , COVID-19 Vaccines , Humans , Macaca mulatta/immunology , Macaca mulatta/virology , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Models, Animal , Models, Molecular , Protein Domains , SARS-CoV-2 , Serum/immunology , Spleen/cytology , Spleen/immunology , T-Lymphocytes/immunology , Vaccination
4.
New Phytol ; 238(4): 1420-1430, 2023 05.
Article in English | MEDLINE | ID: mdl-36843251

ABSTRACT

The basal levels of salicylic acid (SA) vary dramatically among plant species. In the shoot, for example, rice contains almost 100 times higher SA levels than Arabidopsis. Despite its high basal levels, neither the biosynthetic pathway nor the biological functions of SA are well understood in rice. Combining with metabolite analysis, physiological, and genetic approaches, we found that the synthesis of basal SA in rice shoot is dependent on OsAIM1, which encodes a beta-oxidation enzyme in the phenylalanine ammonia-lyase (PAL) pathway. Compromised SA accumulation in the Osaim1 mutant led to a lower shoot temperature than wild-type plants. However, this shoot temperature defect resulted from increased transpiration due to elevated steady-state stomatal aperture in the mutant. Furthermore, the high basal SA level is required for sustained expression of OsWRKY45 to modulate the steady-state stomatal aperture and shoot temperature in rice. Taken together, these results provide the direct genetic evidence for the critical role of the PAL pathway in the biosynthesis of high basal level SA in rice, which plays an important role in the regulation of steady-state stomatal aperture to promote fitness under stress conditions.


Subject(s)
Arabidopsis Proteins , Arabidopsis , Oryza , Oryza/metabolism , Salicylic Acid/metabolism , Plants/metabolism , Arabidopsis/genetics , Phenylalanine Ammonia-Lyase/genetics , Phenylalanine Ammonia-Lyase/metabolism , Gene Expression Regulation, Plant , Multienzyme Complexes/genetics , Multienzyme Complexes/metabolism , Arabidopsis Proteins/metabolism
5.
J Med Virol ; 95(6): e28846, 2023 06.
Article in English | MEDLINE | ID: mdl-37282766

ABSTRACT

Since the first SARS-CoV-2 outbreak in late 2019, the SARS-CoV-2 genome has harbored multiple mutations, especially spike protein mutations. The currently fast-spreading Omicron variant that manifests without symptoms or with upper respiratory diseases has been recognized as a serious global public health problem. However, its pathological mechanism is largely unknown. In this work, rhesus macaques, hamsters, and BALB/C mice were employed as animal models to explore the pathogenesis of Omicron (B.1.1.529). Notably, Omicron (B.1.1.529) infected the nasal turbinates, tracheae, bronchi, and lungs of hamsters and BALB/C mice with higher viral loads than in those of rhesus macaques. Severe histopathological damage and inflammatory responses were observed in the lungs of Omicron (B.1.1.529)-infected animals. In addition, viral replication was found in multiple extrapulmonary organs. Results indicated that hamsters and BALB/c mice are potential animal models for studies on the development of drugs/vaccines and therapies for Omicron (B.1.1.529).


Subject(s)
COVID-19 , SARS-CoV-2 , Mice , Animals , Cricetinae , Macaca mulatta , Mice, Inbred BALB C , Bronchi
6.
Biochem Genet ; 61(2): 725-741, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36104590

ABSTRACT

Lung cancer is the most commonly diagnosed cancer and the leading reason for tumor-related mortality, while non-small cell lung cancer (NSCLC) is the most usual type of lung cancer. Circular RNAs (circRNAs) have emerged as vital regulators in the development of human cancers, including NSCLC. We aimed to explore the functions of circRNA leukemia inhibitory factor receptor (circLIFR) in NSCLC progression. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to quantify the expression of circLIFR, microRNA-429 (miR-429), and Elav-like family member 2 (CELF2) in NSCLC tissues and cells. Cell proliferation capability of NSCLC cells was determined by Cell Counting Kit-8 (CCK-8) and colony formation assays. The flow cytometry assay was performed to evaluate cell-cycle distribution and apoptosis of NSCLC cells. The abilities of migration and invasion were measured by transwell assay. In addition, the activities of caspase 3 and caspase 9 were measured by the assay kits. The interaction relationship between miR-429 and circLIFR or CELF2 was analyzed by dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays. The expression levels of related proteins were examined by Western Blot assay. The xenograft experiment was established to explore the role of circLIFR in vivo. CircLIFR, circular, and stable transcript in NSCLC cells, was decreased more than 2 folds in NSCLC tissues and cells than controls (P < 0.0001). Importantly, overexpression of circLIFR impeded cell proliferation, migration, invasion, and inactivated protein kinase B (AKT)/phosphatase and tensin homolog (PTEN)-signaling pathways while enhanced apoptosis and cell-cycle arrest in NSCLC cells, which was overturned by upregulation of miR-429 or silencing of CELF2. Furthermore, the upregulation of circLIFR inhibited NSCLC tumor growth in vivo. Overexpression of circLIFR could suppress NSCLC progress by acting as a sponge of miR-429 to regulate the expression of CELF2 and PTEN/AKT-signaling pathways in NSCLC.


