ABSTRACT
Fagopyrum dibotrys, belonging to the family Polygonaceae and genus Fagopyrum, is used in traditional Chinese medicine and is rich in beneficial components, such as flavonoids. As its abundant medicinal value has become increasingly recognized, its excessive development poses a considerable challenge to wild germplasm resources, necessitating artificial cultivation and domestication. Considering these factors, a high-quality genome of F. dibotrys was assembled and the evolutionary relationships within Caryophyllales were compared, based on which 58 individual samples of F. dibotrys were re-sequenced. We found that the samples could be categorized into three purebred populations and regions distributed at distinct elevations. Our varieties were cultivated from the parental populations of the subpopulation in central Yunnan. F. dibotrys is speculated to have originated in the high-altitude Tibetan Plateau region, and that its combination with flavonoids can protect plants against ultraviolet radiation; this infers a subpopulation with a high accumulation of flavonoids. This study assembled a high-quality genome and provided a theoretical foundation for the future introduction, domestication, and development of cultivated varieties of F. dibotrys.
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Biofilm has been used in environmental pollution control in recent years due to its characteristics of adsorption and biodegradation. Beyond the success of its utilization in wastewater treatment, biofilm technique has high application value in the remediation of heavy metals and organic pollutants in soils. With the extensive attention and research of emerging pollutants such as microplastics and antibiotic resistance genes (ARGs), the pivotal role of biofilm can not be overlooked. Here, we presented a comprehensive review of the structure, formation mecha-nism, population, and functional aspects of biofilm, as well as its applications and mechanisms in environmental pollution control in recent years. We emphatically discussed the removal mechanism and application progress of biofilm on heavy metals and organic pollutants. We further expounded some novel environmental challenges posed by biofilm under new circumstances, including the coexistence of various pollutants in plastisphere, the spread of ARGs, and the accumulation of pathogens. Finally, we put forward the gaps of current research and prospects for future research, especially the importance of exploring the interaction relationship and mechanism between biofilm and various pollutants. It is expected to provide theoretical basis for the development of new technology of biofilm remediation.
Subject(s)
Biodegradation, Environmental , Biofilms , Environmental Pollution , Metals, Heavy , Biofilms/growth & development , Environmental Pollution/prevention & control , Environmental Pollutants , Organic ChemicalsABSTRACT
Nonylphenol (NP) is a ubiquitous endocrine disruptor that persists in the environment and can significantly contribute to serious health hazards, particularly intestinal barrier injury. Plant essential oils (EOs) have recently gained widespread interest due to their potential for improving intestinal health. However, the precise mechanism and protective effects of EOs ameliorating the intestinal damages induced by NP exposure remain unclear. To clarify the potential mechanism and protective impact of EOs against intestinal injury induced by NP, a total of 144 one-day-old male ducks were randomly allocated to four groups: CON (basal diet), EO (basal diet + 200 mg/kg EOs), NP (basal diet + 40 mg/kg NP), and NPEO (basal diet + 200 mg/kg EOs + 40 mg/kg NP). The data revealed that NP exposure significantly damaged intestinal barrier, as evidenced by a reduction in the levels of tight junction gene expression and an increase in intestinal permeability. Additionally, it disturbed gut microbiota, as well as interfered with tryptophan (Trp) metabolism. The NP-induced disorder of Trp metabolism restrained the activation of aryl hydrocarbon receptor (AhR) and resulted in decreased the expression levels of CYP1A1, IL-22, and STAT3 genes, which were alleviated after treatment with EOs. Taken together, NP exposure resulted in impairment of the intestinal barrier function, disruption of gut microbiota, and disturbances in Trp metabolism. Dietary EOs supplementation alleviated the intestinal barrier injury induced by NP through the Trp/AhR/IL-22 signaling pathway.
Subject(s)
Gastrointestinal Microbiome , Oils, Volatile , Phenols , Receptors, Aryl Hydrocarbon , Tryptophan , Animals , Male , Cytochrome P-450 CYP1A1/metabolism , Cytochrome P-450 CYP1A1/genetics , Ducks , Endocrine Disruptors/toxicity , Gastrointestinal Microbiome/drug effects , Interleukin-22 , Intestinal Mucosa/metabolism , Intestinal Mucosa/drug effects , Intestines/drug effects , Oils, Volatile/pharmacology , Phenols/toxicity , Receptors, Aryl Hydrocarbon/metabolism , Tryptophan/metabolismABSTRACT
Landfill is a huge pathogen reservoir and needs special attention. Herein, the distribution and spread risk of pathogen were assessed in excavated landfill scenario. The results show that landfill excavation will greatly increase the risk of environmental microbial contamination. The highest total concentration of culturable bacteria among landfill refuse, topsoil and plant leaves was found to be as high as 1010 CFU g-1. Total coliforms, Hemolytic bacteria, Staphylococcus aureus, Salmonella, Enterococci, and Fecal coliforms were detected in the landfill surrounding environment. Notably, pathogens were more likely to adhere to plant leaves, making it an important source of secondary pathogens. The culturable bacteria concentration in the air samples differed with the landfill zone with different operation status, and the highest culturable bacteria concentration was found in the excavated area of the landfill (3.3 × 104 CFU m-3), which was the main source of bioaerosol release. The distribution of bioaerosols in the downwind outside of the landfill showed a tendency of increasing and then decreasing, and the highest concentration of bioaerosols outside of the landfill (6.56 × 104 CFU m-3) was significantly higher than that in the excavated area of the landfill. The risk of respiratory inhalation was the main pathway leading to infection, whereas the HQin (population inhalation hazardous quotient) at 500 m downwind the excavation landfill was still higher than 1, indicating that the neighboring residents were exposed to airborne microbial pollutants. The results of the study provide evidence for bioaerosols control protective measures taken to reduce health risk from the excavated landfill.
Subject(s)
Air Microbiology , Environmental Monitoring , Waste Disposal Facilities , Bacteria/isolation & purification , Refuse Disposal , Aerosols/analysis , Soil Microbiology , Risk AssessmentABSTRACT
Household garbage rooms release abundant bioaerosols and are an important source of pathogens; however, information on the distribution and survival patterns of pathogens in different waste components is limited. In this study, a culture method and 16S rRNA high-throughput sequencing were used to determine bacterial communities, culturable pathogens, and human bacterial pathogens (HBPs). The results showed that abundant culturable bacteria were detected in all waste types, and a large number of S. aureus was detected on the surface of recyclable wastes, whereas S. aureus, total coliforms, Salmonella, Enterococcus, and hemolytic bacteria were detected in food waste and other waste. The activities of these detected pathogenic bacteria decreased after 24 h of storage but re-activated within one week. Factors affecting the emergence of pathogens varied with different waste components. Sequencing results showed that Pseudomonas, Acinetobacter, and Burkholderia were abundant in the waste samples, whereas Achromobacter, Exiguobacteriums, Bordetella, and Corynebacterium were the primary pathogens in the bioaerosol and wall attachment. The results of traceability analysis showed that bioaerosol microbes were mainly derived from raw kitchen waste (5.98%) and plastic and paper contaminated with food waste (19.93%) in garbage rooms. In addition, bioaerosols were the main source of microflora in the wall attachment, which possessed high HBP diversity and required more attention. These findings will help in understanding the microbial hazards in different waste components and provide guidance for the control and risk reduction of bioaerosols during waste management and recycling.
Subject(s)
Aerosols , Air Microbiology , Bacteria , Bacteria/isolation & purification , Bacteria/classification , Bacteria/genetics , Aerosols/analysis , Garbage , Humans , RNA, Ribosomal, 16S/genetics , RNA, Ribosomal, 16S/analysis , Refuse Disposal , Environmental Monitoring/methodsABSTRACT
OBJECTIVE: This study aimed to investigate the correlation between positive psychological capital, post-traumatic growth, social support, and quality of life (QOL) in patients with systemic lupus erythematosus (SLE). METHODS: A cross-sectional study was conducted at the First Affiliated Hospital of Xinjiang Medical University from October 2022 to May 2023. A sample of 330 hospitalized SLE patients was selected for this study. The collected data included demographic information, the SLE disease activity index, the Positive Mental Capital Questionnaire, the Chinese version of the Post-Traumatic Growth Scale, the Social Support Rating Scale, and the Chinese version of the Lupus Quality of Life Scale. RESULTS: The QOL score among the 330 SLE patients was measured as M(P25, P75) of 105 (83.00,124.00). Positive psychological capital, post-traumatic growth, and social support demonstrated significant positive correlations with the QOL in SLE patients (p < 0.05). Multiple linear regression analysis revealed that literacy, disease level, disease duration, occupation, marital status, psychological capital, social support, and post-traumatic growth were influential factors associated with the QOL in SLE patients. CONCLUSION: Medical professionals should be attentive to the psychological well-being of SLE patients and should consider implementing early psychological interventions. These interventions are crucial for enhancing the QOL for individuals diagnosed with SLE.