Subject(s)
CELF Proteins , Carcinoma, Non-Small-Cell Lung , Leukemia Inhibitory Factor Receptor alpha Subunit , Lung Neoplasms , MicroRNAs , Humans , Carcinoma, Non-Small-Cell Lung/genetics , Cell Proliferation , Lung Neoplasms/genetics , MicroRNAs/genetics , Nerve Tissue Proteins , Proto-Oncogene Proteins c-akt , Leukemia Inhibitory Factor Receptor alpha Subunit/genetics
7.
Sensors (Basel) ; 23(11)2023 Jun 05.
Article in English | MEDLINE | ID: mdl-37300063

ABSTRACT

Compared to fixed orthodontic appliances with brackets, thermoplastic invisible orthodontic aligners offer several advantages, such as high aesthetic performance, good comfort, and convenient oral health maintenance, and are widely used in orthodontic fields. However, prolonged use of thermoplastic invisible aligners may lead to demineralization and even caries in most patients' teeth, as they enclose the tooth surface for an extended period. To address this issue, we have created PETG composites that contain piezoelectric barium titanate nanoparticles (BaTiO3NPs) to obtain antibacterial properties. First, we prepared piezoelectric composites by incorporating varying amounts of BaTiO3NPs into PETG matrix material. The composites were then characterized using techniques such as SEM, XRD, and Raman spectroscopy, which confirmed the successful synthesis of the composites. We cultivated biofilms of Streptococcus mutans (S. mutans) on the surface of the nanocomposites under both polarized and unpolarized conditions. We then activated piezoelectric charges by subjecting the nanocomposites to 10 Hz cyclic mechanical vibration. The interactions between the biofilms and materials were evaluated by measuring the biofilm biomass. The addition of piezoelectric nanoparticles had a noticeable antibacterial effect on both the unpolarized and polarized conditions. Under polarized conditions, nanocomposites demonstrated a greater antibacterial effect than under unpolarized conditions. Additionally, as the concentration of BaTiO3NPs increased, the antibacterial rate also increased, with the surface antibacterial rate reaching 67.39% (30 wt% BaTiO3NPs). These findings have the potential for application in wearable, invisible appliances to improve clinical services and reduce the need for cleaning methods.


Subject(s)
Nanocomposites , Streptococcus mutans , Humans , Biofilms , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Nanocomposites/chemistry
8.
J Cell Mol Med ; 26(7): 1969-1978, 2022 04.
Article in English | MEDLINE | ID: mdl-35229451

ABSTRACT

CD44 has shown prognostic values and promising therapeutic potential in multiple human cancers; however, the effects of CD44 silencing on biological behaviors of cancer stem cells (CSCs) have not been fully understood in colorectal cancer. To examine the contribution of siRNA-induced knockdown of CD44 to the biological features of colorectal CSCs, colorectal CSCs HCT116-CSCs were generated, and CD44 was knocked down in HCT116-CSCs using siRNA. The proliferation, migration and invasion of HCT116-CSCs were measured, and apoptosis and cell-cycle analyses were performed. The sensitivity of HCT116-CSCs to oxaliplatin was tested, and xenograft tumor growth assay was performed to examine the role of CD44 in HCT116-CSCs tumorigenesis in vivo. In addition, the expression of epithelial-mesenchymal transition (EMT) markers E-cadherin, N-cadherin and vimentin was quantified. siRNA-induced knockdown of CD44 was found to inhibit the proliferation, migration and invasion, induce apoptosis, promote cell-cycle arrest at the G1/G0 phase and increase the sensitivity of HCT116-CSCs to oxaliplatin in HCT116-CSCs, and knockdown of CD44 suppressed in vivo tumorigenesis and intrapulmonary metastasis of HCT116-CSCs. Moreover, silencing CD44 resulted in EMT inhibition. Our findings demonstrate that siRNA-induced CD44 knockdown suppresses the proliferation, invasion and in vivo tumorigenesis and metastasis of colorectal CSCs by inhibiting EMT.