Subject(s)
Lupus Erythematosus, Systemic , Posttraumatic Growth, Psychological , Humans , Quality of Life/psychology , Cross-Sectional Studies , Lupus Erythematosus, Systemic/complications , Social Support , Surveys and QuestionnairesABSTRACT
During the long-term stabilization process of landfills, the pressure field undergoes constant changes. This study constructed dynamic pressure changes scenarios of high-pressure differentials (0.6 MPa) and low-pressure differentials (0.2 MPa) in the landfill pressure field at 25 °C and 50 °C, and investigated the sulfate reduction behavior in response to landfill dynamic pressure changes. The results showed that the pressurization or depressurization of high-pressure differentials caused more significant differences in sulfate reduction behavior than that of low-pressure differentials. The lowest hydrogen sulfide (H2S) release peak concentration under pressurization was only 29.67% of that under initial pressure condition; under depressurization, the highest peak concentration of H2S was up to 21,828 mg m-3, posing a serious risk of H2S pollution. Microbial community and correlation analysis showed that pressure had a negative impact on the sulfate-reducing bacteria (SRB) community, and the SRB community adjusted its structure to adapt to pressure changes. Specific SRBs were further enriched with pressure changes. Differential H2S release behavior under pressure changes in the 25 °C pressure environments were mediated by Desulfofarcimen (ASV343) and Desulfosporosinus (ASV1336), while Candidatus Desulforudis (ASV24) and Desulfohalotomaculum (ASV94) played a key role at 50 °C. This study is helpful in the formulation of control strategies for the source of odor pollution in landfills.
Subject(s)
Desulfovibrio , Hydrogen Sulfide , Hydrogen Sulfide/chemistry , Waste Disposal Facilities , Sulfates/chemistryABSTRACT
Objective To screen long non-coding RNA(lncRNA)associated with disulfidptosis and investigate the immune landscape between lncRNA and pancreatic cancer,for effective guidance in clinical practice.Methods The normal and pancreatic cancer tissue samples were obtained from The Cancer Genome Atlas database,and the lncRNA associated with disulfidptosis was identified based on the Cox and LASSO regression analyses.A risk prognosis model was constructed,and its predictive performance was verified using comprehensive methods.An accurate nomogram was construted to predict the prognosis of patients with pancreatic cancer.The biological differences were analyzed via Gene Ontology,Gene Set Enrichment Analysis,and an immunoassay.The immunotherapy response was estimated using the tumor mutational burden(TMB)score.Results A total of 251 disulfidptosis-related lncRNAs were successfully identified,and three groups of lncRNAs were selected as the reference for the risk model.Pathway analysis showed that immune-related pathways were associated with disulfidptosis-related lncRNA risk models.The risk score was significantly correlated with immune cell infiltration and the ESTIMATE score.Patients with higher risk scores had elevated TMB,indicating that high-risk patients exhibited a better immune checkpoint blockade response.Conclusion The findings of this study contribute to a deeper understanding of disulfidpto-sis-related lncRNA and provide a potential therapeutic strategy for pancreatic cancer.
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The behavior of sulfate reduction, which was the source of hydrogen sulfide (H2S) odor, was investigated under changing pressure and temperature conditions inside landfills. The results showed that the release of H2S and methyl mercaptan (MM) was significantly inhibited at 25 °C and 50 °C under pressure, and the highest H2S and MM concentrations released were only 0.82 %-1.30 % and 1.87 %-4.32 % of atmospheric pressure, respectively. Analysis of the microbial community structure and identification of sulfate-reducing bacteria (SRB) revealed that temperature significantly altered the microbial community in the landfill environment, while pressure inhibited some bacteria and induced the growth and reproduction of specific bacteria. Key SRB (Desulfosporosinus-ASV212, Desulfitibacter-ASV1744) mediated differentiated sulfate reduction behavior in the pressure-bearing environment at 25 °C, while key SRB (Dethiobacter-ASV177, Desulfitibacter-ASV2355 and ASV316) were involved at 50 °C. This study provides a theoretical basis for the formulation of landfill gas management and control strategies.