Subject(s)
Colorectal Neoplasms , Epithelial-Mesenchymal Transition , Hyaluronan Receptors , Animals , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Colorectal Neoplasms/pathology , Epithelial-Mesenchymal Transition/genetics , Gene Expression Regulation, Neoplastic , Humans , Hyaluronan Receptors/genetics , Neoplastic Stem Cells/metabolism , RNA, Small Interfering/genetics
9.
Gastroenterology ; 160(5): 1647-1661, 2021 04.
Article in English | MEDLINE | ID: mdl-33307034

ABSTRACT

BACKGROUND & AIMS: Gastrointestinal (GI) manifestations have been increasingly reported in patients with coronavirus disease 2019 (COVID-19). However, the roles of the GI tract in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are not fully understood. We investigated how the GI tract is involved in SARS-CoV-2 infection to elucidate the pathogenesis of COVID-19. METHODS: Our previously established nonhuman primate (NHP) model of COVID-19 was modified in this study to test our hypothesis. Rhesus monkeys were infected with an intragastric or intranasal challenge with SARS-CoV-2. Clinical signs were recorded after infection. Viral genomic RNA was quantified by quantitative reverse transcription polymerase chain reaction. Host responses to SARS-CoV-2 infection were evaluated by examining inflammatory cytokines, macrophages, histopathology, and mucin barrier integrity. RESULTS: Intranasal inoculation with SARS-CoV-2 led to infections and pathologic changes not only in respiratory tissues but also in digestive tissues. Expectedly, intragastric inoculation with SARS-CoV-2 resulted in the productive infection of digestive tissues and inflammation in both the lung and digestive tissues. Inflammatory cytokines were induced by both types of inoculation with SARS-CoV-2, consistent with the increased expression of CD68. Immunohistochemistry and Alcian blue/periodic acid-Schiff staining showed decreased Ki67, increased cleaved caspase 3, and decreased numbers of mucin-containing goblet cells, suggesting that the inflammation induced by these 2 types of inoculation with SARS-CoV-2 impaired the GI barrier and caused severe infections. CONCLUSIONS: Both intranasal and intragastric inoculation with SARS-CoV-2 caused pneumonia and GI dysfunction in our rhesus monkey model. Inflammatory cytokines are possible connections for the pathogenesis of SARS-CoV-2 between the respiratory and digestive systems.


Subject(s)
COVID-19/transmission , Gastroenteritis/pathology , Gastrointestinal Tract/pathology , Lung/pathology , Animals , Bronchi/metabolism , Bronchi/pathology , COVID-19/immunology , COVID-19/metabolism , COVID-19/pathology , COVID-19 Nucleic Acid Testing , Caspase 3/metabolism , Cytokines/immunology , Disease Models, Animal , Gastric Mucosa , Gastroenteritis/metabolism , Gastroenteritis/virology , Gastrointestinal Tract/immunology , Gastrointestinal Tract/metabolism , Goblet Cells/pathology , Intestine, Small/metabolism , Intestine, Small/pathology , Ki-67 Antigen/metabolism , Lung/diagnostic imaging , Lung/immunology , Lung/metabolism , Macaca mulatta , Nasal Mucosa , RNA, Viral/isolation & purification , Random Allocation , Rectum/metabolism , Rectum/pathology , SARS-CoV-2 , Trachea/metabolism , Trachea/pathology
11.
BMC Pulm Med ; 22(1): 412, 2022 Nov 10.
Article in English | MEDLINE | ID: mdl-36357869

ABSTRACT

BACKGROUND: Adenocarcinoma has long been an independent histological class of lung cancer, which leads to high morbidity and mortality. We aimed to investigate the contribution of LINC02126 in lung adenocarcinoma. METHODS: RNA sequencing data and clinical information were downloaded. Diagnostic efficiency and survival analysis of LINC02126 were performed, followed by functional analysis of genes co-expressed with LINC02126 and differentially expressed genes (DEGs) in different LINC02126 expression groups. Tumor immune microenvironment (TIME) cell infiltration and correlation analysis of tumor mutation burden were performed in different LINC02126 expression groups. RESULTS: In lung adenocarcinoma, the expression level of LINC02126 was significantly decreased. Significant expression differences of LINC02126 were found in some clinical variables, including T staging, M staging, sex, stage, and EGFR mutation. LINC02126 had potential diagnostic and prognostic value for patients. In the low LINC02126 expression group, the infiltration degree of most immune cells was significantly lower than that in the high LINC02126 expression group. Tumor mutation burden level and frequency of somatic mutation in patients with low LINC02126 expression group were significantly higher than in patients with high LINC02126 expression group. CONCLUSIONS: LINC02126 could be considered as a diagnostic, prognostic and immunotherapeutic target for lung adenocarcinoma.


Subject(s)
Adenocarcinoma of Lung , Lung Neoplasms , Humans , Prognosis , ErbB Receptors/genetics , Adenocarcinoma of Lung/diagnosis , Adenocarcinoma of Lung/genetics , Lung Neoplasms/diagnosis , Lung Neoplasms/genetics , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Immunotherapy , Gene Expression Regulation, Neoplastic , Tumor Microenvironment/genetics
12.
Med Sci Monit ; 23: 4657-4664, 2017 Sep 28.
Article in English | MEDLINE | ID: mdl-28957036

ABSTRACT

BACKGROUND This study aimed to compare the efficacy and safety of vinorelbine plus cisplatin (NP regimen) vs. gemcitabine plus cisplatin (GP regimen) for treatment of metastatic TNBC after failure with anthracyclines and taxanes. MATERIAL AND METHODS A total of 48 patients with metastatic TNBC that failed in anthracyclines and taxanes treatment were enrolled and randomly grouped. Patients in the NP group (n=22) were given 25 mg/m² vinorelbine on days 1 and 8 and 25 mg/m² cisplatin on days 2-4 of each 21-day cycle, while subjects in the GP group (n=26) were administered 1000 mg/m² gemcitabine on days 1 and 8 and 25 mg/m² cisplatin on days 2-4 of each 21-day cycle. The treatment response and adverse events were compared between the 2 groups every 2 cycles. RESULTS The ORR, DCR, and median TTP were 45.5%, 77.3%, and 5 months in the NP group, and 46.2%, 80.8%, and 5.2 months in the GP group, and no significant differences were observed in ORR, DCR, and median TTP between the 2 groups (P>0.05). The major adverse events included grade I-II bone marrow inhibition, gastrointestinal reactions, and phlebitis, and a lower incidence of thrombocytopenia and rash and a higher incidence of phlebitis was found in the NP group than in the GP group (P<0.05). CONCLUSIONS Either NP or GP regimen is active and tolerated in treatment of metastatic TNBC with anthracyclines and/or taxanes resistance, which may be used as a salvage treatment for metastatic TNBC.


Subject(s)
Anthracyclines/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cisplatin/therapeutic use , Deoxycytidine/analogs & derivatives , Taxoids/therapeutic use , Triple Negative Breast Neoplasms/drug therapy , Vinblastine/analogs & derivatives , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cisplatin/adverse effects , Demography , Deoxycytidine/adverse effects , Deoxycytidine/therapeutic use , Disease Progression , Female , Humans , Middle Aged , Neoplasm Metastasis , Treatment Outcome , Vinblastine/adverse effects , Vinblastine/therapeutic use , Vinorelbine , Gemcitabine
13.
Planta ; 240(1): 103-15, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24705986