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Landfills are reservoirs of antibiotic resistance genes (ARGs) and pathogens, and humans are exposed to these pollutants during extensive excavation of old landfills. However, the microbial contamination risk of landfilled waste with different ages has not been assessed. In this study, human bacterial pathogens (HBPs), ARGs, and virulence factors (VFs) were systematically determined using metagenomic analysis. Results showed that the abundance of HBPs, ARGs, and VFs increased with landfill age, the percentage of HBPs in refuse with deposit age of 10-12 years (Y10) was 23.75 ± 0.49%, which was higher than that in fresh refuse (Y0, 17.99 ± 0.14%) and refuse with deposit age of 5-6 years (Y5, 19.14 ± 0.15%), indicating that old refuse had higher microbial contamination risk than fresh refuse. Multidrug, macrolide, lincosamide, streptogramine, and tetracycline resistance genes were the primary ARGs, whereas lipooligosaccharides, type IV pili, and polar flagella were the dominant VFs in refuse. The HBPs showed a significant positive correlation with ARGs and VFs. Listeria monocytogenes, Salmonella enterica, Streptococcus pneumoniae, Acinetobacter baumannii, and Escherichia coli possibly possess both multiple ARGs and VFs and could be listed as high-risk HBPs in refuse. Mobile genetic elements, especially transposons, showed positive correlations with most ARGs and VFs, and they were identified as the primary factors accounting for the variations in ARGs and VFs. These findings will help understand the spread of ARGs and VFs in landfills and evaluate the potential risk of microbiological contamination in refuse of different landfill ages, thus providing guidance for preventing disease infection during landfill excavations.
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In somatic cells, microRNAs (miRNAs) bind to the genomes of RNA viruses and influence their translation and replication. In London and Berlin samples represented in GISAID database, we traced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineages and divided these sequenced in two groups, "Ancestral variants" and "Omicrons," and analyzed them through the prism of the tissue-specific binding between host miRNAs and viral messenger RNAs. We demonstrate a significant number of miRNA-binding sites in the NSP4 region of the SARS-CoV-2 genome, with evidence of evolutionary pressure within this region exerted by human intestinal miRNAs. Notably, in infected cells, NSP4 promotes the formation of double-membrane vesicles, which serve as the scaffolds for replication-transcriptional complexes and protect viral RNA from intracellular destruction. In 3 years of selection, the loss of many miRNA-binding sites in general and those within the NSP4 in particular has shaped the SARS-CoV-2 genomes. With that, the descendants of the BA.2 variants were promoted as dominant strains, which define current momentum of the pandemics.
Subject(s)
COVID-19 , MicroRNAs , Humans , SARS-CoV-2/genetics , SARS-CoV-2/metabolism , COVID-19/genetics , MicroRNAs/genetics , MicroRNAs/metabolism , Binding Sites , Berlin , Genome, ViralABSTRACT
Antibiotics and microplastics (MPs) have become critical concerns worldwide because of their increasing amount and ecological risks to ecosystems. However, how MPs exposure affects the bioaccumulation and risks of antibiotics in waterfowls remains poorly understood. In this study, Muscovy ducks were exposed to single and combined contamination with polystyrene MPs and chlortetracycline (CTC) for 56 days, and the effects of MPs on CTC bioaccumulation and their risks in duck intestines were investigated. MPs exposure reduced the bioaccumulation of CTC in the intestine and liver of ducks and increased their fecal CTC excretion. MPs exposure caused severe oxidative stress, inflammatory response, and intestinal barrier damages. Microbiome analysis showed that MPs exposure induced microbiota dysbiosis by increasing the abundance of Streptococcus and Helicobacter, the increase of which may exacerbate intestinal damages. Co-exposure to MPs and CTC alleviated the intestinal damage by regulating the gut microbiome. Metagenomic sequencing revealed that the combined exposure to MPs and CTC increased the abundance of Prevotella, Faecalibacterium, and Megamonas and incidence of total antibiotic resistance genes (ARGs), especially tetracycline ARGs subtypes in the gut microbiota. The results obtained herein provide new insights into the potential risks of polystyrene MPs and antibiotics in waterfowls living in aquatic environments.