ABSTRACT

Phospholipase D (PLD) is crucial for plant responses to stress and signal transduction, however, the regulatory mechanism of PLD in abiotic stress is not completely understood; especially, in crops. In this study, we isolated a gene, TaPLDα, from common wheat (Triticum aestivum L.). Analysis of the amino acid sequence of TaPLDα revealed a highly conserved C2 domain and two characteristic HKD motifs, which is similar to other known PLD family genes. Further characterization revealed that TaPLDα expressed differentially in various organs, such as roots, stems, leaves and spikelets of wheat. After treatment with abscisic acid (ABA), methyl jasmonate, dehydration, polyethylene glycol and NaCl, the expression of TaPLDα was up-regulated in shoots. Subsequently, we generated TaPLDα-overexpressing transgenic Arabidopsis lines under the control of the dexamethasone-inducible 35S promoter. The overexpression of TaPLDα in Arabidopsis resulted in significantly enhanced tolerance to drought, as shown by reduced chlorosis and leaf water loss, higher relative water content and lower relative electrolyte leakage than the wild type. Moreover, the TaPLDα-overexpressing plants exhibited longer roots in response to mannitol treatment. In addition, the seeds of TaPLDα-overexpressing plants showed hypersensitivity to ABA and osmotic stress. Under dehydration, the expression of several stress-related genes, RD29A, RD29B, KIN1 and RAB18, was up-regulated to a higher level in TaPLDα-overexpressing plants than in wild type. Taken together, our results indicated that TaPLDα can enhance tolerance to drought and osmotic stress in Arabidopsis and represents a potential candidate gene to enhance stress tolerance in crops.


Subject(s)
Arabidopsis/physiology , Gene Expression Regulation, Plant , Phospholipase D/genetics , Signal Transduction , Stress, Physiological , Triticum/enzymology , Amino Acid Sequence , Arabidopsis/enzymology , Arabidopsis/genetics , Arabidopsis/growth & development , Droughts , Gene Expression , Germination , Molecular Sequence Data , Osmotic Pressure , Phospholipase D/metabolism , Phylogeny , Plant Leaves/enzymology , Plant Leaves/genetics , Plant Leaves/growth & development , Plant Leaves/physiology , Plant Proteins/genetics , Plant Proteins/metabolism , Plant Roots/enzymology , Plant Roots/genetics , Plant Roots/growth & development , Plant Roots/physiology , Plants, Genetically Modified , Seedlings/enzymology , Seedlings/genetics , Seedlings/growth & development , Seedlings/physiology , Seeds/enzymology , Seeds/genetics , Seeds/growth & development , Seeds/physiology , Sequence Analysis, DNA , Transgenes , Triticum/genetics
14.
Genet Mol Biol ; 37(1): 73-80, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24688294

ABSTRACT

WRKY transcription factors have been extensively characterized in the past 20 years, but in wheat, studies on WRKY genes and their function are lagging behind many other species. To explore the function of wheat WRKY genes, we identified a TaWRKY68 gene from a common wheat cultivar. It encodes a protein comprising 313 amino acids which harbors 19 conserved motifs or active sites. Gene expression patterns were determined by analyzing microarray data of TaWRKY68 in wheat and of orthologous genes from maize, rice and barley using Genevestigator. TaWRKY68 orthologs were identified and clustered using DELTA-BLAST and COBALT programs available at NCBI. The results showed that these genes, which are expressed in all tissues tested, had relatively higher levels in the roots and were up-regulated in response to biotic stresses. Bioinformatics results were confirmed by RT-PCR experiments using wheat plants infected by Agrobacterium tumefaciens and Blumeria graminis, or treated with Deoxynivalenol, a Fusarium graminearum-induced mycotoxin in wheat or barley. In summary, TaWRKY68 functions differ during plant developmental stages and might be representing a hub gene function in wheat responses to various biotic stresses. It was also found that including data from major cereal genes in the bioinformatics analysis gave more accurate and comprehensive predictions of wheat gene functions.

15.
Heliyon ; 10(3): e25032, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38317951

ABSTRACT

In the era of big data, data processing capability is key to gaining a competitive advantage for businesses. With appropriate technical and organizational resources in place, enterprises can extract considerable value from the vast amount of available data, thereby increasing their competitive advantage. Therefore, to utilize big data resources effectively, enterprises should focus on improving the intellectual abilities of big data analysts. Big data analytics intellectual capability (BDAIC) refers to the specialized skills and knowledge that employees of the enterprise possess, including technical, technical management, business, and relational knowledge, that would enable them to use analytics tools to accomplish organizational tasks and shape the core competitiveness of an enterprise. This study constructs a theoretical model that focuses on the mediating role of person-tool fit and examines the mechanisms by which BDAIC affects an enterprise's operational performance. The results show that BDAIC, which contains four basic categories of knowledge, positively influences an enterprise's operational efficiency. Additionally, person-tool matching mediates BDAIC's effect on an enterprise's operational performance. These findings explore the latest avenues of exploration in the research paradigm of big data analytics. Furthermore, this study has important implications for practitioners trying to use big data to improve business performance.