Subject(s)
Chlortetracycline , Gastrointestinal Microbiome , Microbiota , Animals , Microplastics , Anti-Bacterial Agents/pharmacology , Plastics , Ducks , Polystyrenes , Chlortetracycline/pharmacology , IntestinesABSTRACT
Objective:Based on experience of robotic gastrointestinal surgery at the Department of General Surgery, Clinical Medicine Center of Gansu Provincial Hospital, this study explored the principles and methods of trocar layout for robotic "3+2" mode gastrointestinal surgery, suitable for beginners.Methods:From Apr 2017 to Oct 2022, the robotic gastrointestinal surgery team of Gansu Provincial Hospital completed 998 cases of robotic "3+2" mode gastrointestinal surgery, including 600 cases of gastric cancer, 100 cases of rectal cancer, 98 cases of descending colon and sigmoid colon cancer, 20 cases of transverse colon cancer, and 180 cases of right colon cancer. Through the continuous optimization and improvement of the problems encountered during the operation, combined with the operator's experience, and taking into account various aspects, we developed the robotic "3+2" mode trocar layout for gastrointestinal surgery.Results:Four principles of trocar layout were developed, namely, the principle of lens placement around the navel, the principle of symmetry in the main operation, the principle of 8-10cm distance between trocar holes, and the principle of symmetry in the auxiliary hole lens. Three trocar layout methods and principles applicable to robotic gastric surgery, and four applicable to robotic colorectal surgery were developed.Conclusion:The trocar layout method of robotic "3+2" mode gastrointestinal surgery is established based on a large number of robotic gastrointestinal surgery experiences. This method is simple and easy to learn, with strong repeatability and operability.
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AIM:To clarify the effect of miR-519d-3p on high glucose-induced human retinal microvascular endothelial cells(HRMEC)dysfunction and angiogenesis, and to elucidate the regulatory mechanism of miR-519d-3p on hypoxia inducible factor 1 subunit alpha(HIF-1α).METHODS: The normal glucose(NG)and high glucose(HG)cell models were established by inducing HRMEC with 5 and 30 mmol/L glucose, respectively. Control group: HG cell model was transfected with negative control mimics; mannitol group: the control group was added with 25 mmol/L mannitol; miR-519d-3p overexpression group: HG cell model was transfected with miR-519d-3p mimics; miR-519d-3p combined with HIF-1α overexpression group: HG cell model was co-transfected with miR-519d-3p mimics and HIF-1α overexpression vector. The expression of miR-519d-3p in each group was tested by real-time fluorescence quantitative PCR. The expression of HIF-1α protein in each group was tested by Western blotting. The binding sites between miR-519d-3p and HIF-1α were detected by luciferase reporter gene assay. The cell proliferation of each group was detected by CCK-8. The cell apoptosis of each group was tested by Hoechst 33342 staining. The protein expression of extracellular fluid inflammatory factors tumor necrosis factor-α(TNF-α), interleukin(IL)-1β and IL-6 in each group was tested by ELISA. The formation of new capillary lumen-like structures was detected by tubule formation assay.RESULTS: Compared with the NG, miR-519d-3p expression was significantly reduced in the HG cell model, while HIF-1α protein expression was significantly increased in the HG(all P<0.01). Compared with the control group, HIF-1α protein expression was significantly reduced in the miR-519d-3p overexpression group(P<0.01). The “CGUGAAA” sequence of miR-519d-3p could specifically bind to the “GCACUUU” sequence of HIF-1α 3'-untranslated region(3'-UTR). Compared with the control group, the miR-519d-3p overexpression group showed a significant increase in 24, 48 and 72h absorbance values, a significant decrease in cell apoptotic rate, a significant decrease in the concentrations of TNF-α, IL-1β and IL-6, and a significant decrease in the number of new capillary lumen-like structures(all P<0.01). Compared with the miR-519d-3p overexpression group, the miR-519d-3p combined with HIF-1α overexpression group showed a significant decrease in 24, 48 and 72h absorbance values, a significant increase in cell apoptotic rate, a significant increase in the concentrations of TNF-α, IL-1β and IL-6, and a significant increase in the number of new capillary lumen-like structures(all P<0.01). There was no difference between the control group and mannitol group in the comparison of the above indicators(all P>0.05).CONCLUSION: miR-519d-3p expression is down-regulated while HIF-1α protein expression is up-regulated in high glucose induced HRMEC model. HIF-1α is a target gene of miR-519d-3p. The miR-519d-3p targets HIF-1α to increase cell proliferation and reduce cell apoptosis and inflammation, thereby alleviating high glucose-induced HRMEC dysfunction and inhibiting angiogenesis.