16.
Gut Microbes ; 16(1): 2334970, 2024.
Article in English | MEDLINE | ID: mdl-38563680

ABSTRACT

Gastrointestinal (GI) infection is evidenced with involvement in COVID-19 pathogenesis caused by SARS-CoV-2. However, the correlation between GI microbiota and the distinct pathogenicity of SARS-CoV-2 Proto and its emerging variants remains unclear. In this study, we aimed to determine if GI microbiota impacted COVID-19 pathogenesis and if the effect varied between SARS-CoV-2 Proto and its variants. We performed an integrative analysis of histopathology, microbiomics, and transcriptomics on the GI tract fragments from rhesus monkeys infected with SARS-CoV-2 proto or its variants. Based on the degree of pathological damage and microbiota profile in the GI tract, five of SARS-CoV-2 strains were classified into two distinct clusters, namely, the clusters of Alpha, Beta and Delta (ABD), and Proto and Omicron (PO). Notably, the abundance of potentially pathogenic microorganisms increased in ABD but not in the PO-infected rhesus monkeys. Specifically, the high abundance of UCG-002, UCG-005, and Treponema in ABD virus-infected animals positively correlated with interleukin, integrins, and antiviral genes. Overall, this study revealed that infection-induced alteration of GI microbiota and metabolites could increase the systemic burdens of inflammation or pathological injury in infected animals, especially in those infected with ABD viruses. Distinct GI microbiota and metabolite profiles may be responsible for the differential pathological phenotypes of PO and ABD virus-infected animals. These findings improve our understanding the roles of the GI microbiota in SARS-CoV-2 infection and provide important information for the precise prevention, control, and treatment of COVID-19.


Subject(s)
COVID-19 , Gastrointestinal Microbiome , Animals , SARS-CoV-2 , Virulence , Macaca mulatta
17.
J Appl Biomater Funct Mater ; 21: 22808000231181326, 2023.
Article in English | MEDLINE | ID: mdl-37340729

ABSTRACT

The primary goal of bone tissue engineering is to fabricate scaffolds that can provide a microenvironment similar to that of natural bone. Therefore, various scaffolds have been designed to replicate the bone structure. Although most tissues exhibit complicated structures, their basic structural unit includes stiff platelets arranged in a staggered micro-array. Therefore, many researchers have designed scaffolds with staggered patterns. However, relatively few studies have comprehensively analyzed this type of scaffold. In this review, we have analyzed scientific research pertaining to staggered scaffold designs and summarized their effects on the physical and biological properties of scaffolds. Compression tests or finite element analysis are typically used to evaluate the mechanical properties of scaffolds, and most studies have performed experiments in cell cultures. Staggered scaffolds improve mechanical strength and are beneficial for cell attachment, proliferation, and differentiation in comparison with conventional designs. However, very few have been studied in vivo experiments. Additionally, studies on the effect of staggered structures on angiogenesis or bone regeneration in vivo, particularly in large animals, are required. Currently, with the prevalence of artificial intelligence (AI)-based technologies, highly optimized models can be developed, resulting in better discoveries. In the future, AI can be used to deepen our understanding on the staggered structure, promoting its use in clinical applications.


Subject(s)
Tissue Engineering , Tissue Scaffolds , Animals , Tissue Engineering/methods , Tissue Scaffolds/chemistry , Artificial Intelligence , Bone and Bones , Bone Regeneration , Porosity
18.
Prog Orthod ; 24(1): 25, 2023 Jul 17.
Article in English | MEDLINE | ID: mdl-37455279