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Objective To investigate the expression of CD276 in pan-cancer,its effect on patient prognosis,and its mechanism of action.Methods TCGA and GTEx databases were used to study the differential expression of CD276 in tumor and normal tissues;R language was used to analyze the effects of CD276 on the prognosis of patients with pan-cancer,the tumor microenvironment,the tumor mutation burden,and microsatellite instability;the correlation between the expression of CD276 in tumor tissues and the tumor immune cell infil-tration was further examined;the biological function of CD276 was analyzed using Gene Set Enrichment Analysis(GSEA);and finally,real-time PCR was used to validate the expression of CD276 in tumors in vitro.Results A statistical difference in CD276 expression was detected between tumor and normal tissues(P<0.05).CD276 affects tumor prognosis and is strongly associated with the tumor microenvi-ronment,tumor mutational burden,microsatellite instability,and tumor immune cell infiltration.Conclusion Comprehensive pan-cancer analysis identified CD276 as a biomarker for immune infiltration and poor cancer prognosis,which can be used as a novel immunomodula-tory target for the development of immunotherapeutically-targeted drugs,providing new ideas for tumor therapy.
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Postmenopausal osteoporosis is a kind of degenerative disease, also described as "invisible killer." Estrogen is generally considered as the key hormone for women to maintain bone mineral content during their lives. Iron accumulation refers to a state of human serum ferritin that is higher than the normal value but less than 1000 μg/L. It has been found that iron accumulation and osteoporosis could occur simultaneously with the decrease in estrogen level after menopause. In recent years, many studies indicated that iron accumulation plays a vital role in postmenopausal osteoporosis, and a significant correlation has been found between iron accumulation and fragility fractures. In this review, we summarize and analyze the relevant literature including randomized controlled trials, systematic reviews, and meta-analyses between January 1996 and July 2022. We investigate the mechanism of the effect of iron accumulation on bone metabolism and discuss the relationship of iron accumulation, osteoporosis, and postmenopausal fragility fractures, as well as the main clinical treatment strategies. We conclude that it is necessary to pay attention to the phenomenon of iron accumulation in postmenopausal women with osteoporosis and explore the in-depth mechanism of abnormal bone metabolism caused by iron accumulation, in order to facilitate the discovery of effective therapeutic targets for postmenopausal osteoporosis.
Subject(s)
Humans , Female , Osteoporotic Fractures , Osteoporosis, Postmenopausal/drug therapy , Postmenopause , Osteoporosis , Bone Density , Estrogens , Iron/therapeutic useABSTRACT
OBJECTIVE@#To investigate the occurrence of CSF3R mutation in patients with t(8;21) acute myeloid leukemia (AML) and its correlation with some clinical parameters.@*METHODS@#The clinical and laboratory data of 167 newly diagnosed AML patients with t(8;21) translocation were analyzed retrospectively. High-throughput DNA sequencing technology combined with Sanger sequencing method was used to detect 112 gene mutations. The occurrence of CSF3R gene mutation and its influence on the remission rate after chemotherapy were analyzed.@*RESULTS@#Among 167 patients with t(8;21) AML, 15 patients (9.0%) carried CSF3R mutations, including 6 cases of membrane proximal region mutations and 9 cases of truncation mutations in the cytoplasmic tail. The most common coexisting mutations of CSF3R were KIT (40.0%), TET2 (33.3%), DNMT3A (26.7%), FLT3 (20.0%), CBL (20.0%), IDH1 (13.3%), etc. Compared with the wild type, the CSF3R mutant group had a higher mutation rate of DNA methylation-related genes(P <0.001). The median peripheral white blood cell (WBC) count of patients with CSF3R gene mutation was 5.80 (3.20-8.56)×109/L at initial diagnosis, which was significantly lower than 8.80 (5.26-19.92)×109/L of the CSF3R wild-type patients (P =0.017). There was no significant difference between the two groups in sex, median age, FAB classification, hemoglobin level, platelet count, etc. (P >0.05). The CR rate of the CSF3R gene mutation group (100%) was significantly higher than that of the wild-type group (86.8%), but the difference was not statistically significant (P >0.05). The CSF3R gene mutation group had a significantly higher CD19 positive rate and a higher -X rate than the wild group (86.7% vs 47.4%, P =0.004; 33.3% vs 13.2%, P =0.037).@*CONCLUSION@#There is a high incidence of CSF3R mutation in t (8;21) AML patients. The clinical characteristics and coexisting mutation genes of CSF3R mutation-positive patients are different from those of wild-type patients.
Subject(s)
Humans , Retrospective Studies , Prognosis , Leukemia, Myeloid, Acute/genetics , Mutation , Signal Transduction , Receptors, Colony-Stimulating Factor/geneticsABSTRACT
The BNT162b2 bivalent BA.4/5 COVID-19 vaccine has been authorized to mitigate COVID-19 due to current Omicron and potentially future variants. New sublineages of SARS-CoV-2 Omicron continue to emerge and have acquired additional mutations, particularly in the spike protein, that may lead to improved viral fitness and immune evasion. The present study characterized neutralization activities against new Omicron sublineages BA.4.6, BA.2.75.2, BQ.1.1, and XBB.1 after a 4th dose (following three doses of BNT162b2) of either the original monovalent BNT162b2 or the bivalent BA.4/5 booster in individuals >55 years of age. For all participants, the 4th dose of monovalent BNT162b2 vaccine induced a 3.0x, 2.9x, 2.3x, 2.1x, 1.8x, and 1.5x geometric mean neutralizing titer fold rise (GMFR) against USA/WA1-2020 (a strain isolated in January 2020), BA.4/5, BA.4.6, BA.2.75.2, BQ.1.1, and XBB.1, respectively; the bivalent vaccine induced 5.8x, 13.0x, 11.1x, 6.7x, 8.7x, and 4.8x GMFRs. For individuals without SARS-CoV-2 infection history, BNT162b2 monovalent induced 4.4x, 3.0x, 2.5x, 2.0x, 1.5x, and 1.3x GMFRs, respectively; the bivalent vaccine induced 9.9x, 26.4x, 22.2x, 8.4x, 12.6x, and 4.7x GMFRs. These data suggest the bivalent BA.4/5 vaccine is more immunogenic than the original BNT162b2 monovalent vaccine against circulating Omicron sublineages, including BQ.1.1 that is becoming prevalent globally.
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The SARS-CoV-2 Omicron variant and its sublineages show pronounced viral escape from neutralizing antibodies elicited by vaccination or prior SARS-CoV-2 variant infection owing to over 30 amino acid alterations within the spike (S) glycoprotein. We and others have recently reported that breakthrough infection of vaccinated individuals with Omicron sublineages BA.1 and BA.2 are associated with distinct patterns of cross-neutralizing activity against SARS-CoV-2 variants of concern (VOCs). BA.2 breakthrough infection mediated overall stronger cross-neutralization of BA.2 and its descendants (BA.2.12.1, BA.4, and BA.5) compared to BA.1 breakthrough infection. Here we characterized the effect of Omicron BA.4/BA.5 S glycoprotein exposure on the magnitude and breadth of the neutralizing antibody response upon breakthrough infection in vaccinated individuals and in mice upon booster vaccination. We show that immune sera from triple mRNA-vaccinated individuals with subsequent Omicron BA.4/BA.5 breakthrough infection display broad and robust neutralizing activity against Omicron BA.1, BA.2, BA.2.12.1, and BA.4/BA.5. Administration of a prototypic BA.4/BA.5-adapted mRNA booster vaccine to mice following SARS-CoV-2 wild-type strain-based primary immunization is associated with similarly broad neutralizing activity. Immunization of naive mice with a bivalent mRNA vaccine (wild-type + Omicron BA.4/BA.5) induces strong and broad neutralizing activity against Omicron VOCs and previous variants. These findings suggest that when administered as boosters, mono- and bivalent Omicron BA.4/BA.5-adapted vaccines may enhance neutralization breadth, and in a bivalent format may also have the potential to confer protection to individuals with no pre-existing immunity against SARS-CoV-2.
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The COVID-19 pandemic created stressful working conditions for nurses and challenges for leaders. A survey was conducted among 399 acute and ambulatory care nurses measuring availability of calming and safety resources, perceptions of support from work, and intent to stay. Most nurses reported intent to stay with their employer, despite inadequate safety and calming resources. High levels of support from work were significantly influenced nurses' intent to stay. Leadership actions at the study site to provide support are described, providing context for results. Nurse leaders can positively influence intent to stay through consistent implementation of supportive measures.