ABSTRACT

BACKGROUND: Maxillary molar distalization is a common technique used in the non-extraction treatment of Angle Class II malocclusion that can effectively correct the molar relationship and create spaces for anterior teeth alignment. However, this approach may also impact the temporomandibular joint (TMJ) due to predictable changes in the posterior vertical dimension. Despite its widespread use, Class II malocclusions correction by molar distalization with clear aligners has not been investigated for their effects on the TMJ. Therefore, this study aimed to analyze the impact of sequential molar distalization using clear aligners on the TMJ. METHODS: Three-dimensional CBCT scans of 23 non-growing patients (7 males, 16 females; mean age 29.8 ± 4.6 years) with skeletal class I or II malocclusion and a bilateral molar class II relationship treated by sequential upper molars distalization with orthodontic clear aligners (Invisalign, Align Technology, San Josè, Ca, USA). A total of 46 joints were examined before and after molar distalization using Anatomage InvivoDental 6.0.3. Linear and angular measurements of the mandibular joint were measured, including joint parameters, inclination, position, and the dimension of the condyle and articular fossa. In addition, 3D volumetric spaces of the joint were analyzed. All data were statistically analyzed by paired T test to determine the differences between the pre-and post-orthodontic procedures. RESULTS: No statistically significant differences were found in all primary effects resulting from maxillary molars distalization by clear aligners on TMJ components measurements and joint spaces between T0 and T1. Meanwhile, statistically significant differences were observed in the linear position of the upper molars and the molar relationship parameter with at least P ≤ 0.05. CONCLUSION: Treatment by sequential upper molars distalization with clear aligners does not lead to significant TMJ parameters changes in condyle and fossa spaces, dimensions, and positions.


Subject(s)
Malocclusion, Angle Class II , Orthodontic Appliances, Removable , Tooth Movement Techniques , Adult , Female , Humans , Male , Malocclusion , Malocclusion, Angle Class II/diagnostic imaging , Malocclusion, Angle Class II/therapy , Maxilla/diagnostic imaging , Molar/diagnostic imaging , Temporomandibular Joint/diagnostic imaging , Tooth Movement Techniques/methods , Cone-Beam Computed Tomography
19.
Oncol Rep ; 50(4)2023 Oct.
Article in English | MEDLINE | ID: mdl-37681504

ABSTRACT

Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that a pair of the wound­healing assay data panels featured in Fig. 2E on p. 1011 (namely, the PLZF / 0 h and 48 h data panels for the BGC823 cell line) had also appeared in another article containing a majority of the same authors that had already been published [Chen J­F, Wu P, Xia R, Yang J, Huo X­Y, Gu D­Y, Tang C­J, We D and Yang F: STAT3­induced lncRNA HAGLROS overexpression contributes to the malignant progression of gastric cancer cells via mTOR signal­mediated inhibition of autophagy. Mol Cancer 17: 6, 2018], where the same data had been been used to show the results from differently performed experiments. The authors were able to re­examine their original data files, and realized that this figure had been inadverently assembled incorrectly. The revised version of Fig. 2, containing the correct data for the PLZF / 0 h and 48 h data panels in Fig. 2E, is shown on the next page. Note that the revisions made to this figure do not affect the overall conclusions reported in the paper. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this Corrigendum, and apologize to the readership for any inconvenience caused. [Oncology Reports 41: 1007­1018, 2019; DOI: 10.3892/or.2018.6866].

20.
Heliyon ; 9(3): e13915, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36923844

ABSTRACT

Background: Rhesus macaques and humans are closely related genetically and share similar physiological and pathological characteristics. Exploring the impact of diet on the early establishment of gut microbiota in non-human primates can provide relevant clinical models for healthy infant growth and development. At present, few writers have focused on the composition and changes of the intestinal microbes of infant rhesus macaques throughout their progression from birth to formula feeding after weaning. In this study, we used 16S rRNA sequencing technology to explore the composition of the intestinal flora of rhesus macaques at different ages and analyzed the trends in the microbial changes. Results: The results showed that the relative abundance of Bifidobacterium and Lactobacillus in the intestinal flora of infant rhesus macaques significantly decreased, and Prevotella increased with age. Bifidobacterium longum and Bifidobacterium breve are effective biomarkers to predict grouping. The metabolic pathways enriched in early life mainly concentrated in glycosphingolipid biosynthesis (lacto and neolacto series) and the degradation and metabolism of alcohols and esters. Conclusions: We found that age was an important factor that affected the changes in the intestinal flora. This study revealed the change trend of flora in breastfed and formula-fed infant rhesus monkeys in different growth months, and found that the dominant flora changed greatly. This research provides a medically relevant theoretical basis for understanding the healthy development of infants.

